Highlights • The Scott test gave a cocaine-like reaction to pyrrolidine-type cathinones. • Scott test specificity was improved by filtration of the second-step mixture. • The Chen-Kao test was useful ...for exclusion of cathinones. • A combination of the 2 tests as a new field-test procedure for cocaine is proposed.
The total cross sections were measured for coherent double neutral-pion photoproduction on the deuteron at incident energies below 0.9 GeV for the first time. No clear resonance-like behavior is ...observed in the excitation function for Wγd=2.38–2.61 GeV, where the d⁎(2380) dibaryon resonance observed at COSY is expected to appear. The measured excitation function is consistent with the existing theoretical calculation for this reaction. The upper limit of the total cross section is found to be 0.034 μb for the dibaryon resonance at Wγd=2.37 GeV (90% confidence level) in the γd→π0π0d reaction.
Summary
Background
Epidemiological studies have shown that smoking increases the propensity for atopy and asthma. However, the effects of smoking on atopy and eosinophilic inflammation in asthmatics, ...including the elderly, remain unknown.
Objective
To determine the effects of smoking on serum immunoglobulin E (IgE) levels and eosinophilic inflammation in asthmatics of all ages.
Methods
The associations of serum IgE levels, blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels with smoking and age in steroid‐naive asthmatics were cross‐sectionally assessed (n = 307). Levels of sputum eosinophil and thymic stromal lymphopoietin (TSLP) that promotes Th2 inflammation were also analysed. Current smokers were excluded when analysing contributing factors of FeNO.
Results
Levels of serum IgE, blood eosinophil and FeNO decreased with increasing age in never‐smokers, whereas decrease in serum IgE levels with increasing age was not observed in current smokers. In addition, current smoking was associated with higher blood eosinophil counts. In atopic asthmatics, age‐related declines in serum IgE levels were less steep in ex‐smokers than in never‐smokers, and atopic ex‐smokers with asthma showed higher blood eosinophil counts and higher FeNO irrespective of age. Lastly, sputum TSLP levels were associated with sputum eosinophil proportions and pack‐years. Current and ex‐smokers had higher TSLP levels than never‐smokers.
Conclusions and Clinical Relevance
In steroid‐naive asthmatics, smoking may attenuate the age‐related decrease in IgE levels and maintain eosinophilic inflammation, in which TSLP may be involved.
Highlights • We tried to identify psychoactive drugs by near infrared spectrometry. • We optimized data-pretreatment methods and library search algorithm. • Identification criteria were decided using ...the authentic drug standards. • 8 of 11 forensic samples were truly identified by the criteria.
Abstract
Tumor-treating field (TTF) therapy has been receiving attention as a new minimally invasive treatment for cancer. In this treatment, an alternating electric field applied to target cells ...inhibits cell division by a dielectrophoretic force acting on chromosomes and microtubules. Previous studies have shown that an extremely weak electric field of only a few volts per centimeter interferes with chromosome migration and spindle formation. However, the therapeutic range of TTF treatment is still limited. To increase the efficacy of the treatment, the electric field to the target cells must be optimized. Therefore, the aim of this study was to investigate the effect of the electric field frequency, cell morphology, and electrical properties on the outcome of TTF treatment. Three-dimensional finite element models of a sphere and dividing cell were developed, and the distributions of the electric field and dielectrophoretic force were calculated.
Purpose
This study aims to expose the toxicity of fentanyl analogs and their metabolites by measuring the agonistic activity of these compounds on opioid receptors.
Methods
The agonistic activity of ...fentanyl, four analogs of fentanyl (acetylfentanyl, butyrylfentanyl, tetrahydrofuranylfentanyl, and furanylfentanyl), and their metabolites were evaluated using a cell-based assay system, which measured the cellular cAMP level after the reaction of a test compound with cells expressing opioid receptor.
Results
Fentanyl and its four analogs showed agonistic activity on μ-opioid receptor at < 10 nM, whereas these compounds were inactive at δ- and κ-opioid receptors even at 100 nM. Similarly, no metabolites showed agonistic activity on δ- and κ-opioid receptors. Meanwhile, several metabolites were active at μ-opioid receptor. β-Hydroxy metabolites exhibited strong activity nearly equivalent to those of the parent drugs. Some 4'-hydroxy metabolites and
N
-acyl group-hydroxylated metabolites were still active; however, their activity drastically decreased compared to the parent drugs.
Conclusions
Most of the metabolic reactions drastically diminish the agonistic activity of fentanyl analogs; exceptionally, β-hydroxylation maintains the activity at a level nearly equal to that of the parent drugs. However, β-hydroxy metabolites should contribute less to the poisoning caused by the ingestion of fentanyl analogs.
•A simple system for evaluating PCR amplification efficiencies is constructed.•Methanol is recommended for chemical test before DNA extraction from cannabis resin.•Adsorbents, such as powdered ...activated carbon, are effective for purifying DNA.•Purified DNA can be obtained from cannabis resin in about 10 min by optimal methods.
In recent years, analysis of cannabis DNA has been increasingly used in forensic drug tests. However, in the case of cannabis resin, a processed marijuana product, complicated procedures are required for the extraction of clean DNA, as the presence of various impurities inhibits PCR amplification. Therefore, in this study, we attempted to identify the factors that would allow quick and simple DNA extraction from cannabis resin with a commercially available kit. We also constructed a simple assay system for comparing relative amplification efficiencies by end-point PCR and used it to evaluate the purity of the obtained DNA solutions. For extraction with a kit that contains a silica column, reducing the starting amount of resin, using the residue remaining after methanol extraction, dilution of the final solution, extraction with an equal amount of powdered activated carbon or an excess amount of polyvinylpolypyrrolidone, and the addition of an appropriate amount of polyvinylpyrrolidone to the solution after extraction were effective measures that improved amplification efficiency. Furthermore, the use of the most rapid alkaline extraction kit combined with the addition of powdered activated carbon allowed obtaining DNA solutions with sufficient amplification efficiency in about 10min. These findings should be useful for routine DNA analysis of cannabis resin during forensic examination.
Segmental hair analysis is used to estimate the time of drug intake at monthly precision in drug‐related crimes. Previously, we advanced this analytical method to specify the day of drug intake by ...cutting a strand of hair into 0.4‐mm segments, which correspond to daily hair growth. Herein, we investigated the distributions of 7 compounds in a strand of hair using micro‐segmental analysis. Several strands of hair were collected 33.1−229.4 days after subjects were administered 4 pharmaceutical products that contained 10 drugs in single doses within 32 hours. The administered drugs and resulting metabolites were extracted from 0.4‐mm hair segments and quantified using liquid chromatography–tandem mass spectrometry. Acidic and neutral compounds were detected at low amounts in any of the hair segments analyzed. Epinastine, fexofenadine, dihydrocodeine, chlorpheniramine, and the chlorpheniramine metabolite, desmethylchlorpheniramine each was localized to 2 regions within a strand of hair. By contrast, methylephedrine and its metabolite, ephedrine, each was localized to only a region. Among 20 individual strands of hair associated with different subjects and head regions, few differences in the shapes of drug concentration–hair segment curves for each compound were detected. Our data indicated that 2 mechanisms for drug uptake into hair can operate depending on drug properties and that co‐administered drugs can be localized to different regions in a strand of hair. Micro‐segmental analysis may aid in the identification of the day of drug intake and help to elucidate the mechanisms of drug uptake into hair.
Micro‐segmental analysis of a strand of hair visualized the distributions of 7 compounds in 22 strands of hair. The spatial resolution in the analysis corresponds to 1‐day hair growth length. The differences in localizations between co‐administered drugs were first founded.
Summary
Background
Genetic markers of susceptibility to asthma exacerbations in adults remain unclear.
Objective
To identify genetic markers of asthma exacerbations, particularly in patients with ...type‐2 inflammatory endotype.
Methods
In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin‐4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type‐2 inflammatory endotype) were considered in the analysis.
Results
Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type‐2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37–18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47–11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05–7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type‐2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type‐2 and neutrophilic inflammations.
Conclusions and Clinical Relevance
IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type‐2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.
The transversely polarized target (PT) of the COMPASS (NA58) collaboration at CERN has been used for Drell–Yan measurements in 2015 and 2018. The transverse spin structure of the proton has been ...studied using a negative pion beam and a solid ammonia target. Employing the dynamic nuclear polarization (DNP) method, proton polarization values of more than 80% have been routinely achieved after one day, at a homogeneous magnetic field of 2.5 T and using a 3He/4He dilution refrigerator. During the data-taking the target operates in a transversely oriented magnetic dipole field at 0.6 T. This so-called frozen spin operation mode without the DNP pumping process leads to a slow depolarization of the target material, which is further accelerated by the heat input of the pion beam, produced secondary particles and radiation damage effects to the target material. Ammonia has the highest resistance against radiation-induced depolarization among known solid target materials. The proton polarization has been measured by the nuclear magnetic resonance (NMR). Relaxation times of about 1100 h have been observed for the proton polarization resulting in an average polarization between 68% and 76% during about two weeks long data-taking periods. To achieve a systematic uncertainty of the polarization ΔP/P as low as 3.2% and a statistical one of less than 1.8% two large target cells with appropriate positioning of the NMR-coils have been built.
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