Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase.

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.

Dynamics of bacterial functional genes and community structures during rhizoremediation of diesel-contaminated compost-amended soil.

The objective of this study was to characterize the effects of organic soil amendment (compost) on bacterial populations associated with petroleum hydrocarbon (PH) degradation and nitrous oxide (N2O) dynamics via pot experiments. Soil was artificially contaminated with diesel oil at total petroleum hydrocarbon (TPH) concentration of 30,000 mg·kg-soil-1 and compost was mixed with the contaminated soil at a 1:9 ratio (w/w). Maize seedlings were planted in each pot and a total of ten pots with two treatments (compost-amended and unamended) were prepared. The pot experiment was conducted for 85 days. The compost-amended soil had a significantly higher TPH removal efficiency (51.1%) than unamended soil (21.4%). Additionally, the relative abundance of the alkB gene, which is associated with PH degradation, was higher in the compost-amended soil than in the unamended soil. Similarly, cnorB and nosZ (which are associated with nitric oxide (NO) and N2O reduction, respectively) were also highly upregulated in the compost-amended soil. Moreover, the compost-amended soil exhibited higher richness and evenness indices, indicating that bacterial diversity was higher in the amended soil than in the unamended soil. Therefore, our findings may contribute to the development of strategies to enhance remediation efficiency and greenhouse gas mitigation during the rhizoremediation of diesel-contaminated soils.

Evaluation of rhizoremediation and methane emission in diesel-contaminated soil cultivated with tall fescue (Festuca arundinacea).

Rhizoremediation, CH4 emission, and bacterial community dynamics were evaluated in diesel-contaminated soil cultivated with tall fescue via a pot experiment. At the beginning of the experiment, total petroleum hydrocarbons (TPHs) removal efficiency was 30.2% in tall fescue-cultivated soil, which was significantly higher than that of unplanted soil (19.4%). However, when compost was added as a soil amendment, TPHs removal efficiency increased to 39.2% in tall fescue-cultivated soil. Interestingly, potential CH4 emissions were more affected by the initial diesel concentration than by compost addition or tall fescue planting. Specifically, the potential CH4 emission was approximately 3.8 times higher in the treatment with the highest initial diesel concentration (T-WC38) than that of the treatment with the lowest initial diesel concentration (T-WC5). Functional gene analysis revealed that TPHs removal had a linear correlation with the alkB/16S gene ratio, whereas potential CH4 emission had a linear correlation with pmoA gene copy numbers. Initial diesel concentrations in soil also affected bacterial community structures and the genera Rhizobium, Halothiobacillus, and Geobacter were found to be positively linked to diesel-contaminated soil rhizoremediation. Therefore, this study provides useful insights into the development of strategies to enhance rhizoremediation efficiency and CH4 emission mitigation in diesel-contaminated soils.