The usefulness of measuring n-butyric acid concentration as a new indicator of blood decomposition in forensic autopsy

In forensic medicine, although various alcohols have been reported as indicators of decomposition in collected blood, no studies have examined short-chain fatty acids as indicators. In this study, the blood n-butyric acid concentration was quantified, and the association between n-butyric acid and decomposition was investigated to determine whether the detection of n-butyric acid could be a new indicator of decomposition. Among the forensic autopsies performed from 2016 to 2018 in our laboratory, the cases were divided into decomposed (n = 20) and non-decomposed (n = 20) groups based on macroscopic findings. Blood samples collected at the time of autopsy were derivatized with 3-nitrophenylhydrazine hydrochloride after solid-phase extraction. The n-butyric acid concentration was measured using liquid chromatography–tandem mass spectrometry. In addition, ethanol and n-propanol were measured using a gas chromatography-flame ionization detector. There was a significant difference (p < 0.01) in the concentrations of n-butyric acid between the decomposed and non-decomposed groups (0.343 ± 0.259 [0.030–0.973] and 0.003 ± 0.002 [0.001–0.007] mg/mL, respectively). In the decomposed group, n-butyric acid was detected at high concentrations, even in cases where n-propanol was low. These results suggest that n-butyric acid is more likely to be an indicator of blood decomposition than n-propanol.     

Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

毛霉目病原真菌的实验室鉴定及体外抗真菌药物敏感 性分析

摘要:目的以分子测序为参考 ,评估形态学、基质辅助激光解吸电离飞行时间质谱对毛霉目真菌的鉴定能力,分析毛霉目真菌对两性霉素B、泊沙康唑的体外药敏特点。方法收集 2018年1月-2022年2月广东省人民医院25例毛霉病住院患者标 本,进行镜检并对培养的茵落行形态学鉴定、质谱鉴定、分子测序和体外药敏试验。结果KOH 湿片法阳性率(76%)高于革兰染色法(32%),差异有统计学意义(P<0.05);形态学鉴定可将68%的菌株鉴定到属水平,3株鉴定错误,2株无法鉴定;将所 有菌株进行质谱鉴定,单用IVD和RUO数据库鉴定率分别为56%和44%,两库联合可将鉴定率提高为64%。毛霉目真菌对两性霉素B的抑制50%菌株生长的最小抑菌浓度(MIC3o)为1μg/mL,根霉属相比其他属对两性霉素B表现出较高的MIC 值,其中2株MIC>32 μg/mL,另2株MIC为8 μg/mL;根霉属对泊沙康唑的MICso为0.5 μg/mL,横梗霉属MICgo为4 μg/ mL,小克银汉霉属MICg0为2 μg/mL,有部分菌株表现出较低MIC值,同样亦有部分菌株对泊沙康唑表现出较高的MIC 值。结论 将传统镜检、培养与质谱技术和分子技术相结合,尽量将毛霉目真菌准确鉴定到种,并积极开展毛霉体外药敏试验,可为临床治疗提供参考依据。     

Pan-cancer proteomic map of 949 human cell lines

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Quantification of exhaled propofol is not feasible during single-lung ventilation using double-lumen tubes: A multicenter prospective observational trial

Background

Volatile propofol can be measured in exhaled air and correlates to plasma concentrations with a time delay. However, the effect of single-lung ventilation on exhaled propofol is unclear. Therefore, our goal was to evaluate exhaled propofol concentrations during single-lung compared to double-lung ventilation using double-lumen tubes.

Methods

In a first step, we quantified adhesion of volatile propofol to the inner surface of double-lumen tubes during double- and single-lumen ventilation in vitro. In a second step, we enrolled 30 patients scheduled for lung surgery in two study centers. Anesthesia was provided with propofol and remifentanil. We utilized left-sided double-lumen tubes to separately ventilate each lung. Exhaled propofol concentrations were measured at 1-min intervals and plasma for propofol analyses was sampled every 20 min. To eliminate the influence of dosing on volatile propofol concentration, exhalation rate was normalized to plasma concentration.

Results

In-vitro ventilation of double-lumen tubes resulted in increasing propofol concentrations at the distal end of the tube over time. In vitro clamping the bronchial lumen led to an even more pronounced increase (Δ AUC +62%) in propofol gas concentration over time. Normalized propofol exhalation during lung surgery was 31% higher during single-lung compared to double-lung ventilation.

Conclusion

During single-lung ventilation, propofol concentration in exhaled air, in contrast to our expectations, increased by approximately one third. However, this observation might not be affected by change in perfusion-ventilation during single-lung ventilation but rather arises from reduced propofol absorption on the inner surface area of the double-lumen tube. Thus, it is only possible to utilize exhaled propofol concentration to a limited extent during single-lung ventilation.

Registration of Clinical Trial

DRKS-ID DRKS00014788 ( www.drks.de ).     

Transdermal permeation of curcumin promoted by choline geranate ionic liquid: Potential for the treatment of skin diseases

The transdermal permeation of curcumin aided by choline and geranic acid ionic liquid (CAGE-IL) was addressed as a potential treatment for skin diseases. An in-depth analysis of the effect of CAGE-IL concentration in the enhancement of transdermal permeation of curcumin was performed, and the results were modelled via nonlinear regression analysis. The results obtained showed that a low percentage of CAGE-IL (viz. 2.0%, w/w) was effective in disrupting the skin structure in a transient fashion, facilitating the passage of curcumin dissolved in it.     

Pentobarbital overdose: A case of contract killing

Suicides by pentobarbital overdose have increased since about 2012, which appear to be influenced by technical information on active euthanasia that has spread over the Internet. We encountered a pentobarbital poisoning case of a patient with amyotrophic lateral sclerosis. A caregiver found the patient unconscious immediately after two visitors left the room. The patient was immediately transferred to the emergency hospital but eventually declared dead. A fatal concentration of pentobarbital was detected in peripheral blood samples collected in the emergency hospital and during autopsy (53.8 μg/mL and 29.4 μg/mL, respectively). Because the ratios of pentobarbital concentrations between the gastric contents and peripheral blood were 35 and 29 in the hospital and autopsy samples, respectively, it is likely that pentobarbital was administered via the gastrostomy tube. The patient had contacted the visitors through social media. Although the patient had requested the doctor perform active euthanasia and expressed a desire to end their life on social media, nobody had noticed the plan to commit suicide.     

蒲地蓝消炎口服液联合氢定乳膏治疗PICC局部湿疹临床观察

目的观察蒲地蓝消炎口服液联合应用氢定乳膏治疗PICC局部湿疹的疗效。方法采用病例对照研究的方法,选择PICC门诊2014年1月-2018年12月PICC局部湿疹患者80例,随机分为实验组39例和对照组41例,观察组用蒲地蓝消炎口服液联合氢定乳膏加局部敷料开窗法进行护理。对照组用氢定乳膏加局部敷料开窗法,比较2组的临床疗效。结果观察组39例,总有效34例(87.18%);对照组41例,总有效23例(56.10%)。2组比较差异具有统计学意义(P<0.01)。结论蒲地蓝消炎口服液联合氢定乳膏治疗PICC局部湿疹的效果优于对照组。     

高效液相色谱-荧光检测法测定性早熟女童血浆中双酚A和4-壬基酚的含量

目的：建立高效液相色谱-荧光检测法测定性早熟女童血浆中双酚A和4-壬基酚含量的方法。方法：采用Shim-pack VP-ODS C18色谱柱（150 mm×4.6 mm，5 μm），流动相为乙腈∶水=70∶30，流速1 mL/min，柱温30 ℃，检测激发波长275 nm，发射波长315 nm，外标法定量检测血浆中双酚A和4-壬基酚含量。结果：双酚A和4-壬基酚分别在1.45~5 937.50 ng/mL （r2=0.999 9，n=7），1.53~6 250.00 ng/mL（r2=0.998 8，n=7）范围内线性关系良好；日内、日间RSD均<7.83%，方法回收率均>94.6%。结论：本法简便、快速、灵敏、准确，适用于同时测定性早熟女童血浆中双酚A和4-壬基酚的含量和临床血样常规检测。