Activity

The frontier molecular orbitals of imatinib and ponatinib are contributing to the same amino acid residues, and the ineffectiveness of imatinib against the T315I mutation was discussed.Cryptococcus neoformans is a fungus responsible for infections in humans with a significant number of cases in immunosuppressed patients, mainly in underdeveloped countries. In this context, the thiazolylhydrazones are a promising class of compounds with activity against C. neoformans. The understanding of the structure-activity relationship of these derivatives could lead to the design of robust compounds that could be promising drug candidates for fungal infections. Specifically, modern techniques such as 4D-QSAR and machine learning methods were employed in this work to generate two QSAR models (one 2D and one 4D) with high predictive power (r2 for the test set equals to 0.934 and 0.831, respectively), and one random forest classification model was reported with Matthews correlation coefficient equals to 1 and 0.62 for internal and external validations, respectively. The physicochemical interpretation of selected models, indicated the importance of aliphatic substituents at the hydrazone moiety to antifungal activity, corroborating experimental data.Communicated by Ramaswamy H. Sarma.Reelin is an extracellular matrix glycoprotein that plays a key role in cortical development, maturation, synaptic plasticity, and memory formation in the adult mammalian brain. Glycosylation is a significant post- and co-translational modification of proteins. Although glycosylation contributes to the characteristic of proteins from their production to molecular interactions, the knowledge about the glycosylation pattern of reelin is very limited. In this study, we aimed to predict the potential glycosylation pattern of the 5th-6th repeat of central reelin fragment that responsible for their signaling, by using in silico methods. We found that the predicted glycosylation pattern of the 5th-6th repeat of human reelin was highly conserved between vertebrate species. However, this conservation was not observed in analyzed invertebrates. see more For the first time, we described the sites of glycosylation at a three-dimensional protein structure in human reelin. Because the sites were very closed to EGF-like repeats and receptor binding sites, they could contribute the interaction with a partner of reelin in addition to the effect of thermostability to protein. Many of the residues related glycosylation were also conserved in analyzed species. These findings may guide biochemical, genetic, and glycobiology base on further experiments about reelin glycosylation. The understanding of reelin glycosylation might change the point of view of treatment for many pathological conditions in neurodegenerative diseases such as Alzheimer’s disease.Communicated by Ramaswamy H. Sarma.Biochemical activities of Fluorescein, Rose Bengal and Rhodamine 101 were studied by DNA binding, antibacterial and cytotoxic studies. DNA binding studies were done using spectroscopic, thermodynamic and molecular modeling techniques. Antibacterial activities were investigated against a gram-negative bacteria Escherichia coli and a gram-positive bacteria Staphylococcus aureus. Cytotoxic activities were studied against Wi-38 cell line. We observed these dyes bound to minor groove of DNA and structural diversity of dyes affect the phenomenon. No significant antibacterial and cytotoxic activities of these dyes were found in our observations.Communicated by Ramaswamy H. Sarma.Cognitive problems are common in people with Multiple Sclerosis (MS), and researchers and clinicians have used a vast array of measures to assess cognition. Our aim was to systematically identify cognitive measures routinely used in MS research, and outline their different uses. Previous recommendations of cognitive measures to use in MS have relied on expert consensus approaches. We believe this systematic review is a starting point for an evidence-based approach to recommend cognitive tests for use with people with MS. We systematically searched electronic databases using relevant search terms for studies that assessed cognitive functioning in MS (last search in February 2020). From 11,854 abstracts retrieved, based on title and abstract review, 2563 remained. Data were extracted from 1526 studies. Studies used 5665 measures of cognition, with 316,053 people with MS. Substitutional style tests, serial addition tests, and word list learning tests were the most commonly used individual tests, and the Brief Repeatable Battery of Neuropsychological Tests was the most commonly used battery. Some of the most frequently used measures were potentially inappropriate due to measuring irrelevant domains of cognition, and issues with sensitivity. Further research is needed to ascertain the psychometric properties, and acceptability of measures for people with MS.

Preoperative use of antidepressants and anxiolytics was reported to increase length of hospital stay (LOS) and worsen surgical outcomes. However, the surgical procedures studied were seldom performed with an enhanced recovery programme (ERP). This study investigated whether these medications impaired postoperative recovery after colorectal surgery with an ERP.

The data of all patients scheduled for colorectal surgery between November 2015 and December 2019 prospectively included in our database were analysed. All the patients were managed with the same ERP. Demographic data, risk factors, incidence of postoperative complications, LOS, and adherence to the ERP were compared between patients with and without preoperative antidepressant and/or anxiolytic treatment.

Of the 502 patients, 157 (31.3%) were treated with antidepressants and/or anxiolytics. They were older (65.7 vs. 59.5 years,

 < 0.001), sicker (higher ASA physical status score,

 = 0.001), and underwent surgery more frequently for cancer (73.9 vs. 56.8%,

 < 0.001). Overall adherence to ERP (

 = 0.99) and adherence to the postoperative items of ERP (

 = 0.29), incidence of postoperative complications (35.7 vs. 33.2%,

 = 0.61), and LOS (4 [2-7] vs. 4 [2-7],

 = 0.99) were similar in the two groups.

Our findings suggest that preoperative treatment with antidepressants and/or anxiolytics does not worsen outcome after elective colorectal surgery with an ERP, does not impact adherence to ERP, and does not prolong LOS. ERP seems efficacious in patients treated with these medications, who should therefore not be excluded from this programme.

Our findings suggest that preoperative treatment with antidepressants and/or anxiolytics does not worsen outcome after elective colorectal surgery with an ERP, does not impact adherence to ERP, and does not prolong LOS. ERP seems efficacious in patients treated with these medications, who should therefore not be excluded from this programme.