Microwave-Assisted Atom Transfer Radical Cyclization in the Synthesis of 3,3-Dichloro-γ- and δ-Lactams from N-Alkenyl-Tethered Trichloroacetamides Catalyzed by RuCl2(PPh3)3 and Their Cytotoxic Evaluation.

An expeditious synthesis of γ- and δ-lactams from tethered alkenyl trichloroacetamides in the presence of 5% of RuCl2(PPh3)3 is reported. In this investigation we have demonstrated that microwave activation significantly enhances reaction rates, leading to the formation of the corresponding lactams in yields ranging from good to excellent. Thus, we have been able to prepare a wide range of lactams, including indole and morphan bicyclic scaffolds, where the corresponding reactions were completely diastereoselective. This process was successfully extended to α,α-dichloroamides without affecting either their yield or their diastereoselectivity. Some of the lactams prepared in this work were evaluated for their hemolytic and cytotoxic responses. All compounds were found to be non-hemolytic at the tested concentration, indicating their safety profile in terms of blood cell integrity. Meanwhile, they exhibited interesting cytotoxicity responses that depend on both their lactam structure and cell line. Among the molecules tested, γ-lactam 2a exhibited the lowest IC50 values (100-250 µg/mL) as a function of its cell line, with promising selectivity against squamous carcinoma cells (A431) in comparison with fibroblasts (3T3 cell line).

Pathological personality traits of maladaptive daydreamers measured by the Personality Inventory for DSM-5 in a psychiatric sample.

This study aimed to estimate the frequency of maladaptive daydreaming and to explore the pathological personality traits of probable maladaptive daydreamers. Our sample consisted of 239 psychiatric patients. After screening, 42 persons were probable maladaptive, while 197 participants prove to be normal daydreamers. Two pathological domains and three facets measured by the Personality Inventory for DSM-5 showed a moderate significant correlation with the Maladaptive Daydreaming Scale. The score of nearly every domain and facet was slightly higher among probable maladaptive daydreamers. To quantify the difference between the groups, effect sizes were calculated: Significant difference was found on the domain level in Antagonism, while on the facet level in Hostility, Grandiosity, Attention Seeking, Unusual Beliefs and Experiences, Cognitive and Perceptual Dysregulation. The group of probable maladaptive daydreamers was further examined to identify potential subgroups. Cluster analysis revealed heterogeneity in the severeness and patterns of pathological personality domains. Cluster 1 showed higher mean scores on the PID domains and on the MDS compared to Cluster 2. Clusters 1 and 2 broke further down into two subclusters: Cluster 1a and Cluster 1b differed in their mean scores on the domains of Antagonism and Detachment; the mean scores of Cluster 2a were uniformly low on each domain, while the mean values of Cluster 2b were scattered in a mixed way on the domains. Our results suggest that maladaptive daydreaming might manifest with differently pathological personality profiles in the background. This aspect might worth considering in planning treatment.

Childhood traumatization and dissociative experiences among maladaptive and normal daydreamers in a Hungarian sample.

The aim of the study was to identify some potential etiological segments of maladaptive daydreaming, especially the relationships between maladaptive daydreaming, childhood traumatization, and dissociative propensity. The questionnaire package included the Hungarian version of the Maladaptive Daydreaming Scale, the Traumatic Antecedents Questionnaire, as well as the Dissociation Questionnaire. 717 participants were recruited online, 106 of whom were problematic daydreamers. The results revealed that certain types of childhood trauma occurred significantly more frequently in the group of maladaptive daydreamers. Furthermore, maladaptive daydreamers possessed a significantly higher level of dissociative propensity compared to normal daydreamers. The estimated SEM models showed that dissociative experiences - more precisely Identity confusion and fragmentation and Lack of control - mediated the relationship between certain childhood traumatic experiences and maladaptive daydreaming. The results suggest that we should consider childhood traumatization and increased dissociative propensity as potentially significant factors in the etiology of maladaptive daydreaming.

Cytotoxic Assessment of 3,3-Dichloro-ß-Lactams Prepared through Microwave-Assisted Benzylic C-H Activation from Benzyl-Tethered Trichloroacetamides Catalyzed by RuCl2(PPh3)3.

Natural and synthetic ß-lactam derivatives constitute an interesting class of compounds due to their diverse biological activity. Mostly used as antibiotics, they were also found to have antitubercular, anticancer and antidiabetic activities, among others. In this investigation, six new 3,3-dichloro-ß-lactams prepared in a previous work were evaluated for their hemolytic and cytotoxic properties. The results showed that the proposed compounds have non-hemolytic properties and exhibited an interesting cytotoxic activity toward squamous cell carcinoma (A431 cell line), which was highly dependent on the structure and concentration of these ß-lactams. Among the molecules tested, 2b was the most cytotoxic, with the lowest IC50 values (30-47 µg/mL) and a promising selectivity against the tumor cells compared with non-tumoral cells.

Psychometric properties of the Maladaptive Daydreaming Scale in a sample of Hungarian daydreaming-prone individuals.

OBJECTIVES: The aim of the study is to adapt the Maladaptive Daydreaming Scale (MDS-16) to Hungarian, assess its psychometric properties, and establish its cut-off score. In addition, the relationship between maladaptive daydreaming and adverse childhood experiences was examined. METHOD: Study participants were recruited online via snowball sampling. Based on three inclusion criteria (self-identified MDer status; control over daydreaming; frequency of daydreaming) 160 out of 494 respondents were included in the study. RESULTS: Our results confirm both the high reliability and convergent validity of the questionnaire. The cut-off score of 60 percentiles can reliably discriminate between excessive and normal daydreamers. The general applicability of the MDS-16-HU was tested and confirmed by the use of the Adverse Childhood Experience Questionnaire (ACE-10), a short, self-report questionnaire. Its results showed that certain types of childhood adversities increase the likelihood of maladaptive daydreaming. CONCLUSIONS: The instrument is a valid and reliable measure, therefore it can serve as a useful screening tool in clinical practice. In addition, our findings highlighted the role of childhood adversities in the aetiology of maladaptive daydreaming.

In vitro Interactions of Pseudomonas aeruginosa With Scedosporium Species Frequently Associated With Cystic Fibrosis.

Members of the Scedosporium apiospermum species complex are the second most frequently isolated pathogens after Aspergillus fumigatus from cystic fibrosis (CF) patients with fungal pulmonary infections. Even so, the main risk factors for the infection are unrevealed. According to previous studies, bacterial infections might reduce the risk of a fungal infection, but an antibacterial therapy may contribute to the airway colonization by several fungal pathogens. Furthermore, corticosteroids, which are often used to reduce lung inflammation in children and adults with CF, are also proved to enhance the growth of A. fumigatus in vitro. Considering all the above discussed points, we aimed to test how Pseudomonas aeruginosa influences the growth of scedosporia and to investigate the potential effect of commonly applied antibacterial agents and corticosteroids on Scedosporium species. Direct interactions between fungal and bacterial strains were tested using the disk inhibition method. Indirect interactions via volatile compounds were investigated by the plate-in-plate method, while the effect of bacterial media-soluble molecules was tested using a modified cellophane assay and also in liquid culture media conditioned by P. aeruginosa. To test the effect of bacterial signal molecules, antibacterial agents and corticosteroids on the fungal growth, the broth microdilution method was used. We also investigated the germination ability of Scedosporium conidia in the presence of pyocyanin and diffusible signal factor by microscopy. According to our results, P. aeruginosa either inhibited or enhanced the growth of scedosporia depending on the culture conditions and the mode of interactions. When the two pathogens were cultured physically separately from each other in the plate-in-plate tests, the presence of the bacteria was able to stimulate the growth of several fungal isolates. While in direct physical contact, bacterial strains inhibited the fungal growth. This effect might be attributed to bacterial signal molecules, which also proved to inhibit the germination and growth of scedosporia. In addition, antibacterial agents showed growth-promoting, while corticosteroids exhibited growth inhibitory effect on several Scedosporium isolates. These data raise the possibility that a P. aeruginosa infection or a previously administered antibacterial therapy might be able to increase the chance of a Scedosporium colonization in a CF lung.