Repurposing zileuton as a depression drug using an AI and in vitro approach

Repurposing drugs to target M1 macrophages inflammatory response in depression constitutes a bright alternative for commonly used antidepressants. Depression is a significant type of mood disorder, where patients suffer from pathological disturbances associated with a proinflammatory M1 macrophage phenotype. Presently, the most commonly used antidepressants such as Zoloft and Citalopram can reduce inflammation, but suffer from dangerous side effects without offering specificity toward macrophages. We employed a new strategy for drug repurposing based on the integration of RNA-seq analysis and text mining using deep neural networks. Our system employs a Google semantic AI universal encoder to compute sentences embedding. Sentences similarity is calculated using a sorting function to identify drug compounds. Then sentence relevance is computed using a custom-built convolution differential network. Our system highlighted the NRF2 pathway as a critical drug target to reprogram M1 macrophage response toward an anti-inflammatory profile (M2). Using our approach, we were also able to predict that lipoxygenase inhibitor drug zileuton could modulate NRF2 pathway in vitro. Taken together, our results indicate that reorienting zileuton usage to modulate M1 macrophages could be a novel and safer therapeutic option for treating depression.This research was done under the P_37_732/2016 grant (REDBRAIN) financed by the European Regional Development Fund, Competitiveness Operational Program 2014-2020the

ECONOMIC MEASURES DESIGNED BY INTERNATIONAL FINANCIAL INSTITUTION IN ORDER TO MACROSTABILIZE AND TO AUGUMENT ECONOMIC RECOVERY PROCESS

The recent economic crisis has affected the world economy in general, but the contagion degree for each member economy was different, depending on the specific economic situation existing at the crisis debut. Some European economies were very seriously affected, especially those who have expressed a number of internal and external imbalances in the pre-crisis period, and who did not take countermeasures. The economic crisis and the recession that followed were felt strong also in the USA, but the flexibility of the US economy and the measures taken since the onset of the crisis allowed a faster recovery than in European vulnerable economies. The accommodative US monetary policy permitted to avert liquidity crises and to clean the bank balance sheets, which was also a premise of resuming lending in order to get out of the recession. In this article we conducted an extensive analysis of management measures adopted in different states which are carrying out programs with IFIs, taking into account both short-term effects and implications of these economic policy measures in the medium and long term horizon

Multivariate Analysis of the Predicted Probability of Smoking Behavior of Foster Care Minors: Results of a Study from Romania

Background: There are a multitude of factors that influence smoking status, and minors from the social protection system are a vulnerable category in terms of smoking. Methods: The objective of this research was to assess the degree of smoking dependence and to identify potential predictors of smoking status in foster care teenagers. Smoker status was confirmed by dosing CO in the exhaled air, and the degree of dependence was assessed using the Fagerström score. We performed a multivariate logistic regression analysis. Results: From the 275 foster care minors, 22.5% were current smokers. Exhaled CO was not influenced by general demographic factors, was associated with the frequency of smoking, and was positively correlated with the estimated number of cigarettes consumed daily and with the Fagerström score. The calculated probability of being a smoker was less than 20.4% in 75% of nonsmokers, whereas 75% of actual smokers had a predicted probability higher than 30.3%. Conclusions: In addition to age, gender, social environment, previous exposure to secondhand smoking, and residential type of foster care system, the expressed opinions regarding the health effects of tobacco use were associated with smoking in foster care teenagers