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.     

Assessment of oral ciprofloxacin impaired gut barrier integrity on gut bacteria in mice

Gut bacteria and gut barrier plays important roles in body homeostasis. Ciprofloxacin (CPFX) is widely used to treat bacterial infections. However, whether high dosage of CPFX has side effects on gut barrier integrity is still unclear. Our results indicated that the High CPFX treatment (1 mg/ml) caused weight loss, nervousness, anorexia, and increased apoptosis cells in gut, but less influence was observed in the Low CPFX group (0.2 mg/ml). Meanwhile, the High CPFX treatment impaired tight junction molecules Ocln/ZO-1 level and down-regulated antibacterial genes expression (reg3γ, pla2g2α and defb1). Further, the High CPFX treatment increased pro-inflammatory cytokine IL-1β in intestinal tract, decreased IL-17A of duodenum but increased IL-17A of colon at day 37. In addition, the gut bacterial diversity and richness behaved significantly loss regarding CPFX treatment, especially in the High CPFX group during the experiment. Indole exhibited sharply decline in both Low and High CPFX groups at day 7, and the High CPFX mice needed longer time on restoring indole level. Meanwhile, CPFX treatment strongly decreased the concentrations of butyric acid and valeric acid at day 1. Correlation analysis indicated that the linked patterns between the key bacteria (families Bacteroidales_S247, Ruminococcaceae and Desulfovibrionaceae) and metabolites (indole and butyric acid) were disturbed via the CPFX treatment. In conclusion, the High CPFX treatment impaired the gut barrier with the evidence of reduced expression of tight junction proteins, increased apoptosis cells and inflammatory cells, decreased the bacterial diversity and composition, which suggesting a proper antibiotic-dosage use should be carefully considered in disease treatment.     

Genetic variation of 17 autosomal STR loci in the Lahu population from Yunnan and phylogenetic structure exploration among 28 populations

This study evaluated the genetic variation of 17 autosomal short tandem repeat (STR) loci included in the PowerPlex® 18D Kit. Samples of 562 unrelated healthy Lahu individuals living in Yunnan Province in southwestern China were investigated. The data were analyzed to provide information on allele frequencies and other statistical parameters relevant to the forensic population. Of the 17 loci, 16 reached the Hardy–Weinberg equilibrium after Bonferroni correction. A total of 176 alleles were identified in 17 STR loci, and allele frequencies ranged from 0.000 890 to 0.578 292. The combined discrimination power (CPD) and probability of excluding paternity (CPE) of the 17 STR loci were 0.999 999 999 999 999 999 489 and 0.999 998 301 753 122. The genetic relationships among 28 populations were also estimated.     

Investigation of non-linear Mate1-mediated efflux of trimethoprim in the mouse kidney as the mechanism underlying drug-drug interactions between trimethoprim and organic cations in the kidney

The purpose of this study was to elucidate the involvement of Mate1 in the tubular secretion of trimethoprim and saturation of Mate1-mediated efflux to address the mechanisms underlying the pharmacokinetic drug interactions with trimethoprim. Trimethoprim is a more potent inhibitor of MATE2-K than MATE1 with K_i values (μM) of 0.030–0.28 and 2.4–5.9, respectively. Trimethoprim is a substrate of human MATE1 and MATE2-K with K_m values of 2.3 ± 0.9 and 0.018 ± 0.004 μM, and mouse Mate1, but not human OCT2, mouse Oct1 and Oct2. Pyrimethamine significantly reduced the renal clearance (CL_R) of trimethoprim (mL/min/kg) from 40.0 ± 5.1 to 20.1 ± 3.7 (p < 0.05). Trimethoprim was given to mice at three infusion rates (150, 500, and 1500 nmol/min/kg). Together with an increase in the plasma concentrations of trimethoprim, the CL_R (mL/min/kg) of trimethoprim decreased to 25.9 ± 3.2, 13.5 ± 5.7, and 8.92 ± 1.50 at the respective rates. Trimethoprim decreased the CL_R of rhodamine 123 in an infusion rate-dependent manner: 11.5 ± 1.3 (control), 5.17 ± 1.55, 1.31 ± 0.50, and 0.532 ± 0.180. These results suggest that Mate1 mediates the tubular secretion of trimethoprim, and at therapeutic doses, MATEs-mediated efflux can be saturated, and thereby, cause drug interactions with other MATE substrates.     

The effect of short or long sleep duration on quality of life and depression: an internet-based survey in Japan

BackgroundTo date, no previous studies have evaluated the relationship between sleep duration and quality of life (QOL) or depression in the general population after controlling for daytime sleepiness and sleep disturbances.MethodsA web-based cross-sectional survey was conducted with 8698 subjects aged 20–69 years. We examined the relationships between weekday sleep duration and daytime sleepiness, sleep disturbance, QOL and depression, using the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (without the item for sleep duration), 8-item Short Form and Center for Epidemiological Studies Depression Scale (CES-D).ResultsDaytime sleepiness tended to increase in proportion to shorter weekday sleep durations. Sleep disturbances, physical and mental QOL, and CES-D scores were worse in both the shorter and longer sleep groups compared with the group with 7–8 h of sleep. Hierarchical logistic regression analyses revealed that short sleep duration but not long sleep duration was significantly associated with reduction of both physical and mental QOL, even after controlling for the presence of daytime sleepiness and sleep disturbance. Both short and long sleep duration were independently and significantly correlated with depression after controlling for daytime sleepiness; however, there was no statistically significant association after adjusting for the effects of sleep disturbance.ConclusionsThe results suggested adverse effects of short sleep but not long sleep on both physical and mental QOL. In addition, the negative impact of specific types of sleep disturbance on depression may be greater than the impact of shortening of sleep duration.