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Brain magnetic resonance imaging showed increased ischemic foci and lacunar infarction, worse encephalatrophy, and demyelination after EGFR-TKI therapy. These psychiatric symptoms did not improve but worsened after taking antipsychotic drugs, suggesting that they were irreversible. Masitinib The neuropsychiatric symptoms in EGFR-TKI treatment must be considered, and the underlying reason warrants further study. Copyright © 2020 Zhu et al.Coumarins are well-known for their antioxidant effect and aromatic property, thus, they are one of ingredients commonly added in cosmetics and personal care products. Quantitative structure-activity relationships (QSAR) modeling is an in silico method widely used to facilitate rational design and structural optimization of novel drugs. Herein, QSAR modeling was used to elucidate key properties governing antioxidant activity of a series of the reported coumarin-based antioxidant agents (1-28). Several types of descriptors (calculated from 4 softwares i.e., Gaussian 09, Dragon, PaDEL and Mold2 softwares) were used to generate three multiple linear regression (MLR) models with preferable predictive performance (Q 2 LOO-CV = 0.813-0.908; RMSE LOO-CV = 0.150-0.210; Q 2 Ext = 0.875-0.952; RMSE Ext = 0.104-0.166). QSAR analysis indicated that number of secondary amines (nArNHR), polarizability (G2p), electronegativity (D467, D580, SpMin2_Bhe, and MATS8e), van der Waals volume (D491 and D461), and H-bond potential (SHBint4) are important properties governing antioxidant activity. The constructed models were also applied to guide in silico rational design of an additional set of 69 structurally modified coumarins with improved antioxidant activity. Finally, a set of 9 promising newly design compounds were highlighted for further development. Structure-activity analysis also revealed key features required for potent activity which would be useful for guiding the future rational design. In overview, our findings demonstrated that QSAR modeling could possibly be a facilitating tool to enhance successful development of bioactive compounds for health and cosmetic applications. Copyright © 2020 Worachartcheewan et al.Pseudomonas aeruginosa is considered as foremost cause of hospital acquired infections due to its innate and plasmid mediated resistance to multiple antibiotics making it a multi drug resistant (MDR) pathogen. Biofilm formation is a pathogenic mechanism harbored by this pathogen which further elevates its resistance to antibiotics and host defense system. The aim of the present study was to evaluate the biofilm forming potential and distribution of pslA gene in multi drug resistant Pseudomonas aeruginosa isolates obtained from different clinical samples. A total of 200 different clinical samples were collected after obtaining written consent from the patients. The samples were subjected to isolation and identification of P. aeruginosa by standard microbiological procedures. Confirmation of isolates was done by polymerase chain reaction targeting oprL gene. Kirby Bauer method was performed for detection of MDR isolates. Congo red agar (CRA) test and Microtiter plate assay (MPA) for observing the biofilm forming ability and amplification of pslA gene was also performed on MDR isolates. The results showed that from 200 samples 52 (26 %) were P. aeruginosa and among them 20 (38.46 %) were MDR isolates. The CRA showed 23 (44.23 %) while MPA detected 49 (94.23 %) isolates as biofilm producers while all the MDR isolates showed biofilm formation by MPA method. The pslA gene was detected in all biofilm forming isolates while 90 % in MDR P. aeruginosa. It was concluded that biofilm forming P. aeruginosa are more resistant to tested antibiotics and biofilm formation is strongly associated with presence of pslA gene. Copyright © 2020 Abdulhaq et al.Adenosine is a critical regulator of inflammation and fibrosis, it affects endogenous cell signaling via binding to the A3 adenosine receptor. FM101 is a potent, highly selective A3 adenosine receptor modulator that has been developed as a treatment for glaucoma and hepatitis. We determined that FM101 is a biased ligand with functional activities both as a G protein agonist and a β-arrestin antagonist. The safety of FM101 was evaluated by administering an acute dose in rats, the results indicated that the approximate lethal dose was greater than 2000 mg/kg. In a subchronic toxicity study, FM101 was administered orally once per day to rats at doses of 250, 500, and 1000 mg/kg/day over a period of 28 days. Abnormal posture, irregular respiration, decreased movement, and ear flushing were observed during the early phase of dosing, and loose stools were observed sporadically among the animals that received 500 and 1000 mg/kg/day. Body weight and food consumption were decreased in one male and one female rat in the 1000 mg/kg/day group during the first 2 weeks of observation. However, there were no test substance-related changes or adverse effects observed during our ophthalmological, clinical chemistry, urine, organ weight, and histopathological analysis. These findings indicate that no observed adverse effect level of FM101 was 1000 mg/kg/day in male and female rats. Copyright © 2020 Park et al.This study examines how individuals perceive children, focusing on two dimensions-the positive aspects of having children and the perception of children as a burden-and taking into account relations with both individual- and macro-level characteristics. Three dimensions are examined on the macro-level policies that support families, the cultural environment, and economic conditions. The study is based on the 2012 ISSP module on "Family and Gender Roles" and covers 24 OECD countries. The findings show that countries vary widely in their negative perceptions of children, but evince relatively greater similarity in their positive perceptions. Institutional support for children and working parents and traditional family values as captured by religiosity are important factors in explaining cross-country variation in negative perceptions of children. Further, policies may help men and women adopt a more positive view of children and reduce differences among educational groups in relation to children. © Springer Nature B.
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