Liposomes: A targeted drug delivery system- A review

Liposomes are a novel drug delivery system (NDDS), which are vesicular structures consisting of hydrated bilalyers which form spontaneously whenphospholipids are dispersed in water. They are simple microscopic vesicles in which an aqueous volume is entirely enclosed by a membrane composed of lipid bilayers. Novel drug delivery system aims to deliver the drug at a rate directed by the needs of the body during the period of treatment, and channel the active entity to the siteof action. It has been a study interest in the development of a NDDS. Liposomes are colloidal spheres of cholesterol non-toxic surfactants, sphingolipids, glycolipids, long chain fatty acids and even membrane proteins and drug molecules or it is also called vesicular system. It is differ in size, composition and charge. It is a drug carrier loaded with great variety of molecules such as small drug molecules, proteins, nucleotides and even plasmids. Few drugs are also formulated as liposomes to improve their therapeutic index. Consequently a number of vesicular drug delivery systems such as liposomes, niosomes, transfersomes, and pharmacosomes were developed. The focus of this review is to the various method of preparation, characterization of liposomes, advantages and applications etc

A brief study on Neem (Azarrdirachta indica a.) and its application-A review

Neem, Azadirachta indica A. is a tree, which has a wide application in animal kingdom. Azadirachta indica is fast growing evergreen popular tree found commonly in India, Africa and America. In the application of Neem, Neem used as Fertilizer, Manure, urea coating agent, fumigant, pesticide, Soil Conditioner and Neem pest control is very beneficial for proper crop and pest management. This review is mainly focused on application of neen

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Comparative analysis of soil quality and enzymatic activities under different tillage based nutrient management practices in soybean–wheat cropping sequence in Vertisols

Abstract In the modern era, intensive agricultural practices such as agrochemicals are applied in excessive amounts to enhance agricultural production. However, imbalanced adoption of these chemicals has arisen in the dwindling of agriculture factor productivity and soil quality. To maintain soil fertility and production, these chemical fertilizers must be supplemented with organic inputs. Keeping this in the backdrop, a research trail was established during 2018–19 and 2019–20 years at Research Farm of Agriculture University, Kota, India. The treatment setup was comprised of 5 treatment modules viz., conservation tillage + organic management (CAOM), conservation tillage + chemical management (CACM), conventional tillage + chemical management (CTCM), conventional tillage + organic management (CTOM) and the package of practices (PoPs) with four replications. Results indicated that the highest organic carbon (0.68%), bacterial (29.11 × 107 cfu g−1), fungal (4.77 × 104 cfu g−1), actinomycetes populations (5.67 × 104 cfu g−1), acid phosphatase (44.1 µg g−1 h−1), urease (45.3 µg g−1 h−1) and dehydrogenase (23.3 µg triphenylformazan [TPF] g−1 h−1) activity in soil were found in the treatment of conservation organic system during both the years of study at each soil depth. In contrast to other parameters, the highest system productivity was observed with conservation chemical crop management approaches, with a soybean equivalent yield of 4615 kg ha−1 in a soybean–wheat system of production. Furthermore, the soil quality index (SQI) significantly varied from the lowest score (0.30) at 45–60 cm layer of soil in the package of practices to the highest score (0.92) at 0–15 cm layer of soil with regards to the conservation organic which shows, 206.67 percent enhancement through the soil profile of various crop management practices. The SQI variation from 0–15 to 45–60 cm soil depth was 130.0, 81.08, 60.0, 175.0 and 83.33 percent, respectively, for CAOM, CACM, CTCM, CTOM and PoPs. Amongst, different systems, the highest mean performance was noticed under the conservation organic systems for physical and biological properties. Hence, in line with the salient outcome, we may propose that the conservation chemical system needs to be followed to improve crop productivity, whereas, conservation organic seems a good option for soil health with long-term viability

Predicting city-scale daily electricity consumption using data-driven models

Accurate electricity demand forecasts that account for impacts of extreme weather events are needed to inform electric grid operation and utility resource planning, as well as to enhance energy security and grid resilience. Three common data-driven models are used to predict city-scale daily electricity usage: linear regression models, machine learning models for time series data, and machine learning models for tabular data. In this study, we developed and compared seven data-driven models: (1) five-parameter change-point model, (2) Heating/Cooling Degree Hour model, (3) time series decomposed model implemented by Facebook Prophet, (4) Gradient Boosting Machine implemented by Microsoft lightGBM, and (5) three widely-used machine learning models (Random Forest, Support Vector Machine, Neural Network). Seven models are applied to the city-scale electricity usage data for three metropolitan areas in the United States: Sacramento, Los Angeles, and New York. Results show seven models can predict the metropolitan area's daily electricity use, with a coefficient of variation of the root mean square error (CVRMSE) less than 10%. The lightGBM provides the most accurate results, with CVRMSE on the test dataset of 6.5% for Los Angeles, 4.6% for Sacramento, and 4.1% for the New York metropolitan area. These models are further applied to explore how extreme weather events (e.g., heat waves) and unexpected public health events (e.g., COVID-19 pandemic) influence each city's electricity demand. Results show weather-sensitive component accounts for 30%–50% of the total daily electricity usage. Every degree Celsius ambient temperature increase in summer leads to about 5% (4.7% in Los Angeles, 6.2% in Sacramento, and 5.1% in New York) more daily electricity usage compared with the base load in the three metropolitan areas. The COVID-19 pandemic reduced city-scale electricity demand: compared with the pre-pandemic same months in 2019, daily electricity usage during the 2020 pandemic decreased by 10% in April and started to rebound in summer

Anticoagulation Strategies in Non–Critically Ill Patients with Covid-19

BackgroundOptimal thromboprophylaxis for hospitalized patients with coronavirus disease 2019 (Covid-19) is uncertain.MethodsIn an open-label, adaptive platform trial, we randomly assigned hospitalized adults with Covid-19 to low-dose low-molecular-weight heparin thromboprophylaxis or intermediate-dose or low-dose plus aspirin. In response to external evidence, the aspirin intervention was discontinued and a therapeutic-dose arm added. The primary end point was death or the requirement for new organ support by day 28, analyzed with a Bayesian logistic model. Enrolment was closed as a result of operational constraints.ResultsBetween February 2021 and March 2022, 1574 patients were randomly assigned. Among 1526 participants included in the analysis (India, n=1273; Australia and New Zealand, n=138; and Nepal, n=115), the primary outcome occurred in 35 (5.9%) of 596 in low-dose, 25 (4.2%) of 601 in intermediate-dose, 20 (7.2%) of 279 in low-dose plus aspirin, and 7 (14%) of 50 in therapeutic-dose anticoagulation. Compared with low-dose thromboprophylaxis, the median adjusted odds ratio for the primary outcome for intermediate-dose was 0.74 (95% credible interval [CrI], 0.43 to 1.27; posterior probability of effectiveness [adjusted odds ratioConclusionsIn hospitalized non–critically ill adults with Covid-19, compared with low-dose, there was an 86% posterior probability that intermediate-dose, 65% posterior probability that low-dose plus aspirin, and a 7% posterior probability that therapeutic-dose anticoagulation reduced the odds of death or requirement for organ support. No treatment strategy met prespecified stopping criteria before trial closure, precluding definitive conclusions. (Funded by Australian National Health and Medical Research Council or Medical Research Future Fund Investigator and Practitioner Grants and others; ClinicalTrials.gov number, NCT04483960.