Search results for: in vivo/vitro exposure

Authors: Jagdish S. Patel, Piyush Chudasama

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Context: Over-expression of P-glycoprotein (P-gp) plays critical role in absorption of many drug candidates which results into lower bioavailability of the drug. P-glycoprotein also over expresses in many pathological conditions like diabetes, affecting the drug therapy. Modulation of P-gp expression using inhibitors can help in designing novel formulation enhancing the bioavailability of the drug in question. Objectives: The main focus of the study was to develop advanced glycation end products (AGEs) induced P-gp over expression in Caco-2 cells. Curcumin, piperine and epigallocatechin gallate were used to evaluate their P-gp inhibitory action using combinatorial approach. Materials and methods: Methylglyoxal (MG) induced P-gp over expression was checked in Caco-2 cells using real time PCR. P-gp inhibitory effects of the phytochemicals were measured after induction with MG alone and in combination of any two compounds. Cytotoxicity of each of the phytochemical was evaluated using MTT assay. Results: Induction with MG (100mM) significantly induced the over expression of P-glycoprotein in Caco-2 cells after 24 hr. Curcumin, piperine and epigallocatechin gallate alone significantly reduced the level of P-gp within 6 hr of treatment period monitored by real time PCR. The combination of any two phytochemical also down regulated the expression of P-gp in cells. Combinations of Curcumin and epigallocatechin gallate have shown significant down regulation when compared with other two combinations. Conclusions: Combinatorial approach for down regulating the expression of P-gp, in pathological conditions like diabetes, has demonstrated promising approach for therapeutic purpose.

Keywords: p-glycoprotein, curcumin, piperine, epigallocatechin gallate, p-gp inhibition

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Authors: Nourhan G. Sahly, Ahmed Moustafa, Mohamed S. Zaghloul, Tamer Z. Salem

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The gut microbiome plays important roles in the human body that includes but not limited to digestion, immunity, homeostasis and response to some drugs such as chemotherapy and immunotherapy. Its role has also been linked to radiotherapy and associated gastrointestinal injuries, where the microbial dysbiosis could be the driving force for dose determination or the complete suspension of the treatment protocol. Linking the gut microbiota alterations to different cancer treatment protocols is not easy especially in humans. However, enormous effort was exerted to understand this complex relationship. In the current study, we described the gut microbiota dysbiosis in pediatric sarcoma patients, in the pelvic region, with regards to radiotherapy and antibiotics. Fecal samples were collected as a source of microbial DNA for which the gene encoding for V3-V5 regions of 16S rRNA was sequenced. Two of the three patients understudy had experienced an increase in alpha diversity post exposure to 50.4 Gy. Although phylum Firmicutes overall relative abundance has generally decreased, six of its taxa increased in all patients. Our results may indicate the possibility of radiosensitivity or enrichment of the antibiotic resistance of the elevated taxa. Further studies are needed to describe the extent of radiosensitivity with regards to antibiotic resistance.

Keywords: combined radiotherapy and chemotherapy, gut microbiome, pediatric cancer, radiosensitivity

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Authors: Sunit Kumar Sahoo, Prakash Chandra Senapati

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The main drawback to design drug delivery systems with BCS class II drugs is their low bioavailabilty due to their inherent low permeability characteristics. So the present investigation aspire to develop a self-nanoemulsifying drug delivery system (SNEDDS) of BCS class II anti HIV drug efavirenz (EFZ) using mixtures of non-ionic surfactant mixtures with the main objective to improve the oral bioavailability of said drug. Results obtained from solubility studies of EFZ in various expients utilized for construction of the pseudo ternary phase diagram containing surfactant mixtures. Surfactants in 1:1 combination are used with different co-surfactants in different ratio to delineate the area of monophasic region of the pseudo ternary phase diagram. The formulations which offered positive results in different thermodynamic stability studies were considered for percentage transmittance and turbidity analysis. The various characterization studies like the TEM analysis of post diluted SNEDDS formulations r confirmed the size in nanometric range (below 50 nm) and FT-IR studies confirmed the intactness of the drug the in the preconcentrate. The in vitro dissolution profile of SNEDDS showed that 80% drug was released within 30 min in case of optimized SNEDDS while it was approximately 18.3 % in the case of plain drug powder.. The Pharmacokinetic study using rat model revealed a 2.63 fold increase in AUC (0-∞) in comparison to plain EFZ suspension. The designed delivery system illustrated the confidence in creating a formulation of EFZ with enhanced bioavailability for better HIV treatment.

Keywords: efavirenz, self-nanoemulsifying, surfactant mixture, bioavailability

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Authors: Mensah-Akoto Julius, Kenichi Matsui

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This paper examines the impact of COVID-19 on waste management workers in Ghana. A questionnaire survey was conducted among 60 waste management workers in Accra metropolis, the capital region of Ghana, to understand the impact of the COVID-19 pandemic on waste generation, workers’ safety in collecting solid waste, and service delivery. To find out correlations between the pandemic and safety of waste management workers, a regression analysis was used. Regarding waste generation, the results show the pandemic led to the highest annual per capita solid waste generation, or 3,390 tons, in 2020. Regarding the safety of workers, the regression analysis shows a significant and inverse association between COVID-19 and waste management services. This means that contaminated wastes may infect field workers with COVID-19 due to their direct exposure. A rise in new infection cases would have a negative impact on the safety and service delivery of the workers. The result also shows that an increase in economic activities negatively impacts waste management workers. The analysis, however, finds no statistical relationship between workers’ service deliveries and employees’ salaries. The study then discusses how municipal waste management authorities can ensure safe and effective waste collection during the pandemic.

Keywords: Covid-19, waste management worker, waste collection, Ghana

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Authors: Kerri L. Surbaugh, Lakmini Y. Mallikarachchi, Jason R. Rohr

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Emerging diseases are key factors in the disconcerting rate of contemporary amphibian declines. The chytrid fungus, Batrachochytrium dendrobatidis (Bd), ranks among the chief pathogenic challenges to vulnerable amphibian populations. Although live Bd can immunosuppress amphibian hosts, amphibian exposure to dead Bd can induce an adaptive immune response, leading to acquired resistance to the pathogen. In this experiment, dose and duration of flash-frozen Bd were manipulated over a variety of life-stages of the Cuban treefrog (Osteopilus septentrionalis) and the magnitude of acquired resistance to the pathogen was quantified via qPCR analyses of spore abundance post subsequent live Bd challenges. It was found that Cuban treefrogs can develop resistance to Bd and that life stage, dose and duration thresholds exist for acquired resistance. This experiment will aid in facilitating the development of a vaccine against Bd which could be used on location and could help curb worldwide amphibian declines associated with this pathogen.

Keywords: acquired resistance, ecoimmunology, emerging infectious disease, fungal host response, fungal pathogen, immunization

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Authors: M. A. Lawal, A. Uzairu, M. S. Sallau

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The presence and bioaccumulation of lead (Pb), cadmium (Cd), and chromium (Cr) in blood, urine, nail, and hair samples of electronic repair technicians in Kaduna-Nigeria were assessed using Fast Sequential Atomic Absorption Spectrophotometry. 10 electronic repair technicians from within Kaduna Metropolis volunteered for the pilot study. The mean blood concentrations of Pb, Cd, and Cr in the subjects were 29.33 ± 4.80, 7.78 ± 10.57, and 24.78 ± 21.77 µg/dL, respectively. The mean urine concentrations of Pb, Cd, and Cr were 24.18 ± 2.98, 6.81 ± 10.05, and 14.78 ± 14.20 µg/dL, respectively. Mean nail metal values of 37.13 ± 4.08, 1.00 ± 1.21, and 18.49 ± 12.71 µg/g were obtained for Pb, Cd, and Cr, respectively while mean hair metal values of 39.41 ± 5.63, 1.09 ± 1.14, and 19.13 ± 11.61 µg/g for Pb, Cd, and Cr, respectively. Positive Pearson correlation coefficients were observed between Pb/Cd, Pb/Cr, and Cd/Cr in all samples and they indicate the metals are likely from the same pollution source. The mean concentrations of the metals in all samples were higher than the WHO, ILO, and ACGIH standards, implying the repairers are likely occupationally exposed and are subject to serious health concerns. Social habits like smoking were found to significantly affect the concentrations of these metals. The level of education, use of safety devices, period of exposure, the nature of electronics and the age of the repairers were also found to remarkably affect the concentrations of the metals.

Keywords: bioaccumulation, electronic repair technicians, heavy metals, occupational hazard

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Authors: Deybith Venegas-Rojas, Jens Budde, Dominik Nörz, Manfred Jücker, Hoc Khiem Trieu

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Microfluidics is a promising approach for biomedicine cell culture experiments with microfluidic bioreactors (MBR), which can provide high precision in volume and time control over mass transport and microenvironments in small-scale studies. Nevertheless, shear stress and oxygen concentration are important factors that affect the microenvironment and then the cell culture. It is presented a novel MBR design in which differences in geometry, shear stress, and oxygen concentration were studied and optimized for cell culture. The aim is to mimic the in vivo condition with biocompatible materials and continuous perfusion of nutrients, a healthy shear stress, and oxygen concentration. The design consists of a capture system of PDMS micropillars which keep cells in place, so it is not necessary any hydrogel or complicated scaffolds for cells immobilization. Besides, the design allows continuous supply with nutrients or even any other chemical for cell experimentation. Finite element method simulations were used to study and optimize the effect of parameters such as flow rate, shear stress, oxygen concentration, micropillars shape, and dimensions. The micropillars device was fabricated with microsystem technology such as soft-lithography, deep reactive ion etching, self-assembled monolayer, replica molding, and oxygen plasma bonding. Eight different geometries were fabricated and tested, with different flow rates according to the simulations. During the experiments, it was observed the effect of micropillars size, shape, and configuration for stability and shear stress control when increasing flow rate. The device was tested with several successful HepG2 3D cell cultures. With this MBR, the aforementioned parameters can be controlled in order to keep a healthy microenvironment according to specific necessities of different cell types, with no need of hydrogels and can be used for a wide range of experiments with cells.

Keywords: cell culture, micro-bioreactor, microfluidics, micropillars, oxygen concentration, shear stress

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Authors: Younus Mohammad, Anita B. Fallah, Ben J. Boyd, Shakila B. Rizwan

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N-acylethanolamines (NAEs) are endogenous lipids, which have neuromodulatory properties. NAEs have shown neuroprotective properties in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic stroke. However, NAEs are eliminated rapidly in vivo by enzymatic hydrolysis. We propose to encapsulate NAEs in liquid crystalline nanoparticles (cubosomes) to increase their biological half-life and explore their therapeutic potential. Recently, we have reported the co-formulation and nanostructural characterization of cubosomes containing the NAE, oleoylethanolamide and a synthetic cubosome forming lipid phytantriol. Here, we report on the formulation of cubosomes with the NAE, linoleoylethanolamide (LEA) as the core cubosome forming lipid. LEA-cubosomes were formulated in the presence of three different steric stabilisers: two brain targeting ligands, Tween 80 and Pluronic P188 and a control, Pluronic F127. Size, morphology and internal structure of formulations were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo–TEM) and small angle X–ray scattering (SAXS), respectively. Chemical stability of LEA in formulations was investigated using high-performance liquid chromatography (HPLC). Cytotoxicity of formulations towards human cerebral microvascular endothelial cell line (hCMEC/D3) was also investigated using an MTT (3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. All cubosome formulations had mean particle size of less than 250 nm and were uniformly distributed with polydispersity indices less than 0.2. Cubosomes produced had a bicontinuous cubic internal structure with an Im3m space group but different lattice parameters, indicating the different modes of interaction between the stabilisers and LEA. LEA in formulations was found to be chemically stable. At concentrations of up to 20 µg/mL LEA in the presence of all the stabilisers, greater than 80% cell viability was observed.

Keywords: blood-brain barrier, cubosomes, linoleoyl ethanolamide, N-acylethanolamines (NAEs)

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Authors: Clotilde Guyon, Nada Jmari, Yen-Chin Li, Jean Denoyel, Noriyuki Fujikado, Christophe Blanchet, David Root, Matthieu Giraud

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Aire induces ectopic expression of a large repertoire of tissue-specific antigen (TSA) genes in thymic medullary epithelial cells (MECs), driving immunological self-tolerance in maturing T cells. Although important mechanisms of Aire-induced transcription have recently been disclosed through the identification and the study of Aire’s partners, the fine transcriptional functions underlied by a number of them and conferred to Aire are still unknown. Alternative cleavage and polyadenylation (APA) is an essential mRNA processing step regulated by the termination complex consisting of 85 proteins, 10 of them have been related to Aire. We evaluated APA in MECs in vivo by microarray analysis with mRNA-spanning probes and RNA deep sequencing. We uncovered the preference of Aire-dependent transcripts for short-3’UTR isoforms and for proximal poly(A) site selection marked by the increased binding of the cleavage factor Cstf-64. RNA interference of the 10 Aire-related proteins revealed that Clp1, a member of the core termination complex, exerts a profound effect on short 3’UTR isoform preference. Clp1 is also significantly upregulated in the MECs compared to 25 mouse tissues in which we found that TSA expression is associated with longer 3’UTR isoforms. Aire-dependent transcripts escape a global 3’UTR lengthening associated with MEC differentiation, thereby potentiating the repressive effect of microRNAs that are globally upregulated in mature MECs. Consistent with these findings, RNA deep sequencing of actinomycinD-treated MECs revealed the increased stability of short 3’UTR Aire-induced transcripts, resulting in TSA transcripts accumulation and contributing for their enrichment in the MECs.

Keywords: Aire, central tolerance, miRNAs, transcription termination

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Authors: A. Bhattacharya, Sanjay Gupta, S. H. Bodakhe

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HbA1c is form of the haemoglobin that is used to measure the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic glycation pathway by hemoglobin's exposure to plasma glucose. In diabetes mellitus, higher amounts of glycated hemoglobin, indicating poorer control of blood glucose levels, have been associated with cardiovascular disease, nephropathy, and retinopathy. Guraku’s basic components are nicotine and jaggery, jaggery is made up of sugarcane so can have a diabetogenic potential which is exacerbated in presence of nicotine. This work had done with the aim to find correlation between Diabetic cataract, HbA1c and Guraku. Subjects were enrolled according to the inclusion and exclusion criteria. In this study total 75 subjects were included. In the study it was found that people consuming Guraku had a high level of HbA1c thus are more prone to the development of diabetic cataract. Male subjects are the more than female subjects. Most of the subjects belong to the lower socioeconomical class and not very educated. It could be concluded that this type of study could be useful in indentifying number of subjects suffering from diabetic cataract whose condition get worse by use of nicotine product like Guraku and preventive measure to be taken in prevention of this type of diabetic complication.

Keywords: diabetic cataract, HbA1c, Guraku, diabetogenic potential

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Authors: Lisnawati Hutagalung

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Background: Low birth weight (LBW) is one cause of newborn death. Babies with low birth weight tend to have slower cognitive development, growth retardation, more at risk of infectious disease event at risk of death. Objective: Identifying risk factors and dominant factors that influence the incidence of LBW in Indonesia. Method: This research used some database of public health such as Google Scholar, UGM journals, UI journals and UNAND journals in 2012-2015. Data were filtered using keywords ‘Risk Factors’ AND ‘Cause LBW’ with amounts 2757 study. The filtrate obtained 5 public health research that meets the criteria. Results: Risk factors associated with LBW, among other environment factors (exposure to cigarette smoke and residence), social demographics (age and socio-economic) and maternal factors (anemia, placental abnormal, nutritional status of mothers, examinations antenatal, preeclampsia, parity, and complications in pregnancy). Anemia and nutritional status become the dominant factor affecting LBW. Conclusions: The risk factors that affect LBW, most commonly found in the maternal factors. The dominant factors are a big effect on LBW is anemia and nutritional status of the mother during pregnancy.

Keywords: low birth weight, anemia, nutritional status, the dominant factor

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Authors: Roman Khanferyan

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Endurance exercises and strenuous muscle activity are accompanied by multiple immune dysfunctions due to the activation of cytokines and chemokines synthesis. This study assesses changes in the synthesis of immune regulatory mediators in elite athletes during endurance sports activity. The concentrations of cytokines/chemokines (IL-2, IL-6, IL-8, IL-10, IL-18, MIP-1 beta, GRO-alpha, RANTES, SDF-1a, VEGF) in sera of hockey athletes (n=33) and in supernatants of 24-h cultivated peripheral blood mononuclear cells (PBMC) of boxers (n=6) assayed by ELISA and Luminex xMAP multiplex assays. Estimation of body composition studied by using bioimpedance technology. The dietary energy consumption per person has been estimated using an album of different sizes of portions of the most frequently consumed foods. It has been demonstrated that endurance sports activity enhances the secretions of most pro- and anti-inflammatory cytokines and chemokines in more than 2-6 fold. The study demonstrated that the high increase of more than 3-4 times in the concentration of IL-18 in sera of athletes (327.86 + 45.67 pg/ml) didn’t correlate with BMI (p=0.040) but demonstrated a low correlation with MMI (p=0.234) and BMR (p=0,231). The opposite impact on the concentration of IL-10 has been demonstrated in athletes. It has been shown a negative correlation between its concentration and BMI (p= - 0.251), MMI (p= - 0.327), and BMR (p= - 0.301). In vitro studies in boxers showed greater amounts of chemokines in the PBMC supernatants, including MIP-1β, GRO-α, RANTES, SDF-1α, and IL-8 (P<0.05). At the same time, healthy controls had greater supernatant levels of MCP-1, Eotaxin, and MIP-1α. The study demonstrated a high correlation between physical activity, usual athletes' diet, and consumption of specialized sports nutrition products.

Keywords: sport nutrition, cytokines, chemokines, endurace exercises

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Authors: Popy Bora, L. C. Bora, A. Bhattacharya, Sehnaz S. Ahmed

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Microbial bioagents, viz., Pseudomonas fluorescens, Bacillus subtilis, and Trichoderma viride were assessed for their ability to suppress grey blight caused by Pestalotiopsis theae, a major disease of tea crop in Assam. The expression of defense-related phytochemicals due to the application of these bioagents was also evaluated. The individual bioagents, as well as their combinations, were screened for their bioefficacy against P. theae in vitro using nutrient agar (NA) as basal medium. The treatment comprising a combination of the three bioagents, P. fluorescens, B. subtilis, and T. viride showed significantly the highest inhibition against the pathogen. Bioformulation of effective bioagent combinations was further evaluated under field condition, where significantly highest reduction of grey blight (90.30%), as well as the highest increase in the green leaf yield (10.52q/ha), was recorded due to application of the bioformulation containing the three bioagents. The application of the three bioformulation also recorded an enhanced level of caffeine (4.15%) and polyphenols (22.87%). A significant increase in the enzymatic activity of phenylalanine ammonia-lyase, peroxidase and polyphenol oxidase were recorded in the plants treated with the microbial bioformulation of the three bioagents. The present investigation indicates the role of microbial agents in suppressing disease, inducing plant defense response, as well as improving the quality of tea.

Keywords: enzymatic activity, grey blight, microbial bioagents, Pestalotiopsis theae, phytochemicals, plant defense, tea

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Authors: Houman Tamaddon, Mehrdad Behnia, Masud Behnia

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An accurate study of blood flow is associated with an accurate vascular pattern and geometrical properties of the organ of interest. Due to the complexity of vascular networks and poor accessibility in vivo, it is challenging to reconstruct the entire vasculature of any organ experimentally. The objective of this study is to introduce an innovative approach for the reconstruction of a full vascular tree from available morphometric data. Our method consists of implementing morphometric data on those parts of the vascular tree that are smaller than the resolution of medical imaging methods. This technique reconstructs the entire arterial tree down to the capillaries. Vessels greater than 2 mm are obtained from direct volume and surface analysis using contrast enhanced computed tomography (CT). Vessels smaller than 2mm are reconstructed from available morphometric and distensibility data and rearranged by applying Murray’s Laws. Implementation of morphometric data to reconstruct the branching pattern and applying Murray’s Laws to every vessel bifurcation simultaneously, lead to an accurate vascular tree reconstruction. The reconstruction algorithm generates full arterial tree topography down to the first capillary bifurcation. Geometry of each order of the vascular tree is generated separately to minimize the construction and simulation time. The node-to-node connectivity along with the diameter and length of every vessel segment is established and order numbers, according to the diameter-defined Strahler system, are assigned. During the simulation, we used the averaged flow rate for each order to predict the pressure drop and once the pressure drop is predicted, the flow rate is corrected to match the computed pressure drop for each vessel. The final results for 3 cardiac cycles is presented and compared to the clinical data.

Keywords: blood flow, morphometric data, vascular tree, Strahler ordering system

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Authors: Staniek Halina

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The inappropriate trace elements supply such as iron(III) and chromium(III) may be risk factors of many metabolic disorders (e.g., anemia, diabetes, as well cause toxic effect). However, little is known about their mutual interactions and their impact on these disturbances. The effects of Cr(III) supplementation with a deficit or excess supply of Fe(III) in vivo conditions are not known yet. The objective of the study was to investigate the combined effect of different Fe(III) levels in the diet and simultaneous Cr(III) supplementation on the Ca distribution in organs in healthy rats. The assessment was based on a two-factor (2x3) experiment carried out on 54 female Wistar rats (Rattus norvegicus). The animals were randomly divided into 9 groups and for 6 weeks, they were fed semi-purified diets AIN-93 with three different Fe(III) levels in the diet as a factor A [control (C) 45 mg/kg (100% Recommended Daily Allowance for rodents), deficient (D) 5 mg/kg (10% RDA), and oversupply (H) 180 mg/kg (400% RDA)]. The second factor (B) was the simultaneous dietary supplementation with Cr(III) at doses of 1, 50 and 500 mg/kg of the diet. Iron(III) citrate was the source of Fe(III). The complex of Cr(III) with propionic acid, also called Cr₃ or chromium(III) propionate (CrProp), was used as a source of Cr(III) in the diet. The Ca content of analysed samples (liver, kidneys, spleen, heart, and femur) was determined with the Atomic Absorption Spectrometry (AAS) method. It was found that different dietary Fe(III) supply as well as Cr(III) supplementation independently and in combination influenced Ca metabolism in healthy rats. Regardless of the supplementation of Cr(III), the oversupply of Fe(III) (180 mg/kg) decreased the Ca content in the liver and kidneys, while it increased the Ca saturation of bone tissue. High Cr(III) doses lowered the hepatic Ca content. Moreover, it tended to decrease the Ca content in the kidneys and heart, but this effect was not statistically significant. The combined effect of the experimental factors on the Ca content in the liver and the femur was observed. With the increase in the Fe(III) content in the diet, there was a decrease in the Ca level in the liver and an increase in bone saturation, and the additional Cr(III) supplementation intensified those effects. The study proved that the different Fe(III) content in the diet, independently and in combination with Cr(III) supplementation, affected the Ca distribution in organisms of healthy rats.

Keywords: calcium, chromium(III), iron(III), rats, supplementation

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Authors: Muhammad Waqar Ashraf

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Selected heavy metals, namely Cu, Zn, Fe, Mn, Cd, Pb, and As, in seven popular varieties of edible vegetable oils collected from Saudi Arabia, were determined by graphite furnace atomic absorption spectrometry (GF-AAS) using microwave digestion. The accuracy of procedure was confirmed by certified reference materials (NIST 1577b). The concentrations for copper, zinc, iron, manganese, lead and arsenic were observed in the range of 0.035 - 0.286, 0.955 - 3.10, 17.3 - 57.8, 0.178 - 0.586, 0.011 - 0.017 and 0.011 - 0.018 µg/g, respectively. Cadmium was found to be in the range of 2.36 - 6.34 ng/g. The results are compared internationally and with standards laid down by world health agencies. A risk assessment study has been carried out to assess exposure to these metals via consumption of vegetable oils. A comparison has been made with safety intake levels for these heavy metals recommended by Institute of Medicine of the National Academies (IOM), US Environmental Protection Agency (US EPA) and Joint FAO/WHO Expert Committee on Food Additives (JECFA). The results indicated that the dietary intakes of the selected heavy metals from daily consumption of 25 g of edible vegetable oils for a 70 kg individual should pose no significant health risk to local population.

Keywords: vegetable oils, heavy metals, contamination, health risk assessment

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Authors: Abhishek Kumar Jain, Anki Jain, Yuvraj Singh Dangi, Brajesh Kumar Tiwari

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The plant Eclipta alba Hassk. (Family: Compositae) contains coumestans (wedelolactone and demethyl wedelolactone) used in liver disorders. The objective of the present investigation was to develop a formulation of these coumestans in combination with the soya phosphatidylcholine (PC), in order to overcome the limitation of absorption and to investigate the protective effect of coumestans–phosphatidylcholine complex (C-PC) on carbon tetrachloride induced acute liver damage in rats. Methanolic extract (ME) of the whole plant of Eclipta alba was fractionated with water and then with ehylacetate. Coumestans were characterized in the ethylacetate fraction of methanolic extract (EFME). The C-PC was prepared by dissolving EFME and PC in 1:1 ratio in dichloromethane and heating at 60°C for 2 h. The C-PC was characterized by DSC and FTIR spectroscopy. In vitro drug release from EFME and C-PC through egg membrane was measured using UV-Visible spectrophotometer. The hepatoprotective activity of C-PC (equivalent to 5.35 and 10.7 mg/kg body weight of EFME), ME 250 mg/kg and EFME 5.35 mg/kg was evaluated by measuring various enzymes level. C-PC significantly provided better protection to the liver by restoring the enzyme levels of SGPT, SGOT, ALP and total billirubin with respect to carbon tetrachloride (CCl4) treated group (P < 0.001). Histopathological studies were also performed. The C-PC provided better protection to rat liver than ME and EFME at similar doses as well as shown significant regeneration of hepatocytes, central vein, intact cytoplasm, and nucleus.

Keywords: hepatotoxicity, wedelolactone, soya phosphatidylcholine, eclipta alba

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Authors: Mostafa Sefidgar, Kaamran Raahemifar, Hossein Bazmara, Madjid Soltani

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The computational methods provide condition for investigation related to the process of drug delivery, such as convection and diffusion of drug in extracellular matrices, and drug extravasation from microvascular. The information of this process clarifies the mechanisms of drug delivery from the injection site to absorption by a solid tumor. In this study, an advanced numerical method is used to solve fluid flow and solute transport equations simultaneously to show how capillary network structure induced by tumor affects drug delivery. The effect of heterogeneous capillary network induced by tumor on interstitial fluid flow and drug delivery is investigated by this multi scale method. The sprouting angiogenesis model is used for generating capillary network induced by tumor. Fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network and fluid flow in normal and tumor tissues. The Starling’s law is used for closing this system of equations and coupling the intravascular and extravascular flows. Finally, convection-diffusion-reaction equation is used to simulate drug delivery. The dynamic approach which changes the capillary network structure based on signals sent by hemodynamic and metabolic stimuli is used in this study for more realistic assumption. The study indicates that drug delivery to solid tumors depends on the tumor induced capillary network structure. The dynamic approach generates the irregular capillary network around the tumor and predicts a higher interstitial pressure in the tumor region. This elevated interstitial pressure with irregular capillary network leads to a heterogeneous distribution of drug in the tumor region similar to in vivo observations. The investigation indicates that the drug transport properties have a significant role against the physiological barrier of drug delivery to a solid tumor.

Keywords: solid tumor, physiological barriers to drug delivery, angiogenesis, microvascular network, solute transport

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Authors: Dong-ping Yuan, Lin Gu, Jun Long, Jie Chen, Ni Jie, Ying-Li Shi

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Endometriosis is a common disease in women of reproductive age, whose classic characteristic is mononuclear cell infiltration into lesions. Shikonin is an anti-inflammatory phytocompound from Lithospermum erythrorhizon, whose potential therapeutic effects for the endometriosis remain unclear. The working hypothesis was that shikonin can inhibit the development of endometriosis by the inhibition of chemotactic effect. Shikonin significantly inhibited the growth of human endometrial tissue implanted into mice (P<0.05). No observable adverse effects were found. The mouse regulated upon activation normal T-cell expressed and secreted (mRANTES) level in peritoneal fluid of animal endometriosis model was higher than that in normal SCID mice (P<0.05), and decreased dramatically after shikonin treatment in a dose-dependent manner (P<0.05). Peritoneal fluid from NOD/SCID mice treated with shikonin inhibited monocytes chemotaxis, which could be abolished by mRANTES antibody. In vitro, shikonin significantly inhibited RANTES expression of U937 cells cultured alone or co-cultured with human methothelail cells and endometrial stromal cells, and inhibited RANTES-induced chemotaxis of U937 cells (P<0.05). The present results suggest that shikonin can inhibit the development of endometriosis by mechanisms that at least include the inhibition of RANTES expression and decreased migration of mononuclear cells to lesions. Shikonin may be a useful and safe new approach for treating endometriosis.

Keywords: endometriosis, shikonin, RANTES chemotaxis

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Authors: Marwa M. Abu-Serie, Marwa M. Eltarahony

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The search for reliable, effective, and safe nanoparticles (NPs) as a treatment for cancer is a pressing priority. In this study, Cu-NPs were fabricated by Streptomyces cyaneofuscatus through simultaneous bioreduction strategy of copper nitrate salt. The as-prepared Cu-NPs subjected to structural analysis; energy-dispersive X-ray spectroscopy, elemental mapping, X-ray diffraction, transmission electron microscopy, and ζ-potential. These biological synthesized Cu-NPs were mixed with disulfiram (DS), forming a nanocomplex of Cu-DS with a size of ~135 nm. The prepared nanocomplex (nanoCu-DS) exhibited higher anticancer activity than that of free complex of DS-Cu, Cu-NPs, and DS alone. This was illustrated by the lowest IC50 of nanoCu-DS (< 4 µM) against human breast and liver cancer cell lines comparing with DS-Cu, Cu-NPs, and DS (~8, 22.98-33.51 and 11.95-14.86, respectively). Moreover, flow cytometric analysis confirmed that higher apoptosis percentage range of nanoCu-DS-treated in MDA-MB 231, MCF-7, Huh-7, and HepG-2 cells (51.24-65.28%) than free complex of Cu-DS ( < 4.5%). Regarding inhibition potency of liver and breast cancer cell migration, no significant difference was recorded between free and nanocomplex. Furthermore, nanoCu-DS suppressed gene expression of β-catenine, Akt, and NF-κB and upregulated p53 expression (> 3, >15, > 5 and ≥ 3 folds, respectively) more efficiently than free complex (all ~ 1 fold) in MDA-MB 231 and Huh-7 cells. Our finding proved this prepared nano complex has a powerful anticancer activity relative to free complex, thereby offering a promising cancer treatment.

Keywords: biologically prepared Cu-NPs, breast cancer cell lines, liver cancer cell lines, nanoCu- disulfiram

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Authors: Clarissa L. de Araujo, Kátia N. Suzuki, Wilson T. V. Machado, Luis F. Bellido, Alfredo V.B. Bellido

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This study aims at contributing to the characterization of the process of biological incorporation of chromium by two benthonic species, the macroalgae Ulva sp. and the aquatic macrophyte Ruppia maritima, to subsidize future activities of monitoring the contamination of aquatic biota. This study is based on laboratory experiments to characterize the incorporation kinetics of the radiotracer ⁵¹Cr in two oxidation states (III and VI), under different salinities (7, 15, and 21 ‰). Samples of two benthonic species were collected on the margins of Rodrigo de Freitas Lagoon (Rio de Janeiro, Brazil), acclimated in the laboratory and subsequently subjected to experiments. In tests with 51Cr (III and IV), it was observed that accumulation of the metal in Ulva sp. has inverse relationship with salinity, while for R. maritima, the maximum accumulation occurs in salinity 21‰. In experiments with Cr(III), increases in the uptake of ion by both species were verified. The activity of Cr(III) was up to 19 times greater than the Cr(VI). As regards the potential for accumulation of metals, a better sensitivity of Ulva sp. for any chromium tri or hexavalent forms was verified, while for the Cr(VI) it will require low salinities and longer exposure (>24h). For R. maritima, the results showed the uptake of Cr(VI) increase along with time (>20h), because this species is more resistant for the hexavalent form and useful for any salinity as well.

Keywords: chromium, Cr-51, macroalgae, macrophyte, uptake

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Authors: Agbor Ekama Prisca Anne

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Current data on the prevalence and psychosocial correlates of sexual violence in the Cameroon is lacking, with the most recent sexual abuse and violence survey dating back to 2001. The current study sought to identify what proportion of University students have experienced sexual violence, if there are sex differences in exposure to different forms of sexual violence, and to what extent different forms of sexual violence are associated with adverse psychosocial outcomes. A nationally representative sample of University students (N = 1,020) completed self-report measures of history of sexual violence and mental health. Approximately one-in-three (34.4%) students experienced some form of sexual violence, including 14.8% who were sexually assaulted (raped) and 31.1% who were sexually harassed. Female students were significantly more likely than men to have experienced all forms of sexual violence (ps < .001), with the exception of sexual assault by teachers or guardian. All forms of sexual violence were associated with an increased likelihood of serious mental health problems, with sexual assault by a teacher associated with several other psychosocial outcomes in life, including education achievement, and behavior disorder. Sexual violence is a common experience in the general population and female students are disproportionately affected (1-in-2 girls versus 1-in-5 boys). Additional resources to increase mental health care among survivors of sexual violence is urgently needed.

Keywords: psychosocial, effects sexual, violence, females, students

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Authors: Pheiroijam Pooja, P. Chinnamuthu

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A novel vertical 1D In2O3/TiO2 nanocolumn (NC) axial heterostructure has been successfully synthesized using Glancing Angle Deposition (GLAD) technique inside E-Beam Evaporator chamber. Field emission scanning electron microscope (FESEM) has been used to evaluate the morphology of the structure grown. The estimated length of In2O3/TiO2 NC is ~250 nm and ~300nm for In2O3 and TiO2 respectively with diameter ~60-90 nm. The surface of the heterostructure is porous in nature which can affect the interfacial wettability properties. The grown structure has been further characterized using X-ray Diffraction (XRD) and UV-Visible absorption measurement. The polycrystalline nature of the sample has been examined using XRD with prominent peaks obtained with phase (101) for anatase TiO2 and (211) for In2O3. Here, 1D axial heterostructure NC thus favors efficient segregation of photo-excited carriers due to their type II band alignment between the constituent materials. Moreover, the 1D nanostructure is known for their large surface area and excellent ionic charge transport property. On exposure to UV light illumination, the surface properties of In2O3/TiO2 NC changes whereby the hydrophobic nature of the heterostructure changes to hydrophilic. As a result, the reversible surface wettability of heterostructure on interaction with UV light can give potential applications as antifogging and self-cleaning surfaces.

Keywords: GLAD, heterostructure, In2O3/TiO2 NC, surface wettability

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Authors: Fatma Y. Meligy

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Objectives: The objectives of this study aimed to isolate and characterize mesenchymal stem cells (MSCs) derived from synovial membrane. Then to assess the potentiality of myogenic differentiation of these isolated MSCs. Methods: The MSCs were isolated from synovial membrane by digestion method. Three adult rats were used. The 5 -azacytidine was added to the cultured cells for one day. The isolated cells and treated cells are assessed using immunoflouresence, flowcytometry, PCR and real time PCR. Results: The isolated stem cells showed morphological aspect of stem cells they showed strong positivity to CD44 and CD90 in immunoflouresence while in CD34 and CD45 showed negative reaction. The treated cells with 5-azacytidine was shown to have positive reaction for desmin. Flowcytometric analysis showed that synovial MSCs had strong positive percentage for CD44(%98)and CD90 (%97) and low percentage for CD34 & CD45 while the treated cells showed positive percentage for myogenic marker myogenin (85%). As regard the PCR and Real time PCR, the treated cells showed positive reaction to the desmin primer. Conclusion: The adult MSCs were isolated successfully from synovial membrane and characterized with stem cell markers. The isolated cells could be differentiated in vitro into myogenic cells. These differentiated cells could be used in auto-replacement of diseased or traumatized muscle cells as a regenerative therapy for muscle disorders and trauma.

Keywords: mesenchymal stem cells, synovial membrane, myogenic differentiation

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Authors: S. Thangapandiyan, S. Miltonprabu

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Fl (Fl) exposure engenders neurodegeneration and induces oxidative stress in the brain. The Neuroprotective role of EGCG on oxidative stress-mediated neurotoxicity in Fl intoxicated rat hippocampus has not yet been explored so far. Hence, the present study is focused on witnessing whether EGCG (40mg/kg) supplementation prevents Fl induced oxidative stress in the brain of rats with special emphasis on the hippocampus. Fl (25mg/kg) intoxication for four weeks in rats showed an increase in Fl concentration along with the decrease the AChE, NP, DA, and 5-HT activity in the brain. The oxidative stress markers (ROS, TBARS, NO, and PC) were significantly increased with decreased enzymatic (SOD, CAT, GPx, GR, GST, and G6PD) and non-enzymatic antioxidants (GSH, TSH, and Vit.C) in Fl intoxicated rat hippocampus. Moreover, Fl intoxicated rats exhibited an intrinsic and extrinsic pathway mediated apoptosis in the hippocampus of rats. Fl intoxication significantly increased the DNA damage as evidenced by increased DNA fragmentation. Furthermore, the toxic impact of Fl on hippocampus was also proved by the immunohistochemical, histological, and ultrastructural studies. Pre-administration of EGCG has significantly protected the Fl induced oxidative stress, biochemical changes, cellular apoptotic, and histological alternations in the hippocampus of rats. In conclusion, EGCG supplementation significantly attenuated the Fl induced oxidative stress mediated neurotoxicity via its free radical scavenging and antioxidant activity.

Keywords: brain, hippocampal, NaF, ROS, EGCG

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Authors: Edward Sarich, Jack Ryan

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In contrast to learning new vocabulary incidentally in one’s first language, foreign language vocabulary is often acquired purposefully, because a lack of natural exposure requires it to be studied in an artificial environment. It follows then that foreign language vocabulary may be more efficiently acquired if it is purpose-driven, or linked to a clear and desirable outcome. The research described in this paper relates to the early stages of what is seen as a long-term effort to measure the effectiveness of a methodology for purpose-driven foreign language vocabulary instruction, specifically by analyzing whether directed studying from high-frequency vocabulary lists leads to an improvement in Test of English for International Communication (TOEIC) scores. The research was carried out in two sections of a first-year university English composition class at a small university in Japan. The results seem to indicate that purposeful study from relevant high-frequency vocabulary lists can contribute to raising TOEIC scores and that the test preparation methodology used in this study was thought by students to be beneficial in helping them to prepare to take this high-stakes test.

Keywords: corpus vocabulary, language asssessment, second language vocabulary acquisition, TOEIC test preparation

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Authors: Kaitlyn Deierlein, Janet Lydecker

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Stereotypes surrounding anorexia nervosa are that the illness is commonly perceived as a self-inflicted disorder influenced by controlling parents, vanity, and cultural pressures. According to the authors' best knowledge minimal research has examined interactions with other factors, including gender and racial stereotypes involving this disorder. A common stereotype of this disease is that it mainly only affects Caucasian women and is very rarely seen in any other ethnicity. Previous literature has failed to investigate how visual body image and ethnic stereotypes affect the mental health of different ethnic groups, how various cultures impact the type of anorexia nervosa in the patient, and the different stereotypes associated with their eating disorder. Participants completed a pre-test questionnaire with vignettes, an image exposure portion, and a post-test questionnaire, which will all be evaluated and analyzed by ANOVA t-test and SPSS. Results showed that participants picked Caucasian females as more likely to have anorexia nervosa than those of Asian, Latin American, or African American descent subjects in both picture identification and vignettes. Future research should be conducted to further the results of this study by examining differences between gender stereotypes with anorexia nervosa as well as how sexuality has a role in perception.

Keywords: anorexia nervosa, ethnicity, stereotypes, eating disorders, perception

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Authors: Ncoza Dlova, Tivani Mashamba-Thompson

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Garcinia livingstonei (Clusiaceae) extracts, morelloflavone- 7″- sulphate and sargaol were shown to be effective against hyper-pigmentation through inhibition of tyrosinase enzyme, in vitro . The aim of this study is to elucidate the structural mechanism through which morelloflavone- 7″- sulphate and sargaol binds human tyrosinase. Implementing a homology model to construct a tyrosinase model using the crystal structure of a functional unit from Octopus hemocyanin (PDB: 1JS8) as a reference template enabled us to create a human tyrosinase model. Molecular dynamics and binding free energy calculations were optimized to enable molecular dynamics simulation of the copper dependent inhibitors. Results show the importance of the hydrogen bond formation morelloflavone- 7″- sulphate and sargaol between compound and active site residues. Both complexes demonstrated the metallic coordination between compound and arginine residue as well as copper ions within the active site. The comprehensive molecular insight gained from this study should be vital in understanding the binding mechanism morelloflavone- 7″- sulphate and sargaol. Moreover, these results will assist in the design of novel of metal ion dependent enzyme inhibitors as potential anti-hyper-pigmentation disorder therapies.

Keywords: hyper-pigmentation disorders, dyschromia African skin, morelloflavone- 7″- sulphate, sagoal

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Authors: Ibrahim Bashayreh Al-Bashtawy Mohammed, Al-Azzam Manar Ahmad Rawashda, Abdul-Monim Batiha Mohammad Sulaiman

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Background: Workplace violence against emergency department staff (EDS) is considered one of the most common and widespread phenomena of violence. Purpose: The purpose of this research is to determine the incidence rates of workplace violence and the predicting factors of violent behaviors among emergency departments’ staff in Jordanian hospitals. Methods: A cross-sectional study was used to investigate workplace violence towards a convenience sample of 355 emergency staff departments from 8 governmental and 4 private Jordanian hospitals. Data were collected by a self-administered questionnaire that was developed for the purpose of this study. Results: 72% of workers in emergency departments within Jordanian hospitals are exposed to violent acts, and that patients and their relatives are the main source of workplace violence. The contributing factors as reported by the participants were related to overcrowding, lack of resources, staff shortages, and the absence of effective antiviolence policies. Conclusions/implications for Practice: Policies and legislation regarding violence should be instituted and developed, and emergency department staff should be given training on how to deal with violent incidents, as well as on violence-management policies.

Keywords: Jordan, emergency staff department, workplace violence, community health

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Authors: Kiran Roat, Bhanupriya Sanger, Gayatri Swarnakar

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Amphistomiasis disease is the main health problem throughout of the world and responsible for great economic losses to cattle industries, mostly to poor cattle farmers in developing countries. Among the rumen parasites, the Paramphistomum cervi were collected from the rumen of freshly slaughtered buffalo for the further treatment process. Trigonella foenum-graecum is commonly known as methi and fenugreek and their seeds are known for their therapeutic value. The present study was considered to evaluate in vitro efficacy of aqueous extract of Trigonella foenum-graecum on P. cervi. 130 mg/ml concentration of aqueous extract shows total mortality of P. cervi at 5 hours. The ultrastructural surface topography of untreated animal was compared with a treated animal by scanning electron microscope (SEM). The body of untreated P. cervi in conical shape, tegumental surface is highly ridged with transverse folds and present abundance number of papillaes. Observations demonstrated that the body of treated P. cervi become shrunken & elongated. Treated parasite shows the deep breakage in tegument and the disappearance of tegumental folds & papillae. Severe blebs formations have been found. Above findings, it can be concluded that the seeds of Trigonella foenum-graecum can be used as an anthelminthic agent to eliminate P. cervi from the body of buffalo.

Keywords: Paramphistomum cervi, Trigonella foenum-graecum, scanning electron microscope, buffalo

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