Development of QTMP: A promising anticancer agent through NP-Privileged Motif-Driven structural modulation.

In this study of creating new molecules from clinical trial agents, an approach of Combretastatin structural modulation with the installation of NP-privileged motifs was considered, and a series of trimethoxyphenyl-2-aminoimidazole with functionalized quinolines and isoquinolines was investigated. An exciting method of quinoline C3-H iodination coupled with imidazopyridine-C3-H arylation and hydrazine-mediated fused-ring cleavage enabled synthesizing a class of compounds with two specific unsymmetric aryl substitutions. Interestingly, three compounds (6, 11, and 13) strongly inhibited HeLa cell proliferation with a half-maximal inhibitory concentration (10-46 nM). Among the compounds, compound 6 (QTMP) showed stronger antiproliferative ability than CA-4 (a clinical trial agent) in various cancer cell lines, including cervical, lung, breast, highly metastatic breast, and melanoma cells. QTMP inhibited the assembly of purified tubulin, depolymerized microtubules of A549 lung carcinoma cells, produced defective spindles, and arrested the cells in the G2/M phase. Further, QTMP binds to the colchicine site in tubulin with a dissociation constant of 5.0 ± 0.6 µM. QTMP displayed higher aqueous stability than CA-4 at 37 °C. Further, in silico analysis of QTMP indicated excellent drug-like properties, including good aqueous solubility, balanced hydrophilicity-lipophilicity, and high GI-absorption ability. The results together suggest that QTMP has anticancer potential.

3,5-bis(styryl)pyrazole inhibits mitosis and induces cell death independent of BubR1 and p53 levels by depolymerizing microtubules.

Here, we show that 3,5-bis[(1E)-2-(2,6-dichlorophenyl)ethenyl]-1H-pyrazole 2l depolymerizes microtubules and reduces the number of growing tips of microtubules. The fluorescence recovery after photobleaching experiment in live MCF-7 cells showed that pyrazole 2l suppresses spindle microtubule dynamics. Further, the compound inhibits chromosome movements, activates the spindle assembly checkpoint and blocks mitosis in MCF-7 cells. Pyrazole 2l treatment induced cell death in a variety of pathways. Pyrazole 2l induces cell death independent of BubR1 and p53 levels of MCF-7 cells upon microtubule depolymerization. Further, pyrazole 2l increases the interaction between NF-κB and microtubules and enhances the nuclear localization of NF-κB at its half-maximal proliferation inhibitory concentration while a high concentration of the compound reduced the nuclear localization of NF-κB. Interestingly, the compound exerted significantly stronger antiproliferative effects in cancerous cells than in non-cancerous cells. The results indicated that pyrazole 2l inhibits mitosis by targeting microtubules, induces several types of cell death stimuli and suggests its potential as a lead in developing anticancer agent.

Mini clinical evaluation exercise (Mini-CEX): A tool for assessment of residents in department of surgery.

BACKGROUND: The mini-clinical evaluation exercise (mini-CEX) is a formative assessment tool designed to provide feedback on skills essential to good medical care by observing an actual clinical encounter. However, the bigger advantage of mini-CEX is the structured feedback that it provides to the students as well as the faculty, thus helping them to make better decisions. MATERIALS AND METHODS: This study was a cross-sectional observational study. Sixteen surgery residents volunteered for participation and five professors conducted sessions; hence, 80 mini-CEX encounters. Seven core clinical skill assessments were done, and the performance was rated on a 9-point scale (grouped into unsatisfactory, satisfactory, and superior). Immediate feedback to the residents was given by the faculty. Delayed feedback from faculty and residents regarding the perception of mini-CEX was taken. Statistical analysis was done using SPSS version 20 and analysis of variance (ANOVA) for inferential statistics. RESULTS: As planned, 80 (100%) mini-CEX encounters were conducted. Surgery residents showed improvement that was statistically significant in the competencies of medical interviewing skills, physical examination skills, humanistic qualities/professionalism, and counseling skills. Most of the faculty (80%) were able to identify the gaps in the knowledge of students and areas of improvement for their teaching. However, 60% of the faculty felt that it required more effort than traditional methods. The mean time taken by the assessor for observation and feedback to residents was 12.51 min and 5.68 min, respectively. The mean scores of evaluator satisfaction and resident satisfaction with mini-CEX sessions were 6.04 and 7.49, respectively. CONCLUSIONS: Mini-CEX improves the learning environment in residency and also leads to improvement in medical interviewing skills, physical examination skills, humanistic qualities/professionalism, and counseling skills. It is done in the actual patient encounter and hence prepares the resident better for dealing with patients in the future.

Understanding the multifaceted impact of COVID-19 on migrants in Kerala, India.

Motivation: COVID-19 has disrupted the lives of millions of people worldwide. Migrants in developing economies have been among the most affected. This vulnerable population faces a threat to their livelihood and way of life. Hence, there is an urgent need to understand the impact of pandemic on their lives to be able to tackle subsequent waves of the pandemic or similar exogenous shocks in future. Purpose: We delve into the economic and social disruptions caused by the COVID-19 pandemic on employment, sources of income, and lives of different categories of migrant labourers in the Indian state of Kerala. Methods and approach: Using the livelihood portfolio theory, we dissect this impact in relation to a wide range of issues. This was corroborated by the in-depth semi-structured interviews with three categories of respondents. The interview data was analysed by using the directed qualitative content analysis method. We created themes from the data and juxtaposed them with the livelihood portfolio theory in addressing the research objectives. Findings: Results highlight the impact on livelihood, lifestyles, migration prospects and gender aspects. First, the households dependent on international migrants were more severely affected than those with family members who were internal migrants. Second, a considerable lifestyle change (more reliance on a plant-based diet) and borrowing patterns (more reliance on informal money lending) was reported. Third, opinions on future migration prospects were pessimistic, and a trend in favour of reverse migration was noted. We also captured the resilience measures for each of the themes. Policy implications: We find that blanket responses to mitigate migrants' hardships could be counterproductive. Policy-makers ought to implement tailor-made policies keeping in mind the migrants' classification and socio-economic demographics. Further, we recommend specific measures to address challenges that women face, to ease their workload and mitigate the loss of income. Specific measures aimed at initiating attitudinal change such as creating mental health awareness, curbing misinformation and providing counselling services could also add immense value in tackling the pandemic.