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01-5 ng/mL (R2 = 0.9991) and 0.005-20 ng/mL (R2 = 0.9999) for A-F and B-F, respectively. Extraction recoveries were 91.3%-97.6% with RSD ≤ 11.2% and 90.5%-94.3% with RSD ≤ 10.5% for A-F and B-F, respectively. Plasma matrix effects were 80.61%-84.58% for A-F and 80.67%-81.33% for B-F with RSD ≤ 13.9%. The validated assay indicated no significant differences in pharmacokinetic parameters (AUC0-t, Cmax and T1/2) derived from the assessment of A-F and B-F plasma concentrations between control and ethanol-exposed rats. This assay, for which the LOD was 3 pg/mL for A-F and B-F may help the forensic science field to determine fentanyl analogue-related causes of death and identify illicit drug tampering.The objective of this study is to evaluate in vitro stability of cocaine compounds, cocaine (COC), benzoylecgonine (BE), ecgonine methyl ester (EME) and benzoylecgonine ethyl ester (EBE), in blood and urine, during post-analysis custody. Stability was evaluated by measuring percent recovery. Parameters evaluated were time of custody (1 year), storage temperature (-20°C and 4°C), influence of preservative (only for blood samples) and pH (only for urine samples). The impact of the temperature is very important in blood samples. At -20°C all compounds demonstrated to be stable, with recoveries higher than 80% after 1 year. In contrast, degradation was observed in the concentration for all four compounds when the samples were maintained at 4°C. In these same conditions, the influence of the preservative was also noticeable and a higher stability was found in samples preserved with NaF. COC and EBE had similar profiles, and both compounds disappeared after 30 days in samples without NaF and after 150 days in samples with NaF added. EME disappeared after 185 days and after 215 days in samples without and with preservative, respectively. BE recoveries, after 365 days of storage, were 68.5% (in samples with NaF) and 3.7% (in samples without NaF). In urine samples, the four compounds were stable in all the studied conditions except when samples were at pH 8 and stored at 4°C where the compounds disappeared (COC and EBE after 75 days of storage and EME after 15 days). The exception was BE, with a recovery of 23% after 1 year of storage. Of the temperatures evaluated, -20°C seems to be optimal for storage to maintain the stability of cocaine and metabolites in biological samples. This can be further enhanced by maintaining a pH of 4 in urine samples and adding a NaF preservative to blood.Drug degradation as a consequence of putrefactive bacterial activity is a well-known factor that affects the identification and quantitation of certain substances of forensic interest. 10058-F4 ic50 Current knowledge on putrefaction-mediated degradation of drugs is, however, significantly lacking. This study aimed to investigate the degradation of 4-methylmethcathinone (4-MMC or mephedrone) and to detect its degradation products in putrefied biological matrices containing 4-MMC. The bacteria species Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Proteus vulgaris were grown in brain-heart infusion broth, spiked with 4-MMC and incubated at 37°C for 24 h. Postmortem human blood and fresh porcine liver macerate were also left to putrefy in sample tubes at room temperature for 1 week. Structural elucidation was based on modern spectroscopic analyses including the use of high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. All four putrefactive bacteria were capable of degrading 4-MMC extensively under the experimental conditions explored. Of particular interest was the discovery of a novel degradation product common to all four bacterial species, which was assigned as 2-hydroxy-1-(4-methylphenyl)propan-1-one (HMP) based on the spectroscopic data. This degradation product was detectable in both postmortem human blood and porcine liver samples. The stability of the identified degradation products, especially HMP, should be further investigated to assess their validity of serving as marker analytes for monitoring 4-MMC in postmortem toxicology.
Is there an (epi)genetic basis in patients with central precocious puberty (CPP) associated with multiple anomalies that unmasks underlying mechanisms or reveals novel genetic findings related to human pubertal control?
In a group of 36 patients with CPP associated with multiple phenotypes, pathogenic or likely pathogenic (epi)genetic defects were identified in 12 (33%) patients, providing insights into the genetics of human pubertal control.
A few studies have described patients with CPP associated with multiple anomalies, but without making inferences on causalities of CPP. Genetic-molecular studies of syndromic cases may reveal disease genes or mechanisms, as the presentation of such patients likely indicates a genetic disorder.
This translational study was based on a genetic-molecular analysis, including genome-wide high throughput methodologies, for searching structural or sequence variants implicated in CPP and DNA methylation analysis of candidate regions.
A cohort of 197 patients (188 girls)clinical-genetic approach in the elucidation of mechanisms and factors involved in pubertal control. Chromosome 14q32.2 disruption indicated the loss of imprinting of DLK1 as a probable mechanism of CPP. Two other chromosomal regions (7q11.23 and Xp22.33) represented new candidate loci potentially involved in this disorder of pubertal timing.
This work was supported by grant number 2018/03198-0 (to A.P.M.C.) and grant number 2013/08028-1 (to A.C.V.K) from the São Paulo Research Foundation (FAPESP), and grant number 403525/2016-0 (to A.C.L.) and grant number 302849/2015-7 (to A.C.L.) and grant number 141625/2016-3 (to A.C.V.K) from the National Council for Scientific and Technological Development (CNPq). The authors have nothing to disclose.
N/A.
N/A.In the pig industry, purebred animals are raised in nucleus herds and selected to produce crossbred progeny to perform in commercial environments. Crossbred and purebred performances are different, correlated traits. All purebreds in a pen have their performance assessed together at the end of a performance test. However, only selected crossbreds are removed (based on visual inspection) and measured at different times creating many small contemporary groups (CGs). This may reduce estimated breeding value (EBV) prediction accuracies. Considering this sequential recording of crossbreds, the objective was to investigate the impact of different CG definitions on genetic parameters and EBV prediction accuracy for crossbred traits. Growth rate (GP) and ultrasound backfat (BFP) records were available for purebreds. Lifetime growth (GX) and backfat (BFX) were recorded on crossbreds. Different CGs were tested CG_all included farm, sex, birth year, and birth week; CG_week added slaughter week; and CG_day used slaughter day instead of week.
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