Positive Association Between Limbic Metabotropic Glutamate Receptor 5 Availability and Novelty-Seeking Temperament in Humans: a 18F-FPEB PET study

Heritable temperament traits have been linked to several neuropsychiatric illnesses, including disorders associated with metabotropic glutamate receptor 5 (mGluR5) and dopaminergic dysfunctions. Considering its modulating effect on neurotransmission, we hypothesized that cerebral mGluR5 availability is associated with temperament traits in healthy humans.status: publishe

The electronic nose technology in clinical diagnosis: A systematic review

Background: Volatile organic compounds (VOC) are end products of human metabolism (normal and disease-associated) that can be mainly excreted in breath, urine, and feces. Therefore, VOC can be very useful as markers of diseases and helpful for clinicians since its sampling is noninvasive, inexpensive, and painless. Electronic noses, or eNoses, provide an easy and inexpensive way to analyze gas samples. Thus, this device may be used for diagnosis, monitoring or phenotyping diseases according to specific breathprints (breath profile). Objective: In this review, we summarize data showing the ability of eNose to be used as a noninvasive tool to improve diagnosis in clinical settings. Methods: A PRISMA-oriented search was performed in PubMed and Cochrane Library. Only studies performed in humans and published since 2000 were included. Results: A total of 48 original articles, 21 reviews, and 7 other documents were eligible and fully analyzed. The quality assessment of the selected studies was conducted according to the Standards for Reporting of Diagnostic Accuracy. Airway obstructive diseases were the most studied and Cyranose 320 was the most used eNose. Conclusions: Several case–control studies were performed to test this technology in diverse fields. More than a half of the selected studies showed good accuracy. However, there are some limitations regarding sampling methodology, analysis, reproducibility, and external validation that need to be standardized. Additionally, it is urgent to test this technology in intend-to-treat populations. Thus, it is possible to think in the contribution of VOC analysis by eNoses in a clinical setting.The authors gratefully acknowledge funding from Project NORTE-01-0145-FEDER-000010—Health, Comfort and Energy in the Built Environment (HEBE), cofinanced by Programa Operacional Regional do Norte (NORTE2020), through Fundo Europeu de Desenvolvimento Regional (FEDER). The current work has been supported by the EXPOSE project, which is financed by FEDER/FNR and by Fundação para a Ciência e Tecnologia (EXPOSE 02/SAICT/2016—Project no. 023222)

Discovery and Hit-to-Lead Optimization of Benzothiazole Scaffold-Based DNA Gyrase Inhibitors with Potent Activity against Acinetobacter baumannii and Pseudomonas aeruginosa

We have developed compounds with a promising activity against Acinetobacter baumannii and Pseudomonas aeruginosa, which are both on the WHO priority list of antibiotic-resistant bacteria. Starting from DNA gyrase inhibitor 1, we identified compound 27, featuring a 10-fold improved aqueous solubility, a 10-fold improved inhibition of topoisomerase IV from A. baumannii and P. aeruginosa, a 10-fold decreased inhibition of human topoisomerase IIα, and no cross-resistance to novobiocin. Cocrystal structures of 1 in complex with Escherichia coli GyrB24 and (S)-27 in complex with A. baumannii GyrB23 and P. aeruginosa GyrB24 revealed their binding to the ATP-binding pocket of the GyrB subunit. In further optimization steps, solubility, plasma free fraction, and other ADME properties of 27 were improved by fine-tuning of lipophilicity. In particular, analogs of 27 with retained anti-Gram-negative activity and improved plasma free fraction were identified. The series was found to be nongenotoxic, nonmutagenic, devoid of mitochondrial toxicity, and possessed no ion channel liabilities