QSAR analysis for some β-carboline derivatives as anti-tumor

Abstractβ-Carboline moieties are important structural subunits which occur as components of many biologically interesting molecules for antitumor activity. Quantitative structure–activity relationship (QSAR) studies have been performed on β-carboline derivatives to explore the structural necessities for antitumor activity. 3D QSAR studies were done using V-Life Sciences MDS 3.0 drug designing module to explain the structural requirements for the anti-tumor activity. The 3D-QSAR was performed using the Step Wise K Nearest Neighbour Molecular Field Analysis [(SW) kNN MFA] technique with the partial least-square (PLS) method on a database. Obtained best 3D-QSAR model having high predictive ability with q2=0.743, r2=0.721, pred_r2=0.708 and standard error=0.346, explaining the majority of the variance in the data with partial least square (PLS) components. The results of the present study may be useful on the designing of more potent compounds as antitumor drugs

Low use of statins and other coronary secondary prevention therapies in primary and secondary care in India.

ObjectiveTo determine the frequency of use of pharmacotherapy with aspirin, beta blocker, statin, and angiotensin-converting enzyme (ACE) inhibitor in patients with stable coronary heart disease (CHD) among physicians at different levels of health care in Rajasthan state, India.MethodsPhysicians practicing at tertiary hospitals and clinics at tertiary, secondary and primary levels were contacted. Prescriptions of CHD patients were audited and descriptive statistics reported.ResultsWe evaluated 2,993 prescriptions (tertiary hospital discharge 711, tertiary 688, secondary 1,306, and primary 288). Use of aspirin was in 2,713 (91%) of prescriptions, beta blockers 2,057 (69%), ACE inhibitors or angiotensin receptor blockers (ARBs) 2,471 (82%), and statins 2,059 (69%). Any one of these drugs was prescribed in 2,991 (100%), any two in 2,880 (96%), any three in 1,740 (58%), and all four in 1,062 (35.5%) (P < 0.001). As compared to tertiary hospital, prescriptions at tertiary, secondary, and primary levels were lower: aspirin (96% vs 95%, 91%, 67%), beta blockers (80% vs 62%, 66%, 70%), statins (87% vs 82%, 62%, 21%): two drugs (98% vs 96%, 98%, 85%), three drugs (75% vs 58%, 55%, 28%), or four drugs (54% vs 44%, 28%, 7%) (P < 0.01). Use of ACE inhibitors/ARBs was similar while nitrates (43% vs 23%, 43%, 70%), dihydropyridine calcium channel blockers (12% vs 15%, 30%, 47%), and multivitamins (6% vs 26%, 37%, 47%) use was more in secondary and primary care.ConclusionsThere is suboptimal use of various evidence-based drugs (aspirin, beta blockers, ACE inhibitors, and statins) for secondary prevention of CHD in India

Study, Survey and Analysis for Media Selection

This paper is a literature review on practical techniques and rules using PowerPoint, animation, and video effectively for instruction. Instruction may be teaching, training, coaching, tutoring, schooling etc. This paper must be of awareness to mentors and instructional technology staff who support faculty members in the development of instructional media. Main objective of this paper is to identify and select the proper technologies for enhancing a particular pedagogy or learning goal. Choose media that support instructor's activity

Primary Malignant Melanoma of Female Urethra: A Case Report and Review of Literature

We report a very rare case report of female diagnosed with primary malignant melanoma. A 65 years old diabetic elderly postmenopausal femalepresented with a history of intermittent blood spots on undergarments forfew days. Genital examination revealed a single, tan colored, soft chestnut size and polypoidal non ulcerated mass lesion protruding through theurethral meatus. Mass biopsy revealed poorly differentiated epithelial malignancy and immuno-histological analysis revealed positive with HMB45 and protein S-100 suggestive of melanoma. Metastatic work up for themalignancy was negative. Complete urethrectomy with Mitrofanoff procedure with inguinal lymph node dissection was performed. Histopathological examination was suggestive of malignant melanoma of urethra.Here we discuss the clinicopathological features and management optionpossible in this scenario

Cholesterol Granuloma of Maxillary Sinus – An Unusual Case

Introduction Cholesterol granuloma is a type of foreign body granuloma found in tissues wherein the cholesterol crystals get accumulated. Quite unusual to be present in maxillary sinus owing to its pathogenesis. Case Report A 12 year old male child diagnosed with antrochoanal polyp, underwent endoscopic sinus surgery and the microscopic analyses revealed maxillary sinus cholesterol granuloma. Discussion Cholesterol granuloma is an uncommon tissue reaction to cholesterol crystals in the maxillary sinus owing to its well-ventilated state and is frequently associated with chronic sinuses disease or trauma. Since its signs and symptoms are non–specific, histopathological analysis is essential for correct diagnosis

Improved Enzymatic Hydrolysis of Pilot Scale Pretreated Rice Straw at High Total Solids Loading

Enzymatic hydrolysis at high solids loading has the potential to reduce both capital and operational expenditures. Here, pretreatment of rice straw (PRS) with dilute acid was carried out at a pilot scale (250 kg per day) at 162°C for 10 min and 0.35% acid concentration, followed by enzymatic hydrolysis at different total solids loadings. It showed that although the total sugar concentration increased from 48 to 132 g/l, glucan conversion reduced by 27% (84–66.2%) with increasing solids from 5 to 20% in batch mode. Therefore, two different fed-batch approaches were evaluated to improve the glucan conversion by the sequential addition of a substrate and/or enzyme. At 20% solid loadings and a 3 filter paper units/g enzyme dosage, the highest glucan conversion obtained was 66% after 30 h of hydrolysis in batch mode. However, in an optimized fed-batch approach, the glucan yield was improved to 70% by simply dividing the substrate feeding into three batches, that is, 50% at 0 h, 25% each after 4 h, and 8 h of hydrolysis reaction. The addition of surfactant (Ecosurf E6) further improved the conversion to 72% after 30 h. The role of critical factors, that is, inhibitors, enzyme–lignin binding, and viscosity, was investigated during the course of hydrolysis in the batch and fed-batch approaches. This study suggests a sustainable approach for improved hydrolysis at high solids loadings by fine-tuning a simple process

Synergistic Enzyme Cocktail to Enhance Hydrolysis of Steam Exploded Wheat Straw at Pilot Scale

Multiple enzymes are required for efficient hydrolysis of lignocellulosic biomass and no wild type organism is capable of producing all enzymes in desired levels. In this study, steam explosion of wheat straw was carried out at pilot scale and a synthetic enzyme mixture (EnzMix) was developed by partially replacing the cellulase with critical dosages of commercially available accessory enzymes (β-glucosidase, xylanase and laccase) through central composite design. Highest degree of synergism (DS) was observed with β-glucosidase (1.68) followed by xylanase (1.36). Finally, benchmarking of EnzMix (Celluclast, β-glucosidase and xylanase in a protein ratio of 20.40: 38.43: 41.16, respectively) and other leading commercial enzymes was carried out. Interestingly, hydrolysis improved by 75% at 6 h and 30% at 24 h, respectively in comparison of control. By this approach, 25% reduction in enzyme dosage was observed for obtaining the same hydrolysis yield with opitimized enzyme cocktail. Thus, development of enzyme cocktail is an effective and sustainable approach for high hydrolysis efficiency

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Abstract: The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era