EVALUATION OF ROLE OF FICUS BENGALENSIS IN MODULATION OF COGNITIVE IMPAIRMENT AND OXIDATIVE STRESS IN DIABETIC RATS

Objectives: Our objective was to study the effects of Ficus benghalensis on cognitive behavior and oxidative stress in diabetic rats and to compare with vitamin C and glimepiride. Methods: Wistar rats of either sex randomized into five groups of diabetic rats by streptozocin (STZ), five groups of non-diabetic rats (distilled water) (n=10). Subgroup division (F. benghalensis dose I and II, i.e., 50 mg/kg and 100 mg/kg; Vitamin C 100 mg/kg and glimepiride 0.5 mg/kg) were done. Each drug was given to one diabetic and one non-diabetic group. Other set served as control. Assessment of blood glucose, cognitive function (using continuous avoidance apparatus and Morris water maze test), and oxidative stress (measuring Malondialdehyde (MDA), reduced glutathione (GSH) levels) were done on Day 0 and 30. The acquisition phase of cognitive behavior tests was assessed on 0, 14, and 29 days and retention phase was assessed on 1, 15, and 30 day. Results: As compared to control group, F. benghalensis dose I, dose II, and glimepiride showed significant decrease (p<0.001) in blood glucose. F. benghalensis dose I, dose II, vitamin C, and glimepiride group showed significant decrease in acquisition and retention of transfer latency on 29 and 30 days. Significant increase in retention of step-down latency on 30 day was shown by both the doses of F. benghalensis. Both doses of F. benghalensis, vitamin C and glimepiride group showed significant increase in retention of Quadrant-time in comparison to control on 30 days. Significant decrease in brain MDA levels while a significant increase in brain GSH levels was observed in all groups except control. Conclusion: F. benghalensis reverses behavioral and biochemical changes induced by STZ and effects are comparable with that of vitamin C and glimepiride

Bedaquiline, Delamanid, Linezolid and Clofazimine for Treatment of Pre-extensively Drug-Resistant Tuberculosis.

BACKGROUND Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with Bedaquiline and Delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+). METHODS We prospectively determined the effectiveness and safety of combining two new drugs with two repurposed drugs - Bedaquiline, Delamanid, Linezolid, and Clofazimine for 24-36 weeks in adults with pulmonary MDR-TBFQ+ or/and MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as two consecutive negative cultures taken four weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during treatment period. RESULTS Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: four deaths, seven treatment changes, two bacteriological failures, and one withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500msec. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority. CONCLUSION After 24-36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully

Artificial intelligence, digital technologies and the future of law

Intensive use of artificial intelligence and digital technologies is becoming an integral part of our everyday life. Artificial intelligence algorithms are effectively used to diagnose diseases, help overcome language barriers thanks to automatic translation, make court decisions in cases, analyze the psychological state and consumer needs of social network users and, as a result, affect basic human rights and freedoms. In these examples, the advantages are clear, but there are many ethical and legal problems that can lead to serious negative consequences. It is significant that so far the norms of national and international legislation have regulated relations between individuals, but with the development of artificial intelligence, another plane of interaction appears - "man-machine". Communication takes place between a person and an algorithm without the participation of other people, and it is the algorithm that is authorized to make certain decisions: from a chatbot that will offer the best travel options to a robot that will decide whether to let you cross the border or use a weapon against you or whether to hire you. The purpose of the research is to analyze the specific features of the formation and development of the artificial intelligence, digital technologies and the future of law. The main methods used in the work were: comparative, method of abstraction, deductive method, concretization. The results states that artificial intelligence and digital technologies has not succeeded in surpassing humans in creativity and intellectual abilities. However, it should be remembered that over time it will understand its internal structure and will be capable of self-improvement, so society needs to create certain ethical standards for the development and operation of artificial intelligence technologies. The conclusion is oriented on the fact that, the technological paradigm is changing, management models and social norms are changing, large-scale developments are taking place demographic changes. Therefore, all the mentioned above requires additional analyses

Development of the travel satisfaction scale (TSS) for the assessment of commuters’ satisfaction in public transport: evidence from Delhi metro (India)

The Travel Satisfaction Scale (TSS) was created to gauge public opinion on Delhi Metro travel. It has two affective dimensions and one cognitive dimension. This study leverages data from the Delhi Metro commuter trips to undertake new tests because there has been little research on its reliability and structure in the past. Differences in the TSS's reliability and structure – notably for the Delhi Metro and the demographics of the region – are also considered. Finally, the outcomes of this study imply that a single dimension of the affective dimension, rather than the two sub-dimensions, provides a better fit for the Delhi Metro, as well as other public transportation infrastructures in developing countries like India. Individual objects do not load on the two emotional dimensions as intended in a three-dimensional structure, which is more suited for public transportation. Two of the scale's elements – enthusiastic/bored and relaxed/hurried – were associated with the other items in a previous study differing from ours. Researchers should adapt the structure of the TSS in the future by adding or replacing some items with alternate options, which will make it easier to collect data and reduce the burden on the respondent, as well as increase the reliability of the data while maintaining the TSS's consistency and balance

Economic Value Added Research: Mapping Thematic Structure and Research Trends

The purpose of this article is to examine the academic literature about the function, structure, calculation, and weaknesses of economic value added (EVA). EVA has been used as a measure of economic profit and captures the inadequacies of using traditional rates of return. In addition, this article tackles the main residual earnings (RI) modifications used to calculate EVA. A keyword search for publications was conducted in early 2022. This study couples an inferential analysis with descriptive analyses of the existing research. The articles were sorted into different clusters based on bibliographic coupling analysis. This study identifies the main areas and current dynamics of EVA research while evaluating the quality and impact of the scientific output. Three broad themes emerged from the analysis of the cluster related to the use and application of EVA: residual income and valuation, financial performance, and performance management. In doing so, we hope to enhance the understanding and contributions of EVA research to advance its theory and practice

Microbial contamination of mobile phones of health care providers at a teaching hospital in a hilly North Indian State

Introduction: Mobile phone is a ubiquitous device used in health care settings as well. Its frequent handling, closeness to the body and heat generated during functioning provides a favourable environment for microbial contamination and growth; as well as opportunities for their transfer from one person to another through health care provider. Objective: To investigate whether health care workers mobile phones carry microbes and to identify areas or health personals where this was more common. Material and methods: A cross sectional study was conducted at a medical college and its associated hospital in a northern hilly state of India to determine the prevalence of microbial contamination of mobile phones used by health care providers. Doctors, Nurses, Laboratory Technicians and Medical Interns were contacted at their place of work to collect swab samples from their mobile phones. Sample collection sites included out-patient clinics as well as in-patient wards, emergency department and intensive care unit. All health care providers available at the time of visit to these departments were included in the study. Swab samples collected were immediately transferred to microbiology department where overnight incubation in peptone water at 37°C followed by culture and appropriate testing to identify organisms was done. Result: A total of 100 swab samples were collected, 28 from doctors, 20 from nurses, 25 from technicians and 27 from medical interns. All of them except one showed growth. Single growth were 56 while 43 cultures had multiple growths. Organism of medical importance isolated included Coagulase Negative Staphylococci (CoNS), Methicillin Resistant CoNS, Methicillin Resistant Staphylococcus aureus (MRSA), Klebsiella, S. aureus, E.coli among others. Conclusion: Almost all mobile phones were contaminated, more than half of whom were harbouring pathogenic micro-organisms. It could be a major threat to the health care providers as well as patients in form of nosocomial infections

Genetic Variability and Diversity in Red Onion (<i>Allium cepa</i> L.) Genotypes: Elucidating Morpho-Horticultural and Quality Perspectives

Onion (Allium cepa L.) is a prominent spice and vegetable crop farmed commercially worldwide. Variability is viewed as a key signal for any red onion enhancement effort. The current study was, therefore, carried out to learn about genetic variability and diversity among selected genotypes of 20 red onions at the C Block Farm, Bidhan Chandra Krishi Viswavidyalaya, India, during the winter (rabi) season of 2021–2022, in Randomized Complete Block Design (RCBD) with three replications. The characters, viz., average weight of bulbs (kg), neck thickness (cm), total soluble solids (°Brix), total sugar (%), and reducing sugar (%) demonstrated high heritability (97.38–99.97%) coupled with high genetic gain. Such traits were the least influenced by environmental effects, and additive gene action played a pivotal role in the manifestation of such characters. Traits with high heritability values (51.37–67.94%) demonstrate that the observed variability was under genetic control and provide an enormous range of possibilities for accomplishing selection depending on their phenotypic performances. For traits with moderate heritability, viz., bolting (%) and doubling (%), selection would be less effective but can still be given great importance. Based on correlation analysis, the character’s neck thickness, equatorial diameter, and polar diameter unveiled highly positive genetic correlation with the average weight of bulbs (0.120, 0.112; 0.194, 0.210 and 0.120, 0.112 for phenotypic and genotypic correlation coefficient values, respectively), which indicates that the average weight of a bulb would be increased by an increase in such components. According to path coefficient analysis, the equatorial diameter exhibited the most positive direct effect on the average weight of bulbs (0.968), followed by polar diameter (0.687) and neck thickness (0.159). A wide range of variations for qualitative traits, including foliage colour, leaf width, foliage behaviour, the degree of leaf waxiness, the shape of the bulb, and bulb skin colour were observed. Based on Mahalanobish D2 analysis, the genotypes were divided into four clusters. The highest number of genotypes was found in cluster I (eleven), followed by cluster IV (six genotypes) and cluster II (two genotypes). Cluster III had a single genotype and was monogenic. The study confirmed that a wide genetic variation prevailed in the onion genotypes taken under study, which could thereby be utilized in breeding programmes

Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial

Background The current tuberculosis (TB) drug development pipeline is being re-populated with candidates, including nitroimidazoles such as pretomanid, that exhibit a potential to shorten TB therapy by exerting a bactericidal effect on non-replicating bacilli. Based on results from preclinical and early clinical studies, a four-drug combination of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide (BPaMZ) regimen was identified with treatment-shortening potential for both drug-susceptible (DS) and drug-resistant (DR) TB. This trial aimed to determine the safety and efficacy of BPaMZ. We compared 4 months of BPaMZ to the standard 6 months of isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) in DS-TB. 6 months of BPaMZ was assessed in DR-TB. Methods SimpliciTB was a partially randomised, phase 2c, open-label, clinical trial, recruiting participants at 26 sites in eight countries. Participants aged 18 years or older with pulmonary TB who were sputum smear positive for acid-fast bacilli were eligible for enrolment. Participants with DS-TB had Mycobacterium tuberculosis with sensitivity to rifampicin and isoniazid. Participants with DR-TB had M tuberculosis with resistance to rifampicin, isoniazid, or both. Participants with DS-TB were randomly allocated in a 1:1 ratio, stratified by HIV status and cavitation on chest radiograph, using balanced block randomisation with a fixed block size of four. The primary efficacy endpoint was time to sputum culture-negative status by 8 weeks; the key secondary endpoint was unfavourable outcome at week 52. A non-inferiority margin of 12% was chosen for the key secondary outcome. Safety and tolerability outcomes are presented as descriptive analyses. The efficacy analysis population contained patients who received at least one dose of medication and who had efficacy data available and had no major protocol violations. The safety population contained patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov (NCT03338621) and is completed. Findings Between July 30, 2018, and March 2, 2020, 455 participants were enrolled and received at least one dose of study treatment. 324 (71%) participants were male and 131 (29%) participants were female. 303 participants with DS-TB were randomly assigned to 4 months of BPaMZ (n=150) or HRZE (n=153). In a modified intention-to-treat (mITT) analysis, by week 8, 122 (84%) of 145 and 70 (47%) of 148 participants were culture-negative on 4 months of BPaMZ and HRZE, respectively, with a hazard ratio for earlier negative status of 2·93 (95% CI 2·17–3·96; p&lt;0·0001). Median time to negative culture (TTN) was 6 weeks (IQR 4–8) on 4 months of BPaMZ and 11 weeks (6–12) on HRZE. 86% of participants with DR-TB receiving 6 months of BPaMZ (n=152) reached culture-negative status by week 8, with a median TTN of 5 weeks (IQR 3–7). At week 52, 120 (83%) of 144, 134 (93%) of 144, and 111 (83%) of 133 on 4 months of BPaMZ, HRZE, and 6 months of BPaMZ had favourable outcomes, respectively. Despite bacteriological efficacy, 4 months of BPaMZ did not meet the non-inferiority margin for the key secondary endpoint in the pre-defined mITT population due to higher withdrawal rates for adverse hepatic events. Non-inferiority was demonstrated in the per-protocol population confirming the effect of withdrawals with 4 months of BPaMZ. At least one liver-related treatment-emergent adverse effect (TEAE) occurred among 45 (30%) participants on 4 months of BPaMZ, 38 (25%) on HRZE, and 33 (22%) on 6 months of BPaMZ. Serious liver-related TEAEs were reported by 20 participants overall; 11 (7%) among those on 4 months of BPaMZ, one (1%) on HRZE, and eight (5%) on 6 months of BPaMZ. The most common reasons for discontinuation of trial treatment were hepatotoxicity (ten participants [2%]), increased hepatic enzymes (nine participants [2%]), QTcF prolongation (three participants [1%]), and hypersensitivity (two participants [&lt;1%]).Interpretation For DS-TB, BPaMZ successfully met the primary efficacy endpoint of sputum culture conversion. The regimen did not meet the key secondary efficacy endpoint due to adverse events resulting in treatment withdrawal. Our study demonstrated the potential for treatment-shortening efficacy of the BPaMZ regimen for DS-TB and DR-TB, providing clinical validation of a murine model widely used to identify such regimens. It also highlights that novel, treatment-shortening TB treatment regimens require an acceptable toxicity and tolerability profile with minimal monitoring in low-resource and high-burden settings. The increased risk of unpredictable severe hepatic adverse events with 4 months of BPaMZ would be a considerable obstacle to implementation of this regimen in settings with high burdens of TB with limited infrastructure for close surveillance of liver biochemistry. Future research should focus on improving the preclinical and early clinical detection and mitigation of safety issues together and further efforts to optimise shorter treatments