Modulation of serum brain-derived neurotrophic factor by a single dose of ayahuasca : observation from a randomized controlled trial

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)

Bosch's industry 4.0 advanced Data Analytics: historical and predictive data integration for decision support

Industry 4.0, characterized by the development of automation and data exchanging technologies, has contributed to an increase in the volume of data, generated from various data sources, with great speed and variety. Organizations need to collect, store, process, and analyse this data in order to extract meaningful insights from these vast amounts of data. By overcoming these challenges imposed by what is currently known as Big Data, organizations take a step towards optimizing business processes. This paper proposes a Big Data Analytics architecture as an artefact for the integration of historical data - from the organizational business processes - and predictive data - obtained by the use of Machine Learning models -, providing an advanced data analytics environment for decision support. To support data integration in a Big Data Warehouse, a data modelling method is also proposed. These proposals were implemented and validated with a demonstration case in a multinational organization, Bosch Car Multimedia in Braga. The obtained results highlight the ability to take advantage of large amounts of historical data enhanced with predictions that support complex decision support scenarios.This work has been supported by FCT -Fundacao para a Ciencia e Tecnologia within the Project Scope: UIDB/00319/2020, the Doctoral scholarships PD/BDE/135100/2017 and PD/BDE/135105/2017, and European Structural and Investment Funds in the FEDER component, through the Operational Competitiveness and Internationalization Programme (COMPETE 2020) [Project n degrees 039479; Funding Reference: POCI-01-0247-FEDER039479]. The authors also wish to thank the automotive electronics company staff involved with this project for providing the data and valuable domain feedback. This paper uses icons made by Freepik, from www.flaticon.com

Changes in cortisol but not in brain-derived neurotrophic factor modulate the association between sleep disturbances and major depression

Sleep disturbance is a symptom consistently found in major depression and is associated with a longer course of illness, reduced response to treatment, increased risk of relapse and recurrence. Chronic insomnia has been associated with changes in cortisol and serum brain-derived neurotrophic factor (BDNF) levels, which in turn are also changed in major depression. Here, we evaluated the relationship between sleep quality, salivary cortisol awakening response (CAR), and serum BDNF levels in patients with sleep disturbance and treatment-resistant major depression (n = 18), and in a control group of healthy subjects with good (n = 21) and poor (n = 18) sleep quality. We observed that the patients had the lowest CAR and sleep duration of all three groups and a higher latency to sleep than the healthy volunteers with a good sleep profile. Besides, low CAR was correlated with more severe depressive symptoms and worse sleep quality. There was no difference in serum BDNF levels between groups with distinct sleep quality. Taken together, our results showed a relationship between changes in CAR and in sleep quality in patients with treatment-resistant depression, which were correlated with the severity of disease, suggesting that cortisol could be a physiological link between sleep disturbance and major depression

Scaling Estimates of Vegetation Structure in Amazonian Tropical Forests Using Multi-Angle MODIS Observations

Detailed knowledge of vegetation structure is required for accurate modelling of terrestrial ecosystems, but direct measurements of the three dimensional distribution of canopy elements, for instance from LiDAR, are not widely available. We investigate the potential for modelling vegetation roughness, a key parameter for climatological models, from directional scattering of visible and near-infrared (NIR) reflectance acquired from NASA's Moderate Resolution Imaging Spectroradiometer (MODIS). We compare our estimates across different tropical forest types to independent measures obtained from: (1) airborne laser scanning (ALS), (2) spaceborne Geoscience Laser Altimeter System (GLAS)/ICESat, and (3) the spaceborne SeaWinds/QSCAT. Our results showed linear correlation between MODIS-derived anisotropy to ALS-derived entropy (r(exp 2)= 0.54, RMSE= 0.11), even in high biomass regions. Significant relationships were also obtained between MODIS-derived anisotropy and GLAS-derived entropy(0.52 less than or equal to r(exp 2) less than or equal to 0.61; p less than 0.05), with similar slopes and offsets found throughout the season, and RMSE between 0.26 and 0.30 (units of entropy). The relationships between the MODIS-derived anisotropy and backscattering measurements (sigma(sup 0)) from SeaWinds/QuikSCAT presented an r(exp 2) of 0.59 and a RMSE of 0.11. We conclude that multi-angular MODIS observations are suitable to extrapolate measures of canopy entropy across different forest types, providing additional estimates of vegetation structure in the Amazon

Potential biomarkers of major depression diagnosis and chronicity

Background Molecular biomarkers are promising tools to be routinely used in clinical psychiatry. Among psychiatric diseases, major depression disorder (MDD) has gotten attention due to its growing prevalence and morbidity. Methods We tested some peripheral molecular parameters such as serum mature Brain-Derived Neurotrophic Factor (mBDNF), plasma C-Reactive Protein (CRP), serum cortisol (SC), and the salivary Cortisol Awakening Response (CAR), as well as the Pittsburgh sleep quality inventory (PSQI), as part of a multibiomarker panel for potential use in MDD diagnosis and evaluation of disease's chronicity using regression models, and ROC curve. Results For diagnosis model, two groups were analyzed: Patients in the first episode of major depression (MD: n = 30) and a healthy control (CG: n = 32). None of those diagnosis models tested had greater power than Hamilton Depression Rating Scale-6. For MDD chronicity, a group of patients with treatment-resistant major depression (TRD: n = 28) was tested across the MD group. The best chronicity model (p < 0.05) that discriminated between MD and TRD included four parameters, namely PSQI, CAR, SC, and mBDNF (AUC ROC = 0.99), with 96% of sensitivity and 93% of specificity. Conclusion These results indicate that changes in specific biomarkers (CAR, SC, mBDNF and PSQI) have potential on the evaluation of MDD chronicity, but not for its diagnosis. Therefore, these findings can contribute for further studies aiming the development of a stronger model to be commercially available and used in psychiatry clinical practice

Identification of strain-specific B-cell epitopes in Trypanosoma cruzi using genome-scale epitope prediction and high-throughput immunoscreening with peptide arrays

BACKGROUND: The factors influencing variation in the clinical forms of Chagas disease have not been elucidated; however, it is likely that the genetics of both the host and the parasite are involved. Several studies have attempted to correlate the T. cruzi strains involved in infection with the clinical forms of the disease by using hemoculture and/or PCR-based genotyping of parasites from infected human tissues. However, both techniques have limitations that hamper the analysis of large numbers of samples. The goal of this work was to identify conserved and polymorphic linear B-cell epitopes of T. cruzi that could be used for serodiagnosis and serotyping of Chagas disease using ELISA. METHODOLOGY: By performing B-cell epitope prediction on proteins derived from pair of alleles of the hybrid CL Brener genome, we have identified conserved and polymorphic epitopes in the two CL Brener haplotypes. The rationale underlying this strategy is that, because CL Brener is a recent hybrid between the TcII and TcIII DTUs (discrete typing units), it is likely that polymorphic epitopes in pairs of alleles could also be polymorphic in the parental genotypes. We excluded sequences that are also present in the Leishmania major, L. infantum, L. braziliensis and T. brucei genomes to minimize the chance of cross-reactivity. A peptide array containing 150 peptides was covalently linked to a cellulose membrane, and the reactivity of the peptides was tested using sera from C57BL/6 mice chronically infected with the Colombiana (TcI) and CL Brener (TcVI) clones and Y (TcII) strain. FINDINGS AND CONCLUSIONS: A total of 36 peptides were considered reactive, and the cross-reactivity among the strains is in agreement with the evolutionary origin of the different T. cruzi DTUs. Four peptides were tested against a panel of chagasic patients using ELISA. A conserved peptide showed 95.8% sensitivity, 88.5% specificity, and 92.7% accuracy for the identification of T. cruzi in patients infected with different strains of the parasite. Therefore, this peptide, in association with other T. cruzi antigens, may improve Chagas disease serodiagnosis. Together, three polymorphic epitopes were able to discriminate between the three parasite strains used in this study and are thus potential targets for Chagas disease serotyping

Falha de estimulaçao ventricular por variaçao aguda do limiar de comando induzida pela propafenona em portadora de marcapasso definitivo: relato de caso

Relata-se o caso de uma paciente que, durante troca do gerador do marcapasso definitivo, foi tratada com propafenona após desenvolver fibrilaçao atrial no período intraoperatório. Os limiares eram moderadamente aumentados no pré-operatório, entretanto, estáveis. Horas após a administraçao de 600 mg de propafenona, a paciente apresentou síncope justificada pela perda de comando ventricular. A avaliaçao do dispositivo mostrava perda de captura por aumento do limiar ventricular medido em 5,0V/0,6 ms, corrigida por estimulaçao com energia máxima de saída do gerador. No dia seguinte, após nova avaliaçao, o limiar havia retornado ao valor previamente aferido e a energia de saída do gerador diminuiu, mantendo-se estável após seis meses de seguimento

Falha de estimulaçao ventricular por variaçao aguda do limiar de comando induzida pela propafenona em portadora de marcapasso definitivo: relato de caso

Relata-se o caso de uma paciente que, durante troca do gerador do marcapasso definitivo, foi tratada com propafenona após desenvolver fibrilaçao atrial no período intraoperatório. Os limiares eram moderadamente aumentados no pré-operatório, entretanto, estáveis. Horas após a administraçao de 600 mg de propafenona, a paciente apresentou síncope justificada pela perda de comando ventricular. A avaliaçao do dispositivo mostrava perda de captura por aumento do limiar ventricular medido em 5,0V/0,6 ms, corrigida por estimulaçao com energia máxima de saída do gerador. No dia seguinte, após nova avaliaçao, o limiar havia retornado ao valor previamente aferido e a energia de saída do gerador diminuiu, mantendo-se estável após seis meses de seguimento

Kommentar: Fejde eller fred - Kommentar til antologien "Feider og fred i nordisk middelalder"

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Objective Our aim was to assess renal function using as laboratory measurements serum creatinine and cystatin C concentrations before and after administration of low-osmolarity (nonionic) iodinated contrast medium in patients with cancer undergoing computed tomography (CT). Methods This prospective study included 400 oncologic outpatients. Serum creatinine and cystatin C concentrations were measured before and 72 h after contrast administration. Glomerular filtration rates (GFRs) were estimated using serum creatinine-based [Modification of Diet in Renal Disease (MDRD) and Cockroft-Gault and cystatin C based (Larsson) equations. Exploratory data analysis was performed. The nonparametric Wilcoxon test was used to compare pre and post contrast of test results and estimated clearance. The confidence interval used in the analysis was 95%. Results Compared with the pre-contrast values, the mean serum creatinine concentration was significantly higher and average GFRs estimated using MDRD and Cockcroft-Gault equations were significantly lower after the administration of contrast (p < 0.001). It was also observed a significant increase after contrast in the concentration of Cystatin C (p = 0.015). In addition, a decrease in GFR estimated using the average Larsson (p = 0.021) was observed between time points. However, none of the patients presented clinically significant nephropathy. Conclusions Assessment using serum creatinine and cystatin C concentrations showed changes in renal function among patients with cancer undergoing contrast-enhanced CT examination in this study. No significant renal damage related to the use of low-osmolarity iodinated contrast medium of the type and dosage employed in this study was observed. This contrast medium is thus safe for use in patients with cancer.105Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)AC Camargo Cancer CenterFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP