Bone Mass,Bone Microstructure and Biomechanics in Patients with Hand Osteoarthritis

The impact of primary hand osteoarthritis (HOA) on bone mass, microstructure, and biomechanics in the affected skeletal regions is largely unknown. HOA patients and healthy controls (HCs) underwent high-resolution peripheral quantitative computed tomography (HR-pQCT). We measured total, trabecular, and cortical volumetric bone mineral densities (vBMDs), microstructural attributes, and performed micro–finite element analysis for bone strength. Failure load and scaled multivariate outcome matrices from distal radius and second metacarpal (MCP2) head measurements were analyzed using multiple linear regression adjusting for age, sex, and functional status and reported as adjusted Z-score differences for total and direct effects. A total of 105 subjects were included (76 HC: 46 women, 30 men; 29 HOA: 23 women, six men). After adjustment, HOA was associated with significant changes in the multivariate outcome matrix from the MCP2 head (p < .001) (explained by an increase in cortical vBMD (Δz = 1.07, p = .02) and reduction in the trabecular vBMD (Δz = −0.07, p = .09). Distal radius analysis did not show an overall effect of HOA; however, there was a gender-study group interaction (p = .044) explained by reduced trabecular vBMD in males (Δz = −1.23, p = .02). HOA was associated with lower failure load (−514 N; 95%CI, −1018 to −9; p = 0.05) apparent in males after adjustment for functional status. HOA is associated with reduced trabecular and increased cortical vBMD in the MCP2 head and a reduction in radial trabecular vBMD and bone strength in males. Further investigations of gender-specific changes of bone architecture in HOA are warranted. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

TACE对原发性肝癌患者的疗效及NLR、PLR的影响研究

目的研究经导管动脉化疗栓塞(TACE)对原发性肝癌患者的疗效及中性粒细胞/淋巴细胞计数比(NLR)、血小板/淋巴细胞计数比(PLR)的影响。方法选择2015年6月～2019年1月我院接诊的原发性肝癌患者80例作为研究对象,采用随机数表法将患者分为两组,每组各40例。对照组予传统肝切除术治疗,观察组采用TACE治疗。对比两组治疗后的临床效果,NLR、PLR、癌胚抗原(CEA)、可溶性B7-H4、可溶性白细胞介素-2受体(sIL-2R)及并发症发生情况。结果治疗后,两组患者的总有效率分别为75.00%和52.50%,观察组高于对照组,差异有统计学意义(P0.05);治疗前,两组患者NLR、PLR水平对比,差异无统计学意义(P0.05);治疗后,患者NLR、PLR水平下降,观察组低于对照组,差异有统计学意义(P0.05);治疗前,两组患者CEA、B7-H4、sIL-2R水平对比,差异无统计学意义(P0.05);治疗后,两组患者CEA、B7-H4、sIL-2R水平下降,观察组低于对照组,差异有统计学意义(P0.05);两组患者并发症发生率分别为17.50%、40.00%,观察组低于对照组,差异有统计学意义(P0.05)。结论在原发性肝癌患者中使用TACE效果显著,可有效改善患者肿瘤标志物水平,减少并发症,值得推广应用。     

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.     

How current risk assessment and risk management methods for drinking water in The Netherlands cover the WHO water safety plan approach

In the Netherlands, safe and sufficient drinking water is provided to the general population by ten drinking water companies. To guarantee safe drinking water the World Health Organization (WHO) developed a Water Safety Plan (WSP), a Risk Assessment and a Risk Management (RA/RM) framework. The objective of the study was to identify legally required RA approaches, to document application of RA/RM activities at Dutch drinking water companies and to determine to what extent these RA/RM activities as a whole cover all the elements of the WHO WSP approach. This study could be of interest to both managers of large water utilities and decision makers.The assessment was performed by means of a policy review and interviews with two to four staff members involved in RA/RM from all ten Dutch drinking water companies combined with a joint workshop. The drinking water companies are well aware of the potential hazards and risks that can influence the drinking water quality. To guarantee the supply of safe and sufficient drinking water, the Dutch drinking water sector uses six different legally required RA/RM approaches. This study shows that by using the six legally required RA/RM approaches, all WSP steps are covered. WSP entails a generic risk assessment for identifying all hazards and hazardous events from source to tap, whereas the six legally required RA/RM each focus on specific risks at an advanced level. Each risk assessment provides information on specific hazards and hazardous events covering a part of the water supply chain. These legal requirements are complemented with additional RA/RM activities at sector and water company level such as codes of practices and standard operating procedures. The outcomes of all RA/RM approaches combined provide information from source to tap. When using multiple RA/RM approaches, it is crucial to share and combine information derived from the different activities.     

HIV/AIDS and economic growth: Evidence from West Africa

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) is one of the leading causes of morbidity and mortality in West Africa. Prevalence among the most productive age group in West and Central Africa stood at 1.5%, 3.4.0%, 2.5%, and 2.1% in 1990, 2000, 2010, and 2015 respectively. This study examined the effect of HIV/AIDS on economic growth in West Africa with focus on 11 countries. The augmented Solow model, rooted in the neoclassical growth theory, was used, which was operationalized using dynamic panel data modeling approach. Incidence, prevalence, number of people living with HIV/AIDS (PLWHA), and AIDS‐related deaths were used to measure HIV/AIDS. Estimations using system GMM returned statistically significant results while those of first difference and difference GMM were not. From the outcome of system GMM analysis, a percentage increase in incidence, prevalence, PLWHA, and AIDS deaths correspondingly reduced growth significantly through their effects on life expectancy by 0.15%, 0.02%, 0.004%, and 0.03%. Acquired immune deficiency syndrome deaths and PLWHA lowered economic growth through enrolment but not significantly. The import of the findings is that HIV/AIDS threatens growth through life expectancy in West Africa. Therefore, its spread in the subregion should be effectively contained while proper treatment should be provided for all infected persons.