Reliability of gait and dual-task measures in multiple sclerosis

BackgroundSingle-task (ST) and dual-task (DT) assessments are commonly used to evaluate motor and cognitive impairment in people with multiple sclerosis (MS). Although variability can influence repeated DT testing measures, the reliability of several DT variables over time has not been adequately explored. For instance, a third testing session has never been included to observe whether DT has a learning effect. DT cognition rate reliability has not yet been examined and dual-task cost (DTC), a widely used calculation for DT interpretation, has not been proven reliable.Research questionTo evaluate the reliability of ST and DT measures of gait and cognition over three test sessions.MethodsThis was a cross-sectional study involving 18 people with MS and 12 controls. Participants attended three test sessions, each one week apart. ST and DT (serial seven subtraction) gait variables, DTC, coefficient of variability (CV), and cognition rate were extracted and calculated using an instrumented walkway. Reliability was assessed using intraclass correlation coefficients (ICC) or Kendall’s coefficient of concordance (KCC; nonparametric test) and minimum detectable change (MDC); between-session learning effect was assessed using repeated measures ANOVA.ResultsICC/KCC values for ST and DT gait variables ranged from moderate to excellent (0.50-0.99). However, reliability for DT stride width and cognition rate was lower in controls. In general, DTC and CV variables had poor ICCs and high MDC values (49.19–1478.67 %), although some DTC variables had moderate or higher reliability in controls. Cognition rate was reliable in both MS (ICC 0.91) and controls (ICC 0.84). A learning effect between sessions was observed for DT velocity in both groups and for DTC cadence in people with MS.SignificanceST and DT gait measures as well as DT cognition rate are reliable outcomes for repeated testing, while DTC and CV variables may not be suitable for long-term monitoring.     

肌萎缩侧索硬化案

肌萎缩侧索硬化症(ALS)是一种常见的上、下运动神经元同时损害的一种疾病,临床常见肢体无力、肌肉萎缩等症状。属中医学“痿证”范畴,本例验案患者双上肢及左下肢活动无力伴肌肉萎缩2年余,加重半年,伴随肌张力增高、反射亢进等症状,辨证属肝肾亏虚型痿证,临床以针刺治疗为主,配合静脉注射、穴位注射以补益肝肾,养血柔筋,疗效显著。     

四种大宗常用中药饮片中黄曲霉毒素污染状况分布比较研究

目的 测定不同来源的4种大宗常用中药饮片中黄曲霉毒素（AFB₁、AFB₂、AFG₁和AFG₂）的含量，比较不同基质中药饮片中黄曲霉毒素的分布状况。方法 基于免疫亲和柱净化-高效液相色谱分离-荧光检测器（IAC-HPLC-FLD）方法，分析不同产地共75批中药样品。结果 柏子仁、薏苡仁、决明子及党参共计75批中药饮片中，阳性检出：26批柏子仁（AFs 1.22-46.67 μg·kg^-1，AFB₁ 1.22-31.40 μg·kg^-1）、4批薏苡仁（AFs 1.97-41.13 μg·kg^-1，AFB₁ 1.97-36.40 μg·kg^-1）、1批决明子（AFs 13.65 μg·kg^-1，AFB₁ 12.60 μg·kg^-1），阳性率41%，超标率15%。阳性样品经 LC-MS/MS确证，排除假阳性。4种大宗常用中药饮片柏子仁、薏苡仁、决明子、党参中黄曲霉毒素的污染水平依次降低，阳性检出率分别为77%、29%、7%、0%，表明中药材中黄曲霉毒素的污染状况与药材基质密切相关。结论 针对易污染AFs的中药品种，需进一步加强其污染状况的全面检测分析，为黄曲霉毒素的有效防控以及完善中药的质量标准提供科学依据，从而保障中药用药安全。     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

Acceptance of multiple injectable vaccines in a single immunization visit in The Gambia pre and post introduction of inactivated polio vaccine

BackgroundAs the World Health Organization (WHO) currently recommends that children be protected against 11 different pathogens, it is becoming increasingly necessary to administer multiple injectable vaccines during a single immunization visit. In this study we assess Gambian healthcare providers’ and infant caregivers’ attitudes and practices related to the administration of multiple injectable vaccines to a child at a single immunization visit before and after the 2015 introduction of inactivated polio vaccine (IPV). IPV introduction increased the number of injectable vaccines recommended for the 4-month immunization visit from two to three in The Gambia.MethodsWe conducted a cross-sectional questionnaire-based survey before and after the introduction of IPV at 4 months of age in a representative sample of all health facilities providing immunizations in The Gambia. Healthcare providers who administer vaccines at the selected health facilities and caregivers who brought infants for their 4 month immunization visit were surveyed.FindingsPrior to IPV introduction, 9.9% of healthcare providers and 35.7% of infant caregivers expressed concern about a child receiving more than 2 injections in a single visit. Nevertheless, 98.8% and 90.9% of infants received all required vaccinations for the visit before and after IPV introduction, respectively. The only reason why vaccines were not received was vaccine stock-outs. Infant caregivers generally agreed that vaccinators could be trusted to provide accurate information regarding the number of vaccines that a child needed.ConclusionHealthcare providers and infant caregivers in this resource limited setting accepted an increase in the number of injectable vaccines administered at a single visit even though some expressed concerns about the increase.     

高效液相色谱串联质谱法测定氯沙坦钾中的遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸

目的建立了一种高效液相色谱-三重四极杆串联质谱法,对氯沙坦钾原料药中遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸(NMBA)进行测定。方法色谱柱为岛津Shim-pack XR-ODSⅡ色谱柱(2.0 mm×150 mm,2.2μm),流动相为0.1%甲酸水溶液(A)和甲醇(B),进行梯度洗脱,流速0.3 mL·min^-1,柱温为40℃,采用ESI离子化-三重四极杆质谱多反应监测(MRM)正离子模式检测,碰撞电压分别为-11,-13和-13 V,碰撞气氩气270 kPa,NMBA的离子对分别为m/z 147.15→117.10,147.15→87.10和147.15→44.10。结果该方法中NMBA在1~100 ng·mL^-1内线性关系良好,日内和日间的保留时间和峰面积的重复性良好(RSD均小于1.10%,n=6和n=18),低、中、高3个浓度的平均回收率在94.40%~98.04%之间。结论本方法简单方便,可快速有效的对氯沙坦钾原料药中NMBA进行限度检查并实现定量分析。     

Determination of polycyclic aromatic hydrocarbons (PAHs) in cosmetic products by gas chromatography-tandem mass spectrometry

A gas chromatography coupled with tandem mass spectrometry (GC-MS/MS) method is developed to determine 18 representative polycyclic aromatic hydrocarbons (PAHs) in cosmetics, including Benzo[a]pyrene (BaP) and others. The method offers high sensitivity and selectivity under selected reaction monitoring (SRM) mode to satisfy the requirements of both quantitation and qualitation. The extraction solvent system used in this study is acetone/hexane 1:1 (v/v) and other purification procedure is unnecessary. The linearities of 18 PAHs are validated in different concentration in the range of 0.25–20 ng/mL individually with coefficient correlation (r) higher than 0.996. The recoveries for spiking 3 different concentrations are from 87.40% to 120.44% for 18 PAHs and the coefficient of variation (CV) are below 12.32%. Limit of quantification (LOQ) of 18 PAHs is in the range of 0.05–0.2 mg/kg. A matrix enhancement effect is observed and can be compensated with deuterated internal standard. The method has been successfully applied to 73 samples, over 40 of them are lipsticks. The results show none of the samples detect Benzo[a]pyrene (BaP) and Dibenzo[a,h]anthracene (DBA), both are classified as the most carcinogenic. 8 PAHs are detected and the average value between 0.08 and 0.27 mg/kg. This study offers a sensitive and simple method to analyze 18 representative PAHs successfully and can be applied to cosmetic products and raw materials.