Trace amine-associated receptor 1 (TAAR1) agonism for psychosis:a living systematic review and meta-analysis of human and non-human data

BACKGROUND: Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies.METHODS: We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses.RESULTS: Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D 2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. CONCLUSIONS: TAAR1 agonists may be less efficacious than dopamine D 2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. REGISTRATION: PROSPERO-ID: CRD42023451628.</p

Removal of metronidazole from wastewater by Fe/charcoal micro electrolysis fluidized bed reactor

The aim of the research was to investigate the removal of metronidazole from aqueous solutions by Fe/charcoal micro-electrolysis fluidized bed reactor. The effective variables influencing the metronidazole removal including the initial pH of the solution, the initial concentration of metronidazole, contact time, aeration rate and Fe/charcoal ratio were studied. The amount of secondary iron ions pollution in the reactor effluent was investigated by a flame atomic absorption device. Degradation reaction kinetics were studied. The removal efficiency of metronidazole in the actual hospital wastewater sample was investigated under optimal conditions of the reactor. The stability and performance of the reactor was investigated through 4 consecutive cycles. Data analysis was performed by SPSS-16. The maximum removal efficiencies were obtained in optimal conditions including pH: 7, the contact time of 70 min, aeration rate of 6 L/min, charcoal/Fe ratio 1:1 and initial concentration of metronidazole of 10 mg/L as 90 and 78 percent for synthetic solutions and actual wastewater respectively. No secondary pollution of iron ions was detected. In the study of linear kinetic models, the degradation process followed pseudo-first kinetic order. The Fe/charcoal micro-electrolysis system is well-suited for efficient removal of antibiotics from aqueous solutions and applies to industrial scale. - 2019 Elsevier Ltd.This paper was carried out under the supervision of the Environmental Health Engineering Research Center. Kerman University of Medical Sciences with the support of the Vice-Chancellor for Research and Technology, Department of the University. We thank them for their help.Scopu

Removal of metronidazole from wastewater by Fe/charcoal micro electrolysis fluidized bed reactor

The aim of the research was to investigate the removal of metronidazole from aqueous solutions by Fe/charcoal micro-electrolysis fluidized bed reactor. The effective variables influencing the metronidazole removal including the initial pH of the solution, the initial concentration of metronidazole, contact time, aeration rate and Fe/charcoal ratio were studied. The amount of secondary iron ions pollution in the reactor effluent was investigated by a flame atomic absorption device. Degradation reaction kinetics were studied. The removal efficiency of metronidazole in the actual hospital wastewater sample was investigated under optimal conditions of the reactor. The stability and performance of the reactor was investigated through 4 consecutive cycles. Data analysis was performed by SPSS-16. The maximum removal efficiencies were obtained in optimal conditions including pH: 7, the contact time of 70 min, aeration rate of 6 L/min, charcoal/Fe ratio 1:1 and initial concentration of metronidazole of 10 mg/L as 90 and 78 percent for synthetic solutions and actual wastewater respectively. No secondary pollution of iron ions was detected. In the study of linear kinetic models, the degradation process followed pseudo-first kinetic order. The Fe/charcoal micro-electrolysis system is well-suited for efficient removal of antibiotics from aqueous solutions and applies to industrial scale. © 2019 Elsevier Ltd

Quantifying the reproducibility of scientometric analyses: a case study

Reproducibility of scientific articles and their findings has gained importance in the last years. Although most efforts have been made in biomedicine, health and psychology science, reproducibility is important and necessary in all the research fields. Thus, in this contribution an empirical evaluation of the reproducibility of scientometric studies was carried out. To do so, 285 articles published in the journal of Scientometrics in 2017 were examined in term of the following reproducibility artifacts: workflow, search strategy, database, software, the availability of the source code (where applicable) and the availability of the dataset. Our findings showed that whilst workflow and search strategy were well described in the majority of articles, the dataset used was shared by very few studies. The data was usually retrieved from the WoS and Scopus databases. Finally, a few articles shared the source code where ad-hoc software was used