Preclinical safety evaluation of low molecular weight galactomannans based standardized fenugreek seeds extract

The objective of the present study was to evaluate acute oral toxicity, subchronic toxicity, and mutagenic potential of low molecular weight galactomannans based standardized fenugreek seeds extract (LMWGAL-TF) in laboratory animals rats as per Organization for Economic Co-operation and Development (OECD) guidelines. For the acute toxicity (AOT) study, LMWGAL-TF was orally administered to Sprague-Dawley (SD) rats at a dose of 2000 mg/kg with vehicle control (VC) group (n = 5 per sex per group) as per OECD guideline no. 423. For the repeated dose toxicity study, the SD rats were orally administered with a daily oral dose of LMWGAL-TF 250, 500 and 1000 mg/kg/day with VC group (n = 15 per sex) for a period of 90 days followed by a recovery period of 28 days as per OECD guideline no. 408. The effects on body weight, food and water consumption, organ weights with hematology, clinical biochemistry, and histology were studied. The mutagenic potential of LMWGAL-TF was tested using reverse mutation assay (AMES test, OECD guideline No. 471). The LMWGAL-TF did not show mortality or treatment-related adverse signs during acute (dose 2000 mg/kg) and subchronic (90-days repeated dose 250, 500 and 1000 mg/kg) administration. The LMWGAL-TF showed oral lethal dose (LD50) more than 2000 mg/kg during AOT study. The dose of 1000 mg/kg was found as no observed adverse effect level (NOAEL) in rats during subchronic toxicity study. Furthermore, LMWGAL-TF did not show mutagenic potential in vitro. In conclusion, LMWGAL-TF was found safe during acute and subchronic (90 days repeated dose) toxicity studies in rats with no mutagenicity

Mechatronics: The Synergistic Integration of Mechanical Engineering with Electronics and Control Engineering

Mechatronics, the word itself signifies that it is a combination of “Mechanical” and “Electronics”. It comprises of computer technology, mechanical, electronics, electrical & control engineering. It is an Integration of all technologies together that forms a major part in the design, manufacture and maintenance of wide range engineering products and designs. In industries there is no limit of scope of Mechatronics. This article focuses on the synergistic integration of systems. DOI: 10.17762/ijritcc2321-8169.15057

Sustainable Use of Waste Banana Peel (Musa × sapientum L.) Powder for Enhancement of Nutritional Properties of Dark Chocolate

Dark chocolate is a very popular confectionary product among children, made by combining cocoa (55%) with cocoa butter (7.5%) and sugar (42%) has high antioxidant, anti-inflammatory, and free-radical scavenging properties. Chocolates also have a high concentration of cocoa and flavanols contents which is very beneficial for human health. The nutritional value of the dark chocolate samples prepared was further enhanced by using unripe banana peel powder. The peel of banana fruit is a waste material, but it also has antioxidant, antibacterial, and antibiotic properties which encourages its use in industries like pharmaceuticals. So, after considering the nutritional value of unripe banana fruit peel, the powder of unripe banana peel was added to the dark chocolate in the concentration of 1, 3, 5, 7, and 9% to increase the nutritional value of dark chocolate. The premix powder containing iron, folic acid, and vitamin B12 was also added to the dark chocolate samples in the concentration of 2% in all the variants. The nutritional value of chocolate samples made by using unripe banana peel powder and premix increased significantly but the color of the product decreased significantly as the concentration of banana powder increased

PRENATAL DEVELOPMENTAL TOXICITY EVALUATION OF LOW MOLECULAR WEIGHT GALACTOMANNANS BASED STANDARDIZED FENUGREEK SEED EXTRACT DURING ORGANOGENESIS PERIOD OF PREGNANCY IN RATS

Objective: To evaluate the prenatal developmental toxicity of low molecular weight galactomannans based standardized fenugreek seed extract (LMWGAL-TF).Methods: Rats received oral administration of LMWGAL-TF (250, 500 and 1000 mg/kg) during the period of gestation from day 5 (implantation day)–19 (1 d before expected day of parturition) post conception. Maternal, embryo, and fetal toxicity parameters were evaluated.Results: LMWGAL-TF exposure did not produce maternal (clinical observations, body weight gain, food intake) and embryo–fetal toxicity. Occasional skeletal and visceral malformations, unrelated to the treatments, were seen in both LMWGAL-TF-treated and vehicle control (VC) groups.Conclusion: Oral exposure of LMWGAL-TF during the prenatal period did not induce significant maternal and embryo–fetal toxicity up to a dose of 1000 mg/kg in rats. The dose of 1000 mg/kg was considered as NOAEL for LMWGAL-TF.Keywords: Developmental toxicity, Low molecular weight galactomannans, Standardized fenugreek seed extract, OECD Test No. 414, Reproductive system, Rat

Improved trilateration for indoor localization: Neural network and centroid-based approach

[EN] Location awareness is the key to success to many location-based services applications such as indoor navigation, elderly tracking, emergency management, and so on. Trilateration-based localization using received signal strength measurements is widely used in wireless sensor network-based localization and tracking systems due to its simplicity and low computational cost. However, localization accuracy obtained with the trilateration technique is generally very poor because of fluctuating nature of received signal strength measurements. The reason behind such notorious behavior of received signal strength is dynamicity in target motion and surrounding environment. In addition, the significant localization error is induced during each iteration step during trilateration, which gets propagated in the next iterations. To address this problem, this article presents an improved trilateration-based architecture named Trilateration Centroid Generalized Regression Neural Network. The proposed Trilateration Centroid Generalized Regression Neural Network-based localization algorithm inherits the simplicity and efficiency of three concepts namely trilateration, centroid, and Generalized Regression Neural Network. The extensive simulation results indicate that the proposed Trilateration Centroid Generalized Regression Neural Network algorithm demonstrates superior localization performance as compared to trilateration, and Generalized Regression Neural Network algorithm.Jondhale, SR.; Jondhale, AS.; Deshpande, PS.; Lloret, J. (2021). Improved trilateration for indoor localization: Neural network and centroid-based approach. International Journal of Distributed Sensor Networks (Online). 17(11):1-14. https://doi.org/10.1177/15501477211053997114171

EFFECTS OF A PROPRIETARY BLEND RICH IN GLYCOSIDE BASED STANDARDIZED FENUGREEK SEED EXTRACT (IBPR) ON INFLAMMATORY MARKERS DURING ACUTE ECCENTRIC RESISTANCE EXERCISE IN YOUNG SUBJECTS

  Objective: To assess the efficacy of a proprietary blend rich in glycoside based standardized fenugreek seed extract (400 mg) and minor quantities of curcumin and cinnamon (25 mg each) supplementation (IBPR) on inflammatory markers related to skeletal muscle soreness using double-blind placebo control, parallel design.Methods: A total of 20 healthy non-resistance trained young male and female subjects were assigned to ingest either IBPR or matching placebo for 14 days before the eccentric exercise bout. Subjects were instructed to perform 24 sets with 10 eccentric knee extensor repetitions (with one leg at 30°/s on an isokinetic device). Subjects had their blood drawn at baseline, immediately post, 1 hr, 3 hrs, and 24 hrs post-eccentric exercise. Efficacy in terms of serum levels of anti-inflammatory cytokines interleukin-10 (IL-10), pro-inflammatory cytokines (IL-1ra, IL-1b, IL-6, and tumor necrosis factor) and safety in terms of kidney function (blood urea nitrogen (BUN), serum creatinine, BUN to creatinine ratio), and differential leukocyte count were measured. The data of each parameter were analyzed by two-way repeated measure ANOVA.Results: Significant time-dependent effects were observed in IL1b, IL6, and creatinine values from baseline whereas significant treatment dependent effect was seen in IL-1ra. IBPR was found to be safe and well tolerated.Conclusion: IBPR supplementation showed a significant anti-inflammatory efficacy on eccentric exercise-induced inflammatory markers of skeletal muscle soreness in non-resistance trained subjects

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Rise, Rule, and Graduation: A Study of U.S. Manufacturing Offshoring to China from 1990 to 2016

Despite the abundance of theoretical literature on and qualitative analyses of relocating manufacturing production, consequences of offshoring on labor markets, and foreign trade policy, very little empirical analysis has been conducted in order to examine the trends and patterns in economic variables that led to the rise in manufacturing offshoring in the first place. Focusing on the U.S. manufacturing offshoring to China, this thesis uses a comprehensive dataset of labor compensation costs and labor productivity for 20 manufacturing industries across 27 years for China and the United States to investigate the relationship between U.S. offshoring and productivity per wage for a unit of labor (α) in China vis-a-vis the U.S. I find that the effect of α on growth in offshoring across industries is not only positive but also statistically significant. Further, this thesis also attempts to combine empirical findings with a qualitative analysis of the prominent trends in the data that might help understand the S-shape of the offshoring curve over three periods (or states of the curve): rise (1990-1999), rule (2000-2008), and graduation (2009-2016)