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Anxiety and epilepsy are common worldwide and represent a primary global health concern. Fisetin, a flavonoid isolated from Bauhinia pentandra, has a wide range of biological activities may be a promising alternative to combat diseases related to the central nervous system (CNS). The present study aimed to investigate the anxiolytic and anticonvulsant effects of fisetin on adult zebrafish. Furthermore, molecular docking simulations were performed to improve the results. Fisetin did not present toxicity and caused anxiolytic behavior and delayed seizures in animals. This effect may occur through serotonin neurotransmission at 5-HT 3A and/or 5-HT 3B receptors. Molecular docking simulations showed that fisetin interacts with the orthosteric site of the 5-HT 3A receptor with strong H-bond interactions with the Trp156 residue, with a strong contribution from the catechol ring, a behavior similar to that of the antagonist co-crystallized inhibitor granisetron (CWB). Fisetin may be a promising alternative to combat diseases related to the central nervous system., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Conformational analyses of organic compounds in solution still represent a challenge to be overcome. The traditional methodology uses the relative energies of the conformations to decide which one is most likely to exist in the experimental sample. The goal of this work was to deepen the approach of conformational analysis of flavonoid rutin (a well-known antioxidant agent) in DMSO solution. The methodology we used in this paper involves expanding the sample configuration space to a total of 44 possible geometries, using Molecular Dynamics (MD) simulations, which accesses structures that would hardly be considered with our chemical perception, followed by DFT geometry optimizations using the ω B97X-D/6-31G(d,p) - PCM level of theory. Spectroscopic and thermodynamic analyses were done, by calculating the relative energies and nuclear magnetic resonance ( 1 H-NMR) chemical shifts, comparing the theoretical and experimental 1 H-NMR spectra (DMSO- d 6 ) and evaluating Mean Absolute Error (MAE). The essence of this procedure lies in searching for patterns, like those found in traditional DNA tests common in healthcare. Here, the theoretical spectrum plays the role of the analyzed human sample, while the experimental spectrum acts as the reference standard. In solution, it is natural for the solute to dynamically alter its geometry, going through various conformations (simulated here by MD). However, our DFT/PCM results show that a structure named 32 with torsion angles ϕ 1 and ϕ 2 manually rotated by approx. 20° showed the best theoretical-experimental agreement of 1 H-NMR spectra (in DMSO- d 6 ). Relative energies benchmarking involving 16 DFT functionals revealed that the ω B97X-D is very adequate for estimating energies of organic compounds with dispersion of charge (MAE < 1.0 kcal mol -1 , using ab initio post-Hartree-Fock MP2 method as reference). To describe the stability of the conformations, calculations of Natural Bonding Orbitals (NBO) were made, aiming to reveal possible intramolecular hydrogen bonds that stabilize the structures. Since van der Waals (vdW) interactions are difficult to be identified by NBO donations, the Reduced Density Gradient (RDG) were calculated, which provides 2D plots and 3D surfaces that describe Non-Covalent Interactions (NCI). These data allowed us to analyze the effect of dispersion interactions on the relative stability of the rutin conformations. Our results strongly indicate that a combination of DFT ( ω B97X-D)-PCM relative energies and NMR spectroscopic criterion is a more efficient strategy in conformational analysis of organic compounds in solution., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Cumulative trauma is usually devastating and can lead to severe psychological consequences, including posttraumatic stress disorder (PTSD). Exposure to various types of traumas, particularly during childhood, can be even more deleterious than the sheer number of events experienced. This epidemiological study is the first to investigate the impact of discrete childhood traumatic exposure on the risk of developing lifetime PTSD in a representative sample of the general population of the two biggest Brazilian cities. Participants were aged between 15 and 75 years old, living in São Paulo and Rio de Janeiro, Brazil, who had experienced traumatic events (N = 3,231). The PTSD diagnosis was assessed using the DSM-IV criteria through the version 2.1 of Composite International Diagnostic Interview. To operationalize childhood cumulative trauma, we considered the sum of 15 different childhood trauma categories that occurred before PTSD onset. The final multivariate logistic regression model indicated a strong relationship between the number of discrete types of childhood traumas and the likelihood of the lifetime PTSD development. The lifetime PTSD risk increased 28 % with each different type of childhood trauma when adjusted by confounds. Our study strengthens the evidence associating childhood cumulative trauma to increased lifetime PTSD risk., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: To evaluate the prevalence of abnormal ECG findings and their association with imaging results in male Brazilian football players., Methods: The 'B-Pro Foot ECG' is a multicentre observational study conducted in 82 Brazilian professional clubs. It analysed 6125 players aged 15-35 years (2496 white, 2004 mixed-race and 1625 black individuals) who underwent cardiovascular screening from 2002 to 2023. All ECGs were reviewed by two experienced cardiologists in the athlete's care. Those with abnormal findings underwent further investigations, including a transthoracic echocardiogram (TTE). Cardiac magnetic resonance (CMR) was subsequently performed based on TTE findings or clinical suspicion., Results: In total, 180 (3%) players had abnormal ECGs and 176 (98%) showed normal TTE results. Athletes aged 26-35 years had a higher prevalence of abnormal ECGs than younger athletes (15-25 years). Black players had a higher prevalence of T-wave inversion (TWI) in the inferior leads than white players (2.6% vs 1.4%; p=0.005), as well as in V5 (2.9%) and V6 (2.1%) compared with white (1.2% and 1.0%; p<0.001) and mixed-race (1.5% and 1.2%; p<0.05) players, respectively. TTE parameters were similar across ethnicities. However, four out of 75 players with inferolateral TWI showed abnormal TTEs and CMR findings consistent with cardiomyopathies. CMR also showed cardiomyopathies or myocarditis in four players with inferolateral TWI and normal TTEs. In total, nine (0.1%) athletes were diagnosed with cardiac diseases and were followed for 40±30 months, with no cardiac events documented., Conclusion: This study found a 3% prevalence of abnormal ECGs in male Brazilian football players. Inferolateral TWI was associated with cardiac pathologies confirmed by CMR, even in athletes with a normal TTE., Competing Interests: Competing interests: RS is an Established Investigator of the National Council for Scientific and Technological Development (CNPq), Brasília, Brazil., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)