Bayesian Analyses of the Burr Type ? Distribution under Doubly Type ?? censored samples using different Priors and Loss functions

The Bayesian analysis of the Burr type  distribution (Exponentiated Rayleigh) has been considered in the paper.  The Gamma, Exponential, Chi-Squared and Jeffrey prior have been assumed for posterior analysis. The estimation has been made under doubly type  censored samples. The Bayes estimation has been obtained under eight different loss functions (Squared error, Quadratic, Weighted, Linear exponential, Precautionary, Entropy, De Groot and non-Linear exponential loss functions). The simulation study has been conducted to compare by mean square error (MSE) for the performance of various estimators. Keyword: Bayesian Analyses, Exponentiated Rayleigh Distribution, Burr type  distribution, Loss function, Prior, Posterior, (Squared error, Quadratic, Weighted, Linear exponential, Precautionary, Entropy, De Groot and non-Linear exponential) loss functions

Kinetic Study of Esterification Reaction

The Esterification kinetics of acetic acid with ethanol in the presence of sulfuric acid as a homogenous catalyst was studied with isothermal batch experiments at 50-60°C and at a different molar ratio of ethanol to acetic acid [EtOH/Ac]. Investigation of kinetics of the reaction indicated that the low of [EtOH/Ac] molar ratio is favored for esterification reaction, this is due to the reaction is catalyzed by acid. The maximum conversion, approximately 80% was obtained at 60°C for molar ratio of 10 EtOH/Ac. It was found that increasing temperature of the reaction, increases the rate constant and conversion at a certain mole ratio, that is due to the esterification is exothermic. Activity coefficients were calculated using UNIFAC program. Results showed deviation in activation energy in the non-ideal system of about 20% this is due to the polarities of water and ethanol compared to the non-polar ethyl acetate this dissimilarity leading to strong non- ideal behavior. The homogenous reaction has been described with simple power-law model. The chemical equilibrium combustion calculated form the kinetic model in agreement with the measured chemical equilibrium

In vitro cytotoxic study for partially purified Lasparaginase from fresh leaves, unripe and ripe fruits of Withania somnifera plant

This work aimed to study the cytotoxic effect of L-asparaginase isolated from local Withania somnifera plant on lymphocyte leukemia cells. To achieve this goal, L-asparaginase was purified from W. somnifera fruits by two purification steps, ion-exchange chromatography using DEAE-cellulose and gel filtration chromatography using Sephadex G-150, and the study utilized an in vitro evaluation for the cytotoxic effect of the partially purified L-asparaginase with concentrations ranging (12.5 to 100 μg/ml) in a two fold serial dilutions on some cell suspension culture including, acute lymphocyte leukemia and chronic lymphocyte leukemia culture at different concentrations (12.5 to 100 μg/ml) and different exposure time of treatment (24, 48 and 72 h). This two purification steps raised the specific activity from 1.73 U/mg in crude extract to 2.29 U/mg after ion-exchange and 10.5 U/mg after gel filtration; the purification fold was 1.32 after ion-exchange and 6.06 after gel filtration, the enzyme recovery was 56% after two purification steps and the results, pointed that acute lymphocyte leukemia culture showed highest sensitivity toward the cytotoxic effect (62.3±0.9%) of the partial purified L-asparaginase (100 μg/ml) than other culture after 48 h in a dose dependent manner, and highest cytotoxic inhibitory effect (73.2±1.6%) after 48 h of exposure on chronic lymphocyte leukemia culture, while healthy lymphocyte culture showed novel behavior. The lowest concentration of cell treatment gave the most significant (P< 0.01) inhibitory effect. The conclusion is that there is enough evidence to support the claim that Lasparaginase from W. somnifera may be considered chemotherapeutic agent against cancer, such as acute lymphoblastic leukemia and lymphosarcoma.Keywords: Acute lymphocyte leukemia (ALL), chronic lymphocyte leukemia (CLL), L-asparaginase, cytotoxic assay

Partial synthetic PPARƳ derivative ameliorates aorta injury in experimental diabetic rats mediated by activation of miR-126-5p Pi3k/AKT/PDK 1/mTOR expression

Type 2 diabetes mellitus (T2D) is a world wild health care issue marked by insulin resistance, a risk factor for the metabolic disorder that exaggerates endothelial dysfunction, increasing the risk of cardiovascular complications. Peroxisome proliferator-activated receptor PPAR) agonists have therapeutically mitigated hyperlipidemia and hyperglycemia in T2D patients. Therefore, we aimed to experimentally investigate the efficacy of newly designed synthetic PPARα/Ƴ partial agonists on a High-Fat Diet (HFD)/streptozotocin (STZ)-induced T2D. Female Wistar rats (200 ± 25 g body weight) were divided into four groups. The experimental groups were fed the HFD for three consecutive weeks before STZ injection (45 mg/kg/i.p) to induce T2D. Standard reference PPARƳ agonist pioglitazone and the partial synthetic PPARƳ (PIO; 20 mg/kg/BW, orally) were administered orally for 2 weeks after 72 h of STZ injection. The aorta tissue was isolated for biological ELISA, qRT-PCR, and Western blotting investigations for vascular inflammatory endothelial mediators endothelin-1 (ET-1), intracellular adhesion molecule 1 (ICAM-1), E-selectin, and anti-inflammatory vasoactive intestinal polypeptide (VIP), as well as microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR, endothelial Nitric Oxide Synthase (eNOS) immunohistochemical staining all are coupled with and histopathological examination. Our results revealed that HFD/STZ-induced T2D increased fasting blood glucose, ET-1, ICAM-1, E-selectin, and VIP levels, while decreasing the expression of both microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR phosphorylation. In contrast, the partial synthetic PPARƳ derivative evidenced a vascular alteration significantly more than reference PIO via decreasing (ET-1), ICAM-1, E-selectin, and VIP, along with increased expression of microRNA126-5p and p-AKT/p-Pi3k/p-PDK-1/p-mTOR. In conclusion, the partial synthetic PPARƳ derivative significantly affected HFD/STZ-induced T2D with vascular complications in the rat aorta

Exploring Proteus mirabilis methionine tRNA synthetase active site: homology model construction, molecular dynamics, pharmacophore and docking validation

Currently, the treatment of Proteus mirabilis infections is considered to be complicated as the organism has become resistant to numerous antibiotic classes. Therefore, new inhibitors should be developed, targeting bacterial molecular functions. Methionine tRNA synthetase (MetRS), a member of the aminoacyl-tRNA synthetase family, is essential for protein biosynthesis offering a promising target for novel antibiotics discovery. In the context of computer-aided drug design (CADD), the current research presents the construction and analysis of a comparative homology model for P. mirabilis MetRS, enabling development of novel inhibitors with greater selectivity. Molecular Operating Environment (MOE) software was used to build a homology model for P. mirabilis MetRS using Escherichia coli MetRS as a template. The model was evaluated, and the active site of the target protein predicted from its sequence using conservation analysis. Molecular dynamic simulations were performed to evaluate the stability of the modeled protein structure. In order to evaluate the predicted active site interactions, methionine (the natural substrate of MetRS) and several inhibitors of bacterial MetRS were docked into the constructed model using MOE. After validation of the model, pharmacophore-based virtual screening for a systemically prepared dataset of compounds was performed to prove the feasibility of the proposed model, identifying possible parent compounds for further development of MetRS inhibitors against P. mirabilis

Evaluación de la prescripción y uso de medicamentos supresores de ácido en hospitales centrales en la región de Abha, Arabia Saudita

Objective: The aim of this study was to study and assess the indications of acid suppressive drugs and to find out percentage of irrational prescriptions with acid suppressive drugs. Material/Methods: It is a prospective observational study conducted in the Armed Forces Hospitals Southern Region and Abha Maternity Hospital, both in Abha in Assir region (Saudi Arabia). The sample size of study was 185 patients. The case sheets of the patients’ prescription order were reviewed for acid suppressive drugs prescription and relevant data was taken. Patients’ age above 18 were identified. The duration of study was 8 weeks, between May and June 2017. Results: Our results showed that the majority of the prescriptions of proton pump inhibitors (68.1%) were unjustifiable and that proton pump inhibitor was the most commonly prescribed acid suppressive drugs for the patients (97.8%). The frequency of prescribing for the autism spectrum disorders in our study was found to be higher in patients with an existing risk factor and was mostly recommended by physicians as concomitant medications (67.6%). The most common concomitant medications used with the proton pump inhibitors were non-steroidal anti-inflammatory drugs (29.2%) in which aspirin composed 13.5% of the non-steroidal anti-inflammatory drugs prescribed followed by antimicrobials (9.2%). Conclusion: Acid suppressive drugs are the most commonly prescribed drugs with no proper indications hence irrational. Based on the results of this study, creating awareness about reasonable use of acid suppressive drugs is a necessity.Objetivo: El objetivo de este estudio fue estudiar y evaluar las indicaciones de los medicamentos supresores de ácidos y averiguar el porcentaje de recetas irracionales con medicamentos supresores de ácidos. Material / Métodos: es un estudio observacional prospectivo realizado en los Hospitales de las Fuerzas Armadas del Sur y en el Hospital de Maternidad Abha, ambos en Abha en la región de Assir (Arabia Saudita). El tamaño muestral del estudio fue de 185 pacientes. Se revisaron las hojas de casos de orden de prescripción de los pacientes para la prescripción de medicamentos supresores de ácido y se tomaron los datos pertinentes. Se identificó la edad de los pacientes mayores de 18 años. La duración del estudio fue de 8 semanas, entre mayo y junio de 2017. Resultados: nuestros resultados mostraron que la mayoría de las prescripciones de inhibidores de la bomba de protones (68,1%) eran injustificables y que este era el fármaco supresor de ácido más comúnmente prescrito para los pacientes (97,8%). La frecuencia de prescripción para los trastornos del espectro autistas en nuestro estudio, fue mayor en pacientes con un factor de riesgo existente y fue recomendada principalmente por los médicos como medicamentos concomitantes (67,6%). Los medicamentos concomitantes más comunes que se usaron con los inhibidores de la bomba de protones fueron los antiinflamatorios no esteroideos (29.2%) en los cuales la aspirina supuso el 13,5% de los antiinflamatorios no esteroideos prescritos, seguidos por los antimicrobianos (9.2%) Conclusión: los medicamentos supresores de ácido son los medicamentos más comúnmente recetados sin indicaciones adecuadas, por lo que son irracionales. Basado en los resultados de este estudio, crear conciencia sobre el uso razonable de los medicamentos supresores del ácido es una necesidad

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic interventions in various diseases, including cancers. According to the framework of autophagy, the suppression or induction of autophagy can exert therapeutic properties through the promotion of cell death or cell survival, which are the two main events targeted by cancer therapies. Remarkably, natural products have attracted attention in the anticancer drug discovery field, because they are biologically friendly and have potential therapeutic effects. In this review, we summarize the up-to-date knowledge regarding natural products that can modulate autophagy in various cancers. These findings will provide a new position to exploit more natural compounds as potential novel anticancer drugs and will lead to a better understanding of molecular pathways by targeting the various autophagy stages of upcoming cancer therapeutics

Social and Economic Factors that Influence Health Outcomes in Family Medicine

Over the last twenty years, the social determinants of health (SDOH) have gained more and more attention in the public health community. SDOH are non-medical elements that may be significantly impacted by social policies and have an impact on health. The increasing variety that exists within our societies makes it absolutely necessary for us to incorporate into undergraduate medical education social determinants of health such as racial factors, financial instability, partner violence, insufficient accessibility to transportation, and inadequate social supports, as well as the crucial role of health education.  Nonetheless, a growing body of research indicates that a variety of health outcomes are fundamentally caused by socioeconomic variables including wealth, income, and education together. In this review we highlight the influence of socio-economic factors on health outcomes, approaches to incorporate social determinants of health in family medicine practice, and we also talk about challenges and solutions in addressing social determinants in family medicine. The objective of this research was to assess the impact of social determinants of health on family medicine practice in which socioeconomic determinants of health might have an effect on health outcomes and healthcare delivery within the context of a family medicine clinical environment

Disparities in cardiovascular research output and disease outcomes among high-, middle- and low-income countries - An analysis of global cardiovascular publications over the last decade (2008-2017)

Background: Cardiovascular disease (CVD) is the leading cause of death and disability worldwide. Health research is crucial to managing disease burden. Previous work has highlighted marked discrepancies in research output and disease burden between high-income countries (HICs) and low- and lower-middle-income countries (LI-LMICs) and there is little data to understand whether this gap has bridged in recent years. We conducted a global, country level bibliometric analysis of CVD publications with respect to trends in disease burden and county development indicators.Methods: A search filter with a precision and recall of 0.92 and 0.91 respectively was developed to extract cardiovascular publications from the Web of Science (WOS) for the years 2008-2017. Data for disease burden and country development indicators were extracted from the Global Burden of Disease and the World Bank database respectively.Results: Our search revealed 847,708 CVD publications for the period 2008-17, with a 43.4% increase over the decade. HICs contributed 81.1% of the global CVD research output and accounted for 8.1% and 8.5% of global CVD DALY losses deaths respectively. LI-LMICs contributed 2.8% of the total output and accounted for 59.5% and 57.1% global CVD DALY losses and death rates.Conclusions: A glaring disparity in research output and disease burden persists. While LI-LMICs contribute to the majority of DALYs and mortality from CVD globally, their contribution to research output remains the lowest. These data call on national health budgets and international funding support to allocate funds to strengthen research capacity and translational research to impact CVD burden in LI-LMICs

A mediation approach to understanding socio-economic inequalities in maternal health-seeking behaviours in Egypt.

BACKGROUND: The levels and origins of socio-economic inequalities in health-seeking behaviours in Egypt are poorly understood. This paper assesses the levels of health-seeking behaviours related to maternal care (antenatal care [ANC] and facility delivery) and their accumulation during pregnancy and childbirth. Secondly, it explores the mechanisms underlying the association between socio-economic position (SEP) and maternal health-seeking behaviours. Thirdly, it examines the effectiveness of targeting of free public ANC and delivery care. METHODS: Data from the 2008 Demographic and Health Survey were used to capture two latent constructs of SEP: individual socio-cultural capital and household-level economic capital. These variables were entered into an adjusted mediation model, predicting twelve dimensions of maternal health-seeking; including any ANC, private ANC, first ANC visit in first trimester, regular ANC (four or more visits during pregnancy), facility delivery, and private delivery. ANC and delivery care costs were examined separately by provider type (public or private). RESULTS: While 74.2% of women with a birth in the 5-year recall period obtained any ANC and 72.4% delivered in a facility, only 48.8% obtained the complete maternal care package (timely and regular facility-based ANC as well as facility delivery) for their most recent live birth. Both socio-cultural capital and economic capital were independently positively associated with receiving any ANC and delivering in a facility. The strongest direct effect of socio-cultural capital was seen in models predicting private provider use of both ANC and delivery. Despite substantial proportions of women using public providers reporting receipt of free care (ANC: 38%, delivery: 24%), this free-of-charge public care was not effectively targeted to women with lowest economic resources. CONCLUSIONS: Socio-cultural capital is the primary mechanism leading to inequalities in maternal health-seeking in Egypt. Future studies should therefore examine the objective and perceived quality of care from different types of providers. Improvements in the targeting of free public care could help reduce the existing SEP-based inequalities in maternal care coverage in the short term