Application of a Modified g -Parameter Prior in Bayesian Model Averaging to Water Pollution in Ibadan

A special technique that measures the uncertainties embedded in model selection processes is Bayesian Model Averaging (BMA) which depends on the appropriate choices of model and parameter priors. Inspite the importance of the parameter priors' specification in BMA, the existing parameter priors give exitremely low Posterior Model Probability (PMP). Therefore, this paper elicits modified g-parameter priors to improve the performance of the PMP and predictive ability of the model with an application to the Water Pollution of Asejire in Ibadan.  The modified g-parameter priors gj = , established the consistency conditions and asymptotic properties using the models in the literature. The results show that the PMP with the best prior (gj= ) had the least standard deviations (0.0411 at n=100,000 and 0:000 at n=1000) for models 1 & 2 respectively; and had the highest posterior means (0.9577 at n=100,000 and 1.000 at n=1000) for models 1 & 2 respectively. The point and overall predictive performances for the best prior were 2.357 at n=50 and 2.335 at n=100,000 when compared with the BMA Log Predictive Score threshold of 2.335. Applying this best g-parameter prior in modeling the Asejire river, it indicates that the dissolved solids (mg/l) and total solids (mg/l) are the most important pollutants in the river model with their PIP of 6.14% and 6.1% respectively. Keywords:        Posterior Inclusion Probability (PIP), Log-Predictive Score, Model   Uncertainty, Dissolved Solids DOI: 10.7176/JEES/9-11-06 Publication date: November 30th 201

Fisetin targets YB-1/RSK axis independent of its effect on ERK signaling: insights from in vitro and in vivo melanoma models

Abstract The anti-proliferative activity of dietary flavonoid fisetin has been validated in various cancer models. Establishing its precise mechanism of action has proved somewhat challenging given the multiplicity of its targets. We demonstrated that YB-1 promotes epithelial-to-mesenchymal transition and its inhibition suppressed tumor cell proliferation and invasion. The p90 ribosomal S6 kinase (RSK), an important ERK effector, activates YB-1 to drive melanoma growth. We found that fisetin treatment of monolayer/3-D melanoma cultures resulted in YB-1 dephosphorylation and reduced transcript levels. In parallel, fisetin suppressed mesenchymal markers and matrix-metalloproteinases in melanoma cells. Data from cell-free/cell-based systems indicated that fisetin inhibited RSK activity through binding to the kinase. Affinity studies for RSK isoforms evaluated stronger interaction for RSK2 than RSK1. Competition assays performed to monitor binding responses revealed that YB-1 and RSK2 do not compete, rather binding of fisetin to RSK2 promotes its binding to YB-1. Fisetin suppressed YB-1/RSK signaling independent of its effect on ERK, and reduced MDR1 levels. Comparable efficacy of fisetin and vemurafenib for inhibiting melanoma growth was noted albeit through divergent modulation of ERK. Our studies provide insight into additional modes of regulation through which fisetin interferes with melanoma growth underscoring its potential therapeutic efficacy in disease progression

Chronic toxicological evaluation and reversibility studies of Moringa oleifera ethanolic seed extract in Wistar rats

This study evaluated the chronic toxicity and reversibility Potential of Moringa oleifera seed in Rats. Forty-four Wistar rats were randomized into four groups of 11 rats each, three groups were treated with doses of 50, 200, and 800 mg/kg of MOESE p.o, for 90 days while one group served as control and was administered distilled water p.o. After 90 days, half of the animals were sacrificed and blood samples collected for determination of biochemical and haematological parameters; antioxidants and malondialdehyde (MDA); sperm count, motility and morphology. Organs were harvested for weight determination and histopathological assessments the liver. The other half were left for another 30 days without treatment with the extract, after which they were sacrificed. MOESE produced significant reduction in food and water intake, relative weights of liver, heart, testes, lung and spleen at all treatment dose, these changes were overall small magnitude, within the range of historical control. There was significant increase in AST (200 and 800 mg/kg), LDH (200 mg/kg), ALP (800 mg/k), albumin (800 mg/kg) and K+ (800 mg/kg), but decrease in serum Ca2+ (50 and 200 mg/kg). A significant increase in serum antioxidant was observed at all treatment doses, while semen pH were reduced. These effects on organ relative weights and all biochemical parameters except AST and ALP were reversed after 30 days of the reversibility study. Histopathological presentations showed necrosis in the liver (50 and 200 mg/kg). Our study demonstrated that ethanol extract of Moringa oleifera seeds could cause infertility in male rats due to decreased semen pH. Our results also showed that the extract may be hepatotoxic due to persistent high level of AST and ALP even after cessation of exposure to the extract, this is also consistent with the histopathological results that shows hepatic necrosis associated with chronic exposure to the extract.Keywords: Moringa oleifera seed, Toxicity, Wistar Rat

Identification of neurotherapeutic constituents in Ocimum gratissimum with cholinesterase and mono amine oxidase inhibitory activities, using GC-MS analysis, in vitro, and in silico approaches

Neuroprotective activities of various extracts of Ocimum gratissimum (OG), have been reported, but there is paucity of information on its neurotherapeutic constituents. This study is aimed at identifying the neurotherapeutic constituents in OG leaves using in vitro assays, GC-MS chemical investigation and in silico studies including molecular docking, ensemble-based docking, molecular dynamics (MD) simulation, clustering and ADMET filtering analysis. Methanol extract of O gratissimum (MEOG) and solvent-partition (n-hexane, ethylacetate, and methanol residue fraction) of MEOG were investigated for in vitro acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and monoamine oxidase B (MAO-B) inhibition at concentration of 0.65, 12.5, 2.5, 5, and 10 mg/mL, using donepezil, phenazine methosulfate and selegiline as reference inhibitors for AChE, BChE and MAO B respectively. n-hexane solvent partition fraction was further investigated using GC-MS analysis. Identified compounds were screened against human AChE, BChE and MAO-B activities using molecular docking and molecular dynamics. The lead phytochemicals were further analysed for ADMET in silico analysis. MEOG and the 3 fractions (n-hexane, ethylacetate, and methanol residue fraction) inhibited the activities of AChE, BChE and MAO-B in a concentration-dependent manner with AChE (IC50 = 2.380, 2.022, 2.066 and 1.079 mg/mL respectively), BChE (IC50 = 2.261, 2.126, 2.630 and 1.465 mg/mL respectively) and MAO-B (IC50 = 2.345, 1.584, 2.933 and 2.935 mg/mL respectively). From the 38 GC-MS identified compounds, 7 hit compounds were further subjected to ensemble-docking, the lead phytochemicals (LP): cholestane and 3-methoxy-morphanin presented highest multiple binding tendencies to the three enzymes. Cholestane had the highest binding energies of −9.9, −9.0 and −11 kcal/mol, while 3-methoxy-morphanin presented the second-best binding energies of −9.3, −8.2 and −10.1 kcal/mol respectively. When compared with the binding pattern of reference inhibitors of the enzyme, lead phytochemicals were orientated in the catalytic sites of the enzyme and interacted with important catalytic residues. The LP-enzyme complexes were stable during the MD simulation analysis. Cholestane and 3-methoxy-morphanin presented favorable ADMET properties over several molecular descriptors and filters, with druggable properties and ability to cross the blood-brain barrier. Hence, cholestane and 3-methoxy-morphanin, in part, or in synergy with other hit phytochemicals, may be responsible for the neurotherapeutic activities of MEOG leaves

Adaptation of the Wound Healing Questionnaire universal-reporter outcome measure for use in global surgery trials (TALON-1 study): mixed-methods study and Rasch analysis

BackgroundThe Bluebelle Wound Healing Questionnaire (WHQ) is a universal-reporter outcome measure developed in the UK for remote detection of surgical-site infection after abdominal surgery. This study aimed to explore cross-cultural equivalence, acceptability, and content validity of the WHQ for use across low- and middle-income countries, and to make recommendations for its adaptation.MethodsThis was a mixed-methods study within a trial (SWAT) embedded in an international randomized trial, conducted according to best practice guidelines, and co-produced with community and patient partners (TALON-1). Structured interviews and focus groups were used to gather data regarding cross-cultural, cross-contextual equivalence of the individual items and scale, and conduct a translatability assessment. Translation was completed into five languages in accordance with Mapi recommendations. Next, data from a prospective cohort (SWAT) were interpreted using Rasch analysis to explore scaling and measurement properties of the WHQ. Finally, qualitative and quantitative data were triangulated using a modified, exploratory, instrumental design model.ResultsIn the qualitative phase, 10 structured interviews and six focus groups took place with a total of 47 investigators across six countries. Themes related to comprehension, response mapping, retrieval, and judgement were identified with rich cross-cultural insights. In the quantitative phase, an exploratory Rasch model was fitted to data from 537 patients (369 excluding extremes). Owing to the number of extreme (floor) values, the overall level of power was low. The single WHQ scale satisfied tests of unidimensionality, indicating validity of the ordinal total WHQ score. There was significant overall model misfit of five items (5, 9, 14, 15, 16) and local dependency in 11 item pairs. The person separation index was estimated as 0.48 suggesting weak discrimination between classes, whereas Cronbach's α was high at 0.86. Triangulation of qualitative data with the Rasch analysis supported recommendations for cross-cultural adaptation of the WHQ items 1 (redness), 3 (clear fluid), 7 (deep wound opening), 10 (pain), 11 (fever), 15 (antibiotics), 16 (debridement), 18 (drainage), and 19 (reoperation). Changes to three item response categories (1, not at all; 2, a little; 3, a lot) were adopted for symptom items 1 to 10, and two categories (0, no; 1, yes) for item 11 (fever).ConclusionThis study made recommendations for cross-cultural adaptation of the WHQ for use in global surgical research and practice, using co-produced mixed-methods data from three continents. Translations are now available for implementation into remote wound assessment pathways