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The Yeast Estrogen Screen (YES) has a specific mechanism of action that allows for the analysis of estrogenic EDC at low concentrations, and it has been broadly used to estimate the estrogenic potential of environmental samples. However, the experimental parameters of this assay still demand an investigation, such as cell density, incubation time, wavelength on the experimental outcome, cytotoxicity, and estrogenic activity adsorbed on suspended solids. We studied these interferences and applied the assay to single substances, mixtures, and environmental matrices from different sources. The increase in cell density amplifies the assay sensitivity only to a limited extent, while the reduction in incubation time decreased assay sensitivity - although it was not significant for surface water, no differences were observed between estradiol-equivalents derived of 48 h and 72 h measurements. The particulate phase was of utmost importance for the total estrogenic activity of the landfill leachate and surface water. Surface waters, landfill leachates and sediments also showed antiestrogenic activity and the integration of both estrogenic and antiestrogenic endpoints provided deeper insights into the potential risk associated with EDC. This study elucidated experimental interferences that may arise during the implementation and use of this assay, bringing more understanding to experimental parameters during the application of the assay for estrogenicity screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The presence of estrogenic endocrine disruptors in aquatic environments has been a concern and bioassays are recommended tools for their monitoring. However, the physicochemical properties of contaminants and the environmental matrix features may influence the resultant response. This study aimed to assess this influence on the Yeast Estrogen Screen (YES) assay. Mixtures of 17β-estradiol (E2) and humic acid (HA) were evaluated through the Schild approach aiming to investigate the interactions between estrogens and dissolved organic matter (DOM). Moreover, environmental samples from municipal landfill leachate and wastewater treatment plant (WWTP) influents and effluents were screened for (anti)estrogenic activity at both dissolved and particulate phases. Finally, results were statistically confronted with physicochemical parameters through principal component analysis (PCA). The HA test concentrations strongly reduced the E2 response, even at low levels. Humic substances may not only reduce estrogen bioavailability, but also interfere with the assay mechanism through enzymatic inhibition thus masking the sample estrogenic potential. Landfill leachate had total E2-Eq in the range 1282-2591 ng L -1 , while WWTP influent and effluent were in the range 12.1-41.4 and -1 , so estrogenicity was reduced 92% in average. Particulate phase was responsible for 33-100% of measured E2-Eq between matrices, though cytotoxicity occurred in some extracts. Antiestrogenic activity was observed in both phases and might also have masked the estrogenicity of samples. PCA did not resulted in positive correlations supporting a multiphase distribution pattern of estrogenic compounds. Nevertheless, the solids and organic matter characteristics supported the data interpretation. In conclusion, the in vitro YES assay is subjected to factors intrinsic to the environmental sample that can influence on the measured estrogenic response. Therefore, results interpretation should be performed together with organic matter characterization parameters, cytotoxicity and antiestrogenic activity evaluation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Endocrine disrupting chemicals (EDC) are exogenous substances that can potentially mimic hormonal substances and cause adverse effects on the endocrine system of living beings. The behavior and fate of these compounds in the environment is directly related to their physical-chemical properties, which indicate great affinity for solid and organic particles and suggest an inherent mechanism of fractionation between dissolved and particulate phases of aqueous matrices. However, few studies have been considering this fact when quantifying these pollutants and their effects through bioassays. In this study, the fractionation of estrogenic substances between dissolved and particulate phases in an urban stream was investigated via estrogenic activity evaluation by the YES assay. Two fractions of suspended solids (< 0.7 µm and between 0.45 and 0.7 µm) and the dissolved phase were considered and two approaches of SPE percolations were applied. Total estradiol equivalent (E2-Eq) values were observed in the 29-65 ng L -1 range, of which 35-62% were associated with the particulate phase. Most of the estrogenicity was associated with particles between 0.45 and 0.7 µm, whereas cytotoxicity was induced by extracts of particles greater than 0.7 µm. Results demonstrated the importance of solid fractions analysis towards the quantification of total estrogenic activity from aqueous environmental matrices and highlights the relevance of controlling fine suspended solids in sewage treatment plant effluents, regarding the control of endocrine disrupters in the environment., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Serotonergic psychedelics are emerging as potential antidepressant therapeutic tools, as suggested in a recent randomized controlled trial with ayahuasca for treatment-resistant depression. Preclinical and clinical studies have suggested that serum brain-derived neurotrophic factor (BDNF) levels increase after treatment with serotoninergic antidepressants, but the exact role of BDNF as a biomarker for diagnostic and treatment of major depression is still poorly understood. Here we investigated serum BDNF levels in healthy controls ( N = 45) and patients with treatment-resistant depression ( N = 28) before (baseline) and 48 h after (D2) a single dose of ayahuasca or placebo. In our sample, baseline serum BDNF levels did not predict major depression and the clinical characteristics of the patients did not predict their BDNF levels. However, at baseline, serum cortisol was a predictor of serum BDNF levels, where lower levels of serum BDNF were detected in a subgroup of subjects with hypocortisolemia. Moreover, at baseline we found a negative correlation between BDNF and serum cortisol in volunteers with eucortisolemia. After treatment (D2) we observed higher BDNF levels in both patients and controls that ingested ayahuasca ( N = 35) when compared to placebo ( N = 34). Furthermore, at D2 just patients treated with ayahuasca ( N = 14), and not with placebo ( N = 14), presented a significant negative correlation between serum BDNF levels and depressive symptoms. This is the first double-blind randomized placebo-controlled clinical trial that explored the modulation of BDNF in response to a psychedelic in patients with depression. The results suggest a potential link between the observed antidepressant effects of ayahuasca and changes in serum BDNF, which contributes to the emerging view of using psychedelics as an antidepressant. This trial is registered at http://clinicaltrials.gov (NCT02914769).