IMPORTANCE Tolerability is a key determinant of the effectiveness of epilepsy treatment. It is important to evaluate whether the overall tolerability has improved.OBJECTIVE To identify factors associated with poor tolerability of antiseizure medications (ASMs) and examine temporal changes in tolerability. DESIGN, SETTING, AND PARTICIPANTSThis was a longitudinal cohort study at a specialist clinic in Glasgow, Scotland. Patients with newly diagnosed and treated epilepsy between July 1982 and October 2012 were included from 2282 eligible individuals. They were followed up until April 2016 or death. Data analysis was completed in August 2019. EXPOSURES Antiseizure medications.MAIN OUTCOMES AND MEASURES Univariable and multivariable survival analyses were performed to examine associations between potential risk factors and development of intolerable adverse effects (AEs). Intolerable AE rates of the ASMs as the initial monotherapy were compared between 3 epochs (

This study aimed at describing the experience of academic staff and students with distance education, during the COVID-19 pandemic, at a college of pharmacy in Saudi Arabia. Methods: This study used a mixed-method approach. The first phase implemented a survey that targeted both academic staff and students to evaluate their experiences with distance education during the COVID-19 pandemic. Then, a focus group discussion was conducted to explore, in-depth, their experience. The survey consisted of five domains as follows: readiness for the shift to distance education during the full and partial lockdown, perception towards distance education, barriers against distance education, and the acquisitions due to distance education. A five-point Likert scale was used to assess participants' responses to the different domains (mean score ± standard deviation). Results: Seventy-eight percent of the academic staff and 65% of the students responded to the survey. Participants' views were positive for readiness for the shift to distance education during the full lockdown (3.89±0.42 for academic staff and 3.82±0.50 for students) with almost similar evaluation for the readiness during the blended learning period (3.91±0.44 for staff and 3.83±0.59 for students). The findings showed a generally positive perception towards distance education (3.59± 0.67 for academic staff and 3.47±0.64 for students). The acquisitions due to distance education were also positive (3.95±0.72 for academic staff and 3.78±0.77 for students). Nonetheless, some barriers that affected distance education were raised with an overall neutral view from both academic staff (3.31±0.72) and students (3.31±0.64), with different responses for the individual items. Qualitative findings from the focus group discussions explored the strengths, weaknesses, opportunities, and challenges, with emphasis on the areas for improvement. Conclusion: Although the shift for distance education was out of a sudden, participants showed overall positive views about their experience with distance education and highlighted areas for improvement.

A nicotinamide-based derivative was designed as an antiproliferative VEGFR-2 inhibitor with the key pharmacophoric features needed to interact with the VEGFR-2 catalytic pocket. The ability of the designed congener ((E)-N-(4-(1-(2-(4-benzamidobenzoyl)hydrazono)ethyl)phenyl)nicotinamide), compound 10, to bind with the VEGFR-2 enzyme was demonstrated by molecular docking studies. Furthermore, six various MD simulations studies established the excellent binding of compound 10 with VEGFR-2 over 100 ns, exhibiting optimum dynamics. MM-GBSA confirmed the proper binding with a total exact binding energy of −38.36 Kcal/Mol. MM-GBSA studies also revealed the crucial amino acids in the binding through the free binding energy decomposition and declared the interactions variation of compound 10 inside VEGFR-2 via the Protein–Ligand Interaction Profiler (PLIP). Being new, its molecular structure was optimized by DFT. The DFT studies also confirmed the binding mode of compound 10 with the VEGFR-2. ADMET (in silico) profiling indicated the examined compound’s acceptable range of drug-likeness. The designed compound was synthesized through the condensation of N-(4-(hydrazinecarbonyl)phenyl)benzamide with N-(4-acetylphenyl)nicotinamide, where the carbonyl group has been replaced by an imine group. The in-vitro studies were consonant with the obtained in silico results as compound 10 prohibited VEGFR-2 with an IC50 value of 51 nM. Compound 10 also showed antiproliferative effects against MCF-7 and HCT 116 cancer cell lines with IC50 values of 8.25 and 6.48 μM, revealing magnificent selectivity indexes of 12.89 and 16.41, respectively.

New quinoline and isatin derivatives having the main characteristics of VEGFR-2 inhibitors was synthesised. The antiproliferative effects of these compounds were estimated against A549, Caco-2, HepG2, and MDA-MB-231. Compounds 13 and 14 showed comparable activities with doxorubicin against the Caco-2 cells. These compounds strongly inhibited VEGFR-2 kinase activity. The cytotoxic activities were evaluated against Vero cells. Compound 7 showed the highest value of safety and selectivity. Cell migration assay displayed the ability of compound 7 to prevent healing and migration abilities in the cancer cells. Furthermore, compound 7 induced apoptosis in Caco-2 through the expressive down-regulation of the apoptotic genes, Bcl2, Bcl-xl, and Survivin, and the upregulation of the TGF gene. Molecular docking against VEGFR-2 emerged the interactions of the synthesised compounds in a similar way to sorafenib. Additionally, seven molecular dynamics simulations studies were applied and confirmed the stability of compound 13 in the active pocket of VEGFR-2 over 100 ns.