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Detection of Outliers in Bioequivalence Studies Data Analysis with Williams Design
Background: Drug Regulatory agencies all over the world generally discourage exclusion of outliers in a BE (BE) study; on the other hand in routine bio-statistical work we take these into the account. If the decision rules for identifying the outliers are clearly mentioned before the start of the study and laid down in protocol by the responsible biostatistician in collaboration with clinicians, the problem of outliers can be dealt smartly without jeopardizing the whole study for redoing. The purpose of this article is to introduce procedure for reliably detecting outlier subject(s) with Williams design.
Experimental: Literature review reveals many different methods for the detection of outlier values in BE studies; most of them are for BE of two treatments. For BE studies with more than two treatments use of Williams design seems imperative; but inclusion and deletion of outlying subjects may lead to profound effect on conclusion of BE which in turn may be dangerous for the health. The suggested method is an adjustment to a previously introduced method using exploratory data analysis technique such as principle component analysis and Andrews curves
Glycine Betaine: A Potential Secondary Metabolite against Abiotic Stresses
Abiotic stresses like temperature, water, salinity, ultraviolet (UV) radiations, heavy metals, etc., affect plants’ growth and yield. Despite these constraints, plants produce a variety of metabolites to maintain their survival. Primary metabolites, produced through crucial metabolic processes, are essential for plants survival. Additionally, secondary metabolites (SMs) are synthesized from primary metabolites and are mainly used as a defensive mechanism and a means of interacting with unfavorable environmental conditions. In addition to their defensive function in plants, SMs are significant in the pharmaceutical industry. Glycine betaine (GB) is a quaternary ammonium compound that belongs to a class of SMs, present in plants, animals, and microbes. It functions as a compatible solute and reflects potential bioactivity against various abiotic stresses like salinity, water, heat, heavy metals, UV radiations, etc. Due to high solubility and low viscosity, its accumulation is commonly observed in chloroplasts and plastids. The accumulation level generally depends on plant species, growth stage, exposure duration, and stress\u27s nature. GB reduces oxidative stress and prevents the damaging of photosystems and other biomolecules under stressful conditions. It is important for maintaining the water potential and osmotic pressure of cells and hence functions as a potent osmolyte under salinity stress. Excessive production of ROS during temperature stress is responsible for damage to oxygen-evolving complexes, electron transport chains, and photosystems. In order to protect plants from these damages, GB activates the genes responsible for synthesizing heat shock proteins, glycoproteins, and antioxidants via various signaling pathways. GB alleviates the effect of water stress by maintaining the function of rubisco and calcium ion ATPase activity via crosstalk with Abscisic acid (ABA) and ethylene. GB supports the proper functioning of the ascorbate-glutathione cycle, superoxide dismutase, catalase, peroxidase, and ascorbate peroxidase (antioxidative enzymes) to overcome various stresses. Phytohormones like salicylic acid (SA), jasmonic acid (JA), ABA, ethylene, and polyamines (PAS) coordinate well with GB via different signaling pathways to ensure plant protection under various abiotic stresses. The potential bioactivity of GB against various abiotic stresses in plants has been summarized in this review
Convergence Analysis for Linear Fredholm and Nonlinear Fredholm Hammerstein Integral Equations
In this article, we consider the linear Fredholm integral equations and Fredholm-Hammerstein’s integral equations. We propose the Legendre polynomial based degenerate kernel method to solve linear Fredholm and Fredholm-Hammerstein integral equations. We discuss the convergence and error analysis of the proposed method and also obtain the superconvergence results for iterated degenerate kernel method
Effects of Controlled Culture Conditions on Chemical Composition and Antimicrobial Activities of Mentha rotundifolia Essential Oils
The study objectives were the determination of Mentha rotundifolia essential oils composition using GC/MS analysis and the evaluation of their antimicrobial activities. In addition, the determination of the relationships between plants acclimatization conditions, essential oils composition and antimicrobial activities.
Essential oils extracted via hydrodistillation method from wild plants and acclimatized plants in different culture conditions of Mentha rotundifolia. Five selected pathogenic microbial strains were used to evaluate EOs in vitro antimicrobial activities.
Essential oils GC/MS analysis revealed the dominance of the oxygenated monoterpene (piperitenone oxide). A significant effect of plant culture conditions in acclimatization room on essential oils composition compared to the control was observed. We also noted that antimicrobial activities of extracted essential oils from acclimatized plants were higher than those from field-grown M. rotundifolia plants.
Content of Piperitenone Oxide in acclimatized plantlets is 93.07% for plantlets cultured at 16°C and a photoperiod of 16 hours light / 8 hours dark, statistically higher than wild plants where it is around 78%. We also noted the presence of Limonene (5.7%) in plantlets grown at 35°C which is significantly different than that of the wild plants (1.55 %). Essential oils antimicrobial activities showed that the plantlets grown at 16 °C or in total darkness were more active towards the tested strains. While, the EO of plantlets cultured at 35 °C were the least active
Earth’s Temperature: The Effect of the Sun, Water Vapor, and CO2
The purpose of this study is to show the Sun controls the Earth’s temperature daily and over decades and millennia. A secondary objective is to show CO2 contributes to the warming of the Earth through increased enthalpy (heat content). The methodology is to record temperature and relative humidity at many weather stations around the globe to provide a picture of the constantly changing atmosphere over twelve months. Daily measurements of the molecular fraction of CO2 are converted to weight to calculate the increasing enthalpy of the atmosphere. The Sun controls Earth’s temperature through water vapor up to the dewpoint temperature line and by direct heat radiation from the Sun above it. The enthalpy contribution by CO2 from 1750 to 2022 was up to 0.0000049 kJ/kg of dry air, equivalent to a temperature increase of 0.000181oC over 272 years. The effect of CO2 on warming the Earth has a negligible increase in Earth’s temperature
Validated RP-HPLC Method for the Determination of Zolmitriptan - A Serotonin 5-HT Receptor Agonist
A simple precise, accurate RP-HPLC method has been developed and validated for analysis of Zolmitriptan (ZLM). The separation and quantization were achieved on a 250 mm reversed phase column with a hydrophilic linkage between silica particles and hydrophobic alkyl chains. The mobile phase was constituted (flow rate 0.8 ml min-1) of eluant A (CH3OH) and eluant B (aqueous tetra butyl ammonium hydrogen sulphate) (pH 3.4; 10 mM) using isocratic elution with UV detection at 224 nm. The method showed good linearity for ZMT in the 1–100 μg mL-1 range with regression equation 15576x ± 99401 and correlation coefficient 0.999 respectively. The limit of quantitation (LOQ) and limit of detection (LOD) were found to be 0.8134 and 0.2687 μg mL-1 respectively. Finally the applicability of the method was validated according to ICH guidelines and can be applicable for the analysis of commercial dosage forms
Investigations of In vitro Digestibility of Proteins Bound to Food Colors
Colorants either synthetic or natural are commonly added to a variety of food systems to make them attractive and acceptable for the consumers. Our previous publications on Carmoisine, Allura Red, Sunset yellow and the present study showed that food colorants such as Erythrosine, Amaranth, Tartrazine, Quinoline yellow, Brilliant Blue bind with the proteins in variety of the food environments and the protein color complexes are digested by the proteolytic enzyme. The present study elaborates the active sites of the proteins involved in binding with various functional groups of food colors and on these sites modifies the tryptic digestibility of the different proteins. Colors show strong binding capacity with proteins which may block the active site for hydrolysis by the enzyme. The effect of the tryptic digestibility on color complexes of the protein such as the BSA a high molecular weight and nisin the low moleculer weight proteins are explored. The result shows the different color binding with protein have not similar effect on digestibility but in all cases digestibility decreases significantly as compared with blank
Family Araliaceae in Southern Africa: A Review of Ethnobotanical Uses, Phytochemistry, Pharmacology, and Toxicology
There is widespread use of species belonging to family Araliaceae in traditional medicine in southern Africa. The aim of this review was to assess medicinal uses, phytochemistry, pharmacology and toxicological properties of indigenous species belonging to family Araliaceae in southern Africa. Relevant articles, books, theses, dissertations, patents, and other English-only reports on the medicinal uses, phytochemistry, pharmacological and toxicological properties of species belonging to the family Araliaceae in southern Africa (Angola, Botswana, Eswatini, Lesotho, Malawi, Mozambique, Namibia, South Africa, Zambia and Zimbabwe) were reviewed. Databases such as PubMed, Web of Science, Elsevier, Google Scholar, Scopus, Springer, Science Direct, Taylor and Francis between January and July 2022. Eleven species, namely Cussonia. arborea, C. arenicola, C. natalensis, C. nicholsonii, C. paniculata, C. sphaerocephala, C. spicata, C. transvaalensis, C. thyrsiflora, C. zuluensis and Neocussonia umbellifera are used as traditional medicines against 48 human and animal diseases. This study showed that alkaloids, anthocyanins, anthracene glycosides, botulin, flavonoids, free gallic acid, iridoids, phenolics, saponins, steroids, tannins, triterpenoids and volatile oils have been identified from these species. Pharmacological research revealed that the crude extracts and compounds demonstrated isolated from these species are characterized by Aβ42 protein reduction, acetylcholinesterase, analgesic, antibacterial, antifungal, antiviral, anticancer, antihyperglycemic, anti-inflammatory, antileishmanial, antioxidant, antiplasmodial, antiprotozoal, anti-ulcer, immunomodulatory, larvicidal, molluscicidal, spermicidal, cytotoxicity and toxicity activities. Reports of medicinal uses, phytochemistry, pharmacology and toxicological properties of species belonging to the family Araliaceae in southern Africa could only be found for 11 species, suggesting that further investigation of largely unexplored family members is necessary
The Cross-Sectional Study of Self Efficacy, Diet Compliance, and Blood Sugar Levels on Diabetes Mellitus Patients in Indonesia
Diabetes mellitus (DM) has become a global health problem because the prevalence of diabetes mellitus continues to increase. Data from the West Sumatra Provincial Health Office (2018), DM cases totalled 44,280 cases, with a DM prevalence of 1.6% in 2018. Self-efficacy plays an important role in controlling blood sugar levels. Lack of self-efficacy causes the patient\u27s blood sugar levels to become abnormal, resulting in a risk of complications. This research aims to study the relationship between self-efficacy and diet compliance with blood sugar levels in DM patients at the Andalas Public Health Center, Padang City. The research method is descriptive-analytic with a cross-sectional approach, with a total sample of 75 people. The results showed that 78.7% of the respondents have hyperglycemia, 72.0% with non-compliant to their diet limitation, and 68.0% with low self-efficacy. A relationship exists between diet compliance and blood sugar levels in type 2 DM patients. There is a relationship between self-efficacy and blood sugar levels in type 2 diabetes mellitus patients at the Padang Andalas Public Health Center in 2022
The Sun Versus CO2 as the Cause of Climate Change Projected to 2050
The current controversy over the cause of increasing global temperatures since the middle of the 20th century comes from the IPCC First Assessment Report issued in 1990. The report states rising carbon dioxide (CO2) warms the air, thereby holding more of the significant warming gas, water vapor. This additional water vapor feeds back to amplify the warming by CO2. The IPCC has continually promoted this concept in its reports since 1990. Up-to-date science proves the IPCC concept is faulty. Scientists discovered that when the Sun\u27s energy output changes, it impacts the Earth\u27s temperature, and it does this cyclically. Current, reliable evidence shows the Earth has just come through a warm period. It is now in the early stages of cooling that might be similar to the Dalton Minimum and last for three or four decades. Average temperatures can drop by up to 1.5oC and increase the rate of crop failures that have already started. It won\u27t be easy to maintain the benefits of the recent warm phase of the Sun during the upcoming solar minimum