2D/3D-QSAR, DOCKING AND OPTIMIZATION OF 5-SUBSTITUTED-1H-INDAZOLE AS INHIBITORS OF GSK-3β

Objective: Glycogen synthase kinase-3 beta (GSK-3β) plays a crucial role in several human diseases. GSK-3β is being one of the most attractive therapeutic targets for several decades across the research communities to discover new potent and selective inhibitors of GSK-3β. The objective of the research is to develop new compounds based on the QSAR and molecular docking studies. Methods: 2D/3D QSAR studies were conducted on a series of 5-substituted Indazole derivatives in order to optimize the GSK-3β inhibitors. Optimized inhibitors were subjected to molecular docking studies to find best inhibitors towards GSK-3β. Results: The significant QSAR model-3 (2D) and model-6 (3D) elucidate that T_C_N_5, T_2_N_0, SlogP, electrostatic potential (E_451, E_229) and hydrophobicity (H_1052) are important descriptors to conclude the biological activities of compounds. Docking study illustrates Val135, Gln185, Arg141 and Asp200 were essential interacting residues in the active site of the receptor with ligands. Based on QSAR models, 450 compounds were optimized and validated through docking studies. Conclusion: The best 31 optimized compounds, which showed good interaction energy, docking score and preferred interactions were selected as GSK-3β inhibitors

Field Evaluation of Three Entomopathogenic fungi on Groundnut Pest

Entomopathogenic fungi Beauveria bassiana (Balsamo) Vuillemin (Deuteromycotina: Hyphomycetes), Paecilomyces fumosoroseus (Wize) (Deuteromycotina: Hyphomycetes), Verticillium lecani Viegas (Deuteromycotina: Hyphomycetes) were tested against groundnut pests, Aphis craccivora (Koch) (Homoptera: Aphididae), Aproarema modicella (Deventer) (Lepidoptera: Gelechiidae), Mylabris pustulata Faust (Coleoptera: Meloidae) and Spodoptera litura (Fabricius) (Lepidoptera: Noctuidae) in field conditions. Among the tested fungi, V. lecanii suppressed 62% of A. craccivora population at 39 Days After Seedling Emergence (DASE). During the same period, B. bassiana reduced 72% of S. litura larval population (0.73 larvae). The infestation of S. litura and A. modicella were greatly reduced after the treatment of B. bassiana; subsequently the yield (1721.31 kg/ha-1) and cost benefit ratio (1: 1.93) were increased. P. fumosoroseus and V. lecanii were less effective than B. bassiana. The persistence of fungal pathogens was found to be higher in soil than the phyllosphere indicating that they can be naturally favored for the control of pests in groundnut

Adverse Events Sustained by Children in The Intensive Care Unit: Guiding local quality improvement

Objective: To determine the frequency, nature and consequence of adverse events sustained by children admitted to a combined general and cardiac paediatric intensive care unit (PICU). Design: Retrospective analysis of data collected between January 1st 2008 and December 31st 2017 from PICU. Setting: The Royal Children’s Hospital, a paediatric tertiary referral centre in Melbourne, Victoria, Australia. The PICU has thirty beds. Results: During the study period, PICU received 15208 admissions, of which 73% sustained at least one adverse event with a frequency of 67 adverse events per 100 PICU-days and 3 per admission. One adverse event was sustained for every 35 hours of care. The risk of an adverse event was highest in children less than a month of age, or if mechanically ventilated, a high Pediatric Index of Mortality (PIM2) score, longer PICU length of stay, had a pre-existing disability or a high risk adjustment for congenital heart surgery (RACHS) score. Those patients who sustained an adverse event, as compared to those who did not, were mechanically ventilated for longer (80 hrs Vs. 7 hrs, p=<0.001), had a longer PICU length of stay (131 hrs Vs. 35 hrs, p=<0.001), had a longer hospital length of stay (484 hrs Vs. 206 hrs, p=<0.001) and had a higher mortality rate (3% vs. 0.1%, p=<0.001). Conclusion: Whilst admission to PICU is an essential aspect of care for many patients, the risk of adverse events is high and is associated with significant clinical consequences. Monitoring of adverse events as part of quality improvement enables targeted intervention to improve patient safety

Supplementation of Madhuca longifolia Seed oil augments diclofenac-induced organ toxicities: A biochemical and histopathological approach

Diclofenac medication has been extensively used for anti-inflammatory, anti-pyretic, and analgesic actions. Its abiding usage and overdose have induced toxicity and harmful effects on the liver, kidney, and gastrointestinal tract. The research aims to scrutinize the protective effect of Madhuca longifolia seed oil against diclofenac-induced toxicity in female Wistar albino rats. A period of 10 days of study was aimed at 7 groups; Group 1 was assigned as normal control. Group 2 has been administered diclofenac (50 mg/kg b.w. /day, i.p.) only on the last two days of each study period. Group 3 and Group 4 have been pre-treated with 1 mL, and 2 mL of Madhuca longifolia seed oil, respectively, and diclofenac was induced as per Group 2. Group 5 was treated with the standard drug silymarin and diclofenac. Group 6 and Group 7 were given 1 mL and 2 mL of Madhuca longifolia seed oil alone. After the study period, parameters like liver enzyme markers, renal enzyme markers, and antioxidants were measured, and tissue samples were analyzed for histopathological changes. The results proved that pre-treatment of 1 mL of Madhuca longifolia seed oil has efficacy against diclofenac-induced toxicity

Prenatal Diagnosis of Oculocutaneous Albinism by Electron Microscopy of Fetal Skin

Oculocutaneous albinism was diagnosed prenatally by electron microscopic examination of fetal skin samples taken during fetoscopy at 20 weeks of gestation. Melanosome development in hair bulb melanocytes progressed no further than stage II, indicating a lack of melanin synthesis. In 4 age-matched control fetuses, numerous stage IV melanosomes, signifying active melanin synthesis, were identified. The diagnosis was confirmed after the pregnancy was terminated at 22 weeks. Examination of the fetal eye showed absence of pigment in the retinal epithelium and uvea at a stage when ocular melanogenesis would normally be active. This study shows that oculocutaneous albinism can be detected in the second trimester using similar techniques to those employed in the prenatal diagnosis of epidermolysis bullosa and ichthyosis