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Abstract Adenosine-to-inosine (A-to-I) editing is a prevalent post-transcriptional RNA modification within the brain. Yet, most research has relied on postmortem samples, assuming it is an accurate representation of RNA biology in the living brain. We challenge this assumption by comparing A-to-I editing between postmortem and living prefrontal cortical tissues. Major differences were found, with over 70,000 A-to-I sites showing higher editing levels in postmortem tissues. Increased A-to-I editing in postmortem tissues is linked to higher ADAR and ADARB1 expression, is more pronounced in non-neuronal cells, and indicative of postmortem activation of inflammation and hypoxia. Higher A-to-I editing in living tissues marks sites that are evolutionarily preserved, synaptic, developmentally timed, and disrupted in neurological conditions. Common genetic variants were also found to differentially affect A-to-I editing levels in living versus postmortem tissues. Collectively, these discoveries offer more nuanced and accurate insights into the regulatory mechanisms of RNA editing in the human brain.

Introduction and Objectives: Allergic rhinitis is a condition with high global prevalence most effectively treated with antihistamines and antileukotrienes. This study aimed to evaluate the bioequivalence of fexofenadine and montelukast in a fixed-dose combination tablet versus the components administered simultaneously., Materials and Methods: An open, randomized, 2×2 crossover study was performed in 78 healthy volunteers. Fexofenadine-montelukast tablets containing 120 mg and 10 mg, respectively, were used as the test treatment, and 120 mg fexofenadine tablets and 10 mg montelukast tablets were used as the reference treatment. Concentrations of fexofenadine and montelukast in plasma were determined by protein precipitation and analysis by liquid chromatography/mass spectrometry or liquid chromatography tandem mass spectrometry., Results: The 90% confidence intervals (CIs) obtained for fexofenadine were 87.612-102.144 for area under the curve of the plasma concentration after administration to the last concentration (AUC 0-t ), 88.471-102.282 for the AUC of the plasma concentration extrapolated to infinity (AUC 0-∞ ), and 91.413-108.544 for the maximum plasma concentration (C max ). For montelukast, they were 96.418-108.416 for AUC 0-t , 93.273-106.642 for AUC 0-∞ and 94.749-110.178 for C max . The ratio and CIs of the values subjected to logarithmic transformation for each parameter were within the range of acceptability of 80%-125%, demonstrating the bioequivalence of the combined fixed-dose tablet to the components administered separately at the same doses. No adverse events were recorded during the study., Conclusions: This study has shown the bioequivalence of the combined fixed-dose tablet, which may be considered a new alternative for the treatment of allergic rhinitis., Competing Interests: The authors VC-M and GS-C are employees of Sanofi Aventis de Mexico S.A. de C.V.No conflict of interest from iPharma members.