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Nanotechnology is a multidisciplinary d0omain which has provoked a significant impact on clinical medicine. Throughout the years nanotechnology has evolved in various aspects rendering multiple applications in the field of pharmaceutical development and overcoming the problems of conventional techniques. Nanotechnology has already acquainted with oncology facilitating the treatment of tumours. Nanotechnology posses various characteristics like preferential accumulation of chemotherapeutics in tumour, low distribution in normal tissues, pharmacokinetics, biodistribution and clearanceproviding improved diagnosis and tumour treatment. Though the field of oncology developed massively, limitations still exists in treating neuronal tumours due to intricate structure of the blood-brain barrier. Nanotechnology with its feasibility to attachvarious molecules on their surface and transform them into excellent transport vehicles with ability to cross cell and/or tissue barriers, including the BBB. This review elaborately delivers the techniques and strategies used to improve the diagnosis and to treat neuronal tumours unlike conventional cancer therapies. [ABSTRACT FROM AUTHOR]

Personalized medicine is a clinical model that isolates individuals into various groups with clinical choices, practices, intercessions and additionally items being customized to the individual patient dependent on their anticipated reaction or danger of disease. The utilization of genetic data has assumed a significant part in personalized medicine (e g pharmacogenomics). Modern advances in personalized medicine depend on innovation that affirms a patient's major DNA, RNA, biology or protein, which at last prompts confirming disease. The ideas of personalized medication can be applied to new and extraordinary ways to deal with medical services. The history of personalized medicine is clearly discussed in this article. And with that, literature review on various type of clinical trial was done. The two types of clinical trials are conventional clinical trial and differential clinical trial. The conventional clinical trial is a regular trial in which simple drugs are evaluated and the study can be done by observing all the phases. But in the case of differential clinical trial, the clinical trial is been carried out on complicated diseases and personalized medicines, where there are no proper regulatory guidelines to be followed. It is concluded that the advancing field of personalized medication is an emerging zone with a range of applications for rare diseases, which include actual advances in clinical trial outcomes for properly chosen patient sub-sets. [ABSTRACT FROM AUTHOR]

A thermodynamic model of cholesterol-phospholipid complexes is used as a starting point for calculating fluctuations in membranes containing cholesterol and phospholipids. The calculations describe fluctuations in the concentration of complexes formed between cholesterol and phospholipids with longer saturated fatty acid chains. The fluctuations in complex concentrations arise by two distinct mechanisms. In one, the chemical composition of the sample varies from point to point, and the concentration of the complexes varies according to local chemical equilibrium. In the second, the composition remains fixed, and the complexes form and dissociate according to chemical reaction kinetics. In both cases the nuclear resonance frequency of a deuterium labeled phospholipid undergoes fluctuations and line broadening as a consequence of the formation and dissociation of complexes. For a specific ternary lipid mixture at its critical composition, deuterium nuclear resonance line broadening of chain labeled phospholipids is calculated for temperatures up to 10°–20° above the miscibility critical temperature. This line broadening is associated with fluctuations in the degree of phospholipid chain ordering related to the formation and dissociation of complexes. [ABSTRACT FROM AUTHOR]

Scap is a polytopic membrane protein that functions as a molecular machine to control the cholesterol content of membranes in mammalian cells. In the 21 years since our laboratory discovered Scap, we have learned how it binds sterol regulatory element-binding proteins (SREBPs) and transports them from the endoplasmic reticulum (ER) to the Golgi for proteolytic processing. Proteolysis releases the SREBP transcription factor domains, which enter the nucleus to promote cholesterol synthesis and uptake. When cholesterol in ER membranes exceeds a threshold, the sterol binds to Scap, triggering several conformational changes that prevent the Scap-SREBP complex from leaving the ER. As a result, SREBPs are no longer processed, cholesterol synthesis and uptake are repressed, and cholesterol homeostasis is restored. This review focuses on the four domains of Scap that undergo concerted conformational changes in response to cholesterol binding. The data provide a molecular mechanism for the control of lipids in cell membranes. [ABSTRACT FROM AUTHOR]

Cells employ regulated transport mechanisms to ensure that their plasma membranes (PMs) are optimally supplied with cholesterol derived from uptake of low-density lipoproteins (LDL) and synthesis. To date, all inhibitors of cholesterol transport block steps in lysosomes, limiting our understanding of post-lysosomal transport steps. Here, we establish the cholesterol-binding domain 4 of anthrolysin O (ALOD4) as a reversible inhibitor of cholesterol transport from PM to endoplasmic reticulum (ER). Using ALOD4, we: (1) deplete ER cholesterol without altering PM or overall cellular cholesterol levels; (2) demonstrate that LDL-derived cholesterol travels from lysosomes first to PM to meet cholesterol needs, and subsequently from PM to regulatory domains of ER to suppress activation of SREBPs, halting cholesterol uptake and synthesis; and (3) determine that continuous PM-to-ER cholesterol transport allows ER to constantly monitor PM cholesterol levels, and respond rapidly to small declines in cellular cholesterol by activating SREBPs, increasing cholesterol uptake and synthesis. [ABSTRACT FROM AUTHOR]

[Display omitted] Peptidylarginine deiminase-4 (PAD4) is a calcium-dependent enzyme that catalyzes the conversion of arginine into citrulline of macromolecules in the body. It governs several processes including apoptosis, innate immunity (Netosis), and pluripotency. Dysregulated PAD4 plays a vital role in the occurrence and development of Rheumatoid arthritis (RA). Therefore, PAD4 is considered a promising target for diagnosing and treating RA. Over the last few years research has been carried out on PAD4 inhibitors. When administered it circulates to the entire body and inhibits PAD4 causing immunosuppression which may lead to infection. A growing number of studies have demonstrated infiltration and differentiation of monocytes and macrophages into the inflamed synovium, inducing overexpression of PAD4 levels in the inflamed joints. To overcome the above-mentioned critical issues, the targeted drug delivery systems inhibit PAD4 at the inflamed site. This review provides an update on the PAD4 inhibitors and emerging advanced drug delivery systems for the treatment of RA. Finally, we concluded that active targeting of PAD4 inhibitors to inflamed joints via hybrid nanocarriers provided an improved therapeutic efficacy, minimized extra synovial toxicity, and prevent the occurrence of inflammation in RA. [ABSTRACT FROM AUTHOR]

Abstract: Given the increasing penetration and health care related use of the Internet, we examined the evidence on the impact of Internet-based interventions on pain. A search of Medline, CINAHL, PsycINFO, and the Cochrane Library was conducted for literature published from 1990 to 2010 describing randomized controlled trials that assessed the effects of Internet-based interventions on patients with pain of any kind. Of 6724 citations, 17 articles were included. The studies evaluated the effects of interventions that provided cognitive and behavioral therapy, moderated peer support programs, or clinical visit preparation or follow-up support on 2503 people in pain. Six studies (35.3%) received scores associated with high quality. Most cognitive and behavioral therapy studies showed an improvement in pain (n=7, 77.8%), activity limitation (n=4, 57.1%) and costs associated with treatment (n=3, 100%), whereas effects on depression (n=2, 28.6%) and anxiety (n=2, 50%) were less consistent. There was limited (n=2 from same research group) but promising evidence that Internet-based peer support programs can lead to improvements in pain intensity, activity limitation, health distress and self-efficacy; limited (n=4 from same research group) but promising evidence that social networking programs can reduce pain in children and adolescents; and insufficient evidence on Internet-based clinical support interventions. Internet-based interventions seem promising for people in pain, but it is still unknown what types of patients benefit most. More well-designed studies with diverse patient groups, active control conditions, and a better description of withdrawals are needed to strengthen the evidence concerning the impact of Internet-based interventions on people in pain. This systematic review of Internet-based treatments for pain indicates that the evidence for such treatment is promising. [Copyright &y& Elsevier]

Defects in Niemann-Pick, Type C-1 protein (NPC1) cause cholesterol, sphingolipids, phospholipids, and glycolipids to accumulate in lysosomes of liver, spleen, and brain. In cultured fibroblasts, NPC1 deficiency causes lysosomal retention of lipoprotein-derived cholesterol after uptake by receptor-mediated endocytosis. NPC1 contains 1278 amino acids that form 13 membrane-spanning helices and three large loops that project into the lumen of lysosomes. We showed earlier that NPC1 binds cholesterol and oxysterols. Here we localize the binding site to luminal loop-1, a 240-amino acid domain with 18 cysteines. When produced in cultured cells, luminal loop-1 was secreted as a soluble dimer. This loop bound [3H]cholesterol (Kd, 130 nM) and [3H]25-hydroxycholesterol (25-HC, Kd, 10 nM) with one sterol binding site per dimer. Binding of both sterols was competed by oxysterols (24-, 25-, and 27-HC). Unlabeled cholesterol competed strongly for binding of [3H]cholesterol, but weakly for [3H]25-HC binding. Binding of [3H]cholesterol but not [3H] 25-HC was inhibited by detergents. We also studied NPC2, a soluble protein whose deficiency causes a similar disease phenotype. NPC2 bound cholesterol, but not oxysterols. Epicholesterol and cholesteryl sulfate competed for [3H]cholesterol binding to NPC2, but not NPC1. Glutamine 79 in luminal loop-1 of NPC-1 is important for sterol binding a Q79A mutation abolished binding of [3H]cholesterol and [3H]25-HC to full-length NPC1. Nevertheless, the Q79A mutant restored cholesterol transport to NPC1-deficient Chinese hamster ovary cells. Thus, the sterol binding site on luminal loop-1 is not essential for NPC1 function in fibroblasts, but it may function in other cells where NPC1 deficiency produces more complicated lipid abnormalities. [ABSTRACT FROM AUTHOR]

Cholesterol synthesis in animals is controlled by the regulated transport of sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum to the Golgi, where the transcription factors are processed proteolytically to release active fragments. Transport is inhibited by either cholesterol or oxysterols, blocking cholesterol synthesis. Cholesterol acts by binding to the SREBP-escort protein Scap, thereby causing Scap to bind to anchor proteins called Insigs. Here, we show that oxysterols act by binding to Insigs, causing Insigs to bind to Scap. Mutational analysis of the six transmembrane helices of Insigs reveals that the third and fourth are important for Insig's binding to oxysterols and to Scap. These studies define Insigs as oxysterol-binding proteins, explaining the long-known ability of oxysterols to inhibit cholesterol synthesis in animal cells. [ABSTRACT FROM AUTHOR]

A general theoretical model is described for the NMR spectra of mixtures of sterols and deuterium-labeled phospholipids. In the case of homogeneous membranes, the average quadrupole splittings are determined by equilibria between lipids in cholesterol-phospholipid complexes and lipids not in complexes. Chemical exchange of lipids between those in the free state and those in the complex state affects the deuterium resonance line shapes. The lifetime of a phospholipid molecule in an ergosterol-dipalmitoylphosphatidylcholine complex is estimated to be of the order of 10-5 s on the basis of the observed line broadenings. In the vicinity of a critical point of a cholesterol-phospholipid mixture, fluctuations in the concentration of complexes also can contribute to the deuterium nuclear resonance line broadening. At the critical point, the temperature derivative of the concentration of complexes is discontinuous. There is a corresponding jump in the calculated heat capacity as well as in the temperature derivative of the deuterium NMR first moment. [ABSTRACT FROM AUTHOR]

Animal cell membranes pose conceptual problems related to the physical chemistry of liquids. An avenue to the solution of some of these problems has been opened by the discovery of liquid-liquid immiscibility in synthetic membranes composed of cholesterol and phospholipids. This discovery has led to the development of a thermodynamic model involving condensed complexes. In this model, the phospholipids with longer fatty-acid chains react reversibly with cholesterol to form complexes. The complexes themselves can have a repulsive interaction with other phospholipids, leading to immiscibility. A striking example of this effect is revealed in the phase diagrams of ternary mixtures of cholesterol, a saturated phosphatidylcholine (or sphingomyelin), and an unsaturated phosphatidylcholine. As found by a number of investigators, all binary pairs are miscible in bilayers, whereas the ternary mixture can form two liquid phases. The model of condensed complexes accounts for this effect. Condensed complexes also have a major effect on the chemical activity of cholesterol and on the ordering of phospholipid acyl chains both in the presence and absence of phase separations. Model calculations of phospholipid order parameters account for several features of the deuterium NMR spectra of labeled phospholipid molecules in bilayer mixtures with cholesterol. [ABSTRACT FROM AUTHOR]

The polytopic membrane protein SCAP transports sterol regulatory element-binding proteins (SREBP5) from the endoplasmic reticulum (ER) to the Golgi, thereby activating cholesterol synthesis. Choles- terol accumulation in the ER membranes changes SCAP to an alternate conformation in which it binds ER retention proteins called Insigs, thereby terminating cholesterol synthesis. Here, we show that the conserved Asp-428 in the sixth transmembrane helix of SCAP is essential for SCAP's dissociation from Insigs. In transfected hamster cells, mutant SCAP in which Asp-428 is replaced by alanine (D428A) remained in an Insig-binding conformation when cells were depleted of sterols. As a result mutant SCAP failed to dissociate from Insigs, and it failed to carry SREBPs to the Golgi. These data identify an important functional residue in SCAP, and they provide genetic evidence that the conformation of SCAP dictates the rate of cholesterol synthesis in animal cells. [ABSTRACT FROM AUTHOR]

Mammalian cells control their membrane composition by regulating the vesicular transport of membrane-bound sterol regulatory element binding proteins (SREBPs) from endoplasmic reticulum (ER) to Golgi. Transport is blocked by cholesterol, which triggers SCAP, the SREBP escort protein, to bind to Insigs, which are ER retention proteins. The cholesterol trigger mechanism is unknown. Using recombinant SCAP purified in detergent, we show that cholesterol acts by binding with high affinity and specificity to the 767 amino acid octahelical membrane region of SCAP. This octahelical region contains a conserved pentahelical sterol-sensing domain found in six other polytopic membrane proteins. We show that the membrane domain of SCAP is a tetramer and that cholesterol binding is inhibited by cationic amphiphiles, raising the possibility of allosteric regulation by positively charged phospholipids. The current studies show that cells control their cholesterol content through receptor-ligand interactions and not through changes in the physical properties of the membrane. [Copyright &y& Elsevier]

There is overwhelming evidence that lipid bilayer regions of animal cell membranes are in a liquid state. Quantitative models of these bilayer regions must then be models of liquids. These liquids are highly non-ideal. For example, it has been known for more than 75 years that mixtures of cholesterol and certain phospholipids undergo an area contraction or condensation in lipid monolayers at the air–water interface. In the past 3 years, a thermodynamic model of “condensed complexes” has been proposed to account for this non-ideal behavior. Here we give an overview of the model, its relation to other models, and to modern views of the properties of animal cell membranes. [Copyright &y& Elsevier]

Presents critical points in charged membranes containing cholesterol. Technique used to determine phase diagrams for lipid monolayers containing binary mixtures of cholesterol; Association of critical points with the formation of condensed complexes between lipids and cholesterol.

We report that the monolayer phase diagram for binary mixtures of dimyristoylphosphatidylethanolamine (DMPE) and dihydrocholesterol (DChol) is largely unchanged when each phospholipid molecule is replaced by two myristic acid (MA) molecules or various mixtures of the lysophospholipid and myristic acid. The corresponding phase diagrams all show the formation of “condensed complexes” of DChol and lipid. The condensed complex stoichiometry is thus largely determined by the C14 fatty acid acyl chains, in this case about 4–4.6 per DChol molecule. [Copyright &y& Elsevier]

Describes a liquid-state model for theoretical approximation of nonideal thermodynamic properties of coexisting liquid phases of cholesterol and phospholipids at the air-water interface of cell membranes. Theoretical pressure-composition phase diagrams; Role of cholesterol and phospholipids on cellular functions.

Reports on measurements for the rate constants for the release of cholesterol to beta-cyclodextrin from mixtures with phospholipids in homogeneous monolayers at the air-water interface. Sharp decrease in release rate with the decrease of cholesterol concentration; Stoichiometry of the complex.

Presents a study which examined electric field effect on dihydrocholesterol and phospholipids. Challenges in understanding the chemical activity of cholesterol in cell membranes; Materials and methods used in the study; Results.

The cholesterol-sensing protein Scap induces cholesterol synthesis by transporting membrane-bound transcription factors called sterol regulatory element-binding proteins (SREBPs) from the endoplasmic reticulum (ER) to the Golgi apparatus for proteolytic activation. Transport requires interaction between Scap's two ER luminal loops (L1 and L7), which flank an intramembrane sterol-sensing domain (SSD). Cholesterol inhibits Scap transport by binding to L1, which triggers Scap's binding to Insig, an ER retention protein. Here we used cryoelectron microscopy (cryo-EM) to elucidate two structures of full-length chicken Scap: (1) a wild-type free of Insigs and (2) mutant Scap bound to chicken Insig without cholesterol. Strikingly, L1 and L7 intertwine tightly to form a globular domain that acts as a luminal platform connecting the SSD to the rest of Scap. In the presence of Insig, this platform undergoes a large rotation accompanied by rearrangement of Scap's transmembrane helices. We postulate that this conformational change halts Scap transport of SREBPs and inhibits cholesterol synthesis. [Display omitted] • Cryo-EM structures of wild-type Scap and a mutant Scap bound to Insig • Scap's two ER luminal loops, L1 and L7, intertwine tightly to form a globular domain • Scap's binding to Insig triggers a large rotation of the luminal L1-L7 domain • L1-L7 rotation suggests how cholesterol blocks Scap's transport of SREBPs Visualization of Scap, the cholesterol sensor that modulates SREBP activation, alone and in complex with Insig, implicates movement of a cholesterol-interacting domain in patrolling proximal membrane regions for sterols. [ABSTRACT FROM AUTHOR]

The paper proposes a new stochastic multiobjective technoeconomic model for integrating photovoltaic (PV) and wind energy resources in electricity price (EP)‐driven distribution systems. The primary goal of this paper is to determine the optimal location and capacity for renewable energy‐based distributed generation, specifically PV and wind resources, while considering weather and system uncertainties. These uncertainties include stochastic variations in PV illumination intensity, wind speed, EP, and load fluctuations. To address these uncertainties, the paper employs scenario modeling techniques named as Latin hypercube sampling with Cholesky decomposition. This technique generates multiple correlated scenarios that represent uncertain variables. Subsequently, a scenario reduction technique is applied to identify the scenario with the highest probability. Later, a mathematical model is developed to minimize an objective function that encompasses various factors like system losses, node voltage deviations, the cost of purchasing power from the grid; and simultaneously maximize the total annual energy savings. The objective is to find optimal solutions that strike a balance between different objectives. To obtain an efficient optimum solution, this paper employs an effective meta‐heuristic technique named as JAYA algorithm. The results obtained by the JAYA algorithm are juxtaposed with those obtained using particle swarm optimization and genetic algorithm techniques. The proposed method is evaluated using Institute of Electrical and Electronics Engineers (IEEE) 33‐node and IEEE 69‐node test feeders to validate its feasibility and effectiveness. However, the effectiveness of the proposed method is not limited to any size of test systems. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the leading diseases in men all over the world caused due to over-expression of prostate-specific membrane antigen (PSMA). Currently, the detection and targeting of PCa is one of the major challenges in the prostate gland. Therefore, Bruton tyrosine kinase inhibitor molecules like ibrutinib (Ibr) loaded with nanomaterials like multiwalled carbon nanotubes (MWCNTs), which has good physico-chemical properties may be the best regimen to treat PCa. In this strategy, the chemically modified MWCNTs have excellent 'Biosensing' properties makes it easy for detecting PCa without fluorescent agent and thus targets particular site of PCa. In the present study, Ibr/MWCNTs conjugated with T30 oligonucleotide may selectively target and inhibit PSMA thereby reduce the over-expression in PCa. Hence, the proposed formulation design can extensively reduce the dosage regimen without any toxic effect. Additionally, the present hypothesis also revealed the binding mode of Ibr in the catalytic pocket of PSMA by in silico method. Therefore, we presume that if this hypothesis proves correct, it becomes an additional novel tool and one of the conceivable therapeutic options in treating PCa. [ABSTRACT FROM AUTHOR]

[Display omitted] Low dose mixing and its optimization process parameters are facing more challenges. Moreover, minor variation in a dose will tend to significantly have a huge impact on the products' performance including safety and efficacy of the dosage form. Hence, the characterization in every stage of product development of a low dose compound is mandatory. For this purpose, glimepiride and metformin in the ratio of 1:500 was formulated into tablet deciphering a fixed-dose combination product. The tablet was prepared by wet granulation method and optimized by time-dependent random mixing. Confocal Raman microscopy was employed for the present work for evaluation of compatibility studies, in-process and post-compression parameters. Further, the microscopical evaluation was done for the particle scout analysis. The obtained results indicated that the powder blend was compatible and provided uniform mixing in 20 min. Microscopical evaluation has shown that glimepiride still existed in the amorphous state even after compression. Moreover, the glimepiride area in the single-layer was found to be 0.06%. With this, we propose that confocal Raman microscopy plays the promising role in the detectability of the glimepiride. Therefore, in future, the layer by layer analysing can be opted to study the entire spatial arrangement of the API and excipients, which may tend to have a better understanding of dissolution and their related parameters. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is one of the major causes of cancer-related mortality worldwide. Despite advances in treatment modalities, its prevalence continues to rise, notably among younger populations. Unhealthy dietary habits, sedentary routines, and obesity have been identified as one of the key contributors to the development of colorectal cancer, apart from genetic and epigenetic modifications. Recognizing the profound impact of diet and lifestyle on the intricate gut microbiota ecosystem offers a promising avenue for understanding CRC development and its treatment. Gut dysbiosis, characterized by imbalances favoring harmful microbes over beneficial ones, has emerged as a defining feature of CRC. Changes in diet and lifestyle can profoundly alter the composition of gut microbes and the metabolites they produce, potentially contributing to CRC onset. Focusing on recent evidence, this review discussed various dietary factors, such as high consumption of red and processed meats and low fiber intake, and lifestyle factors, including obesity, lack of physical activity, smoking, and excessive alcohol consumption, that influence the gut microbiome composition and elevate CRC risk. [ABSTRACT FROM AUTHOR]

The ovules inside the ovary of a plant are the precursors of seeds and they are important for the perpetuation of the plants. The genus Passiflora L., produce fruits with numerous seeds and they have economic and medicinal value. The edible portion of the Passiflora are the seeds surrounded by pulp. Being the edible parts of a fruit, it is important to investigate the early development of ovules in Passiflora that lead to the formation of seeds after pollination. Wild relatives of the domesticated crops are increasingly being investigated for possible genetic resources that can be used for crop improvement programs. The present study was designed to investigate the comparative ovule development between a wild (Passiflora foetida L.) and a cultivated (Passiflora edulis Sims) species of Passiflora with an aim that it may provide important information about the common and diverging regulatory mechanisms during ovule development between the wild and the cultivated species. We also investigated the pollen morphology between the wild and cultivated species using light and scanning electron microscopy. Our results show that wild type P. foetida ovule growth is faster when compared with that of cultivated P. edulis. Furthermore, wild species harbour ovules of large size (0.14 mm²) but less in number (6) as compared to cultivated ones which show smaller size (0.05 mm²) of ovules but relatively more in number (21). The differences in ovary wall thickness were also stark between the two species. The ovary wall thickness was 0.10 mm in the wild type whereas it was 0.74 mm in cultivated species. Notable differences were also observed in diameter where the wild type (2.45 mm) reported smaller diameter than cultivated species (3.25 mm). We observed little difference in the pollen morphology between the two species. [ABSTRACT FROM AUTHOR]

The new approach to develop quality in pharmaceuticals is by implementing Quality by Design (QbD). It explains the use of Quality by Design to guarantee pharmaceutical quality. In this review, the QbD is described and some of its components are specified. Even though the Quality can be checked on products, integrating within the design will be more effective. The quality by design is based on the ICH guidelines and USP also requires compendial product consistency evaluation checks on the market. As far as industry is concern - it is improving the quality and safety of their products by application of DoE using various software, since the cost of each software is higher, choosing the best software which has easy user interface as well as more performance is concerned. These QbD is implemented with creating DoE in the statistical application of production data with the help of various commercially available software (JMP®, MODDE®, MINITAB®, STATISTICA®, etc.,). The potential power of each software is unique and their functionalities are reviewed in this article. And it also gives you a brief idea about the software towards advancement in pharmaceutical sector in term of quality and safety. [ABSTRACT FROM AUTHOR]

Lipid synthesis is regulated by the actions of Scap, a polytopic membrane protein that binds cholesterol in membranes of the endoplasmic reticulum (ER). When ER cholesterol levels are low, Scap activates SREBPs, transcription factors that upregulate genes for synthesis of cholesterol, fatty acids, and triglycerides. When ER cholesterol levels rise, the sterol binds to Scap, triggering conformational changes that prevent activation of SREBPs and halting synthesis of lipids. To achieve a molecular understanding of how cholesterol regulates the Scap/SREBP machine and to identify therapeutics for dysregulated lipid metabolism, cholesterol-mimetic compounds that specifically bind and inhibit Scap are needed. To accomplish this goal, we focused on Anthrolysin O (ALO), a pore-forming bacterial toxin that binds cholesterol with a specificity and sensitivity that is uncannily similar to Scap. We reasoned that a small molecule that would bind and inhibit ALO might also inhibit Scap. High-throughput screening of a ~300,000-compound library for ALO-binding unearthed one molecule, termed UT-59, which binds to Scap's cholesterol-binding site. Upon binding, UT-59 triggers the same conformation changes in Scap as those induced by cholesterol and blocks activation of SREBPs and lipogenesis in cultured cells. UT-59 also inhibits SREBP activation in the mouse liver. Unlike five previously reported inhibitors of SREBP activation, UT-59 is the only one that acts specifically by binding to Scap's cholesterol-binding site. Our approach to identify specific Scap inhibitors such as UT-59 holds great promise in developing therapeutic leads for human diseases stemming from elevated SREBP activation, such as fatty liver and certain cancers. [ABSTRACT FROM AUTHOR]

At present, In the pharmaceutical industry, the quality by design approach is widely used to obtain products with reliability and efficacy. Quality by design allows us to understand both product and process control through clear research and quality risk management. As QbD helps in building quality in all pharmaceutical products, it widely practised. But it may also be a drawback for few industries in which processes are fixed in time. It is one of the growing area which helps maintaining high quality standards and real time release of the drug product. To deliver a product performing its intended action by maintaining its quality, is the prime aim of pharmaceutical development. Implementation of QbD is widely encouraged by Food and Drug Administration (FDA) and International Conference on Harmonization (ICH). This study explored the pharmaceutical QbD and discusses how it can be used within the specified time frame to produce pharmaceutical products efficiently. In this review, a brief overview about QbD and its elements such as quality target product profile (QTPP) critical quality attributes (CQAs), Quality Risk management (QRM), Control strategy and continual improvement will be discussed. Moreover, an overview about water as a QbD element was also discussed. Understanding the concepts of QbD is essential as most of the pharmaceutical industry are moving towards implementing QbD in their area. So, QbD will act as a bridge between drug application review and risk-based drug development. [ABSTRACT FROM AUTHOR]

Personalized medicine, which is both encouraging and exciting that a new effort is underway to create tailormade medicine and medical treatments by drawing on exceptionally detailed and extensive biomedical data. Each patient is unique; hence "one size fits all" is not effective which are currently used in HealthCare. Here these are the tailoring of medicine in which dosage forms can be formulated in a challenging basis, based on the Genomic information of the patients which may lead to a success rate of completely curing the disease. Personalized medicine also helps to diagnose patients in a highly specific manner, allowing more effective and targeted therapy. Formulation opportunities are more for these approaches, which already exist in a market particularly 3D Printing of Tablet, mini pills, film dosage forms and also in immunotherapy. Though it having more advantages, it faces more challenges as we are already in a Prescribing medication using "Trial & Error method" which was preferred by long period of time; and numerous issues which have started to arise, including legal (intellectual property rights and Regulatory frameworks), Ethical and Social issues (Confidentiality and Privacy of Patients). Patient privacy, if patient's genetic data was leaked, many issues may be presented. For example, inappropriate use of this information by insurance companies, who may not offer policies to certain individuals with genetic diseases. As all the industries presently targeting prescribing medicine, because of personalized medicine the excipient grade may have to change because of Technologies involved, such as 3D printing, and it may lead to change in formulation strategy. In other hand, Scientific and Technological advances in the genomics field mean that cost and time are no longer a barrier for precision medicine. Moreover personalized medicine, the effort is ambitious, challenging and possible. [ABSTRACT FROM AUTHOR]

Capsules are the unit solid dosage forms in which the drug can be incorporated into the shell. Gelatin is the major polymer used for capsule preparation which is natural polymer obtained from animal source i.e. skin and bones of pigs and cows. The usage of gelatin in capsule making is decreased due to many reasons like source of gelatin is from animals which causes mad cow disease and cross linking of gelatin with drugs which decreases the efficiency of drug. Because of this reason, development of capsule shell using various raw materials is necessary to replace the gelatin. Moreover this review helps the capsule manufacturer to prepare the capsule shell using other synthetic and natural polymer. [ABSTRACT FROM AUTHOR]

Human activity recognition (HAR) is one of the key applications of health monitoring that requires continuous use of wearable devices to track daily activities. The most efficient supervised machine learning (ML)-based approaches for predicting human activity are based on a continuous stream of sensor data. Sensor data analysis for human activity recognition using conventional algorithms and deep learning (DL) models shows promising results, but evaluating their ambiguity in decision-making is still challenging. In order to solve these issues, the paper proposes a novel Wasserstein gradient flow legonet WGF-LN-based human activity recognition system. At first, the input data is pre-processed. From the pre-processed data, the features are extracted using Haar Wavelet mother- Symlet wavelet coefficient scattering feature extraction (HS-WSFE). After that, the interest features are selected from the extracted features using (Binomial Distribution integrated-Golden Eagle Optimization) BD-GEO. The important features are then post-processed using the scatter plot matrix method. Obtained post-processing features are finally given into the WGF-LN for classifying human activities. From these experiments, the results can be obtained and showed the efficacy of the proposed model. [ABSTRACT FROM AUTHOR]

Background: In jurisdictions where medical aid in dying (MAiD) is legal, there is an obligation to ensure the competence of those who assess eligibility and provide MAiD to patients. Entrustable professional activities (EPAs) are one framework for incorporating competency-based training and assessment into the workplace, so we convened a group of experienced MAiD providers to develop an EPA descriptor for MAiD. Methods: We performed a mixed-methods sequential qualitative (focus group via 2 teleconferences) and quantitative (survey) study to generate and refine a consensus descriptor using open coding followed by a modified Delphi approach. Participants were experienced MAiD assessors and providers identified purposively from a national community of practice in Canada. Results: Of the 22 MAiD assessors and providers invited to participate in the focus group, 13 (59%) agreed. The focus group divided MAiD into 3 components: assessment, preparation and provision of MAiD. Participants identified key knowledge, skills and attitudes for each component. They also suggested teaching approaches, potential sources of information to evaluate progress and a potential basis for evaluating progress and entrustment. Key points from this descriptor were sent via survey to 88 assessors and providers, of whom 64 (73%) responded. Respondents agreed on all key points except for the conditions of entrustment; these were modified based on feedback and sent back to the respondents for a second Delphi round, where agreement was achieved. Interpretation: We achieved a high degree of agreement on a competency-based descriptor of MAiD in the form of an EPA. This can be used to inform practice standards, curriculum development and/or assessment of competence among learners and practising providers alike. [ABSTRACT FROM AUTHOR]

The phenomenon of separation into constituent layers connecting the core and laminate of a composite sandwich complex is a vital complication that leads to early failure of such material. The direction of the sandwich construction's exfoliation rigidity is increased between interlaminar low fiber augmentation. The bioinspired technique of hybrid material layers was used on an aluminium face sheet with an interlayer composition of PET foam core and glass fabric of a material that appears to have greater potential as a flimsy substitute for materials currently used in automotive, aeronautical, and marine applications. This examination seeks to develop the making of such material along the retardation in fibre supplements. Fibre bridging has been recognized as an important appliance in the progress of this operating procedure. Consequently, this method points to promoting the event of fibre bridging by differing aggregates, including the mass and extent of augmented fibres and the quantity of epoxy resin applied. A few advancements were made to the production methods, and though the outcomes for the resisting ability of specimens were found to be indecisive, it was found that the layer separation hardness had even improved. This was confirmed through the operation of scanning electron microscopy and also predicted the mechanically peeled material surfaces which identified the adhesive strength variations with respect to the face sheet surface modified with the sand blasting process. The analysis also revealed the need for further research into optimizing the attachment between aluminium sheet and pet foam and glass fabric based hybrid sandwich panels. [ABSTRACT FROM AUTHOR]

Most of the cholesterol in the plasma membranes (PMs) of animal cells is sequestered through interactions with phospholipids and transmembrane domains of proteins. However, as cholesterol concentration rises above the PM's sequestration capacity, a new pool of cholesterol, called accessible cholesterol, emerges. The transport of accessible cholesterol between the PM and the endoplasmic reticulum (ER) is critical to maintain cholesterol homeostasis. This pathway has also been implicated in the suppression of both bacterial and viral pathogens by immunomodulatory oxysterols. Here, we describe a mechanism of depletion of accessible cholesterol from PMs by the oxysterol 25-hydroxycholesterol (25HC). We show that 25HC-mediated activation of acyl coenzyme A: cholesterol acyltransferase (ACAT) in the ER creates an imbalance in the equilibrium distribution of accessible cholesterol between the ER and PM. This imbalance triggers the rapid internalization of accessible cholesterol from the PM, and this depletion is sustained for long periods of time through 25HC-mediated suppression of SREBPs and continued activation of ACAT. In support of a physiological role for this mechanism, 25HC failed to suppress Zika virus and human coronavirus infection in ACAT-deficient cells, and Listeria monocytogenes infection in ACAT-deficient cells and mice. We propose that selective depletion of accessible PM cholesterol triggered by ACAT activation and sustained through SREBP suppression underpins the immunological activities of 25HC and a functionally related class of oxysterols. [ABSTRACT FROM AUTHOR]

In addition to hemostasis and thrombosis, blood platelets are involved in various processes such as inflammation, infection, immunobiology, cancer metastasis, wound repair and angiogenesis. Platelets' hemostatic and non‐hemostatic functions are mediated by the expression of various membrane receptors and the release of proteins, ions and other mediators. Therefore, specific activities of platelets responsible for the non‐hemostatic disease are to be inhibited while leaving the platelet's hemostatic function unaffected. Platelets' anti‐aggregatory property has been used as a primary criterion for antiplatelet drugs/bioactives; however, their non‐hemostatic activities are not well known. This review describes the hemostatic and non‐hemostatic function of human blood platelets and the modulatory effects of bioactive food components. Practical applications: In this review, we have discussed the antiplatelet effects of several food components. These bioactive compounds inhibit both hemostatic and non‐hemostatic pathways involving blood platelet. Platelets have emerged as critical biological factors of normal and pathologic vascular healing and other diseases such as cancers and inflammatory and immune disorders. The challenge for therapeutic intervention in these disorders will be to find drugs and bioactive compounds that preferentially block specific sites implicated in emerging roles of platelets' complicated contribution to inflammation, tumour growth, or other disorders while leaving at least some of their hemostatic function intact. [ABSTRACT FROM AUTHOR]

Background: We compared patient and caregiver knowledge and confidence for managing asthma, and participant experiences when comprehensive asthma education was delivered in person versus in the virtual setting. Methods: We performed a multi-methods study using structured surveys and qualitative interviews to solicit feedback from patients and caregivers following participation in a comprehensive asthma education session between April 2018 and October 2021. We compared participant knowledge and confidence for managing asthma as well as user experience when the education was attended in-person or virtually. Quantitative responses were summarized descriptively, and qualitative feedback was analyzed for major themes. Results: Of 100 caregivers/patients who completed post education satisfaction surveys and interviews, 52 attended in person and 48 virtually, with the mean age of patients being 6.7 years (range: 1.2–17.0). Participant reported gains in knowledge and confidence for asthma management were not different between groups and 65.2% preferred attending virtual asthma education. The majority of participants described virtual education as a safer modality that was more convenient and accessible. Conclusions: We demonstrated the successful implementation of a novel, virtual asthma education program for patients and caregivers of children with asthma. Both virtual and in-person delivered asthma education were equally effective for improving perceived knowledge and confidence for asthma self-management and virtual education was considered safer, more convenient and accessible. Virtual asthma education offers an attractive and effective option for improving the reach of quality asthma education programs and may allow more children/patients to benefit. [ABSTRACT FROM AUTHOR]

The run-on flat tire is an important technology in the area of vehicle safety technology. Nowadays, traveling by a personal vehicle from one place to another has increased due to the increase in the global economy. The main problem that is faced while traveling is tire puncture. The tire may get punctured by any sharp objects on the road such as screws and iron pins that traps the tire surface. A situation like this may be overcome by the usage of the drive on a puncher tire device which will be used to reach the destination without any need for a puncher shop. Using this device will reduce the damage of the tire and tube. This device is portable and can be placed in a vehicle itself. For this reason, a design has been developed by the CATIA 3D experience. The drive on a puncher tire device was designed using the software developed by the Dassault systems named CATIA 3D experience. Aluminum alloy was chosen as the base material to design and simulate this product. Also, the network distribution simulations were used to develop the mathematical equations to check the adequacy of the model. This device is very useful while traveling long distances if any puncher will occur. The sensors were attached to the product to receive the signal from the vehicle, so that the vehicle will run smoothly for a short distance. Drive on a puncher tire will be suitable for both two- and four-wheeler vehicles and also useful for all the areas like villages, towns, panchayats, and cities. If the tire is puncher, we cannot drive the vehicle; hence, a skating device is fixed at a tired bottom, which is used to move the vehicle. The proposal will be beneficial for a huge number of people who own two and four wheelers. This design and simulation will address the problem of the two- and four-wheeler owners traveling long distances. [ABSTRACT FROM AUTHOR]

The Industrial Internet of Things (IIoT) has received significant attention from several leading industries like agriculture, mining, transport, energy, and healthcare. IIoT acts as a vital part of Industry 4.0 that mainly employs machine learning (ML) to investigate the interconnection and massive quantity of the IIoT data. As the data are generally saved at the cloud server, security and privacy of the collected data from numerous distributed and heterogeneous devices remain a challenging issue. This article develops a novel multi-agent system (MAS) with deep learning-based privacy preserving data transmission (BDL-PPDT) scheme for clustered IIoT environment. The goal of the BDL-PPDT technique is to accomplish secure data transmission in clustered IIoT environment. The BDL-PPDT technique involves a two-stage process. Initially, an enhanced moth swarm algorithm-based clustering (EMSA-C) technique is derived to choose a proper set of clusters in the IIoT system and construct clusters. Besides, multi-agent system is used to enable secure inter-cluster communication. Moreover, multi-head attention with bidirectional long short-term memory (MHA-BLSTM) model is applied for intrusion detection process. Furthermore, the hyperparameter tuning process of the MHA-BLSTM model can be carried out by the stochastic gradient descent with momentum (SGDM) model to improve the detection rate. For examining the promising performance of the BDL-PPDT technique, an extensive comparison study takes place and the results are assessed under varying measures. A significant amount of capital is required. It goes without saying that one of the most obvious industrial IoT concerns is the high cost of adoption. Secure data storage and management connectivity failures are common among IoT devices due to the massive amount of data they create. The simulation results demonstrate the enhanced outcomes of the BDL-PPDT technique over the recent methods. Despite the fact that the offered BDL-PPDT technique has an accuracy of just 98.15 percent, it produces the best feasible outcome. Because of the data analysis conducted as detailed above, it was determined that the BDL-PPDT technique outperformed the other current techniques on a range of different criteria and was thus recommended. [ABSTRACT FROM AUTHOR]

In recent days, for smart grid network updates, video sensors are used where each node needs to be compressed before transmission. This is very much useful for developing countries as in future the smart grid communication process will play a major role in entire society. Therefore, in this article, minimization of power, energy consumption, and delay for wireless video sensor networks have been computed by providing better quality of service at a similar period. Also, the problem of optimizing transmission and delivery rate has been studied. For solving the aforementioned problems, the intuitive migrant algorithm has been implemented for providing better energy consumption. Additionally, modified larvae optimization tool has been integrated for providing better convergence rate, where all the nodes will be compressed at a better rate with necessary quality of service. The simulation results show that by applying algorithms in two folds, and each video sensor node is compressed by satisfying necessary constraints with fast convergence rate. [ABSTRACT FROM AUTHOR]

Approximate computing is an upsurging technique to accelerate the process through less computational effort while keeping admissible accuracy of error-tolerant applications such as multimedia and deep learning. Inheritance properties of the deep learning process aid the designer to abridge the circuitry and also to increase the computation speed at the cost of the accuracy of results. High computational complexity and low-power requirement of portable devices in the dark silicon era sought suitable alternate for Complementary Metal Oxide Semiconductor (CMOS) technology. Gate Diffusion Input (GDI) logic is one of the prompting alternatives to CMOS logic to reduce transistors and low-power design. In this work, a novel energy and area efficient 1-bit GDI-based full swing Energy and Area efficient Full Adder (EAFA) with minimum error distance is proposed. The proposed architecture was constructed to mitigate the cascaded effect problem in GDI-based circuits. It is proved by extending the proposed 1-bit GDI-based adder for different 16-bit Energy and Area Efficient High-Speed Error-Tolerant Adders (EAHSETA) segmented as accurate and inaccurate adder circuits. The proposed adder's design metrics in terms of delay, area, and power dissipation are verified through simulation using the Cadence tool. The proposed logic is deployed to accelerate the convolution process in the Low-Weight Digit Detector neural network for real-time handwritten digit classification application as a case study in the Intel Cyclone IV Field Programmable Gate Array (FPGA). The results confirm that our proposed EAHSETA occupies fewer logic elements and improves operation speed with the speed-up factor of 1.29 than other similar techniques while producing 95% of classification accuracy. [ABSTRACT FROM AUTHOR]

Tamil is an old Indian language with a large corpus of literature on palm leaves, and other constituents. Palm leaf manuscripts were a versatile medium for narrating medicines, literature, theatre, and other subjects. Because of the necessity for digitalization and transcription, recognizing the cursive characters found in palm leaf manuscripts remains an open problem. In this research, a unique Convolutional Neural Network (CNN) technique is utilized to train the characteristics of the palm leaf characters. By this training, CNN can classify the palm leaf characters significantly on training phase. Initially, a preprocessing technique to remove noise in the input image is done through morphological operations. Text Line Slicing segmentation scheme is used to segment the palm leaf characters. In feature processing, there are some major steps used in this study, which include text line spacing, spacing without obstacle, and spacing with an obstacle. Finally, the extracted cursive characters are given as input to the CNN technique for final classification. The experiments are carried out with collected cursive Tamil palm leaf manuscripts to validate the performance of the proposed CNN with existing deep learning techniques in terms of accuracy, precision, recall, etc. The results proved that the proposed network achieved 94% of accuracy, where existing ResNet achieved 88% of accuracy. [ABSTRACT FROM AUTHOR]

Accurate prediction of cardiovascular disease is necessary and considered to be a difficult attempt to treat a patient effectively before a heart attack occurs. According to recent studies, heart disease is said to be one of the leading origins of death worldwide. Early identification of CHD can assist to reduce death rates. When it comes to prediction using traditional methodologies, the difficulty arises in the intricacy of the data and relationships. This research is aimed at applying recent machine learning technology to identify heart disease from past medical data to uncover correlations in data that can greatly improve the accuracy of prediction rates using various machine learning models. Models have been implemented using naive Bayes, random forest algorithms, and the combinations of two models such as naive Bayes and random forest methods. These methods offer numerous attributes associated with heart disease. This proposed system foresees the chance of rising heart disease. The proposed system uses 14 parameters such as age, sex, quick blood sugar, chest discomfort, and other medical parameters which are used in the proposed system. Our proposed systems find the probability of developing heart disease in percentages as well as the accuracy level (accuracy of 93%). Finally, this proposed method will support the doctors to analyze the heart patients competently. [ABSTRACT FROM AUTHOR]

Photovoltaic (PV) cell has a characteristic of decrease in power beyond a certain temperature. This decrease in power is due to a drop in the open circuit cell voltage. This decreases the efficiency of the PV cell. The objective of this research is to increase the efficiency of PV cells by reducing the PV cell temperature and reflection loss. The cell temperature and reflection loss can be reduced by spraying water over the PV cells. On spraying water over the USP36, 24V PV module, the power is found to be increased. The test result shows a 1V to 2V increase in voltage, with an efficiency increment of 1% to 1.27%. The test results of USP37 show the voltage increase of 1.2 V to 2.1 V in the PV module voltage. Due to the increase in voltage, efficiency increment of 1.29% is observed. The efficiency of USP36 with water spraying is more than the efficiency of USP37 without water spraying. In the PV power systems, an average increase in efficiency of 0.5% is observed. [ABSTRACT FROM AUTHOR]

A handoff model has been proposed to explain the egress from lysosomes of cholesterol derived from receptor-mediated endocytosis of LDL Cholesterol is first bound by soluble Niemann-Pick C2 (NPC2) protein, which hands off the cholesterol to the N-terminal domain of membrane-bound NPC1. Cells lacking NPC1 or NPC2 accumulate LDL-derived cholesterol in lysosomes and fail to deliver LDL cholesterol to the endoplasmic reticulum (ER) for esterification by acyl-CoA acyltransferase (ACAT) and for inhibition of sterol regulatory element-binding protein cleavage. Here, we support this model by showing that the cholesterol transport defect in NPC1 mutant cells is restricted to lysosomal export. Other cholesterol transport pathways appear normal, including the movement of cholesterol from the plasma membrane to the ER after treatment of cells with 25-hydroxycholesterol or sphingomyelinase. The NPC1 or NPC2 block in cholesterol delivery to the ER can be overcome by 2-hydroxypropyl-β-cyclodextrin, which leads to a marked increase in ACAT-mediated cholesterol esterification. The buildup of cholesteryl esters in the cytosol is expected to be much less toxic than the buildup of free cholesterol in the lysosomes of patients with mutations in NPC1 or NPC2. [ABSTRACT FROM AUTHOR]

The Niemann-Pick, Type C1 protein (NPC1) is required for the transport of lipoprotein-derived cholesterol from lysosomes to endoplasmic reticulum. The 1278-amino acid, polytopic membrane protein has not been purified, and its mechanism of action is unknown. Unexpectedly, we encountered NPC1 in a search for a membrane protein that binds 25-hydroxycholesterol (25-HC) and other oxysterols. A 25-HC-binding protein was purified more than 14,000-fold from rabbit liver membranes and identified as NPC1 by mass spectroscopy. We prepared recombinant human NPC1 and confirmed its ability to bind oxysterols, including those with a hydroxyl group on the 24, 25, or 27 positions. Hydroxyl groups on the 7, 19, or 20 positions failed to confer binding. Recombinant human NPC1 also bound [3H]cholesterol in a reaction inhibited by Nonidet P-40 above its critical micellar concentration. Low concentrations of unlabeled 25-HC abolished binding of [3H]cholesterol, but the converse was not true, i.e. unlabeled cholesterol, even at high concentrations, did not abolish binding of [3H]25-HC. NPC1 is not required for the known regulatory actions of oxysterols. Thus, in NPC1-deficient fibroblasts 25-HC blocked the processing of sterol regulatory element-binding proteins and activated acyl-CoA:cholesterol acyltransferase in a normal fashion. The availability of assays to measure NPC1 binding in vitro may further the understanding of ways in which oxysterols regulate intracellular lipid transport. [ABSTRACT FROM AUTHOR]

A long- standing mystery in vertebrate Hedgehog signaling is how Patched 1 (PTCH1), the receptor for Hedgehog ligands, inhibits the activity of Smoothened, the protein that transmits the signal across the membrane. We previously proposed (Kinnebrew et al., 2019) that PTCH1 inhibits Smoothened by depleting accessible cholesterol from the ciliary membrane. Using a new imagingbased assay to directly measure the transport activity of PTCH1, we find that PTCH1 depletes accessible cholesterol from the outer leaflet of the plasma membrane. This transport activity is terminated by binding of Hedgehog ligands to PTCH1 or by dissipation of the transmembrane potassium gradient. These results point to the unexpected model that PTCH1 moves cholesterol from the outer to the inner leaflet of the membrane in exchange for potassium ion export in the opposite direction. Our study provides a plausible solution for how PTCH1 inhibits SMO by changing the organization of cholesterol in membranes and establishes a general framework for studying how proteins change cholesterol accessibility to regulate membrane- dependent processes in cells. [ABSTRACT FROM AUTHOR]

In this article, data processing of a supply chain management system has been monitored using the Internet of Space (IoS) which can be able to create possessions for managing the business process. In modern circumstances, many business inventiveness are trading and exporting products on their possession, but in many cases, information on such manufactured products is not monitored in an effective manner. To overcome the abovementioned issue, a precise model of monitoring several distributed products in supply chain management has been introduced with high sustainability error reduction. The framed model in the management process has been integrated with the boosting algorithm, a type of machine learning algorithm where training dataset has been introduced appropriately. This variation in the incorporation of the boosting optimization process not only increases the efficiency of the proposed model but also attempts to prove the success strategy under five different scenarios, where after sequential tests IoS model delivers high improvement in the distribution process for an average percentile of 67% than the existing methods. [ABSTRACT FROM AUTHOR]

This article highlights the importance of implementing intelligent monitoring devices with the internet of things (IoT) for observing the amount of charges on different appliances in each household. In India, it has been observed that 20% of power is wasted due to commercial appliances where the amount of charge flow is much excess to corresponding appliances. Therefore, to perceive information about the flow of charges, it is necessary to implement an intelligent device, and it is possible to obtain exact information on the flow of charges with the help of wireless sensor networks (WSN). Even most of the researchers have developed an intelligent device for monitoring the amount of charges but delay, energy consumption, and cost of implementation are much higher. It is always necessary to extract precise information at corresponding time periods for reducing the delay in packet transmission of a specific network. To excerpt such real-time data in the network layer, an active procedure should be followed by integrating dissimilar network areas inside a single cluster, and binary coded artificial neural network (BCANN) is introduced to acquire information about hidden layers. To prove the effect of such integration process, several tests have been prepared using online and offline analyses where simulation results prove to be much effective in case of all different scenarios to an extent of 52.4% when compared to existing methods. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate the effects of ethanolic root Ethanolic extract of Azima tetracantha. Lam roots (EEATR) in adenine-induced chronic kidney failure in Wistar albino rats To assess the antioxidant activity of EEATR. MATERIALS AND METHODS: Thirty rats were selected and allocated to five groups with six animals in each group. Group 1 was given normal saline (control), Group 2 – adenine, 0.75% 40 mg/kg, Group 3 – adenine and 250 mg/kg of EEATR, Group 4 – adenine and 500 mg/kg EEATR, and Group 5 – EEATR 500 mg/kg. Saline, adenine, and EEATR were given orally once daily for 28 days. EEATR was given 60 min before adenine administration. Urine output, blood urea nitrogen (BUN), creatinine, albumin, and total proteins were estimated. The histopathological changes in the kidneys were examined, and antioxidant property of the extract was assessed in the renal tissue. RESULTS: Adenine treated rats had a reduction in urine output (‒45%), food intake (‒46%), body weight (‒28%), total proteins (‒66%) and albumin (‒59%) and an increase in creatinine (950%), BUN (73.6%), and kidney weight (43.75%). Histological examination of the kidneys showed capillary congestion, tubular damage, glomerular distortion, and many oxalate crystals. Rats co-administered with EEATR 250 and 500 mg/kg had marked improvement (P ≤ 0.0001%) in all the above parameters with a marked reduction in size and number of oxalate crystals in the kidney. In the anti-oxidant assays, EEATR exhibited significant antioxidant activity. CONCLUSION: EEATR was found to be an effective nephroprotective agent in adenine-induced chronic renal failure in Wistar albino rats. [ABSTRACT FROM AUTHOR]

Post market examination is to safeguard end users through the close watch of IVDs offered for sale or distribution in the country. Through this action product owner must aware of the problems arises with the IVD in use and analysis the risk associated with the problem reported and take appropriate action to avoid repetition and ensure quality of the IVDs in the market. Rigorous pre-market assessment of IVDs is done by the regulatory authorities; however, there is no enough system and guidance in place for the monitoring of the post-marketing phase of IVDs in most countries including India. This article has been prepared to facilitate and strengthen the reporting of Events attributable to in-vitro diagnostic medical devices in India, harmonized with WHO, National and International best practices. This article suggested the various stakeholders follow this guidance involved in the post market phase of IVDs relates to monitoring of adverse events, reporting of adverse events, reporting timeline, examination of the complaint to determine source, and the subsequent suitable action. This article also aims to create awareness among users about the importance of reporting adverse events relating to the IVDs in India. In order to monitor the quality of the IVDs available in the country and encourage the reporting, this article also urges the central government to make online portal under respective authorities for mandatory reporting, report suspected counterfeit IVDs, for voluntary reporting serious adverse event, product quality problem, product use/medication error, or/failure that is associated with the use of an IVDs. [ABSTRACT FROM AUTHOR]