Search results for: extremely drug- resistant

Authors: Dalia Jomehpour, Sara Sheikhlary, Esmaeil Heydari, Mohammad Hossien Majles Ara

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In this study, we report fulvic acid-coated iron oxide nanoparticles of 10.7 ± 2.7 nm size, which serve to inhibit amyloid fibrillation formation. Although the effect of fulvic acid on tau fibrils was investigated, to our best knowledge, its inhibitory impacts on amyloid aggregation formation have been assessed neither in-vitro nor in-vivo. On the other hand, iron oxide nanoparticles exhibit anti-amyloid activity on their own. This study investigates the inhibitory effect of fulvic acid coated iron oxide nanoparticles on amyloid aggregations formed from the commonly used in-vitro model, lysozyme from chicken egg white. FESEM, XRD, and FTIR characterization confirmed that fulvic acid was coated onto the surface of the nanoparticles. The inhibitory effects of the fulvic acid coated iron oxide nanoparticles were verified by Thioflavin T assay, circular dichroism (CD), and FESEM analysis. Furthermore, the toxicity of the nanoparticles on the neuroblastoma SH-SY5Y human cell line was assessed through an MTT assay. Our results indicate that fulvic acid coated iron oxide nanoparticles can efficiently inhibit the formation of amyloid aggregations while exhibiting negligible in-vitro toxicity; thus, they can be used as anti-amyloid agents in the development of the potential drug for neurodegenerative diseases.

Keywords: Alzheimer’s disease, fulvic acid coated iron oxide nanoparticles, fulvic acid, amyloid inhibitor, polyphenols

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Authors: Mohammad Javad Behzadnia, Hamidreza Javadzadeh

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Background: Pain management is essential to surmounting multi-injured people in an overcrowded emergency setting. Its role would be more apparent when the physician encounters a mass casualty in a war zone or even a military prehospital. Having sedative and analgesic properties, rapid onset and offset effects, and maintaining the cardiovascular and respiratory contain are the main reason for selecting Ketamine as a good choice in the war zone. Methods: In a prospective interventional study in a war zone, we have selected and followed two groups of casualties for pain management. All were men with an average age of 26.6±8 y/o and 27.5 ±7 y/o in A and B groups, respectively. Group A received only Ketamine and Group B received Ketamine and diazepam. Results: This study showed that all of the injured patients who received Ketamine had experienced some agitation, and they may finally need benzodiazepines for sedation, but in group B that received benzodiazepine before or simultaneous with Ketamine, the agitation was significantly reduced. (P Value ≤0.05) Conclusion: Various factors may affect pain score and perception; patients' culture, mental health, previous drug usage, and addiction could alter the pain score in similar situations. It seems that the significant agitation is due to catecholamine release in stressful Moments of the battlefield. Accordingly, this situation could be exacerbated due to ketamine properties. Nonetheless, as a good choice in the war zone, Ketamine is now recommended to combine with benzodiazepines for procedural sedation and analgesia (PSA).

Keywords: battlefield, ketamine, benzodiazepine, pain control

Procedia PDF Downloads 102

Authors: Yan Bachtiar Muslih, Hangga Wijaya, Trio Fani, Putri Agustin

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Demand of Energy in Indonesia always increases 5-6% a year, but production of conventional energy always decreases 3-5% a year, it means that conventional energy in 20-40 years ahead will not able to complete all energy demand in Indonesia, one of the solve way is using unconventional energy that is gas hydrate, gas hydrate is gas that form by biogenic process, gas hydrate stable in condition with extremely depth and low temperature, gas hydrate can form in two condition that is in pole condition and in deep-sea condition, wherein this research will focus in gas hydrate that association with methane form methane hydrate in deep-sea condition and usually form in depth between 150-2000 m, this research will focus in process of methane hydrate formation that is biogenic process and the important role of deep-sea sediment so can produce accumulation of methane hydrate, methane hydrate usually will be accumulated in find sediment in deep-sea environment with condition high-pressure and low-temperature this condition too usually make methane hydrate change into white nodule, methodology of this research is geology field work and laboratory analysis, from geology field work will get sample data consist of 10-15 samples from Kerek Formation outcrops as random for imagine the condition of deep-sea environment that influence the methane hydrate formation and also from geology field work will get data of measuring stratigraphy in outcrops Kerek Formation too from this data will help to imagine the process in deep-sea sediment like energy flow, supply sediment, and etc, and laboratory analysis is activity to analyze all data that get from geology field work, the result of this research can used to exploration activity of methane hydrate in another prospect deep-sea environment in Indonesia.

Keywords: methane hydrate, deep-sea sediment, kerek formation, sub-basin of kendeng, central java, Indonesia

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Authors: Debasish Pradhan, Shaktiprasad Pradhan, Rakesh Kumar Pradhan, Gitanjali Tripathy

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Suppressors of cytokine signalling (SOCS1), a newly indentified antiapoptotic molecule is a downstream effector of the receptor tyrosine kinase-Ras signalling pathway. The current study has uncovered that SOCS1 may have wide and imperative capacities, particularly because of its close correlation with malignant tumors. To investigate the impact of SOCS1 on MDR, we analyzed the expression of P-gp and SOCS1 by immunohistochemistry and found there was a positive correlation between them. At that point, we effectively interfered with RNA translation by the contamination of siRNA of SOCS1 into MCF7/ADM breast cancer cell lines through a lentivirus, and the expression of the target gene was significantly inhibited. After RNAi, the drug resistance was reduced altogether and the expression of MDR1 mRNA and P-gp in MCF7/ADM cell lines demonstrated a significant decrease. Likewise, the expression of P53 protein increased in a statistically significant manner (p ≤ 0.01) after RNAi exposure. Moreover, flow cytometry analysis uncovers that cell cycle and anti-apoptotic enhancing capacity of cells changed after RNAi treatment. These outcomes proposed SOCS1 may take part in breast cancer MDR by managing MDR1 and P53 expression, changing cell cycle and enhancing the anti-apoptotic ability.

Keywords: breast cancer, multidrug resistance, SOCS1 gene, MDR1 gene, RNA interference

Procedia PDF Downloads 356

Authors: Mae C. Pavilario

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This study employs a sequential explanatory mixed method. Quantitatively it investigated the profile of grade VII students. Qualitatively, the prevailing contextual variables that affect their frustration-level were sought based on their perspective and that of their parents and teachers. These students were categorized as frustration-level in reading based on the data on word list of the Philippine Informal Reading Inventory (Phil-IRI). The researcher-made reading factor instrument translated to local dialect (Hiligaynon) was subjected to cross-cultural translation to address content, semantic, technical, criterion, or conceptual equivalence, the open-ended questions, and one unstructured interview was utilized. In the profile of the 26 participants, the 12 males are categorized as grade II and grade III frustration-levels. The prevailing contextual variables are personal-“having no interest in reading”, “being ashamed and fear of having to read in front of others” for extremely high frustration level; social environmental-“having no regular reading schedule at home” for very high frustration level and personal- “having no interest in reading” for high frustration level. Kendall Tau inferential statistical tool was used to test the significant relationship in the prevailing contextual variables that affect frustration-level readers when grouped according to perspective. Result showed that significant relationship exists between students-parents perspectives; however, there is no significant relationship between students’ and teachers’, and parents’ and teachers’ perspectives. The themes in the narratives of the participants on frustration-level readers are existence of speech defects, undesirable attitude, insufficient amount of reading materials, lack of close supervision from parents, and losing time and focus on task. Intervention was designed.

Keywords: contextual variables, frustration-level readers, perspective, inquiry

Procedia PDF Downloads 164

Authors: Carmela Perta

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In Italy the coexistence of standard language, its varieties and different minority languages - historical and migration languages - has been a way to study language contact in different directions; the focus of most of the studies is either the relations among the languages of the social repertoire, or the study of contact phenomena occurring in a particular structural level. However, studies on contact facts in relation to a given sociolinguistic situation of the speech community are still not present in literature. As regard the language level to investigate from the perspective of contact, it is commonly claimed that the lexicon is the most volatile part of language and most likely to undergo change due to superstrate influence, indeed first lexical features are borrowed, then, under long term cultural pressure, structural features may also be borrowed. The aim of this paper is to analyse language contact in two historical minority communities where Francoprovençal is spoken, in relation to their sociolinguistic situation. In this perspective, firstly lexical borrowings present in speakers’ speech production will be examined, trying to find a possible correlation between this part of the lexicon and informants’ sociolinguistic variables; secondly a possible correlation between a particular community sociolinguistic situation and lexical borrowing will be found. Methods used to collect data are based on the results obtained from 24 speakers in both the villages; the speaker group in the two communities consisted of 3 males and 3 females in each of four age groups, ranging in age from 9 to 85, and then divided into five groups according to their occupations. Speakers were asked to describe a sequence of pictures naming common objects and then describing scenes when they used these objects: they are common objects, frequently pronounced and belonging to semantic areas which are usually resistant and which are thought to survive. A subset of this task, involving 19 items with Italian source is examined here: in order to determine the significance of the independent variables (social factors) on the dependent variable (lexical variation) the statistical package SPSS, particularly the linear regression, was used.

Keywords: borrowing, Francoprovençal, language change, lexicon

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Authors: Gabriele Ciasca, Tanya E. Sassun, Eleonora Minelli, Manila Antonelli, Massimiliano Papi, Antonio Santoro, Felice Giangaspero, Roberto Delfini, Marco De Spirito

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Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by a diffuse infiltration of neoplastic cells into the brain parenchyma. Although rarely considered, mechanical cues play a key role in the infiltration process that is extensively mediated by the tumor microenvironment stiffness and, more in general, by the occurrence of aberrant interactions between neoplastic cells and the extracellular matrix (ECM). Here we provide a nano-mechanical characterization of the viscoelastic response of human GBM tissues by indentation-type atomic force microscopy. High-resolution elasticity maps show a large difference between the biomechanics of GBM tissues and the healthy peritumoral regions, opening possibilities to optimize the tumor resection area. Moreover, we unveil the nanomechanical signature of necrotic regions and anomalous vasculature, that are two major hallmarks useful for glioma staging. Actually, the morphological grading of GBM relies mainly on histopathological findings that make extensive use of qualitative parameters. Our findings have the potential to positively impact on the development of novel quantitative methods to assess the tumor grade, which can be used in combination with conventional histopathological examinations. In order to provide a more in-depth description of the role of mechanical cues in tumor progression, we compared the nano-mechanical fingerprint of GBM tissues with that of grade-I (WHO) meningioma, a benign lesion characterized by a completely different growth pathway with the respect to GBM, that, in turn hints at a completely different role of the biomechanical interactions.

Keywords: AFM, nano-mechanics, nanomedicine, brain tumors, glioblastoma

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Authors: Bashar Al-Sabti, Jehad Harbali

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Background: Pyridine is a reactive base that might be used in preparing sitagliptin. International Agency for Research on Cancer classifies pyridine in group 2B; this classification means that pyridine is possibly carcinogenic to humans. Therefore, pyridine should be monitored at the allowed limit in sitagliptin pharmaceutical ingredients. Objective: The aim of this study was to develop a novel ultra high performance liquid chromatography mass spectrometry (UHPLC-MS) method to estimate the quantity of pyridine impurity in sitagliptin pharmaceutical ingredients. Methods: The separation was performed on C8 shim-pack (150 mm X 4.6 mm, 5 µm) in reversed phase mode using a mobile phase of water-methanol-acetonitrile containing 4 mM ammonium acetate in gradient mode. Pyridine was detected by mass spectrometer using selected ionization monitoring mode at m/z = 80. The flow rate of the method was 0.75 mL/min. Results: The method showed excellent sensitivity with a quantitation limit of 1.5 ppm of pyridine relative to sitagliptin. The linearity of the method was excellent at the range of 1.5-22.5 ppm with a correlation coefficient of 0.9996. Recoveries values were between 93.59-103.55%. Conclusions: The results showed good linearity, precision, accuracy, sensitivity, selectivity, and robustness. The studied method was applied to test three batches of sitagliptin raw materials. Highlights: This method is useful for monitoring pyridine in sitagliptin during its synthesis and testing sitagliptin raw materials before using them in the production of pharmaceutical products.

Keywords: genotoxic impurity, pyridine, sitagliptin, UHPLC -MS

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Authors: Yu Zhang, Il Kim

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Polypeptides with defined peptide sequences illustrate the power of remarkable applications in drug delivery, tissue engineering, sensing and catalysis. Especially the cyclic polypeptides, the distinctive topological architecture imparts many characteristic properties comparing to linear polypeptides. Here, a facile and highly efficient strategy for the synthesis of linear and cyclic polypeptides is reported using N-heterocyclic carbenes (NHCs)-mediated ring-opening polymerization (ROP) of α-amino acid N-carboxyanhydrides (NCA) in the presence or absence of primary amine initiator. The polymerization proceeds rapidly in a quasi-living manner, allowing access to linear and cyclic polypeptides of well-defined chain length and narrow polydispersity, as evidenced by nuclear magnetic resonance spectrum (1H NMR and 13C NMR spectra) and size exclusion chromatography (SEC) analysis. The cyclic architecture of the polypeptides was further verified by matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectra (MALDI-TOF MS) and electrospray ionization (ESI) mass spectra, as well as viscosity studies. This approach can also simplify workup procedures and make bulk scale synthesis possible, which thereby opens avenues for practical uses in diverse areas, opening up the new generation of polypeptide synthesis.

Keywords: α-amino acid N-carboxyanhydrides, living polymerization, polypeptides, N-heterocyclic carbenes, ring-opening polymerization

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Authors: Mária Csernoch, Piroska Biró

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The legends about “user-friendly” and “easy-to-use” birotical tools (computer-related office tools) have been spreading and misleading end-users. This approach has led us to the extremely high number of incorrect documents, causing serious financial losses in the creating, modifying, and retrieving processes. Our research proved that there are at least two sources of this underachievement: (1) The lack of the definition of the correctly edited, formatted documents. Consequently, end-users do not know whether their methods and results are correct or not. They are not aware of their ignorance. They are so ignorant that their ignorance does not allow them to realize their lack of knowledge. (2) The end-users’ problem-solving methods. We have found that in non-traditional programming environments end-users apply, almost exclusively, surface approach metacognitive methods to carry out their computer related activities, which are proved less effective than deep approach methods. Based on these findings we have developed deep approach methods which are based on and adapted from traditional programming languages. In this study, we focus on the most popular type of birotical documents, the text-based documents. We have provided the definition of the correctly edited text, and based on this definition, adapted the debugging method known in programming. According to the method, before the realization of text editing, a thorough debugging of already existing texts and the categorization of errors are carried out. With this method in advance to real text editing users learn the requirements of text-based documents and also of the correctly formatted text. The method has been proved much more effective than the previously applied surface approach methods. The advantages of the method are that the real text handling requires much less human and computer sources than clicking aimlessly in the GUI (Graphical User Interface), and the data retrieval is much more effective than from error-prone documents.

Keywords: deep approach metacognitive methods, error-prone birotical documents, financial losses, human and computer resources

Procedia PDF Downloads 382

Authors: Ahmed Jibrin Uttu, Maimuna Waziri

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The root bark of Glossonema boveanum (Decne), a member of Apocynaceae family, is used by traditional medicine practitioner to treat urinary and respiratory tract infections, bacteremia, typhoid fever, bacillary dysentery, diarrhea and stomach pain. This present study aims to validate the medicinal claims ascribed to the root bark of the plant. Preliminary phytochemical study of the root bark extracts (n-hexane, ethyl acetate, chloroform and methanol extracts) showed the presence of alkaloids, carbohydrates, steroids, triterpenes, cardiac glycosides, saponins, tannins and flavonoids. Antimicrobial study of the extracts showed activities against Staphylococus aureus, Bacillus subtilis, Salmonella typhii, Shigella dysenteriae, Escherichia coli, Enterobacter cloacae, Streptococcus agalactiae and Candida albicans while Micrococcus luteus, Pseudomonas aeruginosa and Klebsiella Pneumoniae showed resistance to all the extracts. The inhibitory effect was compared with the standard drug ciprofloxacin and fluconazole. MIC and MBC for both extracts were also determined using the tube dilution method. This study concluded that the root bark of G. boveanum, used traditionally as a medicinal plant, has antimicrobial activities against some causative organisms.

Keywords: Glossonema boveanum (Decne.), phytochemical, antimicrobial, minimum inhibitory concentration, minimum bactericidal concentration

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Authors: Salem Abdalla

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Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

Procedia PDF Downloads 240

Authors: S. Mondal, L. M. Olsen-Kettle, L. Gross

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Fracture propagation and damage evolution are extremely important for many industrial applications including mining industry, composite materials, earthquake simulations, hydraulic fracturing. The influence of pre-existing flaws and rock heterogeneity on the processes and mechanisms of rock fracture has important ramifications in many mining and reservoir engineering applications. We simulate the damage evolution and fracture propagation in an isotropic sandstone specimen containing a pre-existing 3-D surface flaw in different configurations under uniaxial compression. We apply a damage model based on the unified strength theory and solve the solid deformation and damage evolution equations using the Finite Element Method (FEM) with tetrahedron elements on unstructured meshes through the simulation software, eScript. Unstructured meshes provide higher geometrical flexibility and allow a more accurate way to model the varying flaw depth, angle, and length through locally adapted FEM meshes. The heterogeneity of rock is considered by initializing material properties using a Weibull distribution sampled over a cubic grid. In our model, we introduce a length scale related to the rock heterogeneity which is independent of the mesh size. We investigate the effect of parameters including the heterogeneity of the elastic moduli and geometry of the single flaw in the stress strain response. The generation of three typical surface cracking patterns, called wing cracks, anti-wing cracks and far-field cracks were identified, and these depend on the geometry of the pre-existing surface flaw. This model results help to advance our understanding of fracture and damage growth in heterogeneous rock with the aim to develop fracture simulators for different industry applications.

Keywords: finite element method, heterogeneity, isotropic damage, uniaxial compression

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Authors: Sifiso Vilakazi, Lerato Mzenzi

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BACKGROUND :- Human mind is a double-edged sword, it is both arduous and obtuse, vague and explicit. The neuroscience of brain has baffled all and left none. In this labyrinth, a novel neurotransmitter has set its foot. D-Aspartic acid, which has been established in rats and animals’ brain as a neurochemical in controlling behaviour, aggression, fertility, cognition and memory is set to formulate a new benchmark as a marker among suicidal and accidental death victims. Without losing sight of the fact, we have endeavoured to dig out the biochemical relation behind suicide in our research. We in our research have exerted to decipher the puzzle among humans for D-Aspartic acid using HPLC. METHODS:- We have taken 30 samples each of pre-frontal cortex of brain from suicide and road traffic accidents victims for our case-control research to establish brain D-Aspartic acid level using HPLC as a marker for suicide. RESULTS:- By using Independent/Unpaired T-Test Analysis:- The two-tailed P value is less than 0.0044. MEAN (mMOL/mL/G) for D-Aspartic acid in control is 24.2737±7.5958 and for cases is 19.5540±4.2647. By conventional criteria, this difference is considered to be extremely statistically significant. CONCLUSION:- (1) Brain D-Aspartic acid has an effect in the act of suicide and its values show a large drop before the act of suicide is commenced as compared to road traffic accidents which correlates with the study where D-AA was studied as a novel endogenous neurotransmitter in case of mental health disorders in humans, though never studied on suicide victims, likely getting it reference from research occurring on rats where it was discovered that D-AA plays a role in cognition, personality development, thought process, aggression. (2)The other study which was related to humans and signified the role of D-AA in reproduction, where low D-AA leads to infertility and depression and hence providing the much needed proof of role of D-AA in mental health disorders and suicide, and subsequently to the act of suicide.

Keywords: green energy, policy, technology, implementation

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Authors: Joe Modise, Bamidel Joseph Okoli, Nas Molefe, Imelda Ledwaba

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The present study describes the chemical profile and antioxidant potential of the stem bark of Acacia decurrens. The methanol fraction of A. decurrens stem bark gave the highest yield (20 %), while the hexane fraction had the lowest yield (0.2 %). The GC-MS spectra of the hexane, chloroform and ethyl acetate fractions confirm the presence of fifty two major compounds and the ICP-OES analysis of the stem bark was found to contain Co(0.41), Zn(1.75), Mn(3.69), Ca(8.67), Ni(10.54), Mg(12.98), Cr(24.38), K(47.88), Fe(154.62) ppm; which is an indication of hyper-accumulation capacity. The UV-Visible spectra of showed four absorption maxima for hexane fraction at 665 (0.028), 410 (0.116), 335 (0.278) and 250 (0.007) nm, three for chloroform fraction at 665 (0.028), 335 (0.278) and 250 (0.007) nm , three for ethyl acetate fraction at 665 (0.070), 390 (0.648) and 345 (0.663) nm and three for methanol fraction at 385 (0.508), 310 (0.886) and 295 (0.899) nm respectively. Quantitative phytochemical screening indicated that the alkaloid (0.6-3.3) % and saponins (5.1-8.6) % contents of the various fractions were significantly lower than the tannin (30.9-55.8) mg TAE/g, steroid(13.92-41.2) %, phenol (40.6-65.5) mgGAE/g and flavonoids (210.2 -284.9) mg RUE/g contents. The antioxidant activity of the fractions was analysed by different methods and revealed good to moderate antioxidant potential with different IC50 values viz. (42.2-49.6) mg/mL for ABTS and (37.8-75.0) μg/ml for DPPH respectively, compared to standard antioxidants. Based on obtained results, the A.decurrens stem bark fractions can be a source of safe, sustainable natural antioxidant drug and can be exploited as a source of controlled green-heavy metal cleaner.

Keywords: Acacia decurrens, antioxidant, DPPH, ABTS, hyperaccumulation, Menstruum, ICP-OES, GC-MS, UV/visible

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Authors: Uzma Saqib, Mirza S. Baig

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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.

Keywords: drug design, Nur77, MYD88, inflammation

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Authors: Elham Zarenezhad, Ali Zarenezhad, Mehdi Mardkhoshnood

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We described the synthesis and biological study of O-oxime ethers having a-amino acid residues as new analogs of IPS-339. In this synthesis, the reaction of fluorene O-oxime with epichlorohydrin or epibromohydrin afforded the corresponding O-oxime ether adducts. The N-alkylation of valine amino acid with O-oxime ether adducts led to the synthesis of new analogs of IPS-339. The cardiovascular properties of the compound have been studied. In this regard, six clinically healthy same sex mongrel dogs were examined. The dogs were randomly divided into 3 groups of two members. 1 groups received 2 mg kg-1 body weight of compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) intravenously, whereas group 2 and 3 received only DMSO–water (distil.) and propranolol (Inderal) (2 mg kg-1), respectively. The electrocardiograph (ECG) was recorded with lead II. The recording was run successively by 5 min time interval on each dog before, simultaneously, and after compound infusion. Data after administration were taken from normal sinus beats that were closely related to the arrhythmias whenever they occurred. In general, no detectable arrhythmia was observed in all ECG records regardless of increasing the heart rate that likely caused by stress origin from invasive procedure just after infusion. Compound diminished the heart rate during study especially at 20th minute compared to propranolol as a reference drug. Compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) was the most effective compound with remarkable ability in declining of the heart rate.

Keywords: electrocardiograph (ECG), cardiovascular, IPS-339, dogs

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Authors: Abdullah Mohammad, Abdullah Alshemali, Esmaeil Alsaleh

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The chemical composition of desalinated water is modified to make it more acceptable to the end-user. Sometimes, this modification is approached by mixing with brackish water that is known to contain a variety of minerals. Expectedly, besides minerals, brackish water indigenous bacterial communities access the final mixture hence reaching the end consumer. The current project examined the safety of using brackish water as an ingredient in potable water. Pseudomonas aeruginosa strains were detected in potable and brackish water samples collected from storage facilities in residential areas as well as from main water distribution and storage tanks. The application of molecular and biochemical fingerprinting methods, including phylogeny, RFLP (restriction fragment length polymorphism), MLST (multilocus sequence typing) and substrate specificity testing, suggested that the potable water P. aeruginosa strains were most probably originated from brackish water. Additionally, all the sixty-four isolates showed multi-drug resistance (MDR) phenotype and harboured the three genes responsible for biofilm formation. These virulence factors represent serious health hazards compelling the scientific community to revise the WHO (World Health Organization) and USEP (US Environmental Protection Agency) A potable water quality guidelines, particularly those related to the types of bacterial genera that evade the current water quality guidelines.

Keywords: potable water, brackish water, pseudomonas aeroginosa, multidrug resistance

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Authors: Luís Rocha, Adam Gąska, Enrico Savio, Michael Marxer, Christoph Battaglia

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The changes observed in the last years in the field of manufacturing and production engineering, popularly known as "Fourth Industry Revolution", utilizes the achievements in the different areas of computer sciences, introducing new solutions at almost every stage of the production process, just to mention such concepts as mass customization, cloud computing, knowledge-based engineering, virtual reality, rapid prototyping, or virtual models of measuring systems. To effectively speed up the production process and make it more flexible, it is necessary to tighten the bonds connecting individual stages of the production process and to raise the awareness and knowledge of employees of individual sectors about the nature and specificity of work in other stages. It is important to discover and develop a suitable education method adapted to the specificities of each stage of the production process, becoming an extremely crucial issue to exploit the potential of the fourth industrial revolution properly. Because of it, the project “Train4Dim” (T4D) intends to develop complex training material for digital manufacturing, including content for design, manufacturing, and quality control, with a focus on coordinate metrology and portable measuring systems. In this paper, the authors present an approach to using an active learning methodology for digital manufacturing. T4D main objective is to develop a multi-degree (apprenticeship up to master’s degree studies) and educational approach that can be adapted to different teaching levels. It’s also described the process of creating the underneath methodology. The paper will share the steps to achieve the aims of the project (training model for digital manufacturing): 1) surveying the stakeholders, 2) Defining the learning aims, 3) producing all contents and curriculum, 4) training for tutors, and 5) Pilot courses test and improvements.

Keywords: learning, Industry 4.0, active learning, digital manufacturing

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Authors: Youcef Serhane, Abdelkrim Bouzaza, Dominique Wolbert, Aymen Amin Assadi

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Throughout history, the use of chemical weapons is not exclusive to combats between army corps; some of these weapons are also found in very targeted intelligence operations (political assassinations), organized crime, and terrorist organizations. To improve the speed of action, important technological devices have been developed in recent years, in particular in the field of protection and decontamination techniques to better protect and neutralize a chemical threat. In order to assess certain protective, decontaminating technologies or to improve medical countermeasures, tests must be conducted. In view of the great toxicity of toxic chemical agents from (real) wars, simulants can be used, chosen according to the desired application. Here, we present an investigation about using a photocatalytic filtering reactor (PFR) for highly contaminated environments containing diethyl sulfide (DES). This target pollutant is used as a simulant of CWA, namely of Yperite (Mustard Gas). The influence of the inlet concentration (until high concentrations of DES (1200 ppmv, i.e., 5 g/m³ of air) has been studied. Also, the conversion rate was monitored under different relative humidity and different flow rates (respiratory flow - standards: ISO / DIS 8996 and NF EN 14387 + A1). In order to understand the efficacity of pollutant neutralization by PFR, a kinetic model based on the Langmuir–Hinshelwood (L–H) approach and taking into account the mass transfer step was developed. This allows us to determine the adsorption and kinetic degradation constants with no influence of mass transfer. The obtained results confirm that this small configuration of reactor presents an extremely promising way for the use of photocatalysis for treatment to deal with highly contaminated environments containing real chemical warfare agents. Also, they can give birth to an individual protection device (an autonomous cartridge for a gas mask).

Keywords: photocatalysis, photocatalytic filtering reactor, diethylsulfide, chemical warfare agents

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Authors: Saji George, Eng Khuan Seng, Christof Luda

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Nanotechnology has been recognized as an important tool for modern agriculture and has the potential to overcome some of the pressing challenges faced by aquaculture industry. A strategy for optimizing nanotechnology-based therapeutic delivery platform for immunizing farmed fish was developed. Accordingly, a compositional library of nanomaterials of natural chemistry (Halloysite (clay), Chitosan, Hydroxyapatite, Mesoporous Silica and a composite material of clay-chitosan) was screened for their toxicity and efficiency in delivering models antigens in cellular and zebrafish embryo models using high throughput screening platforms. Through multi-parametric optimization, chitosan modified halloysite (clay) nanomaterial was identified as an optimal vaccine delivery platform. Further, studies conducted in juvenile seabass showed the potential of clay-chitosan in delivering outer membrane protein of Tenacibaculum maritimum- TIMA (pathogenic bacteria) to and its efficiency in eliciting immune responses in fish. In short, as exemplified by this work, the strategy of using compositional nanomaterial libraries and their biological profiling using high-throughput screening platform could fasten the discovery process of nanomaterials with potential applications in food and agriculture.

Keywords: nanotechnology, fish-vaccine, drug-delivery, halloysite-chitosan

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Authors: Anil Kumar Kursenge

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In the State of united Andhra Pradesh, many Adivasi People live in areas rich in living and non-living resources, including forests that contain abundant biodiversity, water and minerals. Of united Andhra Pradesh 76.2m population, over five million are Adivasi population of forest landscape. They depend on forests for a substantial part of their livelihoods and close cultural affinity with forests. However, they are the most impoverished population of the State, and the high levels of poverty in Andhra Pradesh forest landscapes are largely an outcome of historically-rooted institutionalised marginalisation. As the State appropriated forests and forest land for itself, it deprived local people of their customary rights in the forest. The local realities of the forest rights deprivations are extremely complex, reflecting a century and a half of compounded processes. With growing population pressure and ever-increasing demands for natural and mineral resources, Adivasi Peoples' lands, which are often relatively rich in resources, become more and more attractive to 'developers.' The development projects and institutionalised marginalisation have been deprived Adivasi people's rights over natural resources has resulted in serious negative effects on Adivasi people and on their lands. Historically, the desire for development for such resources has resulted in the removal, decimation, or extermination of many tribal communities. These deprivations have led to highly conflictual relations between the State and the Adivasi people and forest areas in Andhra Pradesh. Today, the survival of the Adivasi Peoples requires recognition of their rights to the forest resources found in their lands and territories on which they depend for their economic, cultural, survival, spiritual and physical well-being. In this context, this paper attempts to discuss the issues of deprivation with regard to access to forest resources and development projects where many Adivasis in State uprooted from their homes and lands.

Keywords: tribal people, forest rights, livelihoods, deprivation, marginalisation, Andhra Pradesh

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Authors: Jhonas Geraldo Peixoto Flauzino, Pedro Pompeo Boechat Araujo, Alexia Allis Rocha Lima, Giovanna Biângulo Lacerda Chaves, Victor Ryan Ferrão Chaves

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Schizophrenia is characterized as a set of psychiatric signs and symptoms (syndrome) that commonly erupt in the stages of adolescence or early adulthood, being recognized as one of the most serious diseases, as it causes important problems during the life of the patient. carrier - both in mental health and in physical health and in social life. Objectives: This is an integrative literature review that aimed to verify what has been produced of scientific knowledge in the field of child and adolescent psychiatry regarding schizophrenia in these stages of life, correlated to the most discussed themes and methodologies of choice for the preparation of studies. Methods: Articles were selected from the following databases: Virtual Health Library and CAPES Journal Portal, published in the last five years; and on Google Scholar, published in 2021, totaling 62 works, searched in September 2021. Results: The studies focus mainly on diagnosis through the DSM-V (25.8%), on drug treatment (25.8%) and in psychotherapy (24.2%), most of them in the literature review format: integrative (27.4%) and systematic (24.2%). Conclusion: The themes and study methods are redundant, and do not cover in depth the immense aspects that encompass Schizophrenia in Childhood and Adolescence, giving attention to the disease in a general way or focusing on the adult patient.

Keywords: schizophrenia, mental health, childhood, adolescence

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Authors: Ahlam H. Mahmoud, Samir F. Zohny, Ibrahim H. Boraia, Faten S. Bayoumic, Eman Eissa

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Hepatocellular carcinoma is one of the most common cancers worldwide and is known to be resistant to conventional chemotherapy. Therefore, we aimed to assess the Salsola inermis extract as a novel chemopreventive and/or therapeutic agent against N-nitrosodiethylamine (DNE)/phenobarbital (PB)-induced hepatocarcinogenesis in rats. Adult male Wistar albino rats were divided into five groups: group1 rats were served as normal controls; group 2 rats were injected intraperitoneally with S. inermis extract (100 mg/kg body weight/day) for 20 weeks; group 3 rats were subjected to two-phase hepatocarcinogenic regimen (initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of DEN at a dose of 200 mg/kg body weight, 2 weeks later, the carcinogenic effect was promoted by supplementation of rats with 0.05% PB for 16 weeks); group 4 rats were injected intraperitoneally with S. inermis extract 2 weeks prior to the injection of DEN, the daily injection of S. inermis extract was then continued for 18 weeks along with two-phase hepatocarcinogenic regimen (chemoprevention group); and group 5 rats were subjected to the two-phase hepatocarcinogenic regimen, and then, the animals were injected intraperitoneally with S. inermis extract for 4 weeks (treatment group). The activities of serum liver enzymes and levels of total bilirubin, conjugated bilirubin, α-fetoprotein, vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were decreased in chemopreventive and treated rats compared with DEN/PB-administered rats. Interestingly, the serum levels of total protein and albumin were normalized in chemopreventive and treated rats. Moreover, the majority of chemopreventive and treated rats showed an almost normal histological pattern of liver. In conclusion, S. inermis extract possessed chemopreventive and therapeutic activities against hepatocarcinogenesis in rats partially through the inhibition of VEGF and sICAM-1.

Keywords: Salsola inermis extract, hepatocarcinogenesis, α–fetoprotein, VEGF, sICAM-1

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Authors: Shuafeng Yuan, Bojian Zheng

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The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

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Authors: Mehmet Akoz, Mustafa Kul

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Ewes and goats are seasonally polyestrus animals. Their reproductive activities are associated with the reduction or extending of daylight. Melatonin releasing from pineal gland regulates the sexual activities depending on daylight. In recent years, number of ewes decreased in our country. This situation dispatched to developing of some methods to increase productivity. Small ruminants can be synchronized with the natural and medical methods. known methods from natural light set with ram and goat participation. The most important natural methods of male influence, daylight is regulated and feed. On the other hand, progestagens, PGF2α, melatonin, and gonadotropins are commonly used for the purpose of estrus synchranization. But it is not effective PGF2α anestrous season The short-term and long-term progesterone treatment was effective to synchronize estrus in small ruminats during both breeding and anestrus seasons. Alternative choices of progesterone/progestagen have been controlled internal drug release (CIDR) devices, supplying natural progesterone, norgestomet implants, and orally active melengestrol acetate Melatonin anestrous season and should be applied during the transition period, but the season can be synchronized. Estrus synchronisation shortens anestrus season, decreases labor for mating/insemination and estrus pursuit, and induces multiple pregnancies.

Keywords: ewes, goat, synchronization, progestagen, PGF2α

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Authors: Basave Gowda, Lokesh K., Prasanth S. M., Bellad S. B., Radha J., Lokesh G. Y., Patil S. B., Vijayakumar D. K., Ganigar B. S., Rakesh C. Mathad

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Quality seed plays an important role in enhancing the crop productivity. It was reported and confirmed by large scale verification research trials that by use of quality seeds alone, the crop yield can be enhanced by 15 to 20 per cent. At present, the quality seed production and distribution through organised sectors comprising both public and private seed sector was only 20-25% of the requirement and the remaining quantity is met through unorganised sector which include the farmer to farmers saved seeds. With an objective of developing an alternative seed system, the University of Agricultural Sciences, Raichur in Karnataka state has implemented Seed Village Programme in more than 100 villages covering around 5000 farmers every year since 2009-10 and in the selected seed villages, a group of 50-150 farmers were supplied the foundation seeds of new varieties to an extent of 0.4 ha at 50 % subsidy. And two to three training programmes were conducted in the targeted villages for quality seed production and the seed produced in the target group was processed locally in the university seed processing units and arranged for distribution in the local villages by the seed growers themselves. By this new innovative and modified seed system, the university can able to replace old varieties of pigeon pea and green gram by producing 1482, 2978, 2729, 2560, and 4581 tonnes of seeds of new varieties on large scale under farmers and scientists participatory seed village programmes respectively during 2009-10, 2010-11, 2011-12, 2012-13 and 2013-14. From this new alternate model of seed system, there should be large scale promotion of regional seed system involving farmers, NGO and voluntary organisation for quick and effective replacement of old, low yielding, disease susceptible varieties with new high yielding, disease resistant for enhanced food production and food security.

Keywords: seed system, seed village, seed replacement, varietal replacement

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Authors: Abdul Matin, Muazzama Akhtar, Shahid Nisar, Saddaf Mazzar, Umer Rashid

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Antibiotic resistance is an increasing concern worldwide now a day. Neisseria gonorrhea and Staphylococcus aureus are known to cause major human sexually transmitted and respiratory diseases respectively. Nanotechnology is an emerging discipline and its application in various fields especially in medical sciences is gigantic. In the present study, we synthesized multi-walled carbon nanotubes (MWNTs) using acid oxidation method and solubilized MWNTs were with length predominantly >500 nm and diameters ranging from 40 to 50 nm. The locally synthesized MWNTs were used against gram positive and negative bacteria to determine their impact on bacterial growth. Clinical isolates of Neisseria gonorrhea (isolate: 4C-11) and Staphylococcus aureus (isolate: 38541) were obtained from local hospital and normally cultured in LB broth at 37°C. Both clinical strains can be obtained on request from University of Gujarat. Spectophometric assay was performed to determine the impact of MWNTs on bacterial growth in vitro. To determine the effect of MWTNs on test organisms, various concentration of MWNTs were used and recorded observation on various time intervals to understand the growth inhibition pattern. Our results demonstrated that MWNTs exhibited toxic effects to Staphylococcus aureus while showed very limited growth inhibition to Neisseria gonorrhea, which suggests the resistant potential of Neisseria against nanoparticles. Our results clearly demonstrate the gradual decrease in bacterial numbers with passage of time when compared with control. Maximum bacterial inhibition was observed at maximum concentration (50 µg/ml). Our future work will include further characterization and mode of action of our locally synthesized MWNTs. In conclusion, we investigated and reported for the first time the inhibitory potential of locally synthesized MWNTs on local clinical isolates of Staphylococcus aureus and Neisseria gonorrhea.

Keywords: antibacterial activity, multi walled carbon nanotubes, Neisseria gonorrhea, spectrophotometer assay, Staphylococcus aureus

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Authors: Ganeshkumar, Ashika, Valavan, Ramesh, Thangam, Chirayu

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MSCs are found in much higher concentration in the Wharton’s jelly compared to the umbilical cord blood, which is a rich source of hematopoietic stem cells. Umbilical cord tissue is collected at the time of birth; it is processed and stored in liquid nitrogen for future therapeutical purpose. The source of contamination might be either from vaginal tract of mother or from hospital environment or from personal handling during cord tissue sample collection. If the sample were contaminated, decontamination procedure will be done with 70% ethanol (1 minute) in order to avoid sample rejection. Ethanol is effective against a wide range of bacteria, protozoa and fungi and has low toxicity to humans. Among the 1954 samples taken for the study, 24 samples were found to be contaminated with microorganism. The organisms isolated from the positive samples were found to be E. coli, Stenotrophomonas maltophilia, Pseudomonas aueroginosa, Enterococcus fecalis, Acinetobacter bowmani, Staphylococcus epidermidis, Enterobacter cloacae, and Proteus mirabilis. Among these organisms 70% ethanol successfully eliminated E. coli, Enterococcus fecalis, Acinetobacter bowmani, Staphylococcus epidermidis, and Proteus mirabilis. 70% ethanol was unsuccessful in eliminating Stenotrophomonas maltophilia, Pseudomonas aueroginosa, and Enterobacter cloacae. Stenotrophomonas maltophilia and Pseudomonas aueroginosa have the ability to form biofilm that make them resistant to alcohol. Biofilm act as protective layer for bacteria and which protects them from host defense and antibiotic wash. Finally it was found 70% ethanol wash saved 58.3% cord tissue samples from rejection and it is ineffective against 41% of the samples. The contamination rate can be reduced by maintaining proper aseptic techniques during sample collection and processing.

Keywords: umblical cord tissue, decontamination, 70% ethanol effectiveness, contamination

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Authors: A. A. Adebayo, O. Osibanjo

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Informal electronic waste (e-waste) processing is a crude method of recycling, which is on the increase in Nigeria. The release of hazardous substances such as heavy metals (HMs) into the environment during informal e-waste processing has been a major concern. However, there is insufficient information on environmental contamination from e-waste recycling, associated ecological risk in Alaba International Market, a major electronic market in Lagos, Nigeria. The aims of this study were to determine the levels of HMs in soil, resulting from the e-waste recycling; and also assess associated ecological risks in Alaba international market. Samples of soils (334) were randomly collected seasonally for three years from fourteen selected e-waste activity points and two control sites. The samples were digested using standard methods and HMs analysed by inductive coupled plasma optical emission. Ecological risk was estimated using Ecological Risk index (ER), Potential Ecological Risk index (RI), Index of geoaccumulation (Igeo), Contamination factor (Cf) and degree of contamination factor (Cdeg). The concentrations range of HMs (mg/kg) in soil were: 16.7-11200.0 (Pb); 14.3-22600.0 (Cu); 1.90-6280.0 (Ni), 39.5-4570.0 (Zn); 0.79-12300.0 (Sn); 0.02-138.0 (Cd); 12.7-1710.0 (Ba); 0.18-131.0 (Cr); 0.07-28.0 (V), while As was below detection limit. Concentrations range in control soils were 1.36-9.70 (Pb), 2.06-7.60 (Cu), 1.25-5.11 (Ni), 3.62-15.9 (Zn), BDL-0.56 (Sn), BDL-0.01 (Cd), 14.6-47.6 (Ba), 0.21–12.2 (Cr) and 0.22-22.2 (V). The trend in ecological risk index was in the order Cu > Pb > Ni > Zn > Cr > Cd > Ba > V. The potential ecological risk index with respect to informal e-waste activities were: burning > dismantling > disposal > stockpiling. The index of geo accumulation indices revealed that soils were extremely polluted with Cd, Cu, Pb, Zn and Ni. The contamination factor indicated that 93% of the studied areas have very high contamination status for Pb, Cu, Ba, Sn and Co while Cr and Cd were in the moderately contaminated status. The degree of contamination decreased in the order of Sn > Cu > Pb >> Zn > Ba > Co > Ni > V > Cr > Cd. Heavy metal contamination of Alaba international market environment resulting from informal e-waste processing was established. Proper management of e-waste and remediation of the market environment are recommended to minimize the ecological risks.

Keywords: Alaba international market, ecological risk, electronic waste, heavy metal contamination

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