Quantitative structure-activity relationship, molecular docking, drug-likeness, and pharmacokinetic studies of some non-small cell lung cancer therapeutic agents

Background Lung cancer has been reported to be among the leading cancer cases in the world. It was also reported to have caused a lot of death every year and accounted for about one-third of the whole cancer deaths in the globe. The main subset of lung cancers that accounts for about 85% of the problems of lung cancer raised above was non-small cell lung cancer (NSCLC). The most common cause of NSCLCs that mostly affects women and cigarette smokers was recognized to be overexpression of epidermal growth factor receptor tyrosine kinase (EGFR TK). Results Five models on thirty five (35) NSCLC therapeutic agents were developed via quantitative structure-activity relationship (QSAR) technique. The best model among them was selected and reported due to its fitness statistically with the following validation parameters: R2 of 0.8764, R2adj of 0.8370, Qcv2 of 0.7655, R2test of 0.7024, and LOF of 0.3312. Molecular docking was used to elucidate the mode of binding interactions between the thirty five (35) NSCLC therapeutic agents and the binding pose of EGFR tyrosine kinase receptor (3IKA) in this research. Compound 29 was recognized to have the most excellent binding affinity of − 8.8 kcal/mol among others. The drug-likeness and pharmacokinetic properties of all the NSCLC therapeutic agents were predicted using SWISSADME, and none among the molecules under investigation violated more than the permissible limit of the conditions stated by Lipinski’s RO5 filters. Five hit compounds were identified using molecular docking virtual screening. The five (5) hit compounds were further screened and identified compound 16 and 27 as excellent among them using their pharmacokinetic profiles and drug-likeness properties. Conclusion QSAR technique was used to build five models on thirty five (35) NSCLC therapeutic agents. The best model among them was reported because it is statistically significant with good validation parameters. The molecular docking result has identified five (5) hit compounds. The most common amino acid residues to all hit compounds under investigation were Glu762, Leu718, Lys745, and Val726 which might be responsible for the higher inhibitory activities/binding affinities of the compounds under investigation. Furthermore, these five (5) hit compounds were further subjected to drug-likeness and pharmacokinetic properties prediction to determine which among them have the best pharmacokinetic profile. Compounds 16 and 27 among the hit compounds were observed to have high chance of passive absorption by the gastrointestinal tract while the other three have low tendency of passive absorption. More so, only compounds 16 and 27 have higher bioavailability scores, and none of the two have more than one violation of the RO5 criteria. The cause of efficiency of compounds 16 and 27 might be as a result of good pharmacokinetic profiles and drug-likeness properties possessed by the molecules when compared to other hit compounds.

(Un)doing Polishness: Negotiation of Ethnic Belonging in Personal Narratives about Karta Polaka

The article is based on qualitative study of how Polishness is constructed in personal narratives about Karta Polaka (the Polish Card, Polish Charter). The interviews with possessors of the Polish Card, a document issued by the Polish state to the citizens of the former USSR identifying themselves as Poles, was conducted in 2015 in the city of Hrodna in western Belarus. The article uses the example of Karta Polaka to show how people who apply for the Polish Card perceive, negotiate, and reconstruct the idea of Polishness that this document implies. The author suggests that the demand for Karta Polaka among citizens of Belarus cannot be explained by ethnic opportunism entirely. Pragmatic and symbolic reasoning to apply for the document often overlaps. Moreover, as the author argues, Karta Polaka evokes the process of negotiating ethnic belonging among participants of the study. The article departs from the theoretical standpoint that ethnic belonging is neither merely a matter of individual choice nor a passive absorption of ethnic discourses produced by states, laws, or ethnic entrepreneurs. Combining the premises of performative and dialogical approaches to identity construction, the author shows empirically which discourses influence people’s sense of ethnic belonging and how these discourses are negotiated in their personal stories.

Validation and comparison of ammonia measurement techniques used to determine ammonia absorbed by passive absorption samplers

Emission of ammonia from agriculture is a major concern. The analytical analysis of ammonia is known to have some challenges and might be causing systematic errors. The effect of absorbing acids on an ion selective electrode (ISE) and the Berthelot colouring reaction, in terms of precision, was quantified. We show that commonly used acid absorbents do not have a significant influence on the precision of the ISE, whereas the acids had significant influence on measurements using the Berthelot reaction. Using the ISE in low-volume eluates (3 mL) did not influence the precision compared with the recommended 100 mL.

Oral transmucosal opioids

The oral transmucosal routes are buccal and sublingual. The absorption of drugs across the oral mucosa involves a process of passive absorption, and may involve either the transcellular route or the paracellular route. A number of drug factors affect the absorption of drugs across the oral mucosa. Oral transmucosal drug delivery does not require expertise, preparation, or technical equipment. Oral transmucosal administration may be associated with rapid onset of analgesia. A number of fentanyl-based formulations are commercially available to manage breakthrough cancer pain. A variety of other opioids have been subject to oral transmucosal administration. However, many of these opioids are not very lipophilic and, therefore, not suited for buccal or sublingual administration. Some of the more successful ones are alfentanil and sufentanil.

Embedding and assessing project based statistics

Traditional approaches to learning and teaching in statistics often involves the passive absorption of information through lectures, a focus on mathematical theory and assessments which test mastery of procedures. This often results in students struggling to apply their statistics knowledge in practical and authentic contexts particularly within final year projects and in the workplace. For some time, statistics educational literature has recommended shifting the focus of teaching and assessment from theory to statistical problem solving, application based statistics using real-life scenarios, and effective communication of statistics. This research has led to the production of guidelines for statistics educators from the American Statistical Association.This paper discusses how educational literature and guidelines have been used to implement changes in the teaching of a first year probability and statistics module for mathematics undergraduates at Sheffield Hallam University. Changing to project based learning with a focus on active learning, effective decision making and communication enabled students to successfully undertake an open group project by the end of their first year. In addition, attendance, engagement and understanding were noticeably improved. The rationale, challenges and benefits to changing the focus of the course and also the teaching style are discussed.

A preclinical study to model taurine pharmokinetics in the undernourished rat

Malnutrition is a common feature of chronic and acute diseases, often associated with a poor prognosis, including worsening of clinical outcome, owing, among other factors, to dysfunction of the most internal organs and systems affecting the absorption, metabolism and elimination of drugs and nutrients. Taurine is involved in numerous biological processes and is required in increased amounts in response to pathological conditions. The aim of this study was to describe the behaviour of taurine in well-nourished (WN) rats and to analyse the influence of protein–energy undernutrition on the pharmacokinetic (PK) parameters of taurine, using a PK model. Wistar rats were randomly distributed into two groups, WN and undernourished (UN), and taurine was administered intravenously or orally at different doses: 1, 10 and 100 mg. Population pharmacokinetic modelling of plasma levels was performed using the NONMEM 7.2 program. Several distribution and absorption models were explored in combination with dose and/or time covariate effects. Covariates such as nutritional status, serum albumin, body weight and score of undernutrition were used. A two-compartment population pharmacokinetic model with zero-order endogenous formation, passive absorption, first-order kinetics distribution and non-linear elimination with parallel Michaelis–Menten excretion and reabsorption processes best described taurine pharmacokinetics. Undernutrition acted as a covariate reducing theVmaxof the active elimination process. Data analysis showed linear absorption and distribution, and non-linear elimination processes for taurine. Elimination of taurine was reduced in UN animals, suggesting that the reabsorption process via the secretion transporter was modified in that group.

Avaliação macro e microscópica do trato digestório de frangos de corte alimentados com dieta contendo glicerina

This study aimed to evaluate the presence of morphological changes in the digestive tract of broilers fed diets containing 7% glycerol. It was used 16 animals from male Cobb 500® line, distributed in a completely randomized design in two treatments: animals fed diet without glycerin and animals fed diets containing 7% glycerol. It was observed that the addition of glycerin at 7% in the diet of broilers promotes the occurrence of significant inflammatory infiltrates in the proventriculus, caecum and colon of such animals, macroscopically the addition of glycerin in the diet did not cause any significant difference, but these differences had no significant effect on zootechnical development of such animals. It is possible to conclude that the use of glycerin in the diet can cause localized inflammatory processes, due to its alcoholic feature that degrades the protective mucus barrier and it presents passive absorption and exposes the mucus epithelium to the gastric juice action, thus promoting the mucosa inflammatory process. In the large intestine (cecum and colon) the inflammatory response showed greater intensity as a function of these organs have higher lymphatic tissue (nodular and diffuse)concentration and at this portion the intestine performs the fluids reabsorption directly competing with glycerin which is highly hygroscopic.