Synthesis,Pharmacological Evaluation,and Docking Studies of Novel Pyridazinone‐Based Cannabinoid Receptor Type 2 Ligands

In recent years, cannabinoid type 2 receptors (CB₂R) have emerged as promising therapeutic targets in a wide variety of diseases. Selective ligands of CB₂R are devoid of the psychoactive effects typically observed for CB₁R ligands. Based on our recent studies on a class of pyridazinone 4‐carboxamides, further structural modifications of the pyridazinone core were made to better investigate the structure–activity relationships for this promising scaffold with the aim to develop potent CB₂R ligands. In binding assays, two of the new synthesized compounds [6‐(3,4‐dichlorophenyl)‐2‐(4‐fluorobenzyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2,3‐dihydropyridazine‐4‐carboxamide ( 2 ) and 6‐(4‐chloro‐3‐methylphenyl)‐cis‐N‐(4‐methylcyclohexyl)‐3‐oxo‐2‐pentyl‐2,3‐dihydropyridazine‐4‐carboxamide ( 22 )] showed high CB₂R affinity, with K_i values of 2.1 and 1.6 nm , respectively. In addition, functional assays of these compounds and other new active related derivatives revealed their pharmacological profiles as CB₂R inverse agonists. Compound 22 displayed the highest CB₂R selectivity and potency, presenting a favorable in silico pharmacokinetic profile. Furthermore, a molecular modeling study revealed how 22 produces inverse agonism through blocking the movement of the toggle‐switch residue, W6.48.     

Novel fluorine containing polyfluorenes with efficient blue electroluminescence

The synthesis, structural characterization, photo and electroluminescence, thermal and electrochemical properties of a new fluorinated fluorene-containing copolymer are described. The copolymer is formed by alternating mers of [2,3,5,6 tetrafluoro-1,4 phenylene] and [9,9′-dihexyl-2,7 fluorene] and emits blue light with low turn on voltages. The EL performance of the fluorinated copolymer was superior to those of the non-fluorinated analog copolymer and of the corresponding poly(9,9′dihexyl-2,7 polyfluorene) homopolymer.     

Free-radical scavenging capacity and reducing power of wild edible mushrooms from northeast Portugal: Individual cap and stipe activity

The antioxidant properties of two wild edible mushroom species from the northeast of Portugal, Lactarius deliciosus (L.) Gray and Tricholoma portentosum (Fr.) Quél., were evaluated. Methanolic extracts from the entire mushroom, the cap and the stipe, separately, were screened for their reducing power and free radical scavenging capacity by chemical assays. The total phenolic content was determined, in order to assess its effect on the extract’s antioxidant activity. Both two species showed antioxidant potential; but L. deliciosus proved to be more active. The portion of the mushroom used had an influence on the results obtained, with the cap methanolic extracts exhibiting the greatest antioxidant effect.     

Microbiological characterization of randomly selected Portuguese raw milk cheeses with reference to food safety

Seventy raw milk cheeses made in different regions of Portugal, both hard and soft varieties, made with cow's, ewe's, or goat's milk or combinations of these, were sampled within their quoted shelf lives for microbiological safety. On the basis of the presence or numbers of Escherichia coli, E. coli O157, Staphylococcus aureus, Salmonella, and Listeria monocytogenes, cheeses were categorized as satisfactory, acceptable, unsatisfactory, or unacceptable and potentially hazardous. Twenty-two of the 70 cheeses were classified as satisfactory or acceptable. Thirty-seven of the cheeses were considered unsatisfactory because of the presence of E. coli, S. aureus, or both, while 11 of the cheeses were graded as unacceptable and potentially hazardous because of the presence of excessive numbers of S. aureus, E. coli, or L. monocytogenes and the presence of Salmonella in three of these. All cheeses graded as unacceptable and potentially hazardous were soft or semisoft cheeses made with ewe's and goat's milk, with the exception of two hard cheeses made with cow's milk. E. coli O157 was not detected in any of the cheeses. According to the present results, it seems that the presence or counts of pathogenic or indicator organisms in raw milk cheeses cannot be related to the processing conditions, milk type, or region of production.     

Schrifttumsberichte

Ohne Zusammenfassung     

A new contribution to the study of the electrosynthesis of magnetic nanoparticles: the influence of the supporting electrolyte

This paper shows how magnetic nanoparticles are produced by electrochemical synthesis using a low carbon steel bar as an anode and 100 mA cm^?2 electric perturbations at room temperature. Two different kinds of salts, (CH₃)₄NCl and NaCl, were used to prepare the supporting electrolyte solutions. This allowed a comparison to be made between a surfactant and common salt, and allowed their influence on particle size to be analyzed. Additionally, mixtures of water and ethanol were added to the electrolyte solution in order to improve particle size distribution. The nanoparticle samples were characterized by X-ray diffraction, TEM, magnetization measurements, and Raman and Mössbauer spectroscopy. The results showed that after an optimized time of 10 min, the nanoparticles obtained in all the evaluated electrolytes were mainly magnetite (Fe₃O₄). The particles were between 8 and 10 nm in size. Depending on the nature of the electrolyte, the magnetite nanoparticles exhibited high purity and stoichiometry. The presence of ethanol in the electrolyte avoided particle agglomeration during the formation of magnetite. When the magnetic nanoparticles were exposed to an external magnetic field they showed superparamagnetic behavior and negligible coercivity. Such qualities are extremely useful for applications like ferrofluid precursors.     

Predicting post-treatment-initiation alcohol use among patients with severe mental illness and alcohol use disorders.

Few investigators studying alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of posttreatment alcohol outcomes. In the present study, a multivariate approach based on a theoretical model was used to study the relationship between psychosocial factors and post-treatment-initiation alcohol use. Predictors of alcohol use outcomes were examined in 278 individuals diagnosed with a current schizophrenia-spectrum or bipolar disorder and an alcohol use disorder (AUD). At 6-months follow-up, 144 of 228 available participants (63%) had good clinical outcomes. The results of structural equation modeling indicated that type of pretreatment residential setting was directly related to treatment, with participants who lived in supervised settings (41%) reporting significantly more days of treatment (β = .34, p     

Comfort of workers in office buildings: The European HOPE project

Previous studies have shown that building, social and personal factors can influence one’s perceived health and comfort. The aim of the underlying study was to get a better understanding of the relationships between these factors and perceived comfort. Self-administered questionnaires from 5732 respondents in 59 office buildings and building-specific data from the European Health Optimisation Protocol for Energy-efficient buildings (HOPE) study were used. Principal Component Analysis (PCA), reliability analyses, and linear regression analysis were performed. The outcome showed that perceived comfort is strongly influenced by several personal, social and building factors and that their relationships are complex. Results showed that perceived comfort is much more than the average of perceived indoor air quality, noise, lighting and thermal comfort responses. Perceived comfort is a phenomenon that deserves more research.