Search results for: antimicrobial resistance

Authors: S. Mamoucha, N.Tsafantakis, T. Ioannidis, S. Chatzipanagiotou, C. Nikolaou, L. Skaltsounis, N. Fokialakis, N. Christodoulakis

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Introduction: Pistacia lentiscus L. (well known as Mastic tree) is an evergreen sclerophyllous shrub that extensively thrives in the eastern Mediterranean area yet only the trees cultivated in the southern region of the Greek island Chios produces mastic resin. Different parts of P. lentiscus L. var. chia have been used in folk medicine for various purposes, such as tonic, aphrodisiac, antiseptic, antihypertensive and management of dental, gastrointestinal, liver, urinary, and respiratory tract disorders. Several studies have focused on the antibacterial activity of its resin (gum) and its essential oil. However, there is no study combining anatomy of the plant organs, phytochemical profile, and antibacterial screening of the plant. In our attempt to discover novel bioactive metabolites from the mastic tree, we screened its antibacterial activity not only against ATCC strains but also against clinical, resistant strains. Materials-methods: Leaves were investigated using Transmission (ΤΕΜ) and Scanning Εlectron Microscopy (SEM). Histochemical tests were performed on fresh and fixed tissue. Extracts prepared from dried, powdered leaves using 3 different solvents (DCM, MeOH and H2O) the waste water obtained after a hydrodistillation process for essential oil production were screened for their phytochemical content and antibacterial activity. Μetabolite profiling of polar and non-polar extracts was recorded by GC-MS and LC-HRMS techniques and analyzed using in-house and commercial libraries. The antibacterial screening was performed against Staphylococcus aureus ATCC25923, Escherichia coli ATCC25922, Pseudomonas aeruginosa ATCC27853 and against clinical, resistant strains Methicillin-resistant S. aureus (MRSA), Carbapenem-Resistant Metallo-β-Lactamase (carbapenemase) P. aeruginosa (VIM), Klebsiella pneumoniae carbapenemases (KPCs) and Acinetobacter baumanii resistant strains. The antibacterial activity was tested by the Kirby Bauer and the Agar Well Diffusion method. The zone of inhibition (ZI) of each extract was measured and compared with those of common antibiotics. Results: Leaf is compact with inosclereids and numerous idioblasts containing a globular, spiny crystal. The major nerves of the leaf contain a resin duct. Mesophyll cells showed accumulation of osmiophillic metabolites. Histochemical treatments defined secondary metabolites in subcellular localization. The phytochemical investigation revealed the presence of a large number of secondary metabolites, belonging to different chemical groups, such as terpenoids, phenolic compounds (mainly myricetin, kaempferol and quercetin glycosides), phenolic, and fatty acids. Among the extracts, the hydrostillation wastewater achieved the best results against most of the bacteria tested. MRSA, VIM and A. baumanii were inhibited. Conclusion: Extracts from plants have recently been of great interest with respect to their antimicrobial activity. Their use emerged from a growing tendency to replace synthetic antimicrobial agents with natural ones. Leaves of P. lentiscus L. var. chia showed a high antimicrobial activity even against drug - resistant bacteria. Future prospects concern the better understanding of mode of action of the antibacterial activity, the isolation of the most bioactive constituents and the clarification if the activity is related to a single compound or to the synergistic effect of several ones.

Keywords: antibacterial screening, leaf anatomy, phytochemical profile, Pistacia lentiscus var. chia

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the bacteriological profile and antibiotic resistance of the isolates and to find out the potential risk factors for infection with multidrug-resistant organisms. Diabetic foot ulcer is a major medical, social, economic problem and a leading cause of morbidity and mortality, especially in the developing countries like India. 25 percent of all diabetic patients develop a foot ulcer at some point in their lives which is highly susceptible to infections and that spreads rapidly, leading to overwhelming tissue destruction and subsequent amputation. Infection with multidrug resistant organisms (MDRO) may increase the cost of management and may cause additional morbidity and mortality. Proper management of these infections requires appropriate antibiotic selection based on culture and antimicrobial susceptibility testing. Early diagnosis of microbial infections is aimed to institute the appropriate antibacterial therapy initiative to avoid further complications. A total of 200 Type 2 Diabetic Mellitus patients with infection were admitted at GD Hospital and Diabetes Institute, Kolkata. 60 of them who developed ulcer during the year 2013 were included in this study. A detailed clinical history and physical examination were carried out for every subject. Specimens for microbiological studies were obtained from ulcer region. Gram-negative bacilli were tested for extended spectrum Beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method and disc diffusion. Potential risk factors for MDRO-positive samples were explored. Gram-negative aerobes were most frequently isolated, followed by gram-positive aerobes. Males were predominant in the study and majority of the patients were in the age group of 41-60 years. The presence of neuropathy was observed in 80% cases followed by peripheral vascular disease (73%). Proteus spp. (22) was the most common pathogen isolated, followed by E.coli (17). Staphylococcus aureus was predominant amongst the gram-positive isolates. S.aureus showed a high rate of resistance to antibiotic tested (63.6%). Other gram-positive isolates were found to be highly resistant to erythromycin, tetracycline and ciprofloxacin, 40% each. All isolates were found to be sensitive to Vancomycin and Linezolid. ESBL production was noted in Proteus spp and E.coli. Approximately 70 % of the patients were positive for MDRO. MDRO-infected patients had poor glycemic control (HbA1c 11± 2). Infection with MDROs is common in diabetic foot ulcers and is associated with risk factors like inadequate glycemic control, the presence of neuropathy, osteomyelitis, ulcer size and increased the requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.

Keywords: diabetic foot ulcer, bacterial infection, multidrug-resistant organism, extended spectrum beta-lactamase

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Authors: Hui-Hsin Huang, Sheng-Tung Huang, Chi-Ming Lee, Chiao-Han Yen, Chun-Mao Lin

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At initiation stage, there are no symptoms at initiation stage; however, at late stage, patients suffer symptoms as soon as ovarian cancer metastasis. Moreover, ovarian cancer cells are resistant to some anti-ovarian cancer drugs in clinical. Thus, it is very important to find an effective treatment for resistant ovarian cancer. Anthraquinone derivatives are able to induce DNA damage and lead to cell apoptosis, so several derivatives have been used for clinical application. Therefore, to explore more effective anti-ovarian cancer drugs, this study investigates the mechanism of three new anthraquinone compounds bearing different functional groups to camptothecin-resistance ovarian cell line A2780R2000. Cell viability was determined by MTT assay after treating A2780R2000 with the three new anthraquinone compounds. The results indicated that IC50 values are 33.44μM (Compound I), 25.77μM (Compound II) and 24.59μM (Compound III). Next, through cell cycle analysis, the results demonstrated that three new anthraquinone compounds not only induced A2780R2000 cell cycle arrest at early stage but also apoptosis at late stage. Besides, through apoptosis assay, the results indicated new anthraquinone compound induced apoptosis at late stage. Furthermore, the results of western blot show that the three new anthraquinone compounds lead to A2780R2000 apoptosis through intrinsic pathway. Theses results suggested that three new anthraquinone compounds may be potential new drugs for clinical cancer treatment in the future.

Keywords: anthraquinone, camptothecin, resistance, ovarian cancer

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Authors: M. J. Kim, D. B. Lee

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Centrifugal casting is a metal casting method that uses forces make by centripetal acceleration to distribute molten material in mold. Centrifugal cast parts manufactured in industry contain gas pipes and water supply lines, moreover rings, turbocharger, bushings, brake drums. Turbochargers were exposed to exhaust temperatures of 900-1050°C require a material for the corrosion resistance that will withstand such high component temperatures during the entire service life of the vehicle. Hence, the study of corrosion resistance for turbocharger is important for practical application. DIN1.4091 steels were used widely. The DIN1.4091 steels whose compositions were Fe-34.4Cr-14.5Ni-2.5Mo-0.4W-0.4Mn-0.5Si-(0.009 or 0.35)S (wt.%) were centrifugally cast, and oxidized at 900°C for 50-200 h in order to find the effect of sulfur on the high-temperature oxidation of Fe-34.4Cr-14.5Ni-2.5Mo-0.4W-0.4Mn-0.5Si-(0.009 or 0.35)S (wt.%) alloys. These alloys formed oxide scales that consisted primarily of Cr₂O₃ as the major oxide and Cr₂MnO₄ as the minor one through preferential oxidation of Cr and Mn. Cr formed a thin CrOx oxide film on the surface to prevent further oxidation, and when it is added more than 20%, the sulphide decreased corrosion rate. The high affinity of Mn with S, led to the formation of scattered MnS inclusions, particularly in the 0.35S-containing cast alloy. Sulfur was harmful to the oxidation resistance because it deteriorated the scale/alloy adherence so as to accelerate the adherence and compactness of the formed scales. Acknowledgement: This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2016R1A2B1013169).

Keywords: centrifugal casting, turbocharger, sulfur, oxidation, Fe-34.4Cr-14.5Ni alloy

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Authors: Keaghan Brown

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The prioritization of drug resistance mutations impacting protein folding or protein-drug and protein-DNA interactions within macromolecular systems is critical to the success of treatment regimens. With a continual increase in computational tools to assess these impacts, the need for scalability and reproducibility became an essential component of computational analysis and experimental research. Here it introduce a bioinformatics pipeline that combines several structural analysis tools in a simplified workflow, by optimizing the present computational hardware and software to automatically ease the flow of data transformations. Utilizing preestablished software tools, it was possible to develop a pipeline with a set of pre-defined functions that will automate mutation introduction into the HIV-1 Integrase protein structure, calculate the gain and loss of polar interactions and calculate the change in energy of protein fold. Additionally, an automated molecular dynamics analysis was implemented which reduces the constant need for user input and output management. The resulting pipeline, Automated Mutation Introduction and Analysis (AMIA) is an open source set of scripts designed to introduce and analyse the effects of mutations on the static protein structure as well as the results of the multi-conformational states from molecular dynamic simulations. The workflow allows the user to visualize all outputs in a user friendly manner thereby successfully enabling the prioritization of variant systems for experimental validation.

Keywords: automated workflow, variant prioritization, drug resistance, HIV Integrase

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: N. Abbas, S. Lagomarsino, S. Cattari

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Examining existing experimental results for shallow rigid foundations subjected to vertical centric load (N), accompanied or not with a bending moment (M), two main non-linear mechanisms governing the cyclic ‎response of the soil-foundation system can be distinguished: foundation uplift and soil yielding. A soil-foundation failure limit, is defined as a domain of resistance in the two dimensional (2D) load space (N, M) inside of which lie all the admissible combinations of loads; these latter correspond to a pure elastic, non-linear elastic or plastic behavior of the soil-foundation system, while the points lying on the failure limit correspond to a combination of loads leading to a failure of the soil-foundation system. In this study, the proposed resistance domain is constructed analytically based on mechanics. Original elastic limit, uplift initiation ‎limit and iso-uplift limits are constructed inside this domain. These limits give a prediction ‎of the mechanisms activated for each combination of loads applied to the ‎foundation. A comparison of the proposed failure limit with experimental tests existing in the literature shows interesting results. Also, the developed uplift initiation limit and iso-uplift curves are confronted with others already proposed in the literature and widely used due to the absence of other alternatives, and remarkable differences are noted, showing evident errors in the past proposals and relevant accuracy for those given in the present work.

Keywords: foundation uplift, iso-uplift curves, resistance domain, soil yield

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Authors: S. Beekrum, B. Odhav, R. Lalloo, E. O. Amonsou

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Marine microalgae are rich sources of the novel and biologically active metabolites; therefore, they may be used in the food industry as natural food ingredients and functional foods. They have several biological applications related with health benefits, among others. In the past decades, food scientists have been searching for natural alternatives to replace synthetic antioxidants. The use of synthetic antioxidants has decreased due to their suspected activity as promoters of carcinogenesis, as well as consumer rejection of synthetic food additives. The aim of the study focused on screening of phytochemicals from Cymbella biomass extracts, and to examine the in vitro antioxidant and antimicrobial potential. Cymbella biomass was obtained from CSIR (South Africa), and four different solvents namely methanol, acetone, n-hexane and water were used for extraction. To take into account different antioxidant mechanisms, seven different antioxidant assays were carried out. These include free radical scavenging (DPPH assay), Trolox equivalent antioxidant capacity (TEAC assay), radical cation (ABTS assay), superoxide anion radical scavenging, reducing power, determination of total phenolic compounds and determination of total flavonoid content. The total content of phenol and flavonoid in extracts were determined as gallic acid equivalent, and as rutin equivalent, respectively. The in vitro antimicrobial effect of extracts were tested against some pathogens (Staphylococcus aureus, Listeria monocytogenes, Bacillus subtilis, Salmonella enteritidis, Escherichia coli, Pseudomonas aeruginosa and Candida albicans), using the disc diffusion assay. Qualitative analyses of phytochemicals were conducted by chemical tests to screen for the presence of tannins, flavonoids, terpenoids, phenols, steroids, saponins, glycosides and alkaloids. The present investigation revealed that all extracts showed relatively strong antibacterial activity against most of the tested bacteria. The methanolic extract of the biomass contained a significantly high phenolic content of 111.46 mg GAE/g, and the hexane extract contained 65.279 mg GAE/g. Results of the DPPH assay showed that the biomass contained strong antioxidant capacity, 79% in the methanolic extract and 85% in the hexane extract. Extracts have displayed effective reducing power and superoxide anion radical scavenging. Results of this study have highlighted potential antioxidant activity in the methanol and hexane extracts. The obtained results of the phytochemical screening showed the presence of terpenoids, flavonoids, phenols and saponins. The use of Cymbella as a natural antioxidant source and a potential source of antibacterial compounds and phytochemicals in the food industry appears promising and should be investigated further.

Keywords: antioxidants, antimicrobial, Cymbella, microalgae, phytochemicals

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Authors: Asim Abbasi, Muhammad Sufyan, Muhammad Kamran, Iqra

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Development of resistance in insect pests against various groups of insecticides has prompted the use of alternative integrated pest management approaches. Among these induced host plant resistance represents an important strategy as it offers a practical, cheap and long lasting solution to keep pests populations below economic threshold level (ETL). Silicon (Si) has a major role in regulating plant eco-relationship by providing strength to the plant in the form of anti-stress mechanism which was utilized in coping with the environmental extremes to get a better yield and quality end produce. Among biotic stresses, insect herbivore signifies one class against which Si provide defense. Silicon in its neutral form (H₄SiO₄) is absorbed by the plants via roots through an active process accompanied by the help of different transporters which were located in the plasma membrane of root cells or by a passive process mostly regulated by transpiration stream, which occurs via the xylem cells along with the water. Plants tissues mainly the epidermal cell walls are the sinks of absorbed silicon where it polymerizes in the form of amorphous silica or monosilicic acid. The noteworthy function of this absorbed silicon is to provide structural rigidity to the tissues and strength to the cell walls. Silicon has both direct and indirect effects on insect herbivores. Increased abrasiveness and hardness of epidermal plant tissues and reduced digestibility as a result of deposition of Si primarily as phytoliths within cuticle layer is now the most authenticated mechanisms of Si in enhancing plant resistance to insect herbivores. Moreover, increased Si content in the diet also impedes the efficiency by which insects transformed consumed food into the body mass. The palatability of food material has also been changed by Si application, and it also deters herbivore feeding for food. The production of defensive compounds of plants like silica and phenols have also been amplified by the exogenous application of silicon sources which results in reduction of the probing time of certain insects. Some studies also highlighted the role of silicon at the third trophic level as it also attracts natural enemies of insects attacking the crop. Hence, the inclusion of Si in pest management approaches can be a healthy and eco-friendly tool in future.

Keywords: defensive, phytoliths, resistance, stresses

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Authors: Tomofumi Kubota, Mitsuhiro Okayasu

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In recent years, environmental problems and energy problems typified by global warming are intensifying, and transportation devices are required to reduce the weight of structural materials from the viewpoint of strengthening fuel efficiency regulations and energy saving. Carbon fiber reinforced plastic (CFRP) used in this research is attracting attention as a structural material to replace metallic materials. Among them, thermoplastic CFRP is expected to expand its application range in terms of recyclability and cost. High formability and weldability of the unidirectional CFRP sheets conducted by a proposed hot stamping process were proposed, in which the carbon fiber reinforced plastic sheets are heated by a designed technique. In this case, the CFRP sheets are heated by the high electric voltage applied through carbon fibers. In addition, the electric voltage was controlled by the area ratio of exposed carbon fiber on the sample surfaces. The lower exposed carbon fiber on the sample surface makes high electric resistance leading to the high sample temperature. In this case, the CFRP sheets can be heated to more than 150 °C. With the sample heating, the stamping and welding technologies can be carried out. By changing the sample temperature, the suitable stamping condition can be detected. Moreover, the proper welding connection of the CFRP sheets was proposed. In this study, we propose a fusion bonding technique using thermoplasticity, high current flow, and heating caused by electrical resistance. This technology uses the principle of resistance spot welding. In particular, the relationship between the carbon fiber exposure rate and the electrical resistance value that affect the bonding strength is investigated. In this approach, the mechanical connection using rivet is also conducted to make a comparison of the severity of welding. The change of connecting strength is reflected by the fracture mechanism. The low and high connecting strength are obtained for the separation of two CFRP sheets and fractured inside the CFRP sheet, respectively. In addition to the two fracture modes, micro-cracks in CFRP are also detected. This approach also includes mechanical connections using rivets to compare the severity of the welds. The change in bond strength is reflected by the destruction mechanism. Low and high bond strengths were obtained to separate the two CFRP sheets, each broken inside the CFRP sheets. In addition to the two failure modes, micro cracks in CFRP are also detected. In this research, from the relationship between the surface carbon fiber ratio and the electrical resistance value, it was found that different carbon fiber ratios had similar electrical resistance values. Therefore, we investigated which of carbon fiber and resin is more influential to bonding strength. As a result, the lower the carbon fiber ratio, the higher the bonding strength. And this is 50% better than the conventional average strength. This can be evaluated by observing whether the fracture mode is interface fracture or internal fracture.

Keywords: CFRP, hot stamping, weliding, deforamtion, mechanical property

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Authors: Deepika Bhaskar, Neena Wadehra, Megha Gulati, Aruna Narula, R. Vishnu, Gunjan Katyal

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With drug resistance becoming widespread in Plasmodium falciparum infections, development of the alternative drugs is the desired strategy for prevention and cure of malaria. Three drug targets were selected to screen promising drug molecules from the GSK library of around 14000 molecules. Using an in silico structure-based drug designing approach, the differences in binding energies of the substrate and inhibitor were exploited between target sites of parasite and human to design a drug molecule against Plasmodium. The docking studies have shown several promising molecules from GSK library with more effective binding as compared to the already known inhibitors for the drug targets. Though stronger interaction has been shown by several molecules as compare to reference, few molecules have shown the potential as drug candidates though in vitro studies are required to validate the results.

Keywords: plasmodium, malaria, drug targets, in silico studies

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Authors: Mohammed M. Mahdy Tawfeek

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Objective: The aim of this work is to compare the outcome of photoactivated chromophore for keratitis-cross linking (PACK-CXL) window absorption (WA) alone with combined PACK-CXL WA and standard anti-microbial therapy (SAT) for the treatment of infectious keratitis. Patients and Methods: This is a randomized prospective comparative clinical trial. Thirty eyes with clinically suspected infectious keratitis were randomly assigned into two equal groups of 15 eyes each: Group (A) was treated by PACK-CXL WA alone and group (B) was treated by PACK-CXL WA combined with SAT. Identification of organisms was made by lab study before treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT). Written informed consent was obtained from all participants and the study was approved by the research ethics committee of the Faculty of Medicine, Zagazig University. The work has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for studies involving humans. Results: Complete healing and resolution (Successful treatment) were observed in 10 eyes (66.7%) of a group (A) and 14 eyes (93.3%) of group (B) and failure was observed in 5 eyes (33.3%) of a group (A) and one eye (6.67%) of group (B). They were statistically significant (P =0.042 and 0.003) in a comparison between both groups regarding success and failure of treatment, respectively. Complete corneal healing was reported in the third month postoperatively in 10 eyes (66.7%) of group (A) and 14 eyes (93.3%) of group (B). Complications were absent in 12 patients (80%) in group (A) and 14 patients (93.3%) of group (B); however, perforation and impending perforation were found in 3 patients of group (A) and only one patient of group (B). Conclusion: PACK-CXL is a promising, non-invasive treatment option for infectious keratitis, especially when performed with the window absorption (WA) technique, either alone or combined with SAT. It has a synergistic effect with a standard antimicrobial treatment that gives good outcome results in the treatment of infectious keratitis. Also, it avoids the antibiotics resistance that has become rapidly spreading worldwide.

Keywords: corneal cross linking, infectious keratitis, PACK-CXL, window absorption

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Authors: Fang Liu, JunShuai Xue, JiaJia Yao, XueYan Yang, ZuMao Li, GuanLin Wu, HePeng Zhang, ZhiPeng Sun

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III-Nitride resonant tunneling diode (RTD) is one of the most promising candidates for multiple-valued logic (MVL) elements. Here, we report a monolithic integration of GaN resonant tunneling diodes to realize multiple negative differential resistance (NDR) regions for MVL application. GaN RTDs, composed of a 2 nm quantum well embedded in two 1 nm quantum barriers, are grown by plasma-assisted molecular beam epitaxy on free-standing c-plane GaN substrates. Negative differential resistance characteristic with a peak current density of 178 kA/cm² in conjunction with a peak-to-valley current ratio (PVCR) of 2.07 is observed. Statistical properties exhibit high consistency showing a peak current density standard deviation of almost 1%, laying the foundation for the monolithic integration. After complete electrical isolation, two diodes of the designed same area are connected in series. By solving the Poisson equation and Schrodinger equation in one dimension, the energy band structure is calculated to explain the transport mechanism of the differential negative resistance phenomenon. Resonant tunneling events in a sequence of the series-connected RTD pair (SCRTD) form multiple NDR regions with nearly equal peak current, obtaining three stable operating states corresponding to ternary logic. A frequency multiplier circuit achieved using this integration is demonstrated, attesting to the robustness of this multiple peaks feature. This article presents a monolithic integration of SCRTD with multiple NDR regions driven by the resonant tunneling mechanism, which can be applied to a multiple-valued logic field, promising a fast operation speed and a great reduction of circuit complexity and demonstrating a new solution for nitride devices to break through the limitations of binary logic.

Keywords: GaN resonant tunneling diode, multiple-valued logic system, frequency multiplier, negative differential resistance, peak-to-valley current ratio

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Authors: Jairo Alejandro Fernandez Ortega

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Objective: Regarding effects of training velocity on strength in the functional condition of older adults controversy exists. The purpose of this study was to examine the effects of a twelve-week strength training program (PE) performed at high speed (GAV) versus a traditionally executed program (GBV), on functional performance, maximum strength and muscle power in a group of older adult women. Methodology: 86 women aged between 60-81 years participated voluntarily in the study and were assigned randomly to the GAV (three series at 40% 1RM at maximum speed, with maximum losses of 10% speed) or to the GBV (three series with three sets at 70% of 1RM). Both groups performed three weekly trainings. The maximum strength of upper and lower limbs (1RM), prehensile strength, walking speed, maximum power, mean propulsive velocity (MPV) and functional performance (senior fitness test) were evaluated before and after the PE. Results: Significant improvements were observed (p < 0.05) in all the tests in the two groups after the twelve weeks of training. However, the results of GAV were significantly (P < 0.05) higher than those of the GBV, in the tests of agility and dynamic equilibrium, stationary walking, sitting and standing, walking speed over 4 and 6 meters, MPV and peak power. In the tests of maximum strength and prehensile force, the differences were not significant. Conclusion: Strength training performed at high speeds seems to have a better effect on functional performance and muscle power than strength training performed at low speed.

Keywords: power training, resistance exercise, aging, strength, physical performance, high-velocity, resistance training

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Authors: Rajendra Jangde, Deependra Singh

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Present work was based with objective to release of the antimicrobial and debriding agent in sustained manner at the wound surface. In order to provide a long-lasting antimicrobial action and moist environment on wound space, Biocompatible moist system was developed for complete healing. In the present study, a biocompatible moist system of PVA-gelatin hydrogel was developed capable of carrying multiple drugs- Quercetin and Cabopol in controlled manner for effective and complete wound healing. Carbopol and Quercetin were prepared by thin film hydration techniques and optimized system was incorporated in PVA-Gelatin slurry. PVA-Gelatin hydrogels were prepared by freeze thaw method. The prepared dispersion was casted into films to prepare multiphase hydrogel system and characterized by in vitro and in vivo studies. Results revealed the uniform dispersion of microspheres in a three-dimensional matrix of the PVA-Gelatin hydrogel observed at different magnifications. The in vitro release data showed typical biphasic release pattern, i.e., a burst release followed by a slower sustained release for 5 days. Prepared system was found to be stable under both normal and accelerated conditions. Histopathological study showed significant (p<0.05) increase in fibroblast cells, collagen fibres and blood vessels formation. All parameters such as wound contraction, tensile strength, histopathological and biochemical parameters- hydroxyproline content, protein level, etc. were observed significant (p<0.05) in comparison to control group. Present results suggest an accelerated re-epithelialization under moist wound environment with delivery of multiple drugs effective at different stages of wound healing cascade with minimum disturbance of wound bed.

Keywords: multiphase hydrogel, optimization quercetin, wound healing

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Authors: M. F. Alrubaie, S. A. Salih, W. A. Abbas

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Slurry infiltrated fiber concrete (SIFCON) is considered as a special type of high strength high-performance fiber reinforced concrete, extremely strong, and ductile. The objective of this study is to investigate the durability of SIFCON to corrosion in chloride environments. Six different SIFCON mixes were made in addition to two refinance mixes with 0% and 1.5% steel fiber content. All mixes were exposed to 10% chloride solution for 180 days. Half of the specimens were partially immersed in chloride solution, and the others were exposed to weekly cycles of wetting and drying in 10% chloride solution. The effectiveness of using corrosion inhibitors, mineral admixture, and epoxy protective coating were also evaluated as protective measures to reduce the effect of chloride attack and to improve the corrosion resistance of SIFCON mixes. Corrosion rates, half-cell potential, electrical resistivity, total permeability tests had been monitored monthly. The results indicated a significant improvement in performance for SIFCON mixes exposed to chloride environment, when using corrosion inhibitor or epoxy protective coating, whereas SIFCON mix contained mineral admixture (metakaolin) did not improve the corrosion resistance at the same level. The cyclic wetting and drying exposure were more aggressive to the specimens than the partial immersion in chloride solution although the observed surface corrosion for the later was clearer.

Keywords: chloride attack, chloride environments, corrosion inhibitor, corrosion resistance, durability, SIFCON, slurry infiltrated fiber concrete

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Authors: Tooba N. Shamsi, Romana Perveen, Sadaf Fatima

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Protease Inhibitors (PIs) are widespread in nature, produced by animals, plants and microorganisms. They play vital role in various biological activities by keeping a check on activity of proteases. Present study aims to investigate antioxidant and anti-inflammatory properties of PPI from Cajanus cajan (CCTI) and Phaseolus limensis (LBTI). PPI was purified from C. cajan (PUSA-992) by ammonium sulfate precipitation followed by ion exchange chromatography. The anti-oxidant activity was analyzed by two most common radical scavenging assays of FRAP (ferric reducing antioxidant power) and DPPH (1,1- diphenyl-2-picrylhydrazyl). Also, in-vitro anti-inflammatory activity was evaluated using albumin denaturation assay and membrane stabilization assay at different concentrations. Ascorbic acid and aspirin were used as a standards for antioxidant and anti-inflammatory assays respectively. The PPIs were also checked for antimicrobial activity against a number of bacterial strains. The CCTI and LBTI showed DPPH radical scavenging activity in a concentration–dependent manner with IC50 values 544 µg/ml and 506 µg/ml respectively comparative to ascorbic acid which was 258 µg/ml. Following FRAP assay, it was evaluated that LBTI had 87.5% and CCTI showed 84.4% antioxidant activity, taking value of standard ascorbic acid to be 100%. The PPIs also showed in-vitro anti‐inflammatory activity by inhibiting the heat induced albumin denaturation with IC50 values of 686 µg/ml and 615 µg/ml for CCTI and LBTI respectively compared to the standard (aspirin) which was 70.8 µg/ml. Red blood cells membrane stabilization with IC50 values of 641 µg/ml and 587 µg/ml for CCTI and LBTI respectively against aspirin which showed IC50 value of 70.4 µg/ml. PPIs showed antibacterial activity against 7 known strains while there was apparently no action against fungi.

Keywords: Cajanus cajan, Phaseolus limensis, Lima beans, protein protease inhibitor, antioxidant, anti-inflammatory, antimicrobial activity

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Authors: Soroor Ghaziof, Wei Gao

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Sol-enhanced Zn-Ni-Al2O3 nano-composite coatings were electroplated on mild steel by our newly developed sol-enhanced electroplating method. In this method, transparent Al2O3 sol was added into the acidic Zn-Ni bath to produced Zn-Ni-Al2O3 nano-composite coatings. The chemical composition, microstructure and mechanical properties of the composite and alloy coatings deposited at two different agitation speed were investigated. The structure of all coatings was single γ-Ni5Zn21 phase. The composite coatings possess refined crystals with higher microhardness compared to Zn-Ni alloy coatings. The wear resistance of Zn-Ni coatings was improved significantly by incorporation of alumina nano particles into the coatings. Higher agitation speed provided more uniform coatings with smaller grain sized and slightly higher microhardness. Considering composite coatings, high agitation speeds may facilitate co-deposition of alumina in the coatings.

Keywords: microhardness, sol-enhanced electroplating, wear resistance, Zn-Ni-Al2O3 composite coatings

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Authors: Pampita Chakraborty, Sukumar Mukherjee

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This study was done to determine the prevalence of nosocomial infections in the ICU and to identify the common microorganisms causing these infections and their antimicrobial sensitivity pattern. Nosocomial infection or hospital-acquired infection is a localized or a systemic condition resulting from an adverse reaction to the presence of infectious agents. Nosocomial infections are not present or incubating when the patient is admitted to hospital or other health care facility. They are caused by pathogens that easily spread through the body. Many hospitalized patients have compromised immune systems, so they are less able to fight off infections. These infections occur worldwide, both in the developed and developing the world. They are a significant burden to patients and public health. They are a major cause of death and increased morbidity in hospitalized patients, which is a matter of serious concern today. This study was done during the period of one year (2012-2013) in the ICU of the tertiary care hospital in eastern India. Prevalence of nosocomial infection was determined; site of infection and the pattern of microorganisms were identified along with the assessment of antibiotic susceptibility profile. Patients who developed an infection after 48 hours of admission to the ICU were included in the study. A total of 324 ICU patients were analyzed, of these 79 patients were found to have developed a nosocomial infection (24.3% prevalence). Urinary tract infection was found to be more predominant followed by respiratory tract infection and soft tissue infection. The most frequently isolated microorganism was E. coli, Pseudomonas aeruginosa, Klebsiella pneumoniae followed by other organisms respectively. Antibiotic susceptibility test of these isolates was done against commonly used antibiotics. Patients admitted to the ICU are especially susceptible to nosocomial infections. Despite adequate antimicrobial treatment, nosocomial ICU infections can significantly affect ICU stay and can cause an increase in patient’s morbidity and mortality. Adherence to infection protocol, proper monitoring and the judicious use of antibiotics are important in preventing such infections on a regular basis.

Keywords: antibiotic susceptibility, intensive care unit, nosocomial infection, nosocomial pathogen

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Authors: Chee Dhang Chen, Hiroyuki Takaoka, Koon Weng Lau, Poh Ruey Tan, Ai Chdon Chin, Van Lun Low, Abdul Aziz Azidah, Mohd Sofian-Azirun

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Susceptibility status of Simulium (Simulium) nobile (Diptera: Simuliidae) adults obtained from Pahang, Malaysia was evaluated against 11 adulticides representing four major insecticide classes: organochlorines (DDT, dieldrin), organophosphates (malathion, fenitrothion), carbamates (bendiocarb, propoxur) and pyrethroids (etofenprox, deltamethrin, lambdacyhalothrin, permethrin, cyfluthrin). The adult bioassay was conducted according to WHO standard protocol to determine the insecticide susceptibility. Mortality at 24 h post treatment was used as indicator for susceptibility status. The results revealed that S. nobile obtained was susceptible to propoxur, cyfluthrin and bendiocarb with 100% mortality. S. nobile was resistant or exhibited some tolerant against lambdacyhalothrin and deltamethrin with mortality ranged ≥ 90% but < 98%. S. nobile populations in Pahang exhibited different level of resistant against 11 adulticides with mortality ranged from 60.00 ± 10.00 to 100.00 ± 0.00. In conclusion, S. nobile populations in Pahang were susceptible to propoxur, cyfluthrin and bendiocarb. The susceptibility status of S. nobile in descending order was propoxur, cyfluthrin > bendicarb > deltamethrin > lambdacyhalothrin > permethrin > etofenprox > DDT > malathion > fenitrothion > dieldrin. Regular surveys should be conducted to monitor the susceptibility status of this insect vector in order to prevent further development of resistance.

Keywords: black fly, adult bioassay, insecticide resistance, Malaysia

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Authors: M. Khoukhi

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Accurate prediction of the cooling/heating load and consequently, the sizing of the heating, ventilating, and air-conditioning equipment require precise calculation of the heat transfer mainly by conduction through envelope components of a building. The thermal resistance of most thermal insulation materials depends on the operating temperature. The temperature to which the insulation materials are exposed varies, depending on the thermal resistance of the materials, the location of the insulation layer within the assembly system, and the effective temperature which depends on the amount of solar radiation received on the surface of the assembly. The main objective of this paper is to investigate the change of the thermal conductivity of polystyrene insulation material in terms of the temperature at the mid-thickness of the material and its effect on the cooling load required by the building.

Keywords: operating temperature, polystyrene insulation, thermal conductivity, cooling load

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Authors: Muhammad Yousaf Ali, Shahid Mansoor, Javeria Qazi, Imran Amin, Musarrat Shaheen

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Cotton leaf curl disease (CLCuD) is the major threat to the cotton crop and is transmitted by whitefly (Bemisia tabaci). Since multiple begomoviruses and associated satellites are involved in CLCuD, approaches based on the concept of broad-spectrum resistance are essential for effective disease control. Gro-El and G5 are two proteins from whitefly endosymbiont and M13 bacteriophage origin, respectively. Gro-El encapsulates the virus particle when it enters the whitefly and protects the virus from the immune system of the whitefly as well as prevents viral expression in it. This characteristic of Gro-El can be exploited to get resistance against viruses if expressed in plants. G5 is a single-stranded DNA binding protein, expression of which in transgenic plants will stop viral expression on its binding with ssDNA. The use of tissue-specific promoters is more efficient than constitutive promoters. Transgenics of Nicotiana benthamiana for Gro-El under constitutive promoter and Gro-El under phloem specific promoter were made. In comparison to non-transgenic plants, transgenic plants with Gro-El under NSP promoter showed promising results when challenged against cotton leaf curl Multan virus (CLCuMuV) along with cotton leaf curl Multan beta satellite (CLCuMB), cotton leaf curl Khokhran virus (CLCuKoV) along with cotton leaf curl Multan beta satellite (CLCuMB) and Pedilenthus leaf curl virus (PedLCV) along with Tobacco leaf curl beta satellite (TbLCB).

Keywords: cotton leaf curl disease, whitefly, endosymbionts, transgenic, resistance

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Authors: Donna-Marie Phyllis Lanton

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Sarcopenia is a well-known geriatric syndrome characterized by the progressive and generalized loss of muscle quantity or quality. The incidence of sarcopenia increases with age and is associated with adverse outcomes such as the increased risk of falls, cognitive impairment, loss of independence, diminished quality of life, increased health costs, need for care in a skilled nursing facility, and increased mortality. Physical activity, including resistance training, is the most prevalent recommendation for treating and preventing sarcopenia. Residents (N = 23) of a skilled nursing facility in East Orlando, Florida, participated in a 90-day strength training program designed using the PARIHS framework to improve measures of muscle mass, muscle strength, physical performance, and quality of life. Residents engaged in both resistance and balance exercises for 1 hour two times a week. Baseline data were collected and compared to data at Days 30, 60, and 90. T tests indicated significant gains on all measures from baseline to 90 days: muscle mass increased by 1.2 (t[22] = 2.85, p = .009), grip strength increased by 4.02 (t[22] = 8.15, p < .001), balance increased by 2.13 (t[22] = 18.64, p < .001), gait speed increased by 1.83 (t[22] = 17.84, p < .001), chair speed increased 1.87 (t[22] = 16.36, p < .001), and quality of life score increased by 17.5 (t[22] = 19.26, p < .001). For residents with sarcopenia in skilled nursing facilities, a 90-day strength training program with resistance and balance exercises may provide an option for decreasing the incidence of sarcopenia among that population

Keywords: muscle mass, muscle strength, older adults, PARIHS framework

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Authors: Jihye Jeon

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This paper analyzes the political and economic issues that people with disabilities face related to globalization; how people with disabilities have been adapting globalization and surviving under worldwide competition system. It explains that economic globalization exacerbates inequality and deprivation of people with disabilities. The rising tide of neo-liberal welfare policies emphasized efficiency, downsized social expenditure for people with disabilities, excluded people with disabilities against labor market, and shifted them from welfare system to nothing. However, there have been people with disabilities' political responses to globalization, which are characterized by a global network of people with disabilities as well as participation to global governance. Their resistance can be seen as an attempt to tackle the problems that economic globalization has produced. It is necessary paradigm shift of disability policy from dependency represented by disability benefits to independency represented by labor market policies for people with disabilities.

Keywords: economic globalization, people with disability, deprivation, welfare cut, disability right movement, resistance

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Authors: Annisa Ulfah Pristya, Andi Setiawan

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Indonesia placed in sixth rank total Acute Respiratory Infection (ARI) patient in the world and Riau as one of the province with the highest number of people with respiratory infection in Indonesia reached 37 thousand people. Usually society using a mask as prevention action. Unfortunately the commercial mouth mask only can work maximum for 4 hours and the pores are too large to filter out microorganisms and viruses carried by infectious droplets nucleated 1-5 μm. On the other hand, Indonesia is rich with Titanium dioxide (TiO2) and purple sweet potato anthocyanin pigment. Therefore, offered Bio-nano-mask which is a antimicrobial and antiviral mouth mask with Nano-TiO2 coating and purple sweet potato anthocyanins utilization as an effective solution to high ARI patients in Riau, which has the advantage of the mask surface can’t be attached by infectious droplets, self-cleaning and have anthocyanins biosensors that give visual response can be understood easily by the general public in the form of a mask color change from blue/purple to pink when acid levels increase. Acid level is an indicator of microorganisms accumulation in the mouth and surrounding areas. Bio-nano mask making process begins with the preparation (design, Nano-TiO2 liquid preparation, anthocyanins biosensors manufacture) and then superimposing the Nano-TiO2 on the outer surface of spunbond color using a sprayer, then superimposing anthocyanins biosensors film on the Meltdown surface, making bio nano-mask and it pack. Bio-nano mask has the advantage is effectively preventing pathogenic microorganisms and infectious droplets and has accumulated indicator microorganisms that color changes which easily observed by the common people though.

Keywords: anthocyanins, ARI, nano-TiO2 liquid, self cleaning

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Authors: Fengxia Li, Lufeng Zhang, Haibo Wang

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The tight sandstone gas reservoir in the Xujiahe Formation of the Sichuan Basin has huge reserves, but its utilization rate is low. Fracturing and stimulation are indispensable technologies to unlock their potential and achieve commercial exploitation. Slickwater is the most widely used fracturing fluid system in the fracturing and renovation of tight reservoirs. However, its viscosity is low, its sand-carrying performance is poor, and the risk of sand blockage is high. Increasing the sand carrying capacity by increasing the displacement will increase the frictional resistance of the pipe string, affecting the resistance reduction performance. The variable viscosity slickwater can flexibly switch between different viscosities in real-time online, effectively overcoming problems such as sand carrying and resistance reduction. Based on a self-developed indoor loop friction testing system, a visualization device for proppant transport, and a HAAKE MARS III rheometer, a comprehensive evaluation was conducted on the performance of variable viscosity slickwater, including resistance reduction, rheology, and sand carrying. The indoor experimental results show that: 1. by changing the concentration of drag-reducing agents, the viscosity of the slippery water can be changed between 2~30mPa. s; 2. the drag reduction rate of the variable viscosity slickwater is above 80%, and the shear rate will not reduce the drag reduction rate of the liquid; under indoor experimental conditions, 15mPa. s of variable viscosity and slickwater can basically achieve effective carrying and uniform placement of proppant. The layered fracturing effect of the JiangX well in the dense sandstone of the Xujiahe Formation shows that the drag reduction rate of the variable viscosity slickwater is 80.42%, and the daily production of the single layer after fracturing is over 50000 cubic meters. This study provides theoretical support and on-site experience for promoting the application of variable viscosity slickwater in tight sandstone gas reservoirs.

Keywords: slickwater, hydraulic fracturing, dynamic sand laying, drag reduction rate, rheological properties

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Authors: Atefeh Esmailnejad, Gholamreza Nikbakht Brujeni

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Major histocompatibility complex (MHC) is one of the best characterized genetic regions associated with immune responses and controlling disease resistance in chicken. Association of the MHC with a wide range of immune responses makes it a valuable predictive factor for the disease pathogenesis and outcome. In this study, the association of MHC with cell-mediated immune responses was analyzed in commercial broiler chicken. The tandem repeat LEI0258 was applied to investigate the MHC polymorphism. Cell-mediated immune response was evaluated by peripheral blood lymphocyte proliferation assay using MTT method. Association study revealed a significant influence of MHC alleles on cellular immune responses in this population. Alleles 385 and 448 bp were associated with elevated cell-mediated immunity. Haplotypes associated with improved immune responses could be considered as candidate markers for disease resistance and applied to breeding strategies.

Keywords: MHC, cell-mediated immunity, broiler, chicken

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Authors: Alouache Souhila, Messai Yamina, Torres Carmen, Bakour Rabah

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Objective: It has often been reported an association between antibiotic resistance and virulence. However, resistance to quinolones seems to be an exception, it tends instead to be associated with an attenuation of virulence, particularly in clinical strains. The purpose of this study was to evaluate the potential virulence of 28 quinolone-resistant E. coli strains recovered from water at the inflow (n=16) and outflow (n=12) of an urban wastewater treatment plant (WWTP). Methods: E. coli isolates were selected on Tergitol-7 agar supplemented with 2µg/ml of ciprofloxacin, they were screened by PCR for 11 virulence genes related to Extraintestinal pathogenic E. coli (ExPEC): papC, papG, afa/draBC, sfa/foc, kpsMTII, iutA, iroN, hlyF, ompT, iss and traT. The phylogenetic groups were determined by PCR and clonal relationship was evaluated by ERIC-PCR. Results: Genotyping by ERIC-PCR showed 7 and 12 DNA profiles among strains of wastewater (inflow) and treated water (outflow), respectively. Strains were assigned to the following phylogenetic groups: B2 (n = 1, 3.5%), D (n = 3, 10.7%), B1 (n = 10, 35.7%.) and A (n = 14, 50%). A total of 8 virulence-associated genes were detected, traT (n=19, 67.8%), iroN (n= 16, 57 .1%), hlyF (n=15, 53 .5%), ompT (n=15, 53 .5%), iss (n=14, 50%), iutA (n=9, 32.1%) , sfa/foc (n=7, 25%) and kpsMTII (n=2, 7.1%). Combination of virulence factors allowed to define 16 virulence profiles. The pathotype APEC was observed in 17.8% (D=1, B1=4) and human ExPEC in 7% (B2=1, D=1) of strains. Conclusion: The study showed that quinolone-resistant E. coli strains isolated from wastewater and treated water in WWTP harbored virulence genes with the presence of APEC and human ExPEC strains.

Keywords: E. coli, quinolone-resistance, virulence, WWTP

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Authors: Suttijit Sriwatcharakul

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The bioactivity studies from the weed ethanolic crude extracts from leaf, stem, pod and root of wild spider flower; Cleoma viscosa Linn. were analyzed for the growth inhibition of 6 bacterial species; Salmonella typhimurium TISTR 5562, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus TISTR 1466, Streptococcus epidermidis ATCC 1228, Escherichia coli DMST 4212 and Bacillus subtilis ATCC 6633 with initial concentration crude extract of 50 mg/ml. The agar well diffusion results found that the extracts inhibit only gram positive bacteria species; S. aureus, S. epidermidis and B. subtilis. The minimum inhibition concentration study with gram positive strains revealed that leaf crude extract give the best result of the lowest concentration compared with other plant parts to inhibit the growth of S. aureus, S. epidermidis and B. subtilis at 0.78, 0.39 and lower than 0.39 mg/ml, respectively. The determination of total phenolic compounds in the crude extracts exhibited the highest phenolic content was 10.41 mg GAE/g dry weight in leaf crude extract. Analyzed the efficacy of free radical scavenging by using DPPH radical scavenging assay with all crude extracts showed value of IC50 of leaf, stem, pod and root crude extracts were 8.32, 12.26, 21.62 and 35.99 mg/ml, respectively. Studied cytotoxicity of crude extracts on human breast adenocarcinoma cell line by MTT assay found that pod extract had the most cytotoxicity CC50 value, 32.41 µg/ml. Antioxidant activity and cytotoxicity of crude extracts exhibited that the more increase of extract concentration, the more activities indicated. According to the bioactivities results, the leaf crude extract of Cleoma viscosa Linn. is the most interesting plant part for further work to search the beneficial of this weed.

Keywords: antimicrobial, antioxidant activity, Cleoma viscosa Linn., cytotoxicity test, total phenolic compound

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Authors: David Chao, John Lai, Alvin Wu, Carl Wang

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For lithium-ion batteries with multiple cell configurations, some use scenarios can cause uneven aging effects to each cell within the battery because of uneven current distribution. Hence the focus of the study is to explore the aging effect(s) on batteries with different construction designs. In order to systematically study the influence of various factors in some key battery configurations, a detailed analysis of three key battery construction factors is conducted. And those key factors are (1) terminal position; (2) cell alignment matrix; and (3) interconnect resistance between cells. In this study, the 2S2P circuitry has been set as a model multi-cell battery to set up different battery samples, and the aging behavior is studied by a cycling test to analyze the current distribution and recoverable capacity. According to the outcome of aging tests, some key findings are: (I) different cells alignment matrices can have an impact on the cycle life of the battery; (II) symmetrical structure has been identified as a critical factor that can influence the battery cycle life, and unbalanced resistance can lead to inconsistent cell aging status; (III) the terminal position has been found to contribute to the uneven current distribution, that can cause an accelerated battery aging effect; and (IV) the internal connection resistance increase can actually result in cycle life increase; however, it is noteworthy that such increase in cycle life is accompanied by a decline in battery performance. In summary, the key findings from the study can help to identify the key aging factor of multi-cell batteries, and it can be useful to effectively improve the accuracy of battery capacity predictions.

Keywords: multiple cells battery, current distribution, battery aging, cell connection

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