Knowledge, Attitude and Practice in Managing Chronic Kidney Disease with SGLT2 Inhibitors

Background and objective: Chronic kidney disease (CKD), and its increasing global burden, is associated with significant morbidity and mortality. This survey-based study aims to capture the knowledge, attitude and practices (KAP) amongst practicing physicians in considering sodium-glucose co-transporter 2 inhibitors (SGLT2i) for the prevention and progression of CKD in diabetic or nondiabeticindividuals. Methodology: An online questionnaire-based survey was conducted among 262 health care practitioners (HCPs) who manage people with CKD with or without diabetes. The survey was prepared as a Google form and circulated through email to different HCPs. The survey consisted of 6 knowledge-based questions, 4 attitude-based questions and 4 practice-based questions. The forms were filled up voluntarily by the participants and the authors had no control over the response provided. All the responses wereconsolidated using Microsoft Excel and analyzed. Results: A total of 262 HCPs from different regions of the country participated in the survey. About 87% to 94% of the participants were aware that SGLT2i, specifically dapagliflozin, is approved for use in CKD patients with or without diabetes. About threefourths of the HCPs accepted that an initial drop in estimated glomerular filtration rate (eGFR) occursupon initiation of dapagliflozin treatment. Almost 90% of them acknowledged the importance of screening for CKD in diabetic patients, and the majority were aware of the renal benefits of SGLT2i. Almost 96% of HCPs consider that dapagliflozin could be used in all patients with CKD irrespective of their diabetes status. Major determining factors with respect to a setback in practice are fear of side effects (54%) and hesitation in switching to newer medications when older medications work fine (34%). Conclusion:SGLT2i have demonstrated significant clinical benefits in patients with CKD with or without diabetes. This survey has shown good awareness among clinicians of the beneficial role of SGLT2i in CKD.&nbsp

An Event Study Approach to Analyze the Confounding Nature of Bitcoin on Blockchain Disclosures

Background: There is a case to be made that the widely popular and highly valued “Bitcoin” (and other significant cryptocurrencies) has become synonymous with blockchain for many retail investors and other non-informed individuals. This study attempts to answer two important research questions in this space. First, the study aims to understand if companies leverage this proximity in technological awareness of Bitcoin and blockchain to attract more investors and users by riding the Bitcoin wave and strategically timing the disclosures. Second, we aim to compute the value of the confounding effect. Method: To answer these questions, we collected over 4000 blockchain-related announcements from the top 30 NASDAQ-listed firms over the past five years. All announcements are analyzed using text analytics techniques to identify the topic, tone, and complexity. An event study approach adopting a Fama-French four-factor model is developed to detect whether any changes in the market-wide abnormal returns surrounding Bitcoin events influence the company\u27s performance. The relationship between the announcement texts and the abnormal returns is then computed and analyzed. Results: The results evidence a substantial impact of Bitcoin market returns on the abnormal return instances. Further, it is also observed that strategically framing the firm disclosures concerning blockchain announcements has a significant impact on the market returns. Conclusion: This study contributes to the literature on digital business strategies within the emerging purview of cryptocurrency networks. At a practical level, the study aims to alert not-so-well-informed investors about the possible misconception of Bitcoin performance as a direct driver of the performance of the technological companies making blockchain announcements

Engineered mesenchymal stem cells with self-assembled vesicles for systemic cell targeting

Cell therapy has the potential to impact the quality of life of suffering patients. Systemic infusion is a convenient method of cell delivery; however, the efficiency of engraftment presents a major challenge. It has been shown that modification of the cell surface with adhesion ligands is a viable approach to improve cell homing, yet current methods including genetic modification suffer potential safety concerns, are practically complex and are unable to accommodate a wide variety of homing ligands or are not amendable to multiple cell types. We report herein a facile and generic approach to transiently engineer the cell surface using lipid vesicles to present biomolecular ligands that promote cell rolling, one of the first steps in the homing process. Specifically, we demonstrated that lipid vesicles rapidly fuse with the cell membrane to introduce biotin moieties on the cell surface that can subsequently conjugate streptavidin and potentially any biotinylated homing ligand. Given that cell rolling is a pre-requisite to firm adhesion for systemic cell homing, we examined the potential of immobilizing sialyl Lewis X (SLeX) on mesenchymal stem cells (MSCs) to induce cell rolling on a P-selectin surface, under dynamic flow conditions. MSCs modified with SLeX exhibit significantly improved rolling interactions with a velocity of 8 μm/s as compared to 61 μm/s for unmodified MSCs at a shear stress of 0.5 dyn/cm[superscript 2]. The cell surface modification does not impact the phenotype of the MSCs including their viability and multi-lineage differentiation potential. These results show that the transitory modification of cell surfaces with lipid vesicles can be used to efficiently immobilize adhesion ligands and potentially target systemically administered cells to the site of inflammation.American Heart Association (Grant 0970178N)National Institutes of Health (U.S.) (Grant DE019191

QUANTIFICATION OF URAPIDIL IN HUMAN PLASMA USING ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY-ELECTROSPRAY IONIZATION MASS SPECTROMETRY (UPLC-MS/MS) FOR PHARMACOKINETIC STUDY IN HEALTHY INDIAN VOLUNTEERS

Objective: A rapid and selective quantitative method was developed and validated in human plasma for urapidil pharmacokinetic study in healthy Indian volunteers. Methods: The ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) method with solid-phase extraction technique utilized Strata X 33µ polymeric reversed phase (30 mg/mL), extraction cartridge. Simple gradient chromatographic conditions and selective reaction monitoring in mass spectrometric detection enabled accurate and precise measurement of urapidil at nanogram levels in 0.1 mL of human plasma. The method used a deuterium labeled internal standard. Results: The method was validated for a linear range of 5–500 ng/mL for urapidil with a correlation coefficient ³ 0.99 The intra-run and inter-run precision and accuracy were within 10%. The overall recoveries for urapidil and urapidil D4 were more than 90%. The urapidil was found to be stable in plasma matrix and aqueous media. Conclusion: The developed and validated method was specific, sensitive and reproducible in the analysis of clinical samples interspersed with quality control samples under freshly prepared calibration standards. The method was applied for the determination of the pharmacokinetic parameters of urapidil following a single oral administration of urapidil 60 mg capsules in nineteen healthy Indian male volunteers for fasting and fed study

Molecular Docking Study of Conformational Polymorph: Building Block of Crystal Chemistry

Two conformational polymorphs of novel 2-[2-(3-cyano-4,6-dimethyl-2-oxo-2H-pyridin-1-yl)-ethoxy]-4,6-dimethyl nicotinonitrile have been developed. The crystal structure of both polymorphs (1a and 1b) seems to be stabilized by weak interactions. A difference was observed in the packing of both polymorphs. Polymorph 1b has a better binding affinity with the cyclooxygenase (COX-2) receptor than the standard (Nimesulide)

Microbiome profiling of the onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae)

Not AvailableThe gut microbial community structure of adult Thrips tabaci collected from 10 different agro-climatically diverse locations of India was characterized by using the Illumina MiSeq platform to amplify the V3 region of the 16S rRNA gene of bacteria present in the sampled insects. Analyses were performed to study the bacterial communities associated with Thrips tabaci in India. The complete bacterial metagenome of T. tabaci was comprised of 1662 OTUs of which 62.25% belong to known and 37.7% of unidentified/unknown bacteria. These OTUs constituted 21 bacterial phyla of 276 identified genera. Phylum Proteobacteria was predominant, followed by Actinobacteria, Firmicutes, Bacteroidetes and Cyanobacteria. Additionally, the occurrence of the reproductive endosymbiont, Wolbachia was detected at two locations (0.56%) of the total known OTUs. There is high variation in diversity and species richness among the different locations. Alpha-diversity metrics indicated the higher gut bacterial diversity at Bangalore and lowest at Rahuri whereas higher bacterial species richness at T. tabaci samples from Imphal and lowest at Jhalawar. Beta diversity analyses comparing bacterial communities between the samples showed distinct differences in bacterial community composition of T. tabaci samples from different locations. This paper also constitutes the first record of detailed bacterial communities associated with T. tabaci. The location-wise variation in microbial metagenome profile of T. tabaci suggests that bacterial diversity might be governed by its population genetic structure, environment and habitat.Not Availabl

Dynamically mapping tasks with priorities and multiple deadlines in a heterogeneous environment

Includes bibliographical references (pages 166-167).In a distributed heterogeneous computing system, the resources have different capabilities and tasks have different requirements. To maximize the performance of the system, it is essential to assign the resources to tasks (match) and order the execution of tasks on each resource (schedule) to exploit the heterogeneity of the resources and tasks. Dynamic mapping (defined as matching and scheduling) is performed when the arrival of tasks is not known a priori. In the heterogeneous environment considered in this study, tasks arrive randomly, tasks are independent (i.e., no inter-task communication), and tasks have priorities and multiple soft deadlines. The value of a task is calculated based on the priority of the task and the completion time of the task with respect to its deadlines. The goal of a dynamic mapping heuristic in this research is to maximize the value accrued of completed tasks in a given interval of time. This research proposes, evaluates, and compares eight dynamic mapping heuristics. Two static mapping schemes (all arrival information of tasks are known) are designed also for comparison. The performance of the best heuristics is 84% of a calculated upper bound for the scenarios considered