Qatar Foundation Annual Research Conference Proceedings Volume 2014 Issue 1
- تاريخ المؤتمر: 18-19 Nov 2014
- الموقع: Qatar National Convention Center (QNCC), Doha, Qatar
- رقم المجلد: 2014
- المنشور: ١٨ نوفمبر ٢٠١٤
101 - 200 of 480 نتائج
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A Framework For Assessing Soil, Climate And Market Constraints To Improve Food Security In Qatar
المؤلفون: Abul Huda, Simeon Kaitibie, Phil Moody, Munshi Haq, Abukari Issaka, Kenzu Abdella, Ahmed Moustafa, Ipek Goktepe, Kep Coughlan, Marco Pollanen and Noel VockImproving agricultural production in Qatar faces a number of challenges mainly related to adverse climatic conditions, quality of soils, scarcity of irrigation water, inappropriate crop rotations, market constraints and ineffective agricultural subsidies. Strategies to overcome these problems may include a) increasing domestic production in Qatar by using a combination of high-tech water-efficient field and greenhouse production systems focussed on high quality end-products to fill gaps in the supply market, and b) land purchase and contract farming of broad-acre crops in more resource-rich countries such as Australia. Qatar produces only about 8-10 percent of food consumed, yet domestic production is significantly constrained by lack of market access. In this paper, a holistic framework is developed for assessing climate, soil and market constraints, and for generating an optimized list of food crops that could be grown under output price uncertainty and severely limiting arable land and water conditions in Qatar. Components of the framework include assessing the yield potential of selected crops through simulation modelling using historical climate and soils data. In a case study using wheat as a selected crop, potential yields were simulated using soils and long-term climate data for five Australian locations. These locations are Dalby in Queensland; Trangie and Junee in New South Wales; Esperance and Jerramungup in Western Australia. An assessment has been made of the site/soil constraints to identify yield limiting factors. In addition, the module will be adapted to identify suitable locations for producing vegetable crops in Qatar. Soil and climate data from five locations in Qatar (Al Sulaiteen Agricultural and Industrial Complex site, Qatar University Farm site, Arab-Qatari Farm site, Outoriya, and Rodhat Al Faras) are being collected for this purpose. The framework will be informed by a large amount of historical data in Qatar, including crop types and yield, land and water use coefficients, food import and export data, food prices, and food preferences. Output obtained from the framework will allow Qatari investment operations in Australia and other countries to determine the best locations for wheat production. At the same time we will generate a prioritized list of profitable vegetables that can be grown in Qatar in order to improve the food security situation. The findings of this paper will contribute towards achieving the goals of our research project "Improving Food Security in Qatar: Assessing Alternative Cropping Systems Feasibility and Productivity in Variable Climates, Soil and Marketing Environments" (NPRP6-064-4-001) funded by Qatar National Research Fund (QNRF) through its National Research Priority Program.
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Zinc Oxide Nanostructures For High Efficiency Solar Cells
المؤلفون: Amir Abdallah and Nouar TaebtThe main two challenges hindering the deployment of solar cells in large scale are the high cost and low efficiency. One of the strategies to reduce the cost is by using thin film materials with enhanced solar cell conversion efficiency. However, thin film materials suffer from weak absorption and the presence of defects, which act as recombination canters for charge carriers. Various studies were conducted to improve absorption in thin film solar cells. However, those approaches are not optimized yet for high efficiency solar cells. In this study, we focus on enhancing light absorption of thin film silicon solar cells by using Zinc Oxide (ZnO) nanostructures.
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Innovative Non-specific Elemental And Molecular Fingerprint Strategy For Produced Water Before Reuse
المؤلفون: Hugues Preudhomme, Claude Sadois, Philippe Julien, Genevieve Lebas and Basem ShomarBackground and Objectives Produced water for future reuse is a key component of Qatar's Water Security Grand Challenge (WSGC) and forward progress within the Grand Challenge is dependent on comprehensive characterization and potential risks. To date, only major compounds of produced waters are characterized. For safety reason, a global fingerprint of both natural and anthropogenic trace organic and inorganic constituents must be created before any treatment or reuse. The main objective of this innovative strategy is to reach an accurate, non-specific monitoring of organic and inorganic ultra-trace compounds by mass spectrometry. Methods Produced water samples were collected in Qatar's oil field from various Qatar's produced wells with a high water cut in order to evaluate the water quality and to select produced waters for further studies for treatment and reuse. To highlight the benefit of this innovative analytical approach, the study was focused on highly hydrophilic compounds which remain in the aqueous phase even after oil separation. Naphtenic acids, Fluorinated acids, BTEX biodegradation byproducts, halo acetic acids, and trace metals (Ni, Cr, Fe, Cd, U etc.) are related to produced water characteristics, oil and gas industry and well tubing. The quantifications were firstly completed by UHPLC-ESIqQqTOF Maxis HD (Bruker) and by ICP-MS Aurora Elite (Bruker). All analyses were performed in QEERI laboratories. The direct analyses of produced water were based on synergic used of ultra high pressure liquid chromatography, non-specific high resolution and inductively coupled plasma mass spectrometry. The development of robust, accurate and high end methods allows us to generate high quality data for immediate chemical information extraction, long term inter sample comparison and long term raw data storage for further studies. The in silico storage of water's nonspecific fingerprint is an interesting and promising alternative to long term storage of diluted media like water samples which are always critical. Results The current study was performed using Qatar's produced waters and on Congo and Angola's produced waters as reference waters. Despite the sub-ppb level quantification limit, the results of Qatar's produced waters analyzed do not show significant trace of halogenated acetic acids, perfluorinated compounds or BTEX biodegradation byproducts in comparison to the African's produced waters. Trace elements and radionuclides analysis are currently ongoing. Conclusions Here, we introduce innovative analytical strategies on produced water by synergic used of high resolution and multi-elemental mass spectrometry for accurate fingerprint on organic and inorganic ultra-trace contaminants study of water characteristics. Its part of an ongoing process focused on optimizing and developing analytical approaches suitable for Qatar's produced water quality prior to sustainable reuse. The methodology developed (isotopic dilution, standard addition…), is the first bimodal study of its kind. It can be used in the future to perform a non-specific screening of ultra-traces acids, metals and radionuclides compounds. The relative analytical results are being used to drive research efforts within the WSGC.
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Advanced Hard Coatings: Towards A Whole New World
BACKGROUND & OBJECTIVES: Improving materials properties is one of the biggest scientific issues of all the times. When it becomes impossible to further manipulate the raw material, one feasible way to push its properties beyond the theoretical limits is to modify the properties of the surface. That is where advanced surface coatings come in. From a manufacturing point of view, tools for machining are of particular interest. These tools are usually made of hard steels and cemented carbide (WC-Co). For specialized applications, such as aluminium machining, diamond or polycrystalline cubic boron nitride are also used. The main problem with steel, is that it exhibits a relatively low hardness (below 10 GPa) which strongly decreases upon annealing above about 600 K. Thus, the majority of modern tools are nowadays coated with hard coatings, in order to: (i) increase the hardness, (ii) decrease the coefficient of friction, and (iii) protect the tools against oxidation. A similar approach has been recently used to obtain a longer duration of the dies for aluminium die-casting. Multi-component and nanostructured materials represent a promising class of protective hard coatings due to their enhanced mechanical and thermal oxidation properties. METHODS: Three different thin hard nitrogen-rich coatings were mechanically, microstructurally, and thermally characterized: (i) a 2.5 micron-thick nano-layered CrN-NbN, (ii) a 11.7 micron-thick monolayer TiAlN, and (iii) a 2.92 micron-thick multilayer AlTiCrxNy. The main feature of the CrN-NbN coating is the fabrication by the alternate deposition of 4 nm thick-nanolayer of NewChrome (new type of CrN, with strong adhesion and low coating temperature). All the three coatings can reach values of hardness and elastic modulus exceeding 20 and 250 GPa, respectively. Their main applications include stainless steel drawing, plastic materials forming and extrusion, and aluminum alloys die-casting. The here studied TiAlN (SBN, super booster nitride) is one of the latest evolution of TiAlN coatings for cutting applications, where maximum resistance to wear and oxidation are required. The AlTiCrxNy combines the very high wear resistance of the Cr-coatings with peculiarities of the Al-containing coatings, such as high thermal stability and high-temperature hardness. All the coatings were deposited on a S600 tool steel. The coatings were subjected to two different thermal cycling tests: (i) 100 thermal cycles consisting of 60 s dwelling time, respectively at the high- (573 to 1173 K) and at the room-temperature, and (ii) 100 thermal cycles consisting of 115 s dwelling time, at same temperatures of the first test, followed by 5 s dwelling at room-temperature. The temperature induced hardness and elastic modulus coating variations were measured by nanoindentation. RESULTS: During thermal cycling, the TiAlN monolayer coating and the AlTiCrxNy multilayer coating showed a high oxidation resistance even at high temperature, while the CrN-NbN nano-layer coating undergoes a oxidation phenomena, for temperatures above 873 K. CONCLUSIONS: The investigated coatings showed a sufficient-to-optimal thermal response either in terms of mechanical stability, such hardness and elastic modulus, and in terms of oxidation degradation.
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Test Sample Development And Test Procedures For Establishing A Chloride Stress Corrosion Cracking Corrosion Atlas For Qatar
المؤلفون: Hanan Farhat, Roy Johnsen and Demian RoulstonTest Sample Development and Test Procedures for Establishing a Chloride Stress Corrosion Cracking Corrosion Atlas for Qatar H. Farhat*, R. Johnsen** & D. Roulston** Abstract Oil and gas production, and petrochemical plants in offshore and onshore locations in Qatar are exposed to severe environmental conditions. The combination of high humidity, high concentration of chloride ions, high temperature and the presence of residual tensile stresses due to welding or other forming process make these facilities susceptible to chloride-induced stress corrosion cracking (CSCC). High temperature causes seawater to evaporate, condensate, and dry on metal surfaces, thereby enhancing local build-up of aggressive species, such as chloride on the metals' surfaces. If the surface of the metal is insulated, the condensate may be trapped under the insulation leading to high localized corrosion damage. This is complicated by sand storms which leave sand particles with aggressive species such as chloride and sulfide on the surfaces exposed to this environment. A corrosion atlas for chloride stress corrosion cracking was developed in Qatar. Seven different stainless, duplex and high nickel alloy steels were investigated. One hundred samples of each material were exposed to a stress equivalent to 80% and 100% of their yield strength. They were then, distributed in different onshore and offshore sites for Qatar Petroleum, and were inspected periodically for CSCC. The temperature, humidity and time to failure were recorded. This paper describes the samples, and sample rack design, testing procedure, as well as the stress application method applied to the samples. *College of the North Atlantic-Qatar ** Qatar Petroleum Research and Technology Department
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Highly Efficient Electrocatalysts For Recycling Co2
المؤلفون: Shahid Rasul and Kazuhiro TakanabeThe development of artificial photosynthesis is one of the greatest scientific challenges of our times, not only to protect the environment but also to ensure global economic security. To mimic the natural photosynthesis process, a complete understanding of the natural photosynthesis process at the molecular level is essential to enable the production of inexpensive, lightweight, and high-energy-density fuels. Artificial photosynthesis may involve photo/electrocatalytic H2 generation by water splitting or the use of H2 in combination with atmospheric/industrially sourced CO2 conversion products to provide a continuous supply of high-energy carrier fuels at small/medium scales. Recently, Cu2O has received considerable attention in various energy-conversion applications, including photo/electrochemical hydrogen production and the photo/electrochemical conversion of carbon dioxide (CO2) to energy-carrier fuels. The Cu(I) state, with its d10 electronic configuration, is required for cuprous oxides to exhibit photo/electrochemical and chemical catalytic activity. For electrochemical CO2 reduction, Cu(I) sites are proposed to stabilize reaction intermediates such as CO, carbonates (CO23−), formates (HCOO−), and methoxy (H3CO−) adsorbates, as expected from their high heats of adsorption. Although the Cu(I) state makes these materials attractive, the stability of Cu(I) species toward redox reactions remains an issue to be solved. In this study, we report the novel design of multi-metal based electrocatalysts which may introduce different (other than Cu) active species due to effect of the hetro-atoms on the Cu surface. As a result the reaction intermediates on the surface may be stabilized generating CO exclusively as a reaction product of electrochemical reduction of aqueous CO2 while suppressing the competitive H2 generation. The higher selectivity towards CO generation may be attributed to perturbing the d-band metal center or the geometric effects caused by the second metal center around Cu.
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Effect Of Sewage Sludge Application And Method Of Seeding On The Yield Of Barley Using Surface And Sprinkler Irrigation
المؤلفون: Basel Ahmad Alar'raj and Henda MahmoudiArid regions in the world occupy about one quarter of the land surface area. In such regions, satisfactory crop production is impossible without irrigation because of irregular, sporadic and unpredictable rainfall leading to water shortage subsequently supplemental irrigation is a must for reasonable yield. Soil in these regions has poor physical and chemical properties. Since sludge is a source for organic matter and contains many essential nutrients for plant it can be used in these areas to improve soil physical condition and fertility status of such soil. On the other hand a proper irrigation system with proper seeding method will lead to maximum yield. The objectives of current research are to compare the effects of two irrigation systems (sprinkler and surface) on the yield of barley crop in sludge amended arid soil with different sewage sludge rates and to compare the effects of traditional and modern method of seeding. Two experiments were conducted. The first experiment was split plot in randomized complete block design and consisted of two irrigation methods (surface and sprinkler) with four replications. The split plot treatment were two seeding methods the row seeding to a depth of 5 cm and in pre-established furrows of 35 cm depth (5 cm below the bottom of the furrow). Sludge was added at a rate of 30 ton/ha. Results indicated that furrow seeded under diked end surface irrigation treatment produced significantly the highest barley yield because it increases water storage by increasing the infiltration opportunity time. Also the furrows worked as water catchments which reduced run-off. The second experiment was randomized complete block design with four replications. Sludge was added at four different rates (0, 10, 30 and 60 ton/ha). Barley was planted using diked furrow seeding and irrigated by sprinklers. The highest significant barley yield was at 30 ton sludge/ha treatment. The significant increase in barley yield due to sludge is attributed to the increase of soil fertility status by sludge addition as well as to the improvement of soil chemical and physical properties. Using furrow seeding with diked surface irrigation in crusted soils increased barley yield significantly owing to the increase in soil water availability and controlling salinity in the root zone through leaching that affected the yield.
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Roasted-modified Date Pits In Remediation Of Bromide Ions From Desalinated Water: Kinetic Studies
Disinfection of drinking water is one of the extreme public health activities in Qatar. Chlorination, ozonation, ultra-violet, chloramination, and others are the most important treatment processes used and they can cause the formation of toxic by-products. The existence of bromide (Br-), for example, in water sources might cause in formation of brominated toxic by-products. Up-to-date drinking water treatment methodologies are challenged to successfully eliminate Br- before final consumption. Remediation onto activated carbons has a number of restrictions. Date pits are suitable as raw remediating adsorbent for preparing various modified adsorbents, because particular surface functional groups and the micro-pore structures can be attained by active modifications. The overall objective of this study was to develop an economical and environmentally acceptable process to safely eliminate the levels of Br- from desalinated water. Roasted date pits (RODPs) and activated charcoal (AC) (used as a control) were crushed and sieved with four different particles size ranges. The percentage of Br- removal was also studied under different experimental conditions such as pH, sorbent mass and initial concentration. In addition, surface characterization was also investigated. Experimental date analyses were investigated using different isotherm and kinetic sorption models. The modification of the date pits surface enhanced the Br- removal capacity at high initial concentration of bromide (200 ppm) by 27%. Using scanning electron microscope (SEM), the date pits surface images showed a different in pore sizes upon modification. Removal capacity of RODPs reached 39% at pH 4. In this study the heterogeneity of adsorbing mechanisms and the fitting with pseudo second order model and inter particulate diffusion models were concluded, and more than 35% of Br- removal efficiency was achieved within the RODPs at the first hour of contact time. The adsorption Br- onto RODPs was not fitted well with the pseudo-first order model. It was found that the kinetics of Br- adsorption was followed the pseudo-second order. It was also observed fluctuations in the removal efficiency for smaller particle sizes; indicating heterogeneity of adsorption/desorption and potential chemical bindings, this particular behaviour was not observed and investigated elsewhere in the literature (Figure below). The surface of RODPs contains oxygen functional groups such hydroxyl; hence the presence of such functional groups on the surface of date pits considerably influences on the adsorption mechanism of organic and inorganic compounds on the RODP. Economically RODPs are successfully used to remove Br-, comparing to AC. However, both adsorbents have nearly the same removal efficiency after one hour contact time. Apparently, the removal efficiency of both systems was quite significant. This may cover the way for the cheap and widely available date pits to be used as an adsorbent in water purification process.
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Expression Patterns Of Genes Encoding Antioxidative Enzymes In Date Palm(phoenix Dactylifera) In Response To Salinity Stress
Background Salinity is one of the major abiotic stresses threatening crop productivity worldwide. Plants exposed to severe salinity suffer ionic toxicities, osmotic stress and oxidative damage that lead to inhibition of active photosynthesis, reduction of growth and cell death. Plants ability to detoxify reactive oxygen species (ROS, free radicals) and avoid oxidative damage is considered as one of the important mechanisms to cope with salinity. Accumulation of ROS causes oxidation of various cellular components, damage to DNA and proteins, and can lead to oxidative destruction of the cell. Detoxification of ROS in plant cells is controlled by a combination of antioxidants such as ascorbate (AsA) and glutathione (GSH), and antioxidative enzymes such as superoxide dismutase (SOD), ascorbate peroxidase (APX) and catalase (CAT). Antioxidative enzymes involved on the regeneration of AsA and GSH such as monodehydroascorbate reductase (MDAR) and glutathione reductase (GR) are essential to maintain active pools of both antioxidants. Objectives: The aim of this work was to analyze the expression patterns of the date palm genes encoding antioxidative enzymes under various levels of salt stress. Material and methods: Similar plantlets of date palm cultivar (Khalas) were selected for all treatments in MS medium. Plantlets were subjected to various concentrations of NaCl (100mM, 200mM, 300mM and 400 mM) in addition to control. The expression analysis was performed by RT-PCR Results and Conclusions: The expression patterns of the date palm genes encoding antioxidative enzymes under various levels of salt stress was analyzed. Results showed that remarkable induction of PdCAT, PdGR, PdMDAR, PdSOD and PdAPX was observed. Highest induction of PdCAT and PdGR was observed at 100 mM NaCl while PdMDAR maintained its highest expression at up to 400 mM NaCl. Following salt exposure time course, all the genes maintained up-regulated expression levels up to 6 days compared to control conditions. Moreover, a high and steady induction of glutathione S-transferase (PdGST) was observed, the enzyme that plays key roles in the detoxification of xenobiotics compounds and oxidative stress mechanism. These results suggest that antioxidative enzymes involved in either ROS detoxification or antioxidants regeneration may play crucial roles in the tolerance of date palm to salt stress.
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The Sabkhas Of Qatar: An Ideal Place To Study The Origin Of Dolomitic Hydrocarbon Reservoir Rocks
Many hydrocarbon reservoirs - in Qatar and worldwide - are constituted of dolomite. For this reason, the origin of this Ca-Mg carbonate mineral has been extensively studied by generations of geologists, with the goal of exploiting gas and oil from rock reservoirs in the most efficient way. However, despite more than two centuries of research, several fundamental questions regarding the origin of sedimentary dolomite remain without a convincing answer. Recent research conducted in the field of geobiology suggests that dolomite formation may be the result of a microbial process, that is, organic molecules that in natural environments are produced by microorganisms seem to play a key role for dolomite nucleation at low temperatures in many geological settings. However, this innovative hypothesis is far from being unanimously accepted by the scientific community, and many details on the exact mechanism through which microorganisms mediate dolomite formation are still to be fully understood. The aim of this contribution is to summarize the most recent scientific studies that support the microbial model for dolomite formation, providing examples from culture experiments conducted in the laboratory using artificial growth solutions and from modern dolomite forming environments, such as the hypersaline lagoons located in the State of Rio de Janeiro (Brazil), the sabkhas of Abu Dhabi (UAE), and the sabkhas of Dohat Faishakh and Khor Al-Adaid (Qatar). Furthermore, we will elaborate on why we consider the coastal sabkhas of Qatar to be among the most ideal places on Earth where it is possible to study microbe-mineral interactions in evaporitic environments. In fact, thanks to the distinctive geology that characterizes this region, it is possible to obtain samples documenting the progressive transformation of the living microbial mats that mediate dolomite formation and other authigenic minerals into a fully lithified sediment, which is analogous to dolomite formations constituting economically important gas/oil reservoir rocks. This approach will provide key insights to test whether dolomite present in ancient evaporitic sequences can be interpreted as a fully biological product associated with early diagenesis or whether most of the dolomite forms during later stage metamorphic/replacement events that are controlled by purely abiotic processes. Finally, considering not only the scientific importance but also the aesthetic beauty of the Qatari evaporitic environments, we will discuss the idea and the challenges of transforming selected areas of the modern sabkhas into geoparks - protected natural reserves that would be of interest for the local Qatari population, as well as for tourists visiting Qatar.
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Life Cycle Assessment Of Bio Diethyl Carbonate
المؤلفون: Hind Mamlouk, Christian Nissing and Daniel Curulla FerreDue to the continuous increase in Earth's atmosphere of carbon dioxide, under the threat of climate change, green processes based on chemical fixation of CO2 have recently attracted much attention. A systematic and standardized methodology to evaluate environmental impacts of products is life-cycle assessment (LCA). Along the entire life cycle, all material and energy flows are collected. These flows are linked to potential environmental impacts such as global warming and resource depletion, among many others. The approach of LCA allows understanding the different life-cycle stages of our processes and their environmental impacts. Therefore, LCA seems a suitable methodology for evaluating the environmental impacts of CO2. The aim of this TOTAL study is to investigate and to qualify the environmental performance of bio diethyl carbonate (bioDEC) as compared to a fossil fuel in terms of greenhouse gas emissions by means of a Life Cycle Assessment (LCA). The bioDEC synthesis process, from CO2, used as raw material, and bioethanol is studied, where bioethanol is used from three different biomass feedstocks, namely sugar cane, sugar beet and corn. These different biomass feedstocks will give different diethyl carbonate (DEC) synthesis routes. The results were compared to a fossil fuel (gasoline) and ethanol. To facilitate this goal, the study intends to consider the bioDEC molecule as a whole, taking into account the part of its origin from the CO2 raw material. For this purpose, different system boundaries were considered, showing that the CO2 raw material flow can be considered as neutral throughout the system considered, whatever its origin (CO2 raw material input is equal to related CO2 emissions released during combustion of final fuel). In summary, it can be stated in this study that all investigated bioDEC cases are alternatives to fossil gasoline as they emit less GHGs. When comparing bioDEC and ethanol as final fuels, one observes that ethanol has the better environmental performance of both fuels when considering the same feedstock. That means that for improving the environmental performance, from a GHG emissions perspective regarding bioDEC, we have to consider the following points: * Utilization of ethanol as final fuel without further processing to bioDEC, * Production of bioDEC from another ethanol feedstock, * Utilization of bioDEC as a structural molecule (example plastics) and not as a fuel. We report here the description of the bioDEC product and its pathways, the GHG emissions calculation, the life cycle inventory and the results of life cycle impact assessment.
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Peripheral Co2 Flooding To Enhance Gas Recovery In Carbonate Reservoir
المؤلفون: Tarek Ali, Karim Youssef and Michael FraimManagement of production from gas reservoirs can be a challenging process. The challenge gets bigger when the reservoir is characterized by having a small pore size, such as the tight carbonate reservoirs which are prominent in this part of the world. In such conditions, condensate blockage becomes a real threat to productivity. Carbon dioxide can be injected into the reservoir to combat this threat. We built a reservoir model to conduct a simulation study with the goal of finding the most feasible method for overcoming the negative impact of condensate formation. We have attempted to simulate huff-n-puff enhanced gas recovery in the same reservoir model, but this method did not achieve much success in alleviating the damage caused by condensate blockage. As a result, according to the model and data we collected, using huff-n-puff is not efficient since it failed to maintain the average reservoir pressure as well as CO2 did, therefore peripheral CO2 injection have been tested. The minimum requirement again is to achieve gas plateau production, while also maximizing the condensate recovery and minimizing the CO2 breakthrough into the wells. It was decided that seven CO2 injector wells were to be placed at strategic locations (injectors have been planned to be drilled away from the reservoir and producing wells) across the field in order to enhance the sweeping of condensate as well as minimize CO2 breakthrough. In other words, the injectors had to be at a distance where it can achieve all our simulation objectives. We ended up understanding the effect of the CO2 injection on condensate formation. As a result, it could be notice how the saturation of oil is high near the producing end of the core, this kind of saturation can completely nullify the relative permeability of gas, whereas after using CO2 flooding, the saturation is decreased significantly and the amount of condensate throughout the core is also much less.
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Adsorptive Desulfurization Of Thiophene, Benzothiophene And Dibenzothiophene From Model Fuel By Carbons Derived From Waste Rubber Tires
المؤلفون: Tawfik A. Saleh and Ibrahim DanmalikiThe removal of sulfur compounds from petroleum is increasingly important. In addition to its contribution to form particulate pollution, sulfur emission may cause some health problems. Regarding the negative impact of sulfur in industry, small amount of sulfur may poison the catalysts or diminish its efficiency. A commonly used method for the removal of sulfur-bearing species from fuel is hydrodesulphurization. However, due to the regulations required removal of sulfur to very low levels, several alternative technologies have also been reported for sulfur removal from liquids such as catalytic oxidation, biological sulfur removal and membrane separation. Desulfurization by adsorption has been regarded as the most promising approach. In this work, porous activated carbon was derived from waste rubber tires. Then, it was characterized by means field emission scanning electron microscopy, energy-dispersive X-ray, X-ray diffraction and Fourier transform infrared spectroscopies. The carbons then were used as adsorbents for adsorptive desulfurization. Model fuel samples with known amounts of thiophene, benzothiophene and dibenzothiophene compounds were prepared and used to test the efficiency of the derived carbons for adsorptive desulfurization. The amount of compounds adsorbed was found to follow the order of dibenzothiophene > benzothiophene > thiophene. Adsorption process was found to well fit pseudo second-order kinetic model. The adsorption mechanism was studied by intraparticle diffusion model. The experimental data were fitted to Langmuir, Freundlich and Temkin isotherm models. Adsorption capacity is governed by chemical interaction and pore volume of the adsorbents. The results revealed that Freundlich isotherm provided a better fit to the experimental data. The developed sorbent exhibited the advantages of being inexpensive and of double benefit to the environment.
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Trends In Aerosol Optical Thickness Over The Middle East: Impacts On Solar Power Generation
المؤلفون: Mohammed AyoubQatar and the region are experiencing transformative growth over relatively very short periods of time, due primarily to hydrocarbon based energy resources. As the country pushes to meet growing global demand for its finite fossil fuel reserves, it is looking also to capitalize on renewable energy sources including solar power generation. However, the high ambient humidity, high annual average surface temperature, high atmospheric aerosols including haze, secondary organic aerosols and dust particulates, all negatively impact the efficiency of solar power generation technology. We will present over ten years of Aerosol Optical Thickness (AOT) measurements from both ground and satellite based remote sensing data from NASA's Aerosol Robotic Network (AERONET) and Multi-angle Imaging SpectroRadiometer (MISR) instrument onboard the TERRA satellite. AOT is a measure of the atmosphere's ability to attenuate incoming solar radiation. As AOT increases, surface insolation decreases which in-turn decreases the theoretical limit for solar power generation. The data shows a net positive trend in AOT of >1% per annum over most of the Arabian Peninsula, including Qatar. The positive trend is associated with increased intensity of dust events, but not necessarily in the frequency of the events. The trend is observed over the operational spectral range of Photovoltaic (PV) cells (340-1020 nm.) The AOT trend is positive for all months of the year, except November, but exhibits a strong seasonal signature that indicates the dusty months are becoming dustier (March through July) and less productive for solar power generation. Trends in the angstrom parameter, an indicator of the size of the atmospheric aerosols, during the less dusty winter months, indicate an increase in the average size of the atmospheric aerosols, i.e. the winter months too are becoming dustier. Work continues on quantifying the net impact of the observed trend on solar power generation.
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A Systematic Approach To Carbon Footprint Reduction Stategries In Industrial Parks
المؤلفون: Dhabia Al-mohannadi and Patrick LinkeGlobal concerns of the effects of increased carbon dioxide emissions have pushed policy makers to adopt strict emission targets .The introduction of such targets will require strategies to achieve them in efficient ways. In Qatar, the world highest per capita carbon emitter, stationary emission sources are responsible for the majority of the country's footprint. Concentrated in industrial parks or clusters emissions cuts would be more significant and efficient to achieve as part of a national emission reduction strategy. Conventional mitigation techniques involve fossil fuel replacement, increasing energy efficiency and the use of carbon capture and sequestration. This research proposes an alternative method based on utilization or conversion of carbon dioxide within the industrial city. Carbon dioxide can be chemically or biologically converted into fuel, polymers, food supplements, fodder or another value added product could be used in applications of enhanced oil and gas recovery. Based on concepts of classical network design and Industrial Ecology (IE), a systematic approach was developed to obtain a cost-optimal network of carbon reduction. The integrated analysis of utilization options together with the capture, separation, compression and transmission of carbon dioxide will be required to determine the most economically attractive footprint reduction solutions. The optimization was illustrated using a case study.
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Power Monitoring In Integrated Circuits
المؤلفون: Anas Al BastamiPower monitoring is needed in most electrical systems, and is crucial for ensuring reliability in everything from industrial and telecom applications, to automotive and consumer electronics. Power monitoring of integrated circuits (ICs) is also essential, as today ICs exist in most electrical and electronic systems, in a vast range of applications. Many ICs have functional blocks across the chip that are used for different purposes. Power ICs also have multiple circuit blocks, each performing their own function. Measuring circuit block currents in both analog and digital ICs is important in a wide range of applications, including power management as well as IC testing and fault detection and analysis. For example, the presence of different kinds of faults in IC circuit blocks during IC fabrication causes the currents flowing through these circuit blocks to change from the expected values. There has been general interest in monitoring currents through different circuit blocks in an attempt to identify the location and type of the faults. Previous works on nonintrusive load monitoring as well as on power-line communications (PLCs) provide motivation for the work presented here. The techniques are extended and used to develop a new method for power monitoring in ICs. Most solutions to the challenge of measuring currents in different circuit blocks of the IC involve adding circuitry that is both costly and power consuming. In this work, a new method is proposed to enable individual measurement of current consumed in each circuit block within an IC while adding negligible area and power overhead. This method works by encoding the individual current signatures in the main supply current of the IC, which can then be sensed and sampled off-chip, and then disaggregated through signal processing. A demonstration of this power monitoring scheme is given on a modular discrete platform that is implemented based on the UC3842 current-mode controller IC, which can also be used for educational purposes.
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Optical Properties And Surface Structure Of Anatase Tio2 For Solar Cells
المؤلفون: N.h JufairiTitanium dioxide (TiO2) films have been prepared by sol-gel dip coating technique, using titanium isopropoxide (TIP) as precursors. The structure and the phase of TiO2 films were analyzed by x-ray diffraction (XRD) and showed that films were anatase. Optical properties of the films were characterized by ultraviolet-visible (UV) spectroscopy. The optical band gap was calculated for anatase film layers 50, 100, 150 and 200nm as 3.95, 3.87, 3.75 and 3.70eV, respectively. The refractive index of these films was computed by ellipsometry which were in range from 1.9 to 2.3 at a wavelength range from 380 to 600nm. The thickness of the films was obtained from ellipsometry as of 58nm per one dip. The surface of TiO2 thin films were investigated by sanning electron micropscpe (SEM). The images obtained by SEM show cracks and shrinkage particles in the film. Whereas, the images obtained by atomic force microscope (AFM) showed a homogeneous distribution of elongated shapes of nanoparticles through the film. In addition, the composition of TiO2 thin films checked via energy dispersive spectrometer (EDS), which found small amount of Ti. The results showed that anatase titania (TiO2) nanomaterials have a promised potential for applications in solar cells.
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Synthesis Of Transition Metal Nanoparticles Using Combustion Based Techniques
المؤلفون: Anchu Ashok, Anchu Ashok, Anand Kumar and Yussuf Olasunkanmi KutiSolution combustion synthesis (SCS) is a widely used technique for synthesizing variety of high purity oxide nanoparticles. Two basic modes for combustion synthesis are the self-propagating high temperature synthesis (SHS) and Volume Combustion Synthesis (VCS). The first method is based on the reaction that is locally ignited by an external source (laser, tungsten coil etc) which ends up with an exothermic redox reaction in a self-sustained manner without requiring any further energy for the combustion. Second method is the uniform heating of the entire sample in a controlled manner using a constant heat until the reaction occurs simultaneously throughout the volume. SCS typically involved a self-sustained reaction in a homogeneous solution of oxidizer (metal precursor) and oxygen containing fuels (urea, glycine, hydrazine etc). The selection of fuel is based on the reactive groups such as amino, hydroxyl and carboxyl bonded to a hydrocarbon chain. In our total work, we used two modes of synthesis: VCS and ILCS (impregnated layer combustion synthesis) to synthesize transition metal nanoparticles. The precursors used in this work were Nickel nitrate hexahydrate, Ni(NO3)2.6H2O, Copper nitrate hexahydrate, Cu(NO3)23H2O, Cobalt nitrate hexahydrate, Co(NO3)2. 6H2O and Glycine CH2NH2COOH. The ratio of metal nitrates and glycine were optimized to give pure metals of high surface area. The precursors were thermally analyzed using TGA/DTA to understand the metal phase development with increasing temperature. Phase Composition and average particle size were analyzed using XRD and the specific surface area of the synthesized particle was calculated using BET method, while its morphology was analyzed by SEM. The objective of our work is to synthesize nanoparticle with high surface area, selectivity and reactivity, which will be more suitable to be act as catalysts for electrochemical reaction in the conversion of CO2 to valuable products The XRD calculations indicated crystallite size to be in the range of 8nm - 15 nm indicating small nanoparticles with high surface area suitable of catalytic applications. The XRD profile of Copper-Nickel in glycine for different stiochiometric ratios shows the presence of pure alloy of Copper Nickel at its higher value of ?, say it as 1.75. The multiple peaks in XRD for its lower stiochiometric ratio indicates the presence of oxide. The objective of our work is to synthesize nanoparticle with high surface area, selectivity and reactivity, which will be more suitable to be act as catalysts for electrochemical reaction in the conversion of CO2 to valuable products The large surface area for Copper Nanoparticles were synthesized first which having large surface active sites, they become excellent catalysts in metallurgical and petrochemical Investigation has been done based on the basic mechanism to describe the phase transformation in the combustion front. The SEM analysis pointed a remarkable change in the particle distribution, grain size, porosity and its microstructure by changing the oxidizer/ fuel ratio These nanoparticles are currently being investigated for catalytic reduction of CO2 to valuable chemicals.
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Thermodynamic Analysis Of Heat And Mass Transport Phenomina In Phase Change Regenerators With Conductive Packing
المؤلفون: Abdelhakim Mohamed Hassabou, Markus Spinnler and Wolfgang PolifkeThis paper discusses a comparative study on the role of conductive packing in Humidification-Dehumidification (HDH) solar desalination cycles under steady state conditions. Experimental and theoretical studies have been performed at the Technical University of Munich, Germany on HDH desalination system equipped with phase change material (PCM) encapsulated in spherical plastic shells and used as a conductive packing media in the evaporator and condenser. Moreover, a solar collector and an external PCM thermal storage are used to drive the HDH plant. The external PCM thermal storage is used to guarantee continuous operation of the plant day and night round the clock under the transient behaviour of solar irradiation. The objective of using PCM elements in the evaporator and condenser was for heat storage as a backup during cloudy hours or for part-time night operation. During analysis of steady state conditions, it was discovered that the PCM packing media seem to enhance their thermal performance through locally establishing multiple-effects of heating/humidification (MEHH) and cooling/dehumidification (MECD) while air passing through the successive packing layers in the evaporator and condenser respectively. The multiple-effect phenomena are attributed solely to existence of conductive packing media, which act as heat and mass exchangers. Thus, the focus of the study lies on the thermal conductivity rather than the thermal capacity or solid-liquid phase change processes of the packing in the two columns. The performance of the evaporator and condenser technologies filled with PCM as a conductive packing was examined experimentally in comparison with empty spherical shells with the same size as well as with a conventional industrial plastic packing with high specific surface area. Comparisons were made between different packing types under similar operating conditions to examine the thermal behavior of the evaporator and condenser at atmospheric pressure. Transient simulation models for the individual components in the HDH system have been established and validated against experimental measurements. Using both experiment and simulation, a detailed heat and mass transfer analysis for the performance of the evaporator and condenser over a wide range of operation conditions under steady state has been performed using different types of packing materials. Furthermore, a yearly parametric analysis for the whole HDH plant has been performed under real weather conditions for two locations in Egypt. The overall performance analysis focuses on the optimum operation conditions of the HDH system, with optimum conductive filling material, with and without external PCM thermal buffer.
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Qatalum's 1st Cut Spl; Treatment And Applications
المؤلفون: Omar Al-jarod and Aboubakr AbdullahSpent Pot Lining (SPL) is produced in thousands of tons annually as a waste from the aluminum industry. SPL is classified into two types, 1st and 2nd Cut SPL. The 1st cut, which is the material under investigation in this study, is a contaminated graphite/ceramics material (50 - 60% of graphite) that is used in lining the electrolytic cell within which aluminum is produced by the reduction of molten Al2O3. 1st Cut SPL is considered as a hazardous material since it contains many other contaminants such as fluorides, cyanides, lead and chromium in addition to its production of flammable gases when it comes in contact with water e.g. ammonia, phosphine, hydrogen and methane. The aim of this study is threefold: (i) fully characterize the 1st Cut SPL produced by Qatalum in Qatar to help in creating the materials safety data sheet (MSDS), (ii) chemically treat this 1st Cut SPL in order to extract the graphite component to use it in other applications in addition to the Cryolite and finally (iii) use the extracted graphite in removing heavy metal ions from aqueous solutions. In this work, the first treatment for 1st Cut SPL was washing it with deionized water. The produced gases were collected in gas bags and characterized using GC-MS which confirmed the evolution of H2 gas when the 1st Cut SPL comes in contact of water. The second step was washing the 1st Cut SPL powder several times with organic solvents to dissolve the existing organic compounds and characterize the eluent using HPLC-MS technique to identify the dissolved organics. A thermal treatment to get rid of the undissolved organic materials was done. Next, surface characterization was carried out for the dried powder which confirmed the absence of any organic materials. Later, the powder was treated with cycles of different concentrations of NaOH, HNO3 and deionized water to remove the remaining inorganic contaminants. The eluents, resulted from the chemical treatment and washing processes, were collected and analyzed using HPLC-MS and ICP. The purity of the produced graphite powder was characterized using XRD to check its purity. The produced graphite powder was functionalized through boiling in 1:1 of H2SO4 : HNO3, washing with deionized water, hot NaOH and finally with deionized water to increase the carboxylate groups on the graphite surface which increases the negative charge on the graphite's surface once mixed with water. The functionalized graphite was proved to Cu ions from aqueous solutions at different pH values with efficiency close to 100 % at pH 10.
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Synthesizing New Anodes From Qatalum's 1st Cut Spl
المؤلفون: Abdullah Hani Holozadah, Aboubakr Abdullah, Mufeed Odeh and Chris Devadas,Aluminum industry produces hundreds of tons of spent pot lining (SPL) waste every year. SPL is classified into two types: 1st cut and 2nd cut. The 1st cut SPL which is the material under study in this work is mainly composed of graphite (~ 60%), ceramic material and Al metal (~ 10%). On contrary with the 2nd Cut SPL, there is a consensus that the 1st cut SPL is a hazardous material and must be treated before dumping it in a landfill. Recycling it will be more beneficial if possible. The aim of this study is using the extracted graphite material from the 1st Cut SPL to produce new carbonaceous anodes for the Al molten electrolytic cells. The idea is to mix the extracted graphitic material with new binder materials e.g. o-phenylenediamine (C6H4(NH2)2), polyaniline or phosphorous (also a mixture of two or all of them) to increase the thermal and chemical stability and electrical conductivity of these new anodes compared to the currently used anodes in Qatalum (Qatalum uses 70% petroleum coke + 30% Coal Tar Pitch (CTP) as a binder). This might result in extending the life time of the carbon anodes and decrease the number of carbon dioxide kilograms that are released per a ton of produced Al metal. For comparison, the anodes were synthesized using the extracted graphite material from the 1st cut SPL, a commercial one and a petroleum coke (PC). The thermal properties were characterized using thermal gravimetric analysis. Also, the electrical conductivity of the new produced anodes was measured. In addition, the impedance spectra for the new anodes were measured at different temperatures and compared to the currently used anodes at Qatalum. Results have shown that anodes prepared from 50% of the extracted graphite with 10% of the commercial graphite and 40% coal tar pitch have impedance of one order of magnitude lower than the currently used anodes in Qatalum.
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The Use Of Wireless Sensor Networks In Agricultute A Tool For A Sustainable Food Supply In The Arab World
المؤلفون: Mustafa Ibrahim AliTHE USE OF WIRELESS SENSOR NETWORKS IN AGRICULTUTE A TOOL FOR A SUSTAINABLE FOOD SUPPLY IN THE ARAB WORLD In this paper some ideas of how to apply the technological advancement of the wireless sensor networks (WSN) in agriculture as a tool for food security is discussed. This will include some examples where the technology can be applied, what changes can this technology brings to the traditional farming, which can help within the solution of the Arab World food security problems. This will help the region to develop and be part of the global strategy for the World food security. WSN features of having a low power consummation nature with different options of using different energy sources will make it as the just technology suitable in a remote and less or without infrastructural bases environment for many countries within the region. The applications of WSN which are suitable for the purpose will be discussed. Keywords: WSN, Food Security, Agriculture in Arab region, WSN Farmer Kits Tool, Energy Sources. Introduction Arabic countries are naturally rich, many countries within the region have a wide virgin land. But unfortunately some of these countries have been a focus in term of food shortages for long time which cause by many factors like land degradation, water crisis, land deals, climate change, agricultural disease, governing system, wars, population growth, land use change, living style change, high prices and lack of technology. As technology has rational parts in solving the most difficult problems for today's society, WSN can be applied in agriculture to reduce or solve this problem. Use of WSN in Agriculture as a solution As traditional farming is the lead in the region, people use their own human sense to perceive the surrounding to investigate the soil and predict the weather. But the remote sensing of the WSN as an activity of recording, observing, perceiving objects or events, wirelessly these happenings are processes and analyzed in a real time. The idea of applying this technology is to be adopted in different applications shortly can be said here. *Soil Investigation by using the specialized soil test sensor detectors to determine the fertility of soil nutrient deficiencies, elements like Nitrogen is very important for plants. *Weather Prediction by using a web data from WSN can be transmitted enabling a remote online interactive retrieval access, and then these data can be shared with the farmers. *Detection of ground water using WSN the level and the amount of sufficient water can be detected before planting. *Using the WSN the water and the area can be controlled during irrigation which will help in reducing the energy consumption. *Food storage system will be advanced by the use of WSN in knowing usage validity time and the space of storing. *Knowing where how and when to deliver what kind of product by using WSN will help in the logistical distribution of crops. *Farming Dissemination by using an integrated WSN tool kit messages can be disseminated.
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Source Term Modeling Of Cryogenic Liquid Vapor Formation By Experimental Investigation - Evaporation Regime And Convection Effect
المؤلفون: Asma Sadia, Waqas Nawaz, Tomasz Olewski and Luc VechotSafe handling, storage and transportation of Liquefied Natural Gas (LNG) has been the root concern in the process industry due to the growing demand for ecological and clean alternative energy namely natural gas. Due to economic advantages in transportation, natural gas is transported in the liquid form. This calls for a thorough research in LNG safety due to its hazardous flammability properties. The study of consequence of loss of containment of LNG is critical to the risk assessment for LNG facilities. This is especially important for Qatar since it is the largest exporter of LNG accounting for about 32 % of the global LNG exports as of 2013. It is important to conduct fundamental and applied research to enrich the knowledge of LNG related safe operations. It is necessary to be able to model consequences of accidental LNG spill to assure sustainability of its production. The loss of containment of LNG leads to the generation of flammable vapor that gets dispersed in the atmosphere. This phenomenon is the same for any cryogenic liquid and is usually split into two stages: vapor formation (source term) and atmospheric dispersion. The vapor formation rate will be determined by its storage conditions (temperature and pressure) and the condition of the release (geometry and location of the dike/bund and the release point, ground temperature and weather data). During the dispersion stage, the behavior of the fluid is controlled by the atmospheric conditions (atmosphere stability class, wind speed, air temperature). The division of the phenomenon into two stages is a convenient approach from modeling perspective. Historically, less attention has been given to source term modeling. Simultaneously, the output of source term is the input into dispersion modeling, and thus, if the former is not accurately estimated the latter cannot be. Moreover, source term modeling is very complex and it cannot be well defined and validated since there is a lack of useful experimental data. This work aims at filling the gap and improving the experimental database. The scope of this part of project includes study of the convective heat flux to the cryogenic liquid pool, which is a part of source term model and study of evaporation regime. It also looks at different scales (small and medium) of experiments and the effect of spilled liquid composition. Currently, experimental results are available for spill of liquid nitrogen at small (0.001 m3) and medium scale (0.023 m3). The aim is to study the transition to evaporation regime and to validate existing evaporation models. It was determined that at the small scale five of the six models were valid but at the medium scale only one model gave close prediction. The deviation increase with scale up, which could be expected as most of the existing models were developed utilizing small scale experimental data. In near future, more investigations will be carried out at the large scale for better understanding of the phenomena.
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Role Of Aromatics In Synthetic Fuels
المؤلفون: Muaz Selam, Wajdi Ahmed, Moiz Bohra, Hafis Mohamed, Rehan Hussain and Nimir ElbashirThis paper describes our investigation into the effects of adding aromatic compounds to synthetic aviation fuels on the performance of these fuels. The work was done as an undergraduate research (UREP) project and was an extension to our group's previous studies which were aimed at characterizing blends of conventional and synthetic aviation fuels [1] and identifying optimum paraffinic building blocks for SPK [2]. Aromatics play a key role in aviation fuels as they enhance the density and elastomer swelling properties of these fuels. However, they are absent from synthetic gas-to-liquids (GTL) derived aviation fuels such as synthetic paraffinic kerosene (SPK) and thus must be added in from another source. In the first part of this study, standard analytical tests were conducted on blends of SPK and aromatic additives (styrene and Shell A150) in different concentrations from 0 to 25 % to measure certain fuel properties (i.e. density, flash point, freezing point, heat content and viscosity) using relevant ASTM procedures. The measured properties were then compared with the desired values for certification according to the ASTM D-1655 and D-7566 standards for conventional and hybrid (i.e. mixtures of oil-derived and synthetic fuels obtained from either natural gas or coal) jet fuels, respectively. In particular, ASTM D-7566 specifies the use of the 50-50 synthetic fuel blend with jet A-1; our group's efforts are aimed at increasing the workable synthetic ratio in the fuel. The experimental work was conducted in the Fuel Characterization Lab at Texas A&M University at Qatar. The data generated from these experiments was used to identify correlations between blend compositions and properties. In the second part of this study, small amounts (i.e. 1 vol %) of specialty aromatic compounds (such as benzaldehyde) were added to the blends from the first part of the study, specifically to enhance the elastomer swelling characteristics of these blends. This is a crucial property of aviation fuels as it ensures a tight seal in fuel tanks, thus preventing potentially catastrophic leakages. The added aromatic compounds were identified based on a Hansen solubility parameter analysis, and it was found that their addition favorably increased both the density and elastomer swelling characteristics of the SPK. Notably, three of the blends tested outperformed the elastomer swelling characteristics of conventional Jet A-1 by about a factor of 2. With respect to freezing point, viscosity, heat content, and flash point, the performance of all of the blends tested were in agreement with ASTM standards. These experimental results demonstrate the favorability our approach to synthetic fuel design i.e. the focused introduction of additives to improve the performance of synthetic fuels to standards at par with or, in some cases, surpassing those of conventional jet fuel.
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Fiberglass Casing And Tubing In Highly Corrosive Environments
المؤلفون: Ahmed Abdul RaufThe UER formation in the Dukhan Field, Qatar has an aquifer associated with it. The formation water and sour crude associated with the formation and aquifer lead to many corrosion-related problems, and casings are being replaced at an almost bi-annual rate. Our research proposal was to replace these with fiberglass casing and tubing. Any tubing and casing that is replaced would need to withstand similar pressures and temperatures as the original steel and fulfill the same functions. Despite plenty of mechanical testing data available on fiberglass as a material, there is very little existing research on fiberglass tubing and casing. This was essential as the manufacturing and therefore composition of fiberglass varies greatly depending on the application. Therefore field-specific, quantative and mechanical research on fiberglass casing and tubing is required. Before conducting physical research, we compiled industrial advantages of fiberglass through fiberglass manufacturer guarentees and product ratings. In the laboratory, we re-established the high resistance to corrosion of fiberglass, and demonstrated comparable resistances to compressive pressure and shear of fiberglass piping to that of steel. In some cases, the fiberglass even proved to perform better and failed at a higher pressure than steel. Latex cement was used to cement the casing and tubing models together, this cement is oil wet and bonds to the inner surface of the fiberglass piping. The cement bonded very well and held even after until the piping had failed under compression. Piping made of fiberglass would not only be cheaper to transport and install, but also more resistant to corrosion, lighter to handle and easier to push into deviated or horizontal wells. (Williams 1987). Overtime, there will be a lower cost of corrosion-control and remediation. Indeed, fiberglass casing and tubing can be employed in the place of steel not only in the UER formation, but in a large number of highly corrosive environments, both down hole and on surface. The use of fiberglass instead of steel casings will not only reduce the affect on the environment due to pollutants, but also contribute to material safety and cost savings.
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Investigating New Imaging Modality: Magnetic Particle Imaging
المؤلفون: Ahmed El Ghamrawy and Steven M. WrightMagnetic Particle Imaging (MPI) is a newly found imaging modality. It utilizes superparamagnetic materials as tracers in the blood stream to obtain very high resolutions. MPI promises to have high sensitivity, high spatial resolution and no radiation compared to other imaging modalities. Most commercially available MRI tracers (used for MPI for now) are all non-harmful when compared to Iodine (used for CT scan) and Gadolinium (used for MRI). MPI research is divided into three categories: MPI scanner development, superparamagnetic materials development, and image reconstruction techniques. In this project a small scale LabView-based system will be developed for use on small lab created phantoms, using 25 nm superparamagnetic iron oxide (SPIO) particles. At first a relaxometer will be developed, the imager will come as the next step. Transmitting and receiving signals will be implemented using LabView and a National Instruments PXI-1033 Chassis. Lab-built coils will be used to send the excitation signal and receive the signal induced by those SPIO's. The objective of this project is to be introduced to a new imaging modality that can have various applications and at the same time considered safe. The system being built is considered inexpensive and shows most of the aspects of how magnetic particle imaging works, starting with the physical phenomena, superparamagnetic nanoparticle properties and relaxation, signal generation and acquisition, and an introduction to the hardware of MPI. The system can be used to introduce engineers and engineering students to the MPI physical phenomena.
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Screening Of Some Qatari Plant Extracts For Anti Fungal Activities Of Plant Pathogenic Fungi
المؤلفون: Ibtihal Mohamed and Talaat AhmadThe present study aimed to evaluate the antifungal activity of three desert plants extracts grown naturally in Qatar: (Al-rayhan) Ocimum basilicum, Shafallah (Capparis spinosa) and Qwaif(Prosopis juliflora)to study their inhibitory effect against three pathogenic fungi: Aspergillus niger, Fusarium oxysporum and Giberella baccata. Samples were collected from Qatar University farm. Filter disk method was used for antagonistic study and four chemical solvents: distilled water, n-butanol, ethyle acetate and chloroform were used to extract the plant materials. The fungi were diluted by DMSO and then treated by 0,5, 10 and 20 mg/ml concentration of extracts in addition to the control group. The study revealed thatCapparis spinosa and Prosopis juliflora extracts had the highest inhibitory effect against Aspergillus niger, Fusarium oxysporum and Giberella baccata while Osmium basilicum of n-butanol and chloroform extracts showed no significant effecton Gibberella baccata. Distilled water and ethyl acetate extracts of Osmium basilicumat 20% concentration showed high inhibition against Gibberella baccata. The study revealed that ethyl acetate at 20% concentration significantly reduced Aspergillus niger growth when treated with Prosopis juliflora and Capparis spinosa extracts (0.88 and 0.93 cm), respectively. Ocimum basilicumalsosignificantly minimizedthe growth ofFusariumoxysporum (0.92 cm) using the same solvent concentration. It could be concluded that the studied plants are promising in the treatment of pathogenic fungi when treated using the appropriate solvents and concentration.
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Dna Barcoding Of Lizards (reptilia, Squamata) Of Qatar
Recent rapid development in Qatar has brought awareness and recognition of the importance to catalogue, describe and preserve its biodiversity. Traditional methods of using morphological characteristics for species identification, although important, requires years of experience and is in need of complete specimens before identity is certain. Recent worldwide endeavor of DNA barcoding by using a segment of the mitochondrial gene cytochrome oxidase c 1 (CO1) to describe all species in the world, has gained recognition and popularity. In this student-centered research supported by Undergraduate Research Experience Program (UREP) of Qatar National Research Fund (QNRF), the objective is to sequence the barcoding gene CO1 of the lizards in Qatar and to compare the sequence among closely related species to facilitate future identification. The final results of this study will make available the barcode sequences of CO1 to be included in the GenBank database. Lizard species were collected across Qatar and photographs were taken for appropriated morphological identification. About 0.5 cm3 of muscle tissues were obtained from each specimen for DNA extraction. Currently between 8 to 12 different primer pairs suggested in literature and primer pair combinations were used for 7 species and a variety of programs of polymerase chain reaction (PCR) were employed in order to amplify the segment of gene of about 650 bp. Among the successfully amplified sequences from the 7 species currently analyzed, three species, Trachylepis septemtaeniata, Mesalina brevirostris, and Uromastyx aegyptia produced PCR products. To eliminate the presence of multiple sequences in the PCR product, PCR fragments were ligated to cloning vector in order to amplify one single sequence for each species. The current total success rate (<43%) based on the primer sequences obtained from publish results and from internal primers developed in this study further supports that the universal primers for reptiles are difficult to develop due to deep phylogenetic divergence. Future studies seeking universal primers should focus on candidate genes that evolve more slowly than CO1 gene to ensure higher homology of sequences among the reptilian species.
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Bacteriophage Diversity In The Ecology Of Qatar
المؤلفون: Umm-kulthum Ismail Umlai and Annette VincentThe Science Education Alliance (SEA) Phage Hunters Advancing Genomics and Evolutionary Science, or PHAGES, is a national initiative in the United States, funded by the Howard Hughes Medical Institute (HHMI) and led by Professor Graham Hatfull from the University of Pittsburgh. This project is built around the discovery and analysis of mycobacteriophages in the biodiversity of the United States. For the first time, this research is being done in Qatar at Carnegie Mellon University to discover the possible existence of bacteriophages within the soil and sand of this Gulf State. The aim was to isolate and purify the phages present within the local ecology to be used as subjects of phage related medicinal therapy. Mycobacterium smegmatis (M.smeg) was used as the host bacteria strain in order to identify the presence of its phages within the sand and soil. This host was chosen due to its non pathogenic nature, fast growing ability and for being a universal host. M.Smeg also has physiological similarities with pathogenic species from the same family; M.tuberculosis causes tuberculosis, and M.leprae causes leprosy. Such efforts are intended to allow us to better understand the mechanisms by which to treat such bacterial diseases using phage therapy as opposed to using increasingly ineffective drugs. Although M.smeg failed to act as a host for the isolated phages from local environmental samples, future works to identify the suitability of other bacterial hosts such as Arthrobacter sp. for these phages will be carried out. Furthermore, analysis of the microbial composition of environmental samples will be conducted to identify specific bacteria hosts that exist in Qatar's ecology.
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New Hereditary Hearing Loss (hhl) Genes/mutations Identified By High Throughput Technologies In The Qatari Population
Objectives: Hereditary Hearing Loss (HHL) is a common genetic disorder accounting for at least 60% of prelingual deafness in children. The long tradition of consanguinity, which is widespread among populations of Arabian Peninsula, increases the prevalence of HHL. It is one of the most frequent causes for school failure in Qatar. GJB2 gene plays a worldwide major role in HHL recessive forms while in Qatar it has a minor role thus strongly suggesting the presence of additional causative genes. To overcome the remarkable genetic heterogeneity of HHL in Qatar population, an extremely powerful 2 steps "gene-identification strategy" was designed (Figure 1). STEP1 consists in a screening of 96 HHL genes by targeted re-sequencing (TS). Positive cases contribute to define an accurate molecular epidemiology picture while negative ones undergo STEP2, a combination of linkage studies and whole exome sequencing (WES) or directly to WES (depending on pedigree size). Methods: Ion Torrent (Life Technologies) (400X of mean target coverage and 581.000 Kb of targets size) was used for STEP1 and Illumina genotyping and Ion Proton (Life Technologies) (90X of mean coverage and 60Mb of target size) were used for STEP2. Sequencing variants were annotated/filtered according to standard pipelines. This strategy was applied to a first series of Qatari families. Results: STEP1 characterized 53% of Qatari families with HHL leading to the identification of 20 novel alleles in known HHL genes (i.e. GJB2, P2RX2, TECTA, TMPRSS3, LOXHD1, MYO15A, TMC1, TRIOBP, WFS1). STEP2 had already led to the discovery of 1 new gene (BDP1). The p*2625Gluext*11 mutation resulting in an elongation of 11 residues of the BDP1 protein was identified in a Qatari recessive family and its expression in the inner ear was confirmed by immunohistochemistry. Conclusion: This combined and powerful strategy proved to be very successful by explaining several HHL unsolved cases and by defining an accurate molecular epidemiology picture of Qatari genes/mutations. Moreover, this approach will be used for developing a "Qatari tailored" molecular diagnostic assay opening new important diagnostic perspectives for a such heterogeneous disorder as well as for defining targets for new possible therapeutic interventions
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Metformin Reverses Glucose Starvation Induced Endoplasmic Reticulum Stress And Autophagy In The Microvascular Endothelium
المؤلفون: Suparna Ghosh, Samson Mathews Samuel, Hong Ding and Christopher TriggleBackground and Objective: Diabetes Mellitus is associated with a higher incidence of myocardial infarction (MI) and poor prognosis in affected individuals; however, treatment with the oral hypoglycemic drug, metformin, is associated with a reduction in cardiovascular morbidity and mortality. A MI reduces oxygen delivery and results in nutrient/glucose starvation (GS) with micro-vascular endothelial cells (MECs) receiving the initial impact, the effect being more profound in a diabetic individual as glucose levels drop from hyperglycemia to GS. It is, however, not known whether GS triggers endoplasmic reticulum (ER) stress and autophagy in MECs and whether metformin has any effect on GS associated ER stress and autophagy. Thus, protocols were designed to determine whether GS-induced ER stress and autophagic events could be rescued. Methods— Mouse Microvasuclar Endothelial Cells (MMECs) were subjected to GS for 24h in the presence and absence of sodium-4-phenylbutyrate (chemical chaperone, 4PBA, 10mM) or metformin (50µM and 2mM) and western blot analysis was performed to assess the induction of ER stress and autophagy. Immunofluorescence staining was also done to assess LC3B punctae staining in cells, indicating autophagy. Results- GS caused ER stress as evidenced by significant increase in the levels of ER stress markers such as GRP78, ATF4 and CHOP. Significant increases in the levels of LC3A-II and LC3B-II and an increase in the level of LC3B punctae staining in glucose starved cells confirmed autophagic activation. Treatment with 10mM 4PBA significantly reversed GS induced ER stress and subsequent autophagy. The effects of varying concentrations of metformin (10µM-2mM) were studied. Metformin (2mM) significantly reversed ER stress and autophagy in glucose starved endothelial cells while lower concentrations that were in the therapeutic range had no effect. Markedly decreased LC3B punctae staining in metformin treated glucose deprived cells also ascertained the reversal of autophagy. Conclusions— This study demonstrates for the first time that GS induced ER stress and autophagy in the microvascular endothelium can be reversed by metformin, albeit only at mM concentrations. This work has been supported by QNRF grants JSREP- 3- 016-3-009 and NPRP 4-910-3-244.
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Exercise Induced Changes In Erythrocyte Membrane Proteome
More than 30 years ago people have learned that exercise promotes oxidative damage in human tissues. Since then, our knowledge on exercise-induced free radical production and their effect has advanced markedly. In the beginning research has mainly focused on detrimental effects of exercise-induced free radical production (e.g. oxidation of macromolecules); however today a new era of redox biology exist that centers on the cell-signaling effects of exercise-induced free radicals, such as reactive oxygen species (ROS) that were shown to play a crucial role in muscle adaptation to exercise. Erythrocytes are rich in membrane polyunsaturated free fatty acid content and have high cellular concentrations of oxygen and haemoglobin that makes them susceptible to ROS induced damage. However, mild oxidative stress has beneficial effect by increasing endogenous antioxidant mechanisms. Thus, in the present work we have used sensitive mass spectrometry techniques to assess the potentially beneficial oxidative modifications of erythrocyte membrane proteins in response to exercise. We have recruited 3 healthy volunteers and their blood was drawn before exercise, immediately after and few hours after exercise. Erythrocyte membranes ("ghosts") were prepared and membrane proteins isolated. Proteins were then separated by 1-D gel electrophoresis, digested with trypsin and peptides analyzed by Orbitrap ELITE coupled with the Easy n-LC II for nano LC-MS/MS. The acquired data was searched with Proteome Discoverer 1.4 against Homo sapiens database to reveal the changes in the erythrocyte membrane proteome. Furthermore, data acquired was also searched through the database using the comprehensive workflow that included several dynamic modifications of peptides, including N-terminal carboxymethyl, C-terminal oxidation and terminal independent oxidation and trioxidation of peptides. The results obtained revealed several proteins that have translocated from the cytoplasm into the membrane following exercise. Moreover, numerous proteins showed exercise dependent modifications and up/down regulation. Exercise induced proteome changes were demonstrated to play an important role in several signaling pathways related to healthy living and lifestyle.
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The Immune-related Role Of Braf In Melanoma
BACKGROUND. The existence of a dichotomy between immunologically active and quiescent phenotypes has been recently recognized in several types of cancer. The activation of a Th1 type of immune signature has been shown to confer better prognosis and likelihood to respond to immunotherapy. However, whether such dichotomy depends on the genetic make-up of individual cancers is not known yet. In melanoma, BRAF and NRAS mutations are frequently acquired during development. We recently proposed a genetic classification of melanoma metastases based on copy number variation and consistency of genes expressed in vivo and in vitro. We found that genes consistently expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) were critical for oncogenesis and their respective copy number influenced their expression. Most importantly, these genes were able to categorize melanoma metastases into two divergent phenotypes (TARA class: transcriptional adjustments related to amplification/deletions): one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A) and the other one with prevalent expression of genes associated with melanoma signaling and with a Th1 immune phenotype (Class B). An intermediate third class (Class C) was further identified. Here, we tested whether these phenotypes might be at least in part explained by BRAF and NRAS mutations in melanoma. METHODS. One-hundred-thirteen melanoma metastases were processed for microarray analysis and BRAF and NRAS sequencing. Allele-specific PCR (AS-PCR) was also performed to exclude low-frequency mutations. RESULTS. Comparison between BRAF and NRAS mutant versus wild type samples identified mostly constituents or regulators of MAPK and related pathways. When testing gene lists discriminative of BRAF, NRAS and MAPK alterations, we found that 112 BRAF-specific transcripts (p<0.01) were able to distinguish the two immune-related phenotypes already described in melanoma, with the poor phenotype associated mostly with BRAF mutation. Noteworthy, such association resulted stronger in samples displaying low BRAF mRNA expression. When testing NRAS mutation and expression, we could not find the same association. Class comparison between BRAF mutant samples displaying high levels of BRAF mRNA expression and wild type samples revealed that there is much more similarity between the two than with the low expressing BRAF mutant samples. To gain further insights concerning this surprising finding we performed functional interpretation analysis of the 6296 genes differentially expressed between BRAF mutants with high and low expression of the same gene; deregulated pathways included IL-2 and JAK/Stat signaling pathways, supporting the immunoregulatory role of BRAF. CONCLUSION. This study suggests that BRAF mutation-related specific transcripts associate with a poor phenotype in melanoma and provide a nest for further investigation.
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Prevalence Of Conventional Versus Non-conventional Cardiovascular Risk Factors In Patients Following Percutaneous Coronary Intervention For Acute Coronary Syndrome
المؤلفون: R. Jay Widmer, Mohamed Gomaa, Martin Reriani, Timothy Morgenthaler, Jassim Al Suwaidi and Amir LermanTraditional risk factors often fail to correlate with event incidence, thus there is a need for novel risk assessment in order to predict events and guide therapy in patients with acute coronary syndromes (ACS) following percutaneous coronary intervention (PCI). Peripheral endothelial dysfunction (PED) and obstructive sleep apnea (OSA) can both predict cardiovascular events, yet the prevalence of PED and OSA in patients hospitalized for ACS following PCI is unknown. Patients in the USA (n=65) and Qatar (n=352) were consented, enrolled following PCI for ACS, and underwent endothelial function testing (EndoPAT) on day 5 and home OSA testing (WatchPAT) following PCI. Baseline demographics at the time of patient admission showed only a modest prevalence of traditional CVD risk factors (Figure 1). The prevalence of PED (defined by EndoPAT<2.0) in this cohort was 73% (mean EndoPAT score of 1.8+0.5), and that of OSA 82% (Apnea Hypopnea Index>5; Figure 1). These functional, non-traditional risk factors were significantly more prevalent (p<0.0001) in this population than traditional risk factors, such as prior MI (6%), hypertension (52%), hyperlipidemia (47%), BMI>30 (43%), diabetes (36%), smoking (30%), CHF (1%), or family history of CVD (37%). Prevalence of both PED and OSA was present in 57% of participants. The current study demonstrated a higher prevalence of PED and OSA following ACS than the traditional CVD risk factors, underscoring their potential value for patient management. Detection and treatment of these functional risk factors may predict events and guide therapy in patients with ACS.
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Infection Rates And Phylogenetic Analysis Of Hepatitis G Virus (hgv)/gb Virus C (gbv-c) Among Qatari Blood Donors
Background: A new immerging nonpathogenic single stranded human RNA virus known as GBV-C/HGV was discovered in 1995. Both GBV-C virus and HCV have similar genome, but they replicate in different cell types. The incidence of GBV-C infection has been studied worldwide, however, to our knowledge; no previous studies were conducted in Qatar, thus the objectives of this study are: (i) to determine the rate of GBV-C infection in Qatar among healthy blood donors and liver-diseased patient and (ii) to determine the most predominant GBV-C genotype in Qatar. Methods: 755 blood plasma samples from blood bank (593) and virology section (162) at HMC were collected. RNA was extracted, reversed transcribed, and then subjected for GBV-C detection by nested PCR using primers targeting a 205 bp of the 5' hypervariable untranslated region (5'-UTR) of the GBV-C/HGV. For genotyping, the 5'-UTR PCR product were T/A cloned into pDrive plasmid. The plasmids were transformed into DH5α™, and then plasmids were purified and digested by EcoRI to detect the positive clones. Plasmid were then purified and sequenced. Phylogenetic analysis was conducted by analyzing the 5'-UTR sequence from randomly picked positive clones. The resulted sequences were assembled and analyzed using CLC and MEGA5 software. Results: we found that HGV infection rate among healthy blood donors was 13.5 %, while in liver-diseased patient was 8.6 %. Moreover, there was no significant difference in the GBV-C infection rate among Qatari (13.3%) and Non-Qatari (14.4%) healthy donors. Sequence analysis of 25 5'-UTR PCR amplicons yielded the European genotype (genotype 2) as the most predominant in Qatar. Conclusion: Our results indicate that there is no correlation between GVC- infection rate and other liver-infecting viruses such as HB&CV. Not surprising, genotype 2 was also reported to be dominant in countries surrounding Qatar such as UAE and Kuwait. Finally, we think our results should benefit epidemiologists in the region and may have an impact on the blood screening policy in blood banks.
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"whole Exome Sequencing Of A Family With 3 Sibling Affected By Bicuspid Aortic Valve Disease"
المؤلفون: Cornelia Carr, Despina Sanoudou, M. Dilawar, S. Helmi, Emmeleia Nana, Kholoud Al-shafai, Paul Barton, A. Al Khulaifi and Magdi YacoubBackground: Bicuspid aortic valve (BAV) is the most common cardiac malformation affecting 1-2% people worldwide. Despite its high prevalence, the pathogenesis of BAV is largely undetermined, although gene mutations leading to alterations in cell migration and signal transduction, in conjunction with non-genetic factors such as blood flow during valvulogenesis, may contribute to its formation prenatally. Objective: The determination of genetic factors contributing to the presentation of BAV in a family with three affected daughters. Methods: We applied next generation whole exome sequencing (>3Gigabases per individual) to high quality DNA from the blood samples of the three affected daughters and their unaffected parents. The >36.000.000 reads of each of the 5 individuals were analyzed with the bioinformatics tools Burrow-Wheeler Aligner, SOAPsnp, Sam tools, Varscan, and GATK to identify single nucleotide polymorphisms and insertions/deletions. Results: We identified over 38,000 SNPs and 3,400 Indels in each individual, of which >1,000 and >580, respectively, were novel. Forty one SNPs were detected in at least two of the affected siblings but neither parent, and only 3 of those were detected in all three BAV patients: HFM1 (ATP dependent DNA helicase), TSPAN2 (tetraspanin family member) and TTF2 (transcription termination factor, RNA polymerase II - pre-mRNA splicing regulator). All 3 genes carried exonic, non-synonymous SNVs, with highly significant pathogenicity prediction scores (SIFT, PhyloP, MutationTaster, LRT). Eight Indels were detected in at least two of the siblings, and only one of them was common across all three siblings: CCNL2 (cyclin L2). CCLN2 is a regulator of the pre-mRNA splicing process, as well as inducer of apoptosis, by modulating the expression of apoptotic and antiapoptotic proteins. In our patients it was found to carry a four base deletion affecting a splice site. None of the previously reported BAV-related genes were found to carry a common mutation across all, and unique to the BAV patients of this family. Conclusion: We have detected 4 genetic variants, shared by all three BAV patients but neither parent. These genes have not been associated with BAV to date. Of particular interest is the novel variant in TSPAN2, a gene of largely unexplored function, belonging to a transmembrane protein family known to mediate signal transduction events that play a role in the regulation of cell development, activation, growth, adhesion and motility.
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Alterations Of The Tumor Microenvironment By Her-2-neu-induced Creb Activation And Localization And Hypoxia
Cancer incidence is rising fast in Qatar, including in particular breast cancer. The expression of the oncogenic protein HER-2/neu is associated with an aggressive phenotype, and agents targeting this molecule have been successful in prolonging survival of breast cancer patients. Despite treatment progresses, metastatic breast cancer is still a fatal condition, and mechanisms of HER-2/neu regulation/resistance are not fully explained. Therefore a better knowledge of the dynamic of HER-2/neu regulation would enable to define new generation targeted therapy agents. The cAMP responsive element-binding protein (CREB) is involved in tumor initiation as well as tumor progression, but a link between HER-2/neu-induced transformation, CREB activation and alterations of the tumor micromilieu including hypoxia-mediated increased angiogenesis has not yet been established. Therefore, the effect of CREB activation on angiogenesis and its modulation by hypoxia was analysed in CREBhigh and CREBlow HER-2/neu+ murine fibroblasts in vitro as well as in vivo. Human tumor cells transfected with HER-2/neu or a mutant deficient in HER-2/neu signalling served as controls. By determination the number and density of blood vessels, necrosis and hypoxic areas a decreased tumorigenicity coupled with a reduced angiogenesis, but increased necrotic cells and hypoxic areas was found upon injection of CREBlow vs. CREBhigh HER-2/neu-transformed cells. In vitro, a time-dependent increase of pCREBSer133, but not of pCREBSer121 in the presence of hypoxia was detected, which was dependent on HER-2/neu signalling and accompanied by an upregulation of HIF-1α, GLUT1 and VEGF as well as of cell migration and invasion mediated by an increased expression of metalloproteinases. Under normoxic conditions, CREBhigh, but not CREBlow HER-2/neu+ cells showed a low intracellular pH, which was restored by CREB silencing. This was at least partially increased in the presence of hypoxia and correlated with an upregulation of lactate in the cellular supernatant of all cells. Furthermore, a hypoxia-mediated post-transcriptional modification due to an increased ubiquitination of CREB and altered cellular distribution of CREB was found. Under hypoxia CREB was translocated into mitochondria, which was accompanied by an altered expression of mitochondrial genes and enhanced apoptosis sensitivity. Thus, HER-2/neu-mediated CREB activation and localization is modulated by the hypoxic and acidic tumor microenvironment, thereby affecting the tumorigenic phenotype. In conclusion a link between HER-2/neu-mediated CREB activation and changes in the microenvironment and CREB localization was found, which contributes to the pathogenesis of HER-2/neu-expressing tumors, including mammary carcinoma. HER-2/neu-mediated CREB activation stimulates angiogenesis and hypoxia and is increased during hypoxia thereby causing translocation of CREB to the mitochondria, which enhances the malignant phenotype. Thus, targeting molecules downstream of HER-2/neu, like CREB, appear to be promising targets for the development of novel innovative therapies of HER-2/neu overexpressing tumors.
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Effects Of Rituximab On The Response To Influenza Vaccine In Complete Remission Lymphoma Patients
Hematological Malignancies (e.g., leukemia and lymphoma) are among the top 5 causes of cancer death in the Middle Eastern Countries, including Qatar, Kuwait and Saudi Arabia. The monoclonal antibody rituximab, directed at the CD20 antigen, has become an essential drug for the treatment of Non Hodgkin Lymphoma (NHL). Although transient B cells depletion frequently occurs after rituximab treatment, it usually resolves after 6-9 months. Nevertheless, high frequency of non-neutropenic infections and persistent hypogammaglobulinaemia during follow-up period have been recently reported. However, impaired humoral response to the recall and primary antigens was found in NHL patients during (or few months after), rituximab treatment. Influenza vaccination is generally recommended in lymphoma patients, but few data are available about the activity of this vaccine after rituximab-containing regimens (RCR). It is presently unclear whether patients treated with RCR regain normal immunocompetence after achievement of complete remission. We present integrated data of 3 sequential studies conduced at our Institutions assessing the humoral response to seasonal influenza vaccination (2008/2009, 2009/2010 and 2011/2012 seasons; RIT-01, RIT-02, and RIT-03 studies, respectively) in NHL patients in complete remission (CR) for at least 6 months after treatment with rituximab-containing regimens (RCR). Overall, we found that patients treated with RCR have a significant lack of humoral response to both recall and naive influenza antigens as compared with HV and with cancer patients treated with chemotherapy not containing rituximab. This weakness was associated with depletion of CD27+ memory b cells. To determine early transcriptional changes predictive of immunoresponsiveness and to determine differences in innate immunity activation among patients treated with RCR, HV, and patients treated with chemotherapy without rituximab, PBMC were collected just before and 1 day after vaccination (RIT-03 study). Whole-genome gene expression analysis of these samples using microarray analysis reveals that the intradermal vaccination was associated with dramatic transcriptomic changes in PBMC, already detectable 24 hours after vaccination. These changes underlie modulation of innate response (eg, interferon stimulated genes, NK-releted transcripts) and differs according to the treatment administered (eg chemotherapy with or without rituximab). In conclusions: a) patients previously treated with RCR should be strictly monitored during influenza epidemic season; b) anti-neoplastic treatments containing rituximab result in prolonged and specific immune alterations.
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Lifetime Prevalence Of Common Mental Disorders In Qatar: Using Who Composite International Diagnostic Interview (who-cidi)
Background: Mental Disorders, particularly Depression, are recognised as one of the biggest burden of disease worldwide. Two of the top three burdens of disease in Qatar are mental health related. Yet, there is scarcity of lifetime prevalence data available to understand the impact in this country. Aim: This study uses the WHO Composite International Diagnostic Interview (WHO-CIDI), to measure the lifetime prevalence of the most presenting mental disorders in the adult Qatari population, aged 18-65, and examine their symptom patterns and co-morbidity. Design: This is a cross sectional study conducted during the period from April 2010 to October 2011. Setting: Five Primary Health Care (PHC) Centres distributed around the country. Subjects: A total of 1,500 Qatari subjects aged 18 to 65 years were approached; 1,063 (70.8%) gave consent and participated in this study. Methods: Four field supervisors from Qatar were trained and certified as trainers by IDRAAC, the education and training centre responsible for the Arabic translation and validation of CIDI. Variations in Arabic dialect were reported to IDRAAC for verification and approval. In line with the World Health Organization (WHO) World Mental Health (WMH) Survey Initiative, a nationally representative psychiatric epidemiological survey was carried out in Qatar. Prevalence and severity of ICD-10 disorders were assessed with the WHO Composite International Diagnostic Interview (CIDI, Version 3.0). Results: Of the studied 1063 subjects, 50.1% were males and 49.9% were females. Most of the respondents were in the age group 18-34 years (46.1%), followed by 35-49 years (34.1%), then 50-65 years (19.8%). The most common ICD-10 disorders were specific generalized anxiety disorders (20.4)%, and major depression (19.1%), with a higher prevalence in women. 20.6% of the sample had chronic physical conditions. There were high levels of statistically significant differences between age groups and gender regarding Generalized Anxiety Disorders, Social phobia, specific phobia, major depression, and personality disorders screen. Women performed significantly worse as assessed by the 30 day functioning screen (p < 0.001). Conclusion: The findings of this study in lifetime prevalence of mental disorders in Qatar are comparable with international figures. Women were more likely than men to have mental illness. Overall, Generalized Anxiety Disorders; Social phobia, specific phobia, major depression, and personality disorders were the commonest disorders.
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Characterization Of Circular Rnas In Ovarian Cancer
المؤلفون: Ikhlak Ahmed, Thasni K. A. Azis, Eman K. Al-azwani, Yasmin Ali Mohamoud, Arash Rafii and Joel MalekNoncoding RNAs such as ribosomal RNAs (rRNA), transfer RNAs (tRNA) micro RNAs (miRNA), small interfering RNAs (siRNA) and long noncoding RNAs (lncRNA) are the dominant products of eukaryotic transcription and collectively represent more than 95% of total RNA of the cell. In addition to contributing as the core components of the translational machinery (rRNAs and tRNAs), these noncoding RNAs have been shown to be involved in a myriad of biological processes such as gene expression regulation and genome defence. Recently, a novel class of endogenously encoded species of RNA called circular RNAs (circRNA) has been shown to regulate gene expression in mammals by competing with miRNA targets under diverse scenarios. To investigate the role and regulatory potency of circRNAs in ovarian cancer, we performed paired-end RNA sequencing of 9 ovarian cancer samples from three patients at primary and metastatic stages and developed an in-house computational pipeline to identify and characterize the circRNA candidates. Our results show that circRNAs are widely expressed in ovarian cancer and oncogenic factors in cancer-associated pathways are particularly enriched for circRNAs. We also show that isoform diversity of circRNAs is comparable to that of the linear counterparts and a significant fraction of exons are preferentially expressed as circular forms compared to the canonical linear RNA form. Further, these candidate circRNAs are particularly enriched for miRNA seed matches and the hybridization energies of interaction favourably predicts formation of stable structural dimers between circRNAs and miRNA mature sequences. A large number of candidate circRNAs are also differentially expressed between primary and metastatic stages of ovarian cancer and show co-expression with their gene targets, implying a role for circRNAs in regulating expression of oncogenic factors. Taken together this study adds an important new dimension to the role of miRNAs vis-à-vis circRNAs in fine-tuning of gene expression and disease progression in ovarian cancer.
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Hospital 7 Days Working. Recommendations And Feasibility
المؤلفون: Rozh Jalil, Andrew Brodie and Jeetesh BhardwaHospital 7 days working. Recommendations and feasibility Introduction: There is increasing evidence that mortality rates for patients admitted to hospitals are higher at weekends. Furthermore, there is evidence that five-day working costs lives. Increased mortality rates over weekends equate to an increased risk of dying of 11% for a patient presenting on a Saturday and a similar rise of 16% for a Sunday when compared to patients presenting Monday to Friday. One reason suggested for this increased mortality rate is the lack of senior doctor cover and the decreased availability of services over the weekend. During the weekend, on average, only 10-15% of consultants are present in the hospital, even though the weekend comprises 30% of the week. There is also data that shows that the risk of death from an elective procedure is 1.4 times higher if the operation is done on a Friday and 1.8 times higher for a Saturday. We review Sir Bruce Keoh's report -NHS medical Director of the UK by focusing on the feasibility and the impact on health services by putting patient in the centre of care. Methods: The Keoh report was published in November 2013 after concerns have been raised about the discrepancy in mortality and morbidity between weekday and weekends. Levels of service has been categorised into 4 levels as shown in the table 1 Most Hospitals currently are at the level 2-3. Results: In order to implement this change into the health care, 10 standards have been recommended (table 2). The local and national incentives are estimated to be over a 3 year period as follows: Year 1 - local contracts will include an Action Plan to deliver the clinical standards within the Service Year 2 - Clinical standards with the greatest impact will be incorporated into the NHS Standard Contract. Year 3 - all clinical standards will be incorporated nationally into the NHS Standard Contract with sanctions in place for non-compliance. Conclusion: With the implementation of this 7 days working model, morbidity and mortality for the weekends is estimated to decrease to the weekday level, resulting in an overall reduction in total mortality and morbidity rates over the whole week. Furthermore, the inappropriate admissions caused by the decreased availability of weekend senior decision making will diminish, in turn, reducing the costs incurred by unnecessary and protracted hospital stays and additional use of health services. Nevertheless one should consider the constrains of such services (table 3) These recommendations are set for the National Health services of the UK and perhaps could be adjusted as per country, locality and patient needs.
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Apolipoprotein E Gene Polymorphism And The Risk Of Left Ventricular Dysfunction Among Egyptian Β-thalassemia Major.
المؤلفون: Mona El-tagui, Mona Hamdy, Iman Shaheen, Hoda Agha and Hoda Abd-elfatahIn Egypt, β-thalassemia is the most common hereditary hemolytic anemia. Cardiac dysfunction, secondary to iron overload with formation of oxygen free radicals, is the most common cause of death in β-thalassemia patients. This study was designed to determine whether the allelic genotype of apolipoprotein E (Apo E), which exhibits antioxidant properties, could represent a genetic risk factor for the development of left ventricular (LV) dysfunction in β-thalassemia major. Fifty Egyptian β-thalassemia major patients were subjected to echocardiography to assess LV function. Apo E genotyping by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was done for all patients in addition to 50 age and sex matched healthy control subjects. Patients were classified into three groups. Group I and II were clinically asymptomatic. Group II subjects had evidence of LV dilatation, while Group III patients had clinical and echocardiographic findings of LV failure. Apo E4 allele was significantly higher among Group II and III than in controls. In conclusion, Apo E4 allele can be considered as a genetic risk factor for LV dysfunctions in β-thalassemic patients. It could be used as predictive indicator for additional risk of LV failure, particularly in asymptomatic patients with LV dilatation, requiring a closer follow-up, to prevent further disease progression
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A Comprehensive Approach To The Prediction Of Acute Calcular Cholangitis - The Qatar Experience
المؤلفون: Hisham Allam, Mohammed Al Dosouky, Abdulaziz Farooq, Ahmed Naggar and Adarsh VijayIntroduction: The aim of the present study is to identify clinical, laboratory and radiological factors that can predict which patients may develop cholangitis. Methods: This is a retrospective case-control study based on patients admitted to Hamad Hospital from June'06 to November'10 with a diagnosis of AC secondary to CBD stones. The control group included patients with obstructive lithiasic jaundice not complicated by cholangitis. Both groups were compared and analysed with respect to demographics, previous medical/surgical history, laboratory investigations and surgical/endoscopic procedures. Results: The study comprised of 112 patients of 24 different nationalities. 53 patients presented with AC and 59 were admitted for management of obstructive jaundice. Although Asians had a greater prevalence of cholangitis (57.4%) compared to Middle Easterners (35.7%) and Africans (33.3%), this was not statistically significant (P=0.066). Laboratory tests significantly correlated to AC were leukocytosis (P<0.001), elevated Bilirubin (P=0.005), prolonged prothrombin time (P=0.001), elevated INR (P=0.001), elevated serum Creatinine (P=0.001) and BUN (P=0.001). In univariate analysis the logistic regression model showed that dark urine, fever, elevated WBC and BUN were strongly associated with cholangitis. Conclusions: Typical clinical signs of acute cholangitis, history of chronic liver disease, together with certain biochemical criteria are strongly associated with occurrence of acute lithiasic cholangitis. A larger prospective study may probably confirm these findings and help create a reproducible and simple predictive scoring system.
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Environment Gene Interaction In Parkinson's Disease (egi-pd).
المؤلفون: Mohamed Salama, Thomas Rösler, Ali Shalash, Abdelhaleem Tantawy and Günter HöglingerEnvironment Gene Interaction in Parkinson's disease (EGI-PD) Mohamed M. Salama1, Thomas W. Rösler2, Ali Shalash3, Abdelhaleem Tantawy4, , Günter U. Höglinger2,5 1Toxicology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt 2Department for Translational Neurodegeneration, German Center for Neurodegenerative Diseases (DZNE), Munich, Germany 3. Department of Neurology, Faculty of Medicine, Ain Shams University, Cairo, Egypt 4. Department of Neurology, Faculty of Medicine, Mansoura University, Mansoura, Egypt 3 Department of Neurology, Technical University, Munich, Germany Introduction: The prevalence of PD is increased in Egypt compared to reports in other countries. Both genetic and environmental causes might be responsible. E.g. a high rate of LRRK2 mutations has been reported in other North African countries, but has not been systematically studied in Egypt. Also, several epidemiologic studies have supported the hypothesis that broadly defined pesticide exposure may increase the risk of PD. A high degree of pesticide use occurs in Egypt due to the limited availability of agricultural areas in the country. Moreover, lack of precautionary measures on applying pesticides leads to increased pesticide exposures. We aimed to study the link between genes encoding detoxifying enzymes and PD-risk genes on one hand and exposure to pesticides on the other hand in the etiology of PD in Egypt. Methods: This work is undertaken in collaboration between the Technische Universtität München, Germany and a network of 16 Egyptian Universities leaded by Mansoura University (Egyptian Network of Neurodegenerative Diseases [ENND]). PD cases from all over Egypt are recruited. Half of the cases were chosen in areas of low pesticide exposure, the other half with high pesticides exposure (farmers 50 years of age or older). Similar numbers of non-PD controls are chosen from two sources; first, patients arriving to outpatient clinic who are not suffering from any other neurodegenerative disorder; secondly, persons accompanying participating PD patients. Controls are further stratified into low pesticides and high pesticides controls, as described for the PD cases. Patients are assessed with a standardized questionnaire to evaluate past exposure to pesticides or other Parkinson-related environmental factors, a standardized clinical neurological examination to verify presence of PD (UK brain bank criteria) and to quantify disease severity (Hoehn & Yahr stage, UPDRS motor part) and genotyping for presence or absence of risk-carrying alleles in detoxification and Parkinson's associated genes. Results: We were able to establish ENND which is the first collaborative network of this type in Egypt. Moreover, we established a functional Standard Operation Procedure to collect and ship clinical data and blood for analysis to the German cooperation partner at TUM. So far, we collected blood and epidemiological data from 70 cases and 80 controls. Preliminary data on the analysis of gene-environment interaction analysis will be presented. Conclusion: This work will provide further insights into the mechanisms of gene environment interplay in the etiology of PD and hopefully insights which allow the establishment of primary preventive measures. Funding: DAAD-funded Al-Tawasul project EGI-PD
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Overexpression Of Human S100a4 Gene In Drosophila Melanogaster Can Promote Metastasis
مزيد أقلThe major problem with cancer is the ability of cancer cells to infiltrate surrounding tissue (invasion) or to spread to distant organs (metastasis), decreasing patient survival. One of the Ca2+ binding proteins of the S100 family, S100A4, is expressed at elevated level in several forms of cancer and has the ability to induce metastasis and invasion in benign mammary cells. In order to generate a genetically tractable experimental model of S100A4-mediated metastasis, we have expressed the human S100A4 in the fruit fly Drosophila melanogaster to uncover players in tumour progression, invasion and metastasis. Here we demonstrate that the expression of full open reading frame of human S100A4 wild type protein in cooperation with RasVal12 into Drosophila, developed metastatic phenotypes. Fly larvae expressing the human S100A4 as determined by Western blot exhibit metastasis in the ventral nerve cord when crossed with Drosophila strains expressing oncogenic RasVal12 targeted to the optic lobes by the UAS-GAL4 system. However, the mutant of S100A4 (S100A4/∆2) missing the last two lysine reduced the tumour dissemination into the ventral nerve cord in Drosophila flies expressing RasVal12 oncogene. Downstream genes associated with the metastatic behaviour including JNK and MMPs (metalloproteinase) proteins are also investigated. We showed that the MMPs and the JNK are also activated in the flies with S100A4/ RasVal12 genotype. Loss this activation in flies with S100A4∆2/RasVal12 genotype indicated that MMPs and JNK proteins are essential in tumour progression and metastasis pathways. Therefore, MMPs and JNK are excellent targets for cancer therapy.
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Inhaled Magnesium For Moderate And Severe Pediatric Asthma
Objective: We hypothesized that nebulized magnesium sulfate added to combined bronchodilator and systemic steroid therapy would shorten time to discharge without undue risk. Study design: Patients aged 2 to 14 y with moderate and severe asthma (PRAM severity score >4) admitted to infirmary care were randomized double-blind to 800 mg nebulized isotonic magnesium sulfate or normal saline placebo via Aeroneb Pro and Idehaler, after intensive therapy with combined albuterol-ipratropium and intravenous methylprednisolone. Time to medical readiness for discharge was the primary outcome. Improvement over time in PRAM severity score and other secondary outcomes were compared for the overall group and severe asthma subset. Results: 191 magnesium sulfate and 174 placebo patients met criteria for analysis. The groups were similar with mean baseline PRAM scores>7. Blinded active therapy significantly increased blood magnesium level 2 h post-treatment 0.85 (SD 0.07) vs 0.82 (SD 0.06) mmol/L, p=0.001). There were no important adverse effects. Accelerated failure time analysis showed a non-significantly relatively shortened time to medical readiness for discharge of 14% favoring the magnesium sulfate group, OR=1.14, 95% CI 0.93 to 1.40, p=0.20, with an absolute prolonged time at 24 h of 2.1 h, p=0.5 . Mean times until readiness for discharge were 14.6 h [SD 9.7] vs 15.6 h [SD 11.3] for the investigational and placebo groups, respectively, p=0.9. Conclusions: Adding nebulized magnesium sulfate to combined nebulized bronchodilator and systemic steroid therapy is either very weakly or very rarely effective, or futile for benefitting pediatric patients with moderate or severe asthma.
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Application Of Bioluminescence, Cyto And Genotoxicity To Measure The Efficacy Of Oregano Oil As An Antimicrobial Agent
المؤلفون: Nahla Omer Eltai, Vyv Salisbury and John GreenmanObjectives To develop and validate a new technique for hand hygiene for use in healthcare settings; to evaluate correlation between bioluminescence and conventional time consuming viable counting methods; to use bioluminescent constructs of bacterial pathogens as a real time biosensors for rapid bactericidal monitoring and to conduct in vitro toxicity tests of the Himalayan oregano oil (HOO) against human cell lines. The ultimate aim of this study is to improve the quality of care of patients through application of a new hand hygiene which could be more acceptable to users while maintaining the efficacy of current hand hygiene disinfectant. Methods: Representatives of the common UK bacterial pathogens Escherichia coli, Pseudomonas aeruginosa and Methicillin sensitive Staphylococcus aureus were used in experiments. Strains used had been previously genetically modified with addition of lux CDABE operon to express bioluminescence in order that they could be used as reporter of viable metabolically active cells to show a real time in situ antimicrobial effect of HOO. Oregano oil samples were analysed for the percentage contents of thymol and carvacrol using gas chromatography. Potential toxicity of Oregano oil at a range of concentrations on cultured human keratinocytes and Jurkat cells were determined using Neutral Red, WST and MTS assays. Results: High correlation was obtained between viable count and bioluminescence. Application of HOO in concentrations effective against bacteria was found to be safe to human keratinocytes (fig.1 and 2) Conclusions: Bioluminescence has the capability to replace the plate culture method for evaluating the efficacy of a new antimicrobial product as it provides a rapid means of collecting data on the antimicrobial action of HOO. HOO may have the potential as a natural potent antimicrobial agent in the health care setting, as it has demonstrated biocidal action towards significant pathogens in a short time. Application of the oil in the correct dilution was found to be safe on human keratinocytes.
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Insulin Resistance-associated Impairment Of Preadipocyte Differentiation In Human Abdominal Obesity
OBJECTIVE: Differentiation capacity of human preadipocytes exhibits depot specific variation and is influenced by local cytokine production. The effect of obesity-induced insulin resistance on preadipocyte differentiation and its relation to proinflammatory cytokine release was investigated. RESEARCH DESIGN AND METHODS: Differentiation of preadipocytes obtained from subcutaneous & omental tissue biopsies isolated from obese patients undergoing weight reduction surgery and their cytokines release were compared between insulin sensitive and insulin resistant subjects. RESULTS: Compared to subcutaneous-derived cells, omental cells expanded from the same patients showed diminished differentiation, marked by increased proinflammatory cytokines secretion. When subjects were dichotomized into insulin sensitive & insulin resistant depending on their HOMA-IR, preadipocytes derived from insulin sensitive subjects exhibited a greater ability to differentiate into larger adipocytes with more lipid droplets, marked by a lower expression and secretion of IL-6 and TNFα. Addition of these cytokines inhibited preadipocyte differentiation in insulin sensitive-derived cultures, suggesting that proinflammatory cytokines may underlie inhibition of differentiation seen in insulin resistant patients-derived cultures. CONCLUSIONS: These findings suggest that insulin-resistance is associated with impaired preadipocyte differentiation and increased proinflammatory cytokines release. Understanding mechanisms underlying impaired preadipocyte differentiation associated with insulin resistance may help future treatment strategies.
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Map Kinase Phosphatase Dusp1 Is Overexpressed In Human Obese And Modulated By Physical Exercise
Chronic low-grade inflammation and uncontrolled metabolic stress response are cardinal features of obesity; a major risk factor for the development diabetes. Dual specificity protein phosphatase 1 (DUSP1) is implicated in metabolism and energy expenditure. Mice lacking DUSP1 are resistant to high fat diet-induced obesity. However, the expression of DUSP1 has not been investigated in human obesity. In the current study, we compared the expression pattern of DUSP1 between lean and obese non-diabetic human subjects using subcutaneous adipose tissue and peripheral blood mononuclear cells. The levels of DUSP1 mRNA and protein were significantly increased in obese subjects with concomitant decrease in the phosphorylation of p38 MAPK and PGC-1α and an increase in the levels of phospho-JNK and phospho-ERK. Moreover, obese subjects had higher levels of circulating DUSP1 protein that correlated positively with various obesity indicators, triglycerides, glucagon, insulin, leptin and PAI-1 (P<0.05), but negatively with VO2, Max and high-density lipoprotein (P<0.05). The observation that DUSP1 was overexpressed in obese subjects prompted us to investigate if physical exercise could reduce its expression. In this study, we report for the first time that physical exercise significantly attenuated the expression of DUSP1 with a parallel increase in the expression of PGC-1α and a reduction in JNK and ERK activities along with attenuated inflammatory response. Collectively, our data suggest that DUSP1 upregulation is strongly linked to adiposity and physical exercise modulates its expression. This gives further evidence that exercise might be useful as a strategy for managing obesity and preventing its associated complications.
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Effect Of Using Gingival Stem Cells And Therapeutic Ultrasound On Periodontal Ligament During Orthodontic Treatment In Beagle Dogs.
Previous studies have shown that low intensity pulsed ultrasound (LIPUS) can prevent orthodontically induced teeth root resorption (OITRR) in human. Also, stem cells have been used to treat different types of bone defects. Severe OITRR is still untreatable problem in orthodontics. The aim of this study was to evaluate the effect of local injection of osteogenically induced gingival stem cells (OIGSCs) and LIPUS on periodontal ligament (PDL) during tooth movement that induces OITRR in beagle dogs. We hypothesized that local injection of OIGSCs and LIPUS can enhance PDL metabolism and hence enhances the reparative effect of OITRR. Seven adolescent beagle dogs were used and their third and fourth premolars were moved orthodontically. Gingival stem cells were isolated, characterized by flowcytometry and were differentiated into osteoblast -like cells using osteogenic medium to produce osteogenically induced gingival cells (OIGCs). OIGSCs were then re-injected into the alveolar bone in the proximity of the roots of the orthodontically moved teeth. Premolars were randomly divided into five groups. 1) Negative control (OITRR only); 2) Local injection of BMP; 3) OIGSCs; 4) LIPUS and 5) LIPUS +OIGSCs. In LIPUS groups, premolars were treated for four weeks. Animals were then euthanized and tissue blocks were processed for histological and histomorphometric analysis. Cementum thickness, PDL thickness and PDL cell number were counted using Metamorph software. Measurements were made at three levels of the tested roots. Level 1 is the coronal level 9towards the crown); level 2 (middle level of the root) and level 3 (apical, towards the apex of the roots). Variables were compared between groups by Wilcoxon Signed Ranks Test using SPSS statistical package. Results showed that LIPUS, BMP2 and LIPUS+OIGCs significantly increased cementum thickness compared to control group in the apical area of the teeth roots (P<0.05). There was statistically significant increases in PDL thickness and PDL cell count in all groups compared to control group (P<0.05). The combined LIPUS+OIGCs showed the highest cell count between al the groups. Conclusion: LIPUS + OIGCs showed the highest PDL regeneration potential and may be used in clinical cases with severe OITRR.
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Molecular Bases Of The Anti-proliferative Action Of The Hypolipidemic Drug Fenofibrate In Vitro In Angiosarcoma-forming Endothelial Cells
المؤلفون: Yasser Majeed, Tarek Taha, Yanal Shaheen, Christopher Triggle and Hong DingIntroduction: Angiosarcomas are aggressive and malignant endothelial tumors. Several risk factors have been identified (eg. BRCA1/2 mutations, radiation, toxins and lymphedema), but pathological mechanisms remain unclear and the prognosis is poor. Fenofibrate is a hypolipidemic drug widely prescribed to treat dyslipidemia. It reduces LDL, vLDL, and triglycerides and increases HDL levels. The primary mechanism of fenofibrate action involves activation of the transcription factor PPARα, but other PPARα-independent mechanisms also exist. More recently, its efficacy as an anti-tumor drug has emerged. However, little is known about the endothelial actions of fenofibrate and whether these contribute to its anti-tumor properties. Here, we explore the actions of fenofibrate in endothelial cells that are capable of forming angiosarcomas in vivo. Methods: Mouse endothelial cells (MS1 VEGF; # CRL-2460) capable of inducing angiosarcoma were purchased from ATCC. These are primary mouse pancreatic islet cells that were transformed with temperature-sensitive SV40 large T antigen and screened for resistance with G418. The G418-selected immortalized cells were then retro-virally infected with a vector encoding primate VEGF. These cells have been shown to induce angiosarcomas in vivo in mice and are a good model system for studies of cancers, particularly angiosarcomas. Results: Incubation of MS1 VEGF cells with clinically relevant concentrations of fenofibrate (25-100 μM) strongly reduced their viability, with cell numbers reduced by approximately 10-fold after a 48h incubation with 50 μM fenofibrate {Cells/ml: ~1.8 million (control) versus ~0.2 million (50 μM fenofibrate)}. Morphologically, the cells were characterized by the appearance of perinuclear cytoplasmic vacuoles. In contrast, fenofibrate had a smaller effect on cell viability in primary human endothelial cells {Cells/ml: ~0.6 million (control) versus ~0.4 million (50 μM fenofibrate)}, thereby suggesting a relatively selective effect on MS1 VEGF cells. Hypothesizing that the effect of fenofibrate in these cells occurred through the induction of apoptosis, the effect of fenofibrate on the expression of proteins critical for cell survival and apoptosis was investigated biochemically. The data revealed down-regulation of the anti-apoptotic Bcl family protein Bcl-2 and the inhibitor of apoptosis protein survivin after treatment with fenofibrate. Fenofibrate treatment also decreased the expression of Akt and Erk proteins. In contrast, expression of Bcl-xl was relatively unaffected. Expression of the anti-diabetic hormone FGF-21 was detected in MS1 VEGF cells and this was also decreased after fenofibrate incubation. Conclusions: The data revealed a strong anti-proliferative action of fenofibrate in angiosarcoma-inducing endothelial cells but not primary human endothelial cells. These effects potentially occurred through regulation of proteins critical for cell survival and apoptosis. Future studies: Future investigations will focus on: (a) delineating the mechanisms involved (PPARα-dependent or -independent) (b) direct measurements of apoptosis by flow cytometry (c) the effect of fenofibrate on endothelial migration, invasion, proliferation, wound healing and tubule formation and (d) testing the possibility that fenofibrate acts by triggering changes in cellular calcium handling and (e) testing fenofibrate efficacy in angiosarcomas in vivo in mice. Key words: Apoptosis, Bcl-2, cancer, fenofibrate, FGF-21, survivin. This work was supported by a National Priorities Research Program grant (NPRP 6-428-3-113).
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Optimizing The Expression And Purification Of Eukaryotic Cdc25c In E. Coli
المؤلفون: Stephanie Ramadan and Khaled MachacaCdc25C is a member of the dual specific protein phosphatase family capable of dephosphorylating both phospho-Tyr and phospho-Ser/Thr residues. In vertebrates, there are three isoforms of the Cdc25 enzyme (Cdc25A, Cdc25B and Cdc25C). The N-terminal (regulatory domain) region of these three enzymes is highly divergent (~20-25% identity) while the C-terminal (catalytic domain) region is more conserved (~60% identity). The Cdc25C isoform is of particular importance because it dephosphorylates Cdc2, which is part of the Cdc2/Cyclin B complex, allowing the cell to transition into mitosis. We want to gain further insight into how Cdc25C interacts with its substrate Cdc2. One way to do this is to utilize the ability of E. coli to heterologously express recombinant Cdc25c. This will allow us to obtain large amounts of the protein for in vitro characterization. First, several E. coli cell lines were tested (each with unique properties; e.g. expression of toxic protein, expression of disulfide rich proteins) for their ability to overexpress Cdc25C. The cell line and expression condition having the highest yield of full-length protein was chosen and purified using a single immobilized metal affinity chromatography (IMAC) column that will bind a 6xHis affinity tag fused to the N-terminus of Cdc25C or a tandem approach that utilizes two affinity tags (an N-terminal 6xHis affinity tag and a C-terminal StrepII tag). The pure protein will then be subjected to a variety of chromatography techniques such as UV-Vis spectroscopy and circular dichrosim (CD) to characterize structural changes the protein undergoes when binding to its zinc cofactor. Site directed mutagenesis will be used to create mutations in the zinc binding region of Cdc25C and these proteins will also be characterized for their ability to bind or not to bind the zinc cofactor.
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Risk Factors For Wound Infection Following Cardiac Surgery In Qatar.
المؤلفون: Cornelia S Carr, Nasir Mughal and Abdulaziz M AlkhulaifiObjective: Qatar has one of the highest rates of diabetes in the world (20% of the general population), with many patients having poor control. In Qatar 68% of the isolated CABG group has diabetes. We wanted to assess the risk factors involved in the development of wound infections following cardiac surgery in Qatar. Methods: All patients undergoing cardiac surgery between 1/12/2012 and 30/11/2013 were followed and all wound infections noted. Patients' pre-operative haemoglobin, HbA1C, BMI, and ethnicity were also noted. Results: 252 patients underwent cardiac surgery within the study period. There were 24 females and 228 males (90%). The age range was 15 to 74 (mean 51, mode 54, median 54). 54 (21%) developed some form of wound infection. The average (modal) pre-operative haemoglobin for the patients who developed post-operative wound infection was 13.5, and for the non-infected 15.0. The infection group had an average HbA1C of 7.8 (range 4.5 to 12.9) and the non-infection group 7.0 (range 2 to 14.8). There were no differences in BMI or the ethnic group affected. Conclusions: Although there is a high rate of wound infection in our group, the majority are superficial and in the leg. Is the haemoglobin a marker of overall poor nutrition and poor health or a specific risk factor with decreased oxygen carrying capacity leading to the development of wound infections? We also have a high rate of poorly controlled diabetes. We are now doing multivariate analysis on the data.
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Biosynthesis, Characterization And Antibacterial Efficacy Of Silver Nanoparticles From The Soil Fungus Curvularia Tuberculata
المؤلفون: Tawfik Muhammad Muhsin and Ahmad K HachimAbstract Nanobiotechnology has been recently widely applied in multidisciplinary fields including pharmaceutical applications. The last decade has witnessed an increase research interests focused on the biosynthesis of metal nanoparticles from fungi as a natural sources and as bionanofactories. However, silver nanoparticles (AgNPs) are of great importance particularly in medical therapy applications and can be used as antimicrobial agent. The objective of this study was to biosynthesize silver nanoparticles from the soil fungus Curvularia tuberculata and to examine their efficacy against five strains of pathogenic bacteria namely; Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhi and Staphylococcus aureus using agar well diffusion technique. The synergistic efficacy of biosynthesized silver nanoparticles in a combination with commercially used antibiotic Gentamycin against the selected bacteria was also examined. The biosynthesized silver nanoparticles from fungal free-cell filtrate were characterized by using UV-Vis spectrophotometer analysis, Fourier transform infrared spectroscopy (FTIR) and scanning electron microscope (SEM). UV-Vis spectrophotometer analysis revealed a peak at 420 nm indicating the synthesis of silver nanoparticles. FTIR analysis verified the detection of protein capping of silver nanoparticles while SEM micrographs showed that the synthesized silver nanoparticles are dispersed and mostly having spherical shape within the size range between 10-50 nm. The biosynthesized silver nanoparticles possessed a varied growth inhibition activity ranged between 12- 28 mm diam inhibition zones at different concentrations against the tested pathogenic bacterial strains. A remarkable increase of bacterial growth inhibition (25.5-35.5 mm diam) was detected when a combination of silver nanoparticles and Gentamycin was used. A significant increase in fold area of antibacterial efficacy was observed when AgNPs in combination with Gentamycin was applied as compared with the efficacy of Gentamycin alone. The biosynthesized AgNPs did not show any toxicity against human blood. The synthesized silver nanoparticles by the fungus C.tuberculata is promising to be used as an antimicrobial agent in medical therapy due to their broad spectrum efficacy against pathogenic bacteria. Nevertheless, further studies are needed to investigate the activity of silver nanoparticles as antibacterial agent in vivo.
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Mapping New Hiv Infections In Morocco By Modes Of Transmission Model In 2013
Background Countries in the Middle East and North Africa are experiencing emerging HIV epidemics in high-risk populations, including people who inject drugs (PWID), men who have sex with men (MSM), and female sex workers (FSWs). This study was initiated by the Morocco Ministry of Health to identify the key modes of exposure to HIV infection among the Moroccan population and to provide recommendations for national HIV prevention strategies for the coming years. This work represents the second national modes of transmission (MoT) analysis in Morocco after the 2010 MoT study. Methods The MoT mathematical model developed by the Joint United Nations Programme on HIV/AIDS was used to update the 2010 model results. The model was parameterized based on recent integrated bio-behavioral surveillance survey (IBBSS) studies and quality data provided by the Morocco Ministry of Health and through a comprehensive review and synthesis of HIV and risk behavior data in Morocco. Uncertainty analyses were used to assess the reliability of, and uncertainty around, our calculated estimates. Results FSWs, clients of FSWs, MSM, and PWID contributed 11.1%, 24.7%, 22.4%, and 4.8% of new HIV infections, respectively. More than two-thirds (70%) of new HIV infections occurred among FSWs, clients of FSWs, MSM, and PWID, or among the stable sexual partners of these populations. Casual heterosexual sex contributed 8% of HIV infections. About half (44%) of HIV incidence was among females, but 73% of these infections were due to an infected spouse. The vast majority of HIV infections among men (92%) were due to high-risk behavior. A very small HIV incidence was predicted to be arising from medical injections or blood transfusion (0.1%). Conclusions The HIV epidemic in Morocco is driven by HIV incidence in high-risk groups, with commercial heterosexual sex networks being the leading driver of the epidemic, and MSM networks contributing to a larger share of new HIV infections than the 2010 model estimates (24% versus 14%). There is a need to further focus HIV response on high-risk populations through scaling up of prevention services such as condom promotion among FSWs and their clients, voluntary counseling and testing, harm reduction, and expanded treatment coverage. It is also essential to continue with repeated rounds of IBBSS studies among these population groups.
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Seat Belt And Mobile Phone Use Among Drivers In Doha City: An Observational Study
Worldwide 1.24 million deaths occur annually due to road traffic injuries. Additionally, 20-50 million are injured or disabled. Similarly, within the Gulf Cooperation Council countries injury and mortality due to road traffic injury are high. In the State of Qatar, for example, the road traffic fatality rate for the year 2010 is estimated to be 14 per 100,000. Young adult males are disproportionately affected. Road safety risk factor laws namely, seat belt use, driving under the influence of alcohol, helmet use and speed management exist in Qatar but enforcement is lax. An additional new risk factor causing distraction while driving and causing road traffic injury and fatalities is the use of mobile phone whilst driving a vehicle. Currently, in Qatar baseline national data pertaining to seat belt and mobile phone use among drivers is not available. We have thus conducted an observational study to estimate the prevalence of these two variables among vehicle drivers in Doha. Additionally, we will examine and present the associations between phone and seat belt use, and variables such as the gender of the driver, type of vehicle and the time of the day during which the observations were made. Furthermore, policy implications of the study findings will be discussed. Acknowledgement: This work is supported by the Biomedical Research Program at Weill Cornell Medical College in Qatar, a program funded by Qatar Foundation.
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How To Cure Cancer With A Pill? A Structure-based Drug Design Study On Human Hexokinase 2 Targeting Different Tumor Types
المؤلفون: Wael Rabeh and Mir Hussain NawazCancer is a major challenge worldwide with nearly 8 million people die from cancer every year, and it is one of the major causes of death in GCC Countries. Tumor and cancer cells in general utilize glucose at elevated levels to support their growth and proliferation, historically known as the Warburg effect, a phenomena used clinically in the Positron Emission Tomography (PET) scan to detect glycolytic tumors. Targeting glucose metabolism in cancer cells to limit tumor growth will enhance the survival rate and improve quality of life for cancer patients. Hexokinase, the first enzyme in the glycolytic pathway, catalyzes the phosphorylation of glucose, and is one of the three major steps in the regulation of the glycolytic pathway. However, humans have four isozymes of hexokinase in which Hexokinase 2 (HK2) is the most active and specifically expressed in cancer cells but not in normal tissues. In addition, gene expression profiling experiments of different types of cancer showed high expression levels of HK2, and various biological studies highlighted the importance of HK2 in tumor metastasis making it an ideal target for the development of new class of cancer therapeutics. Since HK2 is not found in normal cells, therapeutics that inhibit HK2 activity will target cancer cells only and will have minimum or no side effects. The new class of therapeutic will be safe and can be delivered orally to replace the current traditional chemotherapy that has to be administered on an in-patient basis, which dramatically increases the cost of cancer therapy. We solved the crystal structure of human HK2 in complex with glucose and glucose-6-phosphate (PDB code: 2NZT), where it is a homodimer with catalytically active N- and C-terminal domains linked by a seven-turn helix. A hydrophobic α-helix at the beginning of the protein is known to interact with a voltage-dependent anion channel (VDAC) on the outer mitochondrial membrane (OMM) to facilitate coupling HK2 to ATP used in phosphorylation of glucose, thereby "kicking off" glucose metabolism. In addition, the localization of HK2 to OMM prevents apoptosis through repression of the formation of mitochondrial permeability transition pores. Through biochemical and biophysical characterization of HK2, we found that the N-terminal domain not only catalyze glucose phosphorylation but also regulate the stability and activity of the enzyme. In addition, deletion of the N-terminal helix altered the stability and catalytic activity of the full-length enzyme and N-terminal domain when expressed separately. Understanding the kinetic and regulation mechanism of human HK2 will accelerate the design and development of inhibitors to be used as cancer therapeutics. Our initial screen of a small drug library yielded an inhibitor that is a natural product that is known for its anticancer activity. Currently, we are implementing a structure-based drug design to further develop the target using 3D structural simulations of HK2. The new class of cancer therapeutics will increase the quality and lifespan of cancer patients and will cut the cost dramatically of the current expensive cancer chemotherapy.
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Using Surveillance Data To Identify Areas Of Research And Healthcare System Improvement: The Case Of Diagnosis Delay.
المؤلفون: Humberto Guanche GarcellOne of the key objectives of the surveillance of communicable disease (CDs) is the identification of areas for research and healthcare system improvement. In a recent paper published in Qatar Medical Journal (http://dx.doi.org/10.5339/qmj.2014.9) is shown the delay in diagnosis of CDs of cases reported at The Cuban Hospital (TCH) during 2012 and 2013. Examples of delay in diagnosis was for tuberculosis 61.7 days, acute hepatitis 18.5 days, typhoid fever 17 days, food poisoning 9.5 days, measles 8.0 days and meningitis 3.8 days. These are diseases that require immediate reporting because of their public health importance and some of them are highly transmissible (e.g. tuberculosis and measles). Additional evaluation of patients with tuberculosis admitted at The Cuban Hospital (many reported in Hamad General Hospital and referred to TCH because of bed crisis) from January 2013 to June 2014 (105 patients) show diagnosis delay of 49.5 days (standard deviation 51.9 years) with a maximum figure of 365 days. In patients with positive smear (highly infectious) the delay was 49.7 days (SD 53.5 days) (minimum 2 days, maximum 365 days). The delay was superior in cases with pulmonary tuberculosis (51.3 days (SD 52 days)) than in non pulmonary (36.1 days (SD 51.9 days). Delay in diagnosis of CDs is significant with regard to not only disease prognosis at the individual level but also transmission within the community. The delay could be divided in ¨patient delay and system delay¨. Patient delay refers to the time between onset of symptom and the first contact with a healthcare professional. The system delay refers to the time between this first contact to the diagnosis or confirmation of the disease. The knowledge of the two components of the delay is essential to identify actions to minimize the delay and reduce the probability of disease transmission at the community. In summary data from the surveillance of CDs suggest the need of research to identify the causes of diagnostic delay and subsequently implement actions its reduction, which will contribute to the prevention and control of CDs in Qatar.
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Inflammation And Er Stress Downregulate Bdh2 Expression And Dysregulate Intracellular Iron In Macrophages
المؤلفون: Susu Mahmoud ZughaierAltered iron homeostasis is associated with many chronic diseases and characterized by misdistribution of iron that manifests in hypoferremia and iron retention in the reticuloendothelial system. Macrophages play a very important role in host defense and in iron homeostasis by engulfing senescent red blood cells and recycling iron. Hepcidin is the master iron regulating hormone that limits dietary iron absorption from the gut and limits iron egress from macrophages; therefore, upon infection macrophages retain iron to limit its bioavailability which limits bacterial growth. Recently, a short chain butyrate dehydrogenase type 2 (BDH2) protein was reported to contain an iron responsive element and to mediate cellular iron trafficking by catalyzing the synthesis of the mammalian siderophore that binds labile iron; therefore, BDH2 plays a crucial role in intracellular iron homeostasis. However, BDH2 expression and regulation in macrophages has not yet been described. Here we show that LPS-induced inflammation combined with ER stress led to massive BDH2 downregulation, increased the expression of ER stress markers, upregulated hepcidin expression, downregulated ferroportin, caused iron retention in macrophages, and dysregulated cytokine release from macrophages. We also show that ER stress combined with inflammation synergistically upregulated the expression of the iron carrier protein NGAL and the stress-inducible heme degrading enzyme heme oxygenase 1 (HO-1) leading to iron liberation. However, vitamin D treatment prior to LPS exposure restored BDH2 expression. Taken together, the data suggest that inflammation combined with ER stress dysregulated intracellular iron homeostasis in macrophages. This is the first report to show that inflammation and ER stress downregulates the expression of BDH2 in human THP-1 macrophages. A clinical translational study of this finding will be conducted on patients with Alzheimer disease, cystic fibrosis disease and COPD compared to healthy subjects to investigate iron status i.e. anemia of chronic inflammation, iron indexes, inflammation markers (proinflammatory cytokines and chemokines such as IL-6 and MCP-1) and expression of BDH2, hepcidin-ferroprotin axis and intracellular iron retention in peripheral monocytes. Since vitamin D improves iron status, relieves ER stress and restores BDH2 expression we propose to translate our finding in a double blind clinical study where subjects will receive high dose of vitamin D or placebo as therapy to restore altered iron homeostasis.
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Identification And Genomic Characterization Of Herv-k (hml-10) In Human Genome Grch37/hg19 Assembly
المؤلفون: Marta Cadeddu, Nicole Grandi, Laura Vargiu, Patricia Rodriguez Tomé, Jonas Blomberg and Enzo TramontanoHuman endogenous retroviruses (HERVs) have been classified into three different classes I, II, III. Betaretrovirus-like sequences, including HERV-K, belong to the class II and contains ten groups, termed HML1-10. It has been reported that an HML-10 sequence, termed HERV-K(C4), is inserted within the gene coding for the human complement C4 in an antisense orientation (Tassabehij et al. 1994). The expression of the HERV-K(C4) RNA has been hypothesized to possibly modulate C4 expression as well as to act as a possible mechanism of defense against retroviral infections (Schneider et al 2001). Recently, it has been demonstrated that low HERV-K(C4) copy number is associated with type 1 diabetes, raising the possibility that this retroviral element contributes to functional protection against this autoimmune disease (Mason et al. 2014). Given the correlation between lower HERV-K(C4) copy number and expression, it has also been proposed that HERV-K(C4) may influence C4 RNA processing and/or have an impact on other endogenous retroviral sequences (Mason et al. 2014). To have more insights into this hypothesis, we identified, lassified and characterized the HML-10 sequences that are present in the human genome GRCh37/hg19 assembly. We used the model-based software Retrotector (Sperberg et al 2007) to search HML-10 sequences in the human genome assembly GRCh37/hg19 and identified 10 HML-10 proviruses in chromosomes 1, 6, 16, 19 and Y. These proviruses were confirmed to belong to the HERV-K (HML-10) group and shown to have the Rec sequence. Out of the 10 identified HML-10s, 5 sequences have both LTRs, 4 have only 3'-LTR and 1 sequence is without LTRs. Age estimation analysis performed on the 5 sequences with both LTRs indicated that they inserted into the human genome >25 Mya ago. Five sequences conserved the primer binding site (PBS) region, all recognizing the Lys tRNA. Translational analysis showed that all proviral sequences have multiple stop codons that preclude their production of functional proteins. Phylogenetic analyses were performed with complete DNA sequences as well as with the Pol amino acid sequences and will be presented. Overall, we have identified and characterized 10 HML-10 sequences in the human genome GRCh37/hg19 assembly. Precise knowledge of all HML-10 sequences will allow further investigation of their physiological and pathological role in autoimmune diseases (Yu & Whitacre 2004), particularly their possible involvement in type 1 diabetes, giving new insights into their understanding. References 1. Tassabehij et al. NAR 22, 5211-17 (1994). 2. Mason et al. Diabetes 63, 1789-95 (2014). 3. Sperber et al. NAR 35, 4964-76 (2007). 4. Yu & Whitacre Trends in immunology 25, 694-99 (2004).
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Natural Antioxidants, Antibacterials From Olive Leaf Extracts Used In Cosmetics, Pharmaceutical, And Food Industries
المؤلفون: Fuad Al-rimawi, Imad Odeh, Abdallah Bisher, Hiba Yateem and Mohammad TarawehOlive leaves are rich with polyphenolic compounds which exhibit many activities like antimicrobial, antioxidant activities. Natural compounds from olive leaves are safe antioxidants, antibacterials, and preservatives compared to synthetic ones. In this work, olive leaf samples were collected from different geographical regions of Palestine at different maturation stages. The olive leaves samples were dried, grinded, and extracted with water at room temperature for two hours. The crude extracts were then analyzed for their total phenolic content, total flavonoid content, and antioxidant activity. Results revealed that olive leaves are rich with antioxidants (polyphenolic and flavonoid compounds), and the extracts showed antibacterial activities against two gram positive bacteria (staphylococcus aureus, and staphylococcus epiderrmidis) with activity of about 80-90% compared to well known antibiotic (Neomycin). Based on these results, the olive leaf extracts were used in cosmetics, pharmaceutical, and food applications as natural antioxidant and antibacterial agent. In cosmetics, olive leaves extracts were used in moisturizing day cream, anti- aging cream, and shampoo formulations at three concentrations (0.1%, 0.4% and 1.0%, w/w). Results showed that all physical and rheological properties of the formulations with olive leaves extract were the same as commercial product. Furthermore, stability studies showed stable homogenous appearance and effective during one year storage period at room temperature. A questionnaire analysis on 100 volunteers who used these creams and shampoos showed that they are satisfied with these preparations. In pharmaceutical industry, the olive leaf extracts were used as natural antibacterial, and antioxidant in non-sterile pharmaceutical dosage forms instead of conventional chemical preservatives which have toxicity to human beings even at low concentrations especially when used in pediatric/children preparations. Results showed that the extracts work as natural antibacterials and antioxidants for the prepared pediatric syrup and potentially can substitute the chemical preservatives. Regarding food applications of the extracts, they were added into meat fillets as antioxidants and compared to chemical preservatives that are used usually in meats (BHT), and results indicated significant decrease in the amount of secondary oxidation products (represented as malonodialdehyde) of the tested meat samples treated with different concentrations of olive leaves extracts, indicating that this extract can be used as natural antioxidants in meat substituting synthetic ones. Additionally the extracts were tested for the stabilization of edible oils as substituents to synthetic additives (BHT and BHA), and results showed that incorporation of olive leaves extracts in the unsaturated edible oils resulted in significant decrease in primary and secondary oxidation products of the oil, and therefore this extract has protecting effect against induced lipid peroxidation of edible oils.
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Recombinant Activated Factor Viia For Treatment Of Refractory Lower Gastrointestinal Hemorrhage In A Patient With A Recently Implanted Mechanical Valve
المؤلفون: Amr Salah Omar, Suraj Sudarsanan, Hesham Ahmed Ewila and Ali KindawiAbstract Introduction Bleeding is a common complication after cardiac surgery. However, lower gastrointestinal bleeding is not usually associated with this type of surgery. Case presentation A 50-year-old man with a history of aortic regurgitation underwent elective mechanical valve replacement under cardiopulmonary bypass. He experienced a complicated intraoperative course involving unexplained cardiac arrest following induction of anesthesia. He also developed two episodes of massive lower gastrointestinal bleeding secondary to mucosal ischemia while convalescing in the cardiothoracic surgery intensive care unit. After unsuccessful attempts to control the bleeding, exhaustion of blood products, and consideration of the high risk of mortality associated with surgery and the possibility of early- and long-term surgical complications, the decision was made to administer two successive doses of recombinant activated factor VII at 60 mcg/kg. Hemostasis was achieved without adverse systemic or valvular effects. Conclusions A favorable outcome was achieved after administration of recombinant activated factor VII, which controlled the patient's severe lower gastrointestinal bleeding. This outcome suggests the need to raise awareness about the use of this drug in dire circumstances when other conventional measures fail or are unsuitable.
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Influence Of Time In Range Glucose On Glycemic Control Outcome After Cardiac Surgery. A Qatari Experience
المؤلفون: Amr Salah Omar, Ahmed Salama, Mahmoud Allam, Yasser Elgohary, Shaban Mohammed, Alejandro Kohn Tuli and Rajvir SinghBackground: Optimal glycemic control in postoperative cardiac patients is still under debate. In an attempt to reduce wound infection, and improving overall mortality variable targets had been prescribed. Aim of the work: To study the outcome of glucose control, with a target of 6 to 8.1mmol/L, and the associated factors related to poor control. Methodology: We evaluated 227 consecutive patients diabetics and non-diabetics after cardiac surgery in a prospective descriptive study with purposive sampling. Patients subjected to insulin infusion with a target of 6 to 8.1mmol/L. We collected perioperative individual data including age, gender, race, Euro score, cardiopulmonary bypass time (CPB), aortic cross clamp time (ACC), length of ventilation, stay in intensive care unit (ICU) and in hospital as well as nurses compliance to follow the protocol. Patients divided into 2 groups according to the success of maintaining the target into group I (target maintained over 80% of the time), and group II (target maintained in less than 80 % of the time). The groups were compared by t-test, or Mann-Whitney U test, as appropriate for interval variables, and Chi square tests were for categorical variables. Data expressed as mean±SD or proportions/percentages for interval and categorical variables respectively. P<= 0.05 (two-tailed) was considered the statistical significant level. Results: Both groups were matched regarding the age, sex, gender, and Euro score. Failure to lie within the target was significantly higher in diabetics (p=0.001), patients with glycated hemoglobin (HbA1c) above 8% (p=0.0001), dopamine and adrenaline users (p=0.04&0.05 respectively). No significant difference found between the ethnic groups (Arab and Asians). CPB, and ACC time, lengths of stay ICU and ventilation were significantly higher in group II. Incidence of hypoglycemia, acute kidney injury, and in-hospital mortality did not differ between both groups, although wound infections were higher in group II. Conclusion: Pertinent aspects regarding better control within the studied population did not involve ethnicity as hypothesized, however preoperative high HbA1C appears to be a good predictor of poor control. Patients with proper glucose control had a better outcome in terms of wound infection, lengths of ventilation and ICU stay; moreover they were not subject to frequent hypoglycemic events as claimed.
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Role Of Recombinant Factor Viia In The Management Of Severe Perioperative Bleeding In Cardiac Surgery, Qatari Experience
Introduction: Intractable bleeding is one of common adverse events after cardiac surgeries. Recombinant activated factor VII (rVIIa) showed efficiency in controlling postoperative intractable bleeding (1). Its usage after cardiac surgeries should be more investigated. Patients and methods: - All patients received rVIIa post cardiac surgeries over a period of two years were included in a retrospective descriptive study. All patients were evaluated for base line laboratory results and comorbidities, operative details, dose of rVIIa received, total chest drains pre and post rVIIa administration, total blood and blood products given pre and post rVIIa, post rVIIa laboratory results, complications of rVIIa, length of stay in intensive care unit. Results: -. We recruited 19 patients with a mean age of 49±18 years who received RVIIa in a dose of 90 mcg/kg. Packed red blood cells transfusion post rVIIa administration was decreased from mean of 10±6 units to 3.7±1.7 units P<0.0001. Chest drains post rVIIa administration were decreased from median of 2000 ml and IQR of 1200 to median of 500 ml and IQR of 500 P<0.1 .No complications related to rVIIa administration were observed. Discussion: - The study highlight the following findings: Efficiency and safety of rVIIa in the control of intractable bleeding post cardiac surgeries. Usage of rVIIa saves blood bank resources, decreases the need of surgical reopening and decreases morbidity. More studies needed to elaborate clinical guidelines for the usage of rVIIa in the management of intractable bleeding post cardiac surgeries. Conclusion: - There is increase need for clinical guidelines for the usage of rVIIa post cardiac surgeries. In our experience at Qatar heart hospital recombinant activated factor VII is safe and efficient treatment to control intractable bleeding post cardiac surgeries. Reference: - (1) Conrad V. Bishop, William E.P. Renwick, Chris Hogan, Michael Haeusler, Annabel Tuckfield and James Tatoulis: Recombinant Activated Factor VII: Treating Postoperative Hemorrhage in Cardiac Surgery. Ann Thorac Surg 2006; 81:875-879.
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Post Cardiac Surgery Statins Related Morbidity
المؤلفون: Sameh Aboulnaga, Ahmed Mahfouz, Amr Omar, Hisham Ewila, Alejandro Tuli and R SinghAbstract Introduction: The notion of the favorable outcome related to continuation of statins in the perioperative cardiac surgery settings had gained wide approbation,1 but the complications related to statins therapy in this period remains a major concern. Aim of the work: To study whether perioperative treatment with statins could be associated with increased post-operative complications in terms of increased liver enzymes and rhabdomyolysis with possible associated acute kidney injury (AKI). Methodology: Prospective, observational study with purposive sampling where we analyzed morbidity after cardiac surgery as well as the outcome related to statins therapy in 202 consecutive patients over a period of one year. We collected perioperative individual data including age, gender, race, Euro score, cardiopulmonary bypass time (CPB), aortic cross clamp time (ACC), length of ventilation, length of stay in intensive care unit (ICU), and association of elevation of liver enzymes, rhabdomyolysis, AKI, post-operative atrial fibrillation (POAF), nosocomial infections and post-operative cardiac enzymes. Patients divided into two groups; group I was statins users and group II was non-users. The groups were compared by t-test, or Mann-Whitney U test, as appropriate for interval variables, and Chi square tests used for categorical variables. Data expressed as mean±SD or proportions/percentages for interval and categorical variables respectively. P<= 0.05 (two-tailed) was considered the statistical significant level. Results: Both groups were matched regarding the age, gender, body mass index, Euro score, preoperative liver enzymes, creatinine, and creatine kinase. Statins group did not show significant elevation in liver enzymes, nosocomial infections or higher association of AKI. The incidence of rhabdomyolysis and POAF were significantly lower in the statins group (p=0.025&0.02 respectively). In addition, initial cardiac troponin and CK-MB were significantly lower in the statins group (p=0.01&0.04 respectively). Statins treated group had significant lower lengths of ventilation, stay in ICU and hospital (p=0.002, 00.05&0.001 respectively). Conclusions: Therapy with statins before cardiac surgeries was not associated with high incidence of adverse events; moreover statins treated group had a favorable outcome regarding the POAF events and lengths of stay in ICU as well as hospital. Reference(S). Liakopoulos OJ, Kuhn EW, Slottosch I, Wassmer G&Wahlers T. Preoperative statins therapy for patients undergoing cardiac surgery. Cochrane Database Syst, 2012.Rev, 4. Acknowledgment: I am highly indebted to all members of the department of Cardiothoracic surgery department, as well as medical research center, Hamad Medical Corporation.
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Differential Expression Of Small Rnas In Anchorage Independent Metastatic Tumor Models Of Ovarian Cancer Cell Lines
المؤلفون: Eman Al-dous, Thasni Azis, Yasmin Mohamoud and Joel MalekBackground: Small RNAs play an essential role in fundamental biological processes such as differentiation, proliferation, apoptosis and homeostasis. Evidence suggests that small RNAs may also play function in Cancer progression. The conventional in-vitro two-dimensional (2D) monolayer cell culture models are not sufficient to explain the exact mechanism behind tumor invasion and metastasis. The objective of this study is to analyze the role of small RNAs in tumor invasion and metastasis using in vitro 2D and anchorage independent (3D) models in ovarian cancer cell lines. Methods: Total RNA samples were isolated from several 2D and 3D ovarian cancer cell lines. Small RNA libraries were prepared and sequenced using Next-Generation Sequencing. Results: Gene expression levels of 3D culture differ from 2D culture, especially in epithelial and mesenchymal target genes. We were able to identify the predominant pathways that small RNAs regulate in 3D cultures. These pathways were involved in cellular invasion, migration, metastasis, proliferation, and tumor growth. Conclusion: The Results from this experiment suggest that small RNAs play a crucial role in controlling tumor invasion and metastasis in the studied phenotypes. Therefore, small RNAs may offer a critical target for the development of anti-cancer drugs.
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Novel Isosteviol Derivatives Induced Apoptosis In Human Lung Cancer
المؤلفون: Ahmed Malki and Stephen BergmeierBackground. Cancer metastasis is the major cause of cancer death. We previously reported novel isosteviols derivatives which induced cytotoxicity in lung cancer cells. The understanding of mechanisms which regulate lung cancer sensitivity to our novel isosteviol derivatives is necessary for development of novel set of anticancer derivatives. Aims. Investigate the molecular mechanisms of the optimized ring novel isosteviol derivatives on inhibition of proliferation, migration and tumor growth in lung cancer in vitro and in vivo. Results. Our data showed that novel MOM-ether analogs of isosteviol 8c and 9d decreased cell proliferation and induced apoptosis in H1299 lung cancer cells more than p53 stably transfected H1299 cells. Flow cytometric analysis showed that both isosteviol derivatives 8c and 9d arrested the H1299 cells in G1 phase which is further confirmed by increased expression level of p21. Moreover, both isosteviol derivatives 8c and 9d increased caspase-9 activity in H1299 cells and the induction of apoptosis was significantly reduced after treating cells with caspase-9 inhibitor LEHD-CHO. Both isosteviol derivatives 8c and 9d increased Caspase 3 activities and induced Parp-1 cleavage in H1299 cells. Both derivative 8c and 9d reduced expression levels of AKT and Bcl-2 and increased expression levels of Bax and Bad in H1299cells. Induction of apoptosis was significantly reduced after treating H1299 with AKT inhibitor LY294002. In mice, oral administration of isosteviol derivative 9d inhibited the growth of xenograft tumors, invasion, migration, and anchorage-independent growth in tumor tissues without affecting body weight and it decreased the expression levels of VEGF, MMP-9, MEK and MAPK in tumor tissues. Conclusion. Based on previous results, our data support the development of isosteviols derivatives as potential agent for lung cancer treatment via targeting MEK/MAPK pathways.
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The Epidemiology Of Hepatitis C Virus In Yemen: A Systematic Review And Meta-analysis
المؤلفون: Karima Chaabna and Laith Abu RaddadBackground and Objective: In the Middle East and North Africa, hepatitis C virus (HCV) infection distribution appears to present a wide range of prevalence. The scale and nature of HCV infection exposure in Yemen is poorly known. The objective of this study was to establish the national population-level HCV prevalence in Yemen and to characterize the epidemiology of this infection in the Yemeni population. Methods: We conducted a systematic literature review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Sources of data included PubMed and Embase databases. Our analysis included all primary studies reporting HCV antibody prevalence or incidence measures in Yemen. Extracted measures were then classified and analyzed on the basis of the study population's risk of acquiring HCV. Meta-analyses were conducted incorporating inverse variance weighting and using a random-effects model to pool summary estimates of HCV prevalence among general population groups. Results: We identified 28 studies providing a total of 46 measures on HCV prevalence and none on incidence in Yemen. Pooled HCV prevalence in the general population was 1.8% (95% confidence interval (CI): 1.05-2.75). Among blood donors the prevalence ranged from 0.2 to 3.0% depending on governorate of origin. The highest prevalence within the general population groups was reported among pregnant women in one study (8.5%) followed by a study of African migrant community living in a Shanty town in Sana'a (5.2%). Among high risk populations, HCV prevalence among hemodialysis patients was 40.0% in 1999 and 62.7% in 2007. Among patients with acute and chronic liver disease it was 74.1%. Conclusions: National-level HCV prevalence in Yemen is slightly higher than that in developed countries, but comparable to several other countries in the Middle East and North Africa. The high prevalence found among high risk groups may indicate limitations in implementation of infection control and blood screening protocols, or possibly dates back to exposures before these measures were expanded. These findings are of particular relevance for resource allocation and HCV public health programming in Yemen. HCV prevention policy in Yemen should focus mainly on prevention and infection control in settings of exposure such as in medical care and among people who inject drugs.
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Chicken Is For The Birds: Changing The Deadly Driving Behaviors Of Young Qatari Men
المؤلفون: Susan Dun, Susan Pak, Shaikha Alnaimi, Rouda Al-meghaiseeb, Ibrahim Alhashmi, Mohammed Buhmaid and Owais AliQatar Research Grand Challenges Areas: 1. Integrated health management; cultivate healthy behaviors through public health, safety... campaigns. 2. Road Safety: Mitigate Accidents. Introduction Motor vehicle collisions (MVC) in Qatar are at epidemic rates and expected to continue to rise to 220,000 per year by 2015 (ElGhanem, 2012). The fatalities and economic costs associated with traffic accidents are high in Qatar, with one out of eight deaths attributed to MVCs according to some estimates (The Peninsula, 2013) and is as high as 18% according to others (MOI, 2012) and estimates of the economic impact to the GDP are about 2.73 billion USD (Nehlawi, 2013). While there are many causes of MVCs in Qatar, over half of the accidents involve drivers with little driving experience (ElGhanem, 2012). Because of societal constraints for young women, young drivers in Qatar tend to be mostly male. These young male drivers lack experience and may engage in risky behaviors such as texting, not wearing seat belts, speeding, playing games such as 'chicken,' and other thrill-seeking practices. Though few scientific studies have been undertaken, those that are released are covered widely in the local press, indicating this is a pressing issue for Qatar residents. Qatari male youth are much more likely to stunt drive as compared to expatriate youth (Doha News, 2012). The costs to families in Qatar are high, with young people's lives ending tragically or with them suffering debilitating injuries (ElGhanem, 2012). Objectives, Materials, Methods. Changing the driving attitudes and behaviors of young Qatari men are the objectives of our study. It uses a tailored message campaign developed from research on the target audience. We will conduct an in-depth formative research study with young Arab men, identifying their driving beliefs, attitudes and behaviors. Using the results from the formative research, we will plan and shoot a 7-10 minute persuasive documentary targeting their key beliefs, attitudes and behaviors. Such a tailored message is critical to success, as we must adapt it to the particular attitude structures of the audience for it to succeed. For example, we suspect this population is high on the trait 'sensation seeking'; if verified, then the message must be adapted to this trait to be likely to succeed. We will then screen the documentary to the target audience. We will conduct evaluation research to assess the film's influence on beliefs, attitudes and behavioral intentions in the target population. Results and Conclusions We anticipate being in the documentary shooting stage by the conference, thus will present the results of the formative research and the preliminary documentary. We have a UREP grant for funding. References Doha News (2012, June 19). Study: Young Qatari men more prone to risky driving. Retrieved from http://dohanews.co/study-young-qatari-men-more-prone-to-risky-driving/ ElGhanem, N. (2012, May 3). Qatar has world's highest rate of traffic fatalities study reports. Al-Shorfa.com. Retrieved from http://al-shorfa.com/en_GB/articles/meii/features/main/2012/03/05/feature-02 Nehlawi, M. (2013, April 17). The price of Qatar's high road accidents. The Edge. Retrieved from http://www.theedge.me/the-price-of-qatars-high-road-accidents/ West, B. & Naumann, R. (2011). Motor vehicle related deaths United States, 2003-2007. Retrieved from http://www.cdc.gov/mmwr/preview/mmwrhtml/su6001a10.htm
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Hiv Among People Who Inject Drugs In The Middle East And North Africa: Systematic Review And Data Synthesis
Background It is widely perceived that little is known about the epidemiology of HIV infection among people who inject drugs (PWID) in the Middle East and North Africa (MENA). The primary objective of this study was to assess the status of the HIV epidemic among PWID in MENA by describing HIV prevalence and incidence. Secondary objectives were to describe the risk behavior environment and the HIV epidemic potential among PWID, and to estimate the prevalence of injecting drug use in MENA. Methods This was a systematic review following the PRISMA guidelines and covering 23 MENA countries. PubMed, Embase, regional and international databases, as well as country-level reports were searched up to December 16, 2013. Primary studies reporting 1) the prevalence/incidence of HIV, other sexually transmitted infections, or hepatitis C virus (HCV) among PWIDs; or 2) the prevalence of injecting or sexual risk behaviors, or HIV knowledge among PWID; or 3) the number/proportion of PWID in MENA countries, were eligible for inclusion. The quality, quantity, and geographic coverage of the data were assessed at country level. After multiple level screening, 192 eligible reports were included in the review. There were 197 HIV prevalence measures on a total of 58,241 PWID extracted from reports, and an additional 226 HIV prevalence measures extracted from the databases. Findings We estimated that there are 626,000 PWID in MENA (range: 335,000-1,635,000, prevalence of 0.24 per 100 adults). We found evidence of HIV epidemics among PWID in at least one-third of MENA countries, most of which are emerging concentrated epidemics and with HIV prevalence overall in the range of 10-15%. Some of the epidemics have however already reached considerable levels including some of the highest HIV prevalence among PWID globally (87.1% in Tripoli, Libya). The relatively high prevalence of sharing needles/syringes (18-28% in the last injection), the low levels of condom use (20-54% ever condom use), the high levels of having sex with sex workers and with men who have sex with men (15-30% and 2-10% in the last year, respectively), and of selling sex (5-29% in the last year), indicate a high injecting and sexual risk environment. The prevalence of HCV (31-64%) and of sexually transmitted infections suggest high levels of risk behavior indicative of the potential for more and larger HIV epidemics. Conclusions Our study identified a large volume of HIV-related biological and behavioral data among PWID in the MENA region. The coverage and quality of the data varied between countries. There is robust evidence for HIV epidemics among PWID in multiple countries, most of which have emerged within the last decade and continue to grow. The lack of sufficient evidence in some MENA countries does not preclude the possibility of hidden epidemics among PWID in these settings. With the HIV epidemic among PWID in overall a relatively early phase, there is a window of opportunity for prevention that should not be missed through the provision of comprehensive programs, including scale-up of harm reduction services and expansion of surveillance systems.
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Molecular Determinants Of The Store-operated Ca2+ Entry Channel Orai1 Trafficking In Mammalian Cells
Intracellular calcium ion is a universal messenger that plays a critical role in wide range of physiological functions and failure to maintain calcium homeostasis is linked to cellular dysfunctions in several diseases. Store operated calcium entry (SOCE) is a fundamental Ca2+ influx pathway at the cell membrane that is activated in response to intracellular store depletion. The SOCE machinery consists of the ER Ca2+ sensor STIM1, and Orai1 a Ca2+ selective channel at the plasma membrane (PM). Despite advancements in our understanding of the regulation of STIM1 and Orai1 very little is known about the biogenesis and trafficking of Orai1 and how that affects SOCE in mammalian cells. Here we describe the trafficking dynamics underlying Orai1subcelluar distribution at steady state and after store depletion. We show that at steady state 40% of total cellular Orai1 localizes to the PM of CHO cells. The other 60% of Orai1 localizes intracellularly. Time lapse imaging shows continuous shuttling of Orai1-positive vesicles between the PM and intracellular compartments. Quantitative measurements of the exocytosis and endocytosis rates at steady state show a rapid recycling rate of the protein between the intracellular pool and the plasma membrane. Following store depletion, ~80% of Orai1 is localized at PM. Interestingly, we localized Orai1 to novel sub-plasma membrane vesicular compartment of unknown molecular composition. To study the domain of Orai1 involved in its trafficking, we generated deletions of the N-(1-90) or C-(257-301)-terminus. Deletion of N-terminus did not change the surface to total distribution of Orai1, while C-terminus deletion significantly altered Orai1 distribution, with majority of Orai1-∆C localizes intracellularly. Similarly, deletion of residues 267-301 and residues 276-301 showed significantly decreased surface/total distribution compared to wild type (WT), but a less pronounced defect than Orai1-∆C. In contrast, 1-285 behaved like WT Orai1 showing that residues 286-301 are not required for Orai1 biogenesis and localization to the cell membrane. In conclusion, our data suggest that Orai1 recycles at high rate between PM and intracellular compartments at steady state and is enriched at PM after store depletion. Our results also suggest that the amino acid region (257-285) of Orai1 C-terminus is essential for its biogenesis and PM targeting.
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Identifying Key Factors For Type Ii Diabetes Mellitus Prevention Interventions In Qatar
المؤلفون: Paul J Christos, Hiam Chemaitelly, Laith J Abu-raddad, Mahmoud Ali Zirie, Dirk Deleu and Alvin I MushlinBackground: Type II Diabetes Mellitus (DM) is one of the leading chronic diseases in Qatar as well as worldwide. However, the risk factors for DM in Qatar and their prevalence are not well understood. We conducted a case-control study with the specific aim of estimating, based on data from outpatients with DM in Qatar (cases) and inpatient/outpatient controls, the association between demographic/lifestyle factors and DM. We also estimated the contribution of these factors to the occurrence of DM cases among Qatari nationals and non-Qatari expatriate population. Methods: A total of 459 patients with DM from Hamad Medical Corporation Hospital (HMC) outpatient adult diabetes clinics and 342 control patients from various outpatient clinics and inpatient departments at HMC were identified using rigorous sampling methodologies and recruited between the years 2006 and 2008. The association between risk factors and DM was evaluated using bivariate and multivariate logistic regression analyses, and for the population at large and for only Qatari nationals. In addition to odds ratios (OR) and 95% confidence intervals (95% CI), we calculated the population attributable risk fractions for demographic and lifestyle factors in relation to DM. Results: Qatari nationality was the strongest risk factor for DM (adjusted OR=5.5; 95% CI=3.5-8.6), followed by higher monthly income (defined as ≥ 3000 riyals, OR=5.1; 95% CI=3.0-8.7), age > 65 years (OR=3.3; 95% CI=0.9-11.4), male gender (OR=2.9; 95% CI=1.8-4.8), obesity (body mass index ≥ 30, OR=2.2; 95% CI=1.5-3.2), no college education (OR=1.7; 95% CI=1.2-2.6), and no daily vigorous/moderate activity (OR=1.5; 95% CI=0.9-2.3). Among Qatari nationals, obesity was revealed as the main risk factor for DM (unadjusted OR=3.0; 95% CI=1.6-5.6) followed by no college education (OR=2.7; 95% CI=1.5-5.1), while consanguinity did not appear to play a major role in predicting DM (OR=1.5; 95% CI=0.8-2.8). Our findings further suggested that eliminating obesity and improving access to education could reduce DM cases by up to one third in the population at large (31.7% and 26.8%, respectively) and up to half (46.9% and 49.3%, respectively) among only Qatari nationals. Promoting physical activity may as well reduce the burden of DM by up to 9.4% in the population at large and up to 17.3% among Qatari nationals. Conclusions: Demographic and lifestyle factors were revealed as the main risk factors for the high DM levels observed in Qatar, with a contribution that appears to outweigh that of genetic risk factors. While further evaluation of these factors among the Qatari population (as opposed to the population at large) is important and of interest, these findings highlight the need to focus short-term DM interventions on addressing demographic and lifestyle risk factors to achieve substantial and timely declines in DM levels.
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The Impact Of Scaling Up Voluntary Medical Male Circumcision As An Hiv Intervention In South Sudan
المؤلفون: Susanne F. Awad and Laith J. Abu-raddadBackground: Voluntary medical male circumcision (VMMC) reduces the risk of HIV acquisition in men. Though VMMC programs are being scaled up across sub-Saharan Africa (SSA), no VMMC program has been initiated in the world's youngest nation, South Sudan. The possibly growing HIV epidemic in this nation, currently at a prevalence of 3%, and the stark geographic variability in prevalence, suggests an opportunity for controlling HIV transmission using VMMC with sub-population prioritization. Our aim was to explore, using mathematical modeling, the impact of VMMC programming in South Sudan. Method: We used the Age Structured Model (ASM), recently developed in partnership with the Bill and Melinda Gates Foundation, to assess VMMC impact. The model has been applied in several SSA countries. The ASM stratifies the population into compartments according to sex, circumcision status, age group, risk group, HIV status and stage of infection. Results: To achieve 80% VMMC coverage by 2020 among the 15-49 years old males, 2.17 million VMMCs are needed at a total cost of $187 million USD. An additional 1.52 million VMMCs would be needed by 2030 to maintain this coverage at an additional cost of $115 million. By 2030, 123,057 HIV infections would be averted (29.7% of new infections). The number of VMMCs needed to avert one infection (effectiveness) is 30, while the cost per infection averted is $2,608. Through sub-population prioritization by age, VMMC effectiveness ranges between 28 (25-29 and/or 30-34 years age groups), and 91 (10-14 years age group). The cost per infection averted is $2,453 and $2,548 for the age groups of 25-29 and 30-34, respectively, while it is $6,837 for the 10-14. The effectiveness of geographical prioritization varies across states. The lowest number of VMMCs needed to avert one infection is 19 in the state of West Equatoria, while the highest number is 120 in the states of Warrap or Northern Bahr Ghazal. Prioritization by risk group is very effective with only one VMMC needed per infection averted by targeting the highest risk group, while 180 would be needed by targeting the lowest risk group. Conclusion: Though at higher cost per infection averted compared to other SSA countries, our findings demonstrate that a VMMC program in South Sudan can be effective and cost-saving. The effectiveness of VMMC scale-up can be optimized by sub-population prioritization of 25-34 years old males, states with the highest HIV prevalence, and high-risk populations. A VMMC program in South Sudan should be considered, and donor support should be secured to initiate and sustain its establishment.
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Guidelines For The Use Of Negative Pressure Incision Management To Reduce Wound Complications Following Heart Surgery
Background: Negative Pressure Wound Therapy (NPWT) is well-established in the management of infected surgical wounds. However, it is a relatively new modality of treatment for the protection of clean surgical sites. This study was aimed at developing guidelines for the use of negative pressure incision management to prevent surgical wound complications after heart surgery. Methods: In this prospective study, we included 134 patients at high risk for sternotomy wound complications from September 2011 to June 2014. Selection criteria included: obesity, diabetes, smoking and COPD, fragile sternum, bilateral mammary arteries, delayed primary closure and repeated operations. We applied negative pressure of - 125 mm Hg on the wounds of 67 patients immediately following skin closure, the dressing was removed after 5 to 7 days. The results were compared to a control group with matching criteria (n=67) who had standard dressings. The primary end point of the study was the development of wound complications including surgical site infection, hematoma formation and sternal dehiscence within 30 days. Results: 2 of the 67 patients who underwent negative pressure incision management developed superficial surgical site infection within the 30 days postoperative period (2.99%). The wound infection of the two patients settled with regular dressings and oral antibiotics. While in the control group with conventional wound dressings (n=67), 5 patients developed superficial surgical site infection and one patient suffered a deep sternal wound infection (total 6 out of 67 patients, 8.96%). Based on our experience, we have proposed some selection criteria for the use of negative pressure incision management following heart surgery (table1). Conclusions: Negative pressure is potentially beneficial in the reduction of wound complications. There are no published criteria so far for the application of negative pressure on clean surgical sites post cardiac surgery. Therefore, we proposed some guidelines for the use of negative pressure incision management to protect high risk sternotomy wounds.
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Nuclear Transport Drugs For Cancer: Bench To Bedside
المؤلفون: Asfar S Azmi, Irfana Muqbil and Ramzi M MohammadTrafficking of biological materials across nuclear membrane is an evolutionarily conserved mechanism that maintains normal eukaryotic cell homeostasis. Eukaryotes shuttle proteins and RNAs in and out of the cell nucleus using highly complex gated machinery. Smaller entities can enter and exit the nuclear pore through diffusion. The movement of most of the proteins and RNAs, however, requires active transport that is mediated by specialized carriers in a strictly controlled manner. Such energy dependent trafficking occurs through the nuclear pore complex (NPC) that is embedded in the nuclear membrane. The last two decades have witnessed tremendous advancements in the understanding of the NPC. Such studies have helped in the characterization of major nuclear transport mediators belonging to the Karyopherin family proteins that maintain proper compartmentalization of micro- and macro-molecules. This is functionally critical for tumor suppressor proteins (TSPs) and transcription factors (TFs) that require nuclear retention and sequence specific DNA alignment to modulate their target gene expression or conduct genome surveillance activity. Indeed, cancer cells have evolved methods to disturb the nuclear traffic by abnormal expression of the nuclear exporters particularly exportin 1 (Xpo1) that leads to a cascade of de-regulations favoring uncontrolled growth and loss of surveillance within the cells. Major cancer hallmarks have been shown to be influenced by Xpo1 de-regulation directly or indirectly. Recently, specific inhibitors of nuclear export (SINE) have been developed as a broad form of therapy targeting global re-alignment of multiple TSPs in the correct cellular compartment through inhibition of Xpo1 to rein in cancer. SINEs are currently undergoing Phase I and Phase Ib/II clinical evaluation. The drugs show single agent efficacy both in solid tumors and hematological malignancies.
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Robot-assisted Excision Of An Unusual Apical Pericardial Hydatid Cyst
مزيد أقلBackground: a 30 year old gentleman was referred to our in thoracic surgery clinic with an incidental finding of an abnormal shadow around the apical region of the heart on the chest radiograph. He was asymptomatic and non smoker and he had no chronic medical illness in the past. He had no specific findings on physical examination. Echocardiogram revealed rounded cyst in the pericardium around the hear apex measuring 5.9 by 4.1cm. Chest CT Angiography revealed no evidence of coronary artery disease. Magnetic Resonance Imaging (MRI) showed a well defined round pericardial cyst close to the left ventricular apex but there was no evidence of infiltration the left ventricle or wall abnormal enhancement. Procedure and Findings: He underwent robotic excision of the cardiac apical cyst. An inflamed 5 by 6cm cystic mass was found densely adherent to the apical pericardium. There were no adhesions or pleural effusion and the lungs and pleural surfaces were looking normal. The cyst was excised and the cavity was irrigated with hypertonic saline. A chest drain was left in the left pleural cavity. Postoperatively the patient had no complications.Bethadine diluted in normal saline was instilled into the pleural space via the chest drain for washing any remains of the infection. The drain was removed after 48hrs and the patient was discharged from the hospital on antiparasitic treatment (Albendazole tablets). Results: the patient had an uneventful recovery from surgery; he was reviewed in the clinic and had no evidence of recurrence of the disease. Histopathology report revealed laminated membranes with few protoscolices consistent with hydatid cyst (Eccinococcal infection). Conclusion : this is an unusual presentation of cystic echinococcosis (hydatid disease) which was excised robotically. Cystic Echinococcosis is a parasitic disease caused by infection with the larval stage of a tiny tapeworms of Echinococcus granulosus which usually grows in dogs (definitive host), sheep, cattle, goats, and pigs (intermediate hosts). Although most infections in humans are asymptomatic, hydatid disease can lead to the development of harmful, slowly enlarging cysts mainly in the liver and lungs. However, it might rarely affect other organs but it often remains unnoticed and neglected for years.
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Role Of Stim1 And Orai1 In Mammalian Oocyte Activation
المؤلفون: Satanay Hubrack, Ethel Adap, Stefan Feske and Khaled MachacaUpon fertilization, the mammalian oocyte undergoes a series of Ca2+ oscillations, which results in its activation and initiation of embryo development. It is believed that these periodic and extended Ca2+ responses are a consequence of intracellular Ca2+ release coupled to Ca2+ influx across the plasma membrane due to the activation of a process known as Store Operated Calcium Entry (SOCE). The underlying mechanism of SOCE is known to be controlled by Stim-Orai channels, where IP3-mediated emptying of ER calcium stores results in the aggregation of Stim1 molecules followed by interaction with Orai1 channels on the plasma membrane and activation of Ca2+ entry. Stim1 was shown to redistribute in the form of patches after mouse oocyte fertilization in a manner similar to its redistribution after pharmacological Ca2+ store depletion, while down-regulation of Orai1 expression in pig oocytes inhibited oscillations induced by fertilization. We have further shown that overexpression of Stim1 and Orai1 in mouse oocytes disrupts Ca2+ dynamics and inhibits egg activation. These data support a role for SOCE in Ca2+ signaling during fertilization. To further investigate the importance of Stim1 and Orai1 proteins in regulating events of egg activation, we are generating oocyte-specific Stim1 and Orai1 knockout mice by crossing Stim1-flox and Orai1-flox mice with ZP3-Cre transgenic mice. ZP3 is expressed only in oocytes leading to Cre expression only in this cell type and as such an oocyte-specific knockout. Studying rates of fertilization and Ca2+ entry in these knockout oocytes will provide insight into the role of these two proteins in the initiation and persistence of Ca2+oscillations after fertilization, and will help us determine whether there is an absolute requirement for Stim1 and/or Orai1 in regulating Ca2+ responses in early stages of fertilization.
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In Vivo Characterization Of A New Mouse Model Expressing The Na+/h+ Exchanger Isoform 1 Of Dilated Cardiomyopathy
المؤلفون: Alain-pierre Gadeau, Laura Cetran, Isabelle Belloc, Marie-ange Renault, Larry Fliegel and Fatima MraicheRational: Heart failure is a common, costly, and frequently fatal disease. One in three cases of heart failure is due to dilated cardiomyopathy. NHE1 expression and activity are increased in this cardiac defect. We have previously shown that elevated activity of NHE1 in the cardiomyocytes induced cardiac hypertrophy in transgenic mice. However, it protected the myocardium following ischemia/reperfusion. This overexpression of active NHE1 elicited modulation of gene expression in cardiomyocytes including an up regulation of myocardial osteopontin (OPN) expression and a decrease of peroxisome proliferator-activated receptor (PPAR)γ. Since transgenic mice phenotype is very often influenced by the integration position of the transgene, we decide to create new transgenic mice to ascertain our previous data and to test the role of modulated genes. Method and results: We have created 5 new mouse lines overexpressing a constitutively active form of NHE1 specifically in cardiomyocytes (KNHE1+). We have evaluated by echocardiography the cardiac phenotypes and function of two of these new mouse lines. Then heart were harvested and submitted to histological, immunohistological and QRT-PCR analysis. Our data showed that in the both KNHE1 studied lines, a number of mice demonstrated heart remodeling identified by a significant decrease in diastolic interventricular septal (IVSd) and diastolic left ventricular posterior wall (LVPW) thickness and an increased diastolic left ventricular internal dimension (LVIDd) (see table 1). Moreover these hearts demonstrated impaired function with a decreased fraction shortening (<21 % vs 31% in wild type mouse) and ejection fraction. However, the proportion of 12 weeks old mice demonstrating this defect is different in both lines 13% (3/24) in line #4 and 58% (11/19) in line#1 vs 0% (0/37). ANP and BNP up regulation in line #1 confirmed heart suffering. Current experiment is designed to perform a longitudinal study examining evolution of these proportions with the age of the animals. Conclusions: We have developed an interesting comparative model of active NHE1 transgenic mouse lines with low and high rate dilated cardiomyopathy identifying evidence of early and late mechanisms. Further studies will be conducted to evaluate the phenotypes of the other mouse lines and the mechanism by which these changes are occuring.
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Role Of Inflammatory Cells In Insulin Resistance-associated Impairment Of Preadipocytes Differentiation
المؤلفون: Shamma Abdullah Almuraikhy and Mohamed ElrayessWe have shown previously that insulin-resistance is associated with impairment of preadipocyte differentiation and increased proinflammatory cytokines release in stromal vascular fraction (SVF) cultures. In order to investigate whether depletion of potential sources of these cytokines is sufficient to rescue preadipocyte differentiation, we examined the ability of SVF cells to differentiate into mature adipocytes following depletion of endothelial cells (CD31+) and leukocytes (CD45+) by magnetic cell sorting, together with profiling of gene expression and cytokines levels in the presence or absence of these cells. Our data show that depletion of CD31+/CD45+ cells led to improvement in the differentiation capacity of SVF cultures from insulin resistant but not insulin sensitive or diabetic subjects. These findings suggest that inflammatory cells contribute to insulin resistance-associated impairment of preadipocytes differentiation, perhaps via elevation of cytokines secretion. Understanding the molecular mechanisms underlying impaired preadipocyte differentiation associated with insulin resistance may help future treatment strategies.
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To Be Or Not To Be: Mechanisms Of Regulation Of Stim1 By Its 3'utr In Breast Cancer
المؤلفون: Rashmi Pradyumna Kulkarni, Nancy Nader, Ethel Alcantara-adap, Maya Dib and Khaled MachacaThe endoplasmic reticulum (ER) functions as a storehouse for intracellular calcium. STIM1, a calcium sensor, localizes mostly to the ER membrane. Following Ca2+ store depletion, STIM1 forms puncta that localize to the cortical ER and bind Orai1, a plasma membrane Ca2+ channel, to allow Ca2+ influx. This is the predominant pathway for Ca2+ influx in non-excitable cells and is referred to as Store-Operated Calcium Entry (SOCE). Mutations in STIM1 and Orai1 cause severe combined immunodeficiencies and are linked to several forms of cancers. Tight regulation of the levels of STIM1 and Orai1 is crucial for maintaining the subcellular levels of Ca2+ required for its numerous functions. We are interested in mechanisms of post-transcriptional regulation of STIM1. We have developed a system that allows us to test miRNA-mediated regulation by transfecting different cell types using a GFP and a 3'UTR transcriptional fusion and GFP with no 3'UTR as a control. mCherry expressed from the same vector is used as an internal control of transfection efficiency. The stoichiometry of GFP and mCherry levels in the experimental conditions for Stim1 3' UTR was found to be significantly different from those in the control. Knockdown of Ago2, an important mediator of the miRNA pathway, by siRNA restored GFP expression from these constructs suggesting miRNA-mediated regulation. We have identified a miRNA that regulates Stim1 expression in HEK 293 (embryonic kidney), MCF7 (non-metastatic breast cancer) but not in MDA-MB231 (metastatic breast cancer) cell lines. The mechanisms by which this occurs will be discussed.
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The Kielin/chordin-like Protein Kcp Can Attenuate High Fat Diet Induced Obesity And Metabolic Syndrome In Mice Model
المؤلفون: Abdul SoofiObesity and its associated complications, such as insulin resistance and non-alcoholic fatty liver disease, are reaching epidemic proportions in the developed world, primarily due to the increased availability of high caloric foods and the decrease in daily physical activity. It is well established that energy balance is critical for maintaining normal body weight and homeostasis. When caloric intake chronically exceeds energy expenditures, white adipose tissue stores excess energy in the form of triglycerides, leading to obesity and related complications such as type-2 diabetes, a condition also referred to as metabolic syndrome. In mice, the TGF- superfamily is implicated in the regulation of white and brown adipose tissues differentiation. The KCP protein is a secreted regulator of the TGF- superfamily pathways that can inhibit both TGF- and Activin signals while enhancing the Bone Morphogenetic protein (BMP) signaling. However, the effects of KCP on metabolism and obesity have not been studied in animal models. Thus, we examined the effects of KCP loss or gain of function in mice that were maintained on either a regular or a high fat diet. Loss of KCP sensitized mice to obesity and associated complications such as hepatic steatosis and glucose intolerance. In contrast, transgenic mice that expressed KCP in the kidney, liver and brown adipose tissues were resistant to developing high fat diet induced obesity and had significantly reduced white adipose tissue. KCP over-expression was able to shift the pattern of Smad signaling in vivo, to increase the levels of P-Smad1 and decrease P-Smad3, resulting in resistance to high fat diet induced hepatic steatosis and glucose intolerance. The data demonstrate that shifting the TGF- superfamily signaling with a secreted inhibitor or enhancer can alter the profile of adipose tissue to reduce obesity and can inhibit the initiation and progression of hepatic steatosis to significantly reduce the effects of high fat diet induced metabolic disease. In summary, the results of this suggest that altering TGF-β superfamily signaling pathway by a secreted protein can attenuate renal fibrosis and the negative effects of obesity induced metabolic syndrome. Provide a conceptual basis for the use of secreted protein or derivatives to attenuate profibrotic pathways that depend on continued TGF-β signaling and/or counteraction by BMPs may potentially provide a novel approach to translating the protective role of BMP-7 into clinical benefit.
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12/15-lipoxygenase: A Novel Therapeutic Target In Diabetic Retinopathy
المؤلفون: Mohamed Al-shabrawey, Ahmed Ibrahim, Amany Tawfik, Sally Elshafey and Nasser RizkBackground: Breakdown of blood-retinal barrier (BRB) and subsequent hyperpermeability is a cardinal feature of early diabetic retinopathy (DR) and leading cause of blindness. Fatty acid metabolism is implicated in several biological functions via multiple signaling pathways including the synthesis of bioactive metabolites. Our previous studies established 12/15-lipoxygenase (12/15-LOX)-derived 12- and 15- hydroxyeicosatetraenoic acids or HETEs as proangiogenic mediators during DR via disrupting the retinal levels of vascular endothelial growth factor and pigment epithelium derived factor (PEDF). Purpose: 1) To screen the impact of high glucose (HG) treatment on the levels of bioactive lipids including 12/15-LOX metabolites in cultured human retinal endothelial cells (HREC), 2) To test the impact of 12/15-LOX deletion on BRB function and explore the underlying mechanism in particular the role of NADPH oxidase as a major source of oxidative stress during DR. Material and Methods: Liquid chromatography-mass spectrometry (LC/MS) was used in a comprehensive lipidomic screen of HRECs treated with or without HG (30mM D-glucose). Effect of 12- or 15-HETE (0.1 M) on leukostasis and angiogenesis (tube formation) was examined in HRECs transfected with siRNA against the catalytic subunit of NADPH oxidase (NOX2) or the scrambled siRNA or treated with or without the NADPH oxidase inhibitor (apocynin, 30°M). Human leukocytes (PMNs) labeled with lipophilic fluorescent probe were used for leukostasis assay. Migration assay was performed using the Electrical Cell Impedance Sensor (ECIS). Retinal vascular changes were examined by fluorescein angiogram (FA) and Optical Coherence tomogram (OCT) in streptozotocin-induced diabetic wild type (WT) or 12/15-LOX-knockout mice and in mice received intraocular injection with 12-HETE or 12-HETE with PEDF. Western blotting, immunofluorescence and multiplex system were used to test the changes in the levels of inflammatory markers. Results: Out of 126 bioactive lipids screened, 70 were undetected, 47 un-significantly changed, and 9 metabolites were significantly up-regulated by HG compared to osmotic control (5mM D-glucose+25 mM L-glucose). Intriguingly, six metabolites among the 9-increased are the products of 12/15-LOX pathway (15-HETE, 11-HETE, 8, 15-DiHETE, 12-HETE, 17-HDoHE, and 13-HODE). Of these 15-HETE has the highest fold increase (p value= 0.004). Thereafter, we pursued to determine whether the altered metabolites of 12/15 LOX play a role in BRB dysfunction during diabetes. Retinal vascular leakage was significantly reduced in diabetic mice deficient in 12/15-LOX as evidence by FA and less albumin leakage compared with diabetic wild-type littermates. Furthermore, intravitreal injection of 12-HETE per se in normal WT mice resulted in a marked increases in the vascular leakage and expression of inflammatory markers such as ICAM-1, VCAM-1, CD45 as well as the NOX2 compared to vehicle-injected control or to mice received both 12-HETE and PEDF. In vitro, 12/15-HETEs induced HREC leukostasis, migration, and tube formation. These effects were inhibited by the concomitant use of apocynin and by silencing NOX2. Conclusion: Retinal endothelial 12/15-LOX is activated by hyperglycemia causing overproduction of 12- and 15-HETEs. These metabolites are implicated in the pro-angiogenic, -oxidative and -inflammatory effects of hyperglycemia in HREC. Thus, targeting this signaling system represents an attractive therapeutic strategy to prevent and treat DR.
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In-vitro Cytotoxicity Of Selected Sudanese Medicinal Plants With Potential Antitumor Activity
المؤلفون: Yasmin Hilmi and Muna Abushama1.Introduction: According to unique position and varied climate, terrain, and flora and fauna, the Sudanese have developed a unique traditional culture. Their unique indigenous knowledge of herbs led to the development of numerous general health and preventative remedies. Some are useful and some, although widely accepted due to custom and tradition, proved harmful. Identification of medicinal plants with significant cytotoxic potential useful for the development of cancer therapeutics has gained increasing importance in the last decade and research in this field is expanding. Twenty five extracts of fourteen Sudanese plants, used traditionally as medicines, were previously screened for their safe use by the authors. Preliminary cytotoxicity and antioxidant activity investigations of these plants were carried out using Brine Shrimp Lethality Test (BSL), DPPH (1, 1-diphenyl-2-picrylhidrazil) radical scavenging and Iron Chelating Assays. Thirteen extracts showed significant cytotoxicity on BSL assay with different antioxidant capacities. Therefore, this study was conducted to evaluate the in-vitro cytotoxicity of these thirteen extracts in RAW 264.7 normal cell cultures to verify their traditional safe use and their potential antitumor capacity. Ethanol and aqueous extracts of Sesamum indicum, Acacia senegal, Moringa oleifera, Ambrosia maritima, the ethanol extracts of Nigella sativa and Foeniculum vulgare , the fixed oil of Riccinus communis and the essential oils of Piper nigrum and Coriandrum sativum were investigated. 2.Materials & Methodology: Three concentrations of the tested plants crude extracts were studied for their cytoxicity in normal cell cultures Raw 264.7 (125, 250 and 500 μg/mL), using Microculture Tetrazolium (MTT) cell viability assay to determine 50% inhibitory concentration. Cell inhibition percentages were also investigated using linear regression equation. 3.Results & Discussion: Traditionally, the tested plants have been used for the treatment of several diseases. In our study, two of the tested plant extracts showed significant cytotoxicity in normal cell cultures Raw 264.7. These were the ethanol extract of F. vulgarae which showed 67.86 % ± 0.03 cell inhibition at 125 μg/mL with IC50 1.3 μg/mL, while the aqueous extract of A. senegal showed 57.59 %± 0.09 cell inhibition at 125 μg/mL with IC50 23.5 μg/mL. The toxicity may be due to metabolic activation of chemical compounds of these two plant extracts. 4.Conclusions & Recommendations: The ethanol extract of F. vulgarae and the aqueous extract of A. senegal possessed cytotoxic activity to RAW 264.7 normal cell line at 125 μg/mL. Therefore, the data provide evidence that these extracts could potentially contain selective cytotoxic agents. The antitumor potential of these extracts for therapeutic attempts is considered. Further cytotoxic studied on different tumor cell lines must be carried out to verify the importance of these extracts for tumor therapeutics. The results agree with the ethno botanical use of the other tested plants extracts that had no activity to RAW 264.7 normal cell line. Investigation of active constituents of all extracts under study will provide useful comparative information before justifying their safe use.
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Involvement Of Intracellular Calcium [ca2+]i In The Treatment Of Human Neuroblastoma With Cisplatin (cddp) And Topotecan (topo)
المؤلفون: Elizabeth Varghese, Ana-maria Florea, Guido Reifenberger and Dietrich BusselbergNeuroblastoma is a solid malignant embryonic tumor. It is usually diagnosed in the infancy and rarely found after the age of 10 years. In the current treatment options, CDDP and TOPO are included. Methods: Neuroblastoma (SH SY-5Y) cell death was investigated after treatment with CDDP and TOPO (0.1nM-1μM) using Trypan Blue Cytotoxicity Test and Total Cytotoxicity and Apoptosis Detection Kit (FACS). These data are compared to the drug triggered increase of the intracellular calcium ([Ca2+]i) concentration using live calcium imaging with the calcium sensitive dye Fluo-4 AM. Furthermore, we analyzed changes of gene expression of selected [Ca2+]i signaling related genes such as the calcium binding protein S100A6, IP3 receptors, Ryanodine Receptors, Calmodulin (CALM) and the Calmoduling Binding Transcriptor Activator (CAMTA1). Results: With increasing concentration of either of the two substances the amount of viable cells was reduced after 24h of application. The tests revealed a higher cytotoxicity of TOPO (about 25% cell survival at 0.1μM) compared to CDDP (more than 80% survival). With increasing concentrations the percentage of cells which were in the “late apoptosis” stage increased for both drugs but were more pronounced for TOPO. A similar observation was made when the incubation time for the two drugs was prolonged to 48h or 72h when the amount of viable cells was further reduced. Individual (but not all) neuroblastoma cells increased their [Ca2+]i after the application of either CDDP or TOPO (both 1 μM). Over the period of three to four hours the fluorescence increased about 40%. The increase was time and concentration dependent for CDDP and TOPO, while a concentration of 0.01μM was most efficient to increase [Ca2+]i. CDDP and TOPO influence the gene expression of SHSY-5Y cells, targeting specific calcium signaling related genes. In this context, a concentration and time dependent increase in the expression of S100A6 was observed in the cells treated with CDDP. TOPO showed a more pronounced effect than CDDP in increasing the mRNA expression of S100A6. The expression of ITPR1 and ITPR3 genes encoding the type 1 and 3 of the IP3R were found deregulated in the neuroblastoma cells treated to CDDP and TOPO. The 1μM CDDP exposure for 72h was responsible of ITPR1 and ITPR3 down regulation however; the same concentration applied for 24h transiently increased the mRNA expression of ITPR3. The application of TOPO did diminished concentration and time dependently the mRNA expression of ITPR1 after 24h and 72h exposure and of ITPR3 after 72h exposure, however 24h exposure to TOPO did transiently increased the mRNA expression of ITPR3 for the lower concentrations tested. The expression of Ryanodine Receptor genes RYR1 and RYR3 was found deregulated in the neuroblastoma cells treated to CDDP and TOPO. Conclusion: Time and concentration dependently, the treatment of SHSY-5Y cells with TOPO and CDDP increased the cell death, at clinical relevant concentration. That correlates with increased [Ca2+]i levels and with the deregulation in gene expression of calcium signaling related genes suggesting that [Ca2+]i regulation is involved in the anticancer effects of TOPO and CDDP.
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Store Operated Calcium Entry Controls Intracellular Calcium Waves In Xenopus Oocytes
المؤلفون: Raphael Courjaret and Khaled MachacaIn many non-excitable cells such as glial cells, oocytes or beta-cells, fast transmission and integration of information are encoded in the variations of the intracellular Ca2+ concentration. These variations range from a single calcium peak (wave) to a repetitive pattern (oscillations). Intracellular Ca2+ oscillations are made of highly spatially and timely controlled cytoplasmic waves of Ca2+ fueled by two main Ca2+ sources: the extracellular compartment and the endoplasmic reticulum (ER). Specific and highly regulated ion channels and pumps located on the plasma and ER membranes control the cytoplasmic Ca2+ levels as well as the refilling of the ER stores. When the ER Ca2+ stores are depleted, a mechanism termed Store Operated Calcium Entry (SOCE) drives Ca2+ inside the cell to refill them. In the oocytes of the frog Xenopus laevis intracellular Ca2+ variations are converted into chloride currents by Ca2+-Activated Chloride Channels (CACC) located in the plasma membrane, allowing real time monitoring of cytoplasmic Ca2+ levels. We recently showed that SOCE and IP3 receptors (IP3R) define a functional complex allowing mid-range Ca2+ signaling to CACC in those oocytes (Courjaret and Machaca, Nat. Commun. 2014). Here we aimed at understanding how SOCE influences intracellular Ca2+ release by IP3R and oscillations. Injecting an IP3 analog induced a Ca2+ transient oscillation and triggered SOCE. When SOCE influence was increased using hyperpolarizing pulses or reduced by removing extracellular Ca2+, the duration of the Ca2+ oscillation was respectively reduced or increased. Intracellular Ca2+ imaging also revealed that increasing SOCE was reducing the amplitude and increasing the frequency of the individual Ca2+ waves that constitute the oscillation. In addition, removing extracellular Ca2+ more than 30 minutes after the end of the oscillation restored the Ca2+ release, indicating that the ER stores are not fully depleted during the process. Surprisingly, while a short SOCE was able to inhibit intracellular Ca2+ release, increasing the duration/amplitude of the SOCE event was able to trigger a new Ca2+ wave at a very precise timing. This indicated that a strong reloading of the ER stores could overcome the inability of IP3R receptors to release Ca2+ and suggested a luminal regulation of the receptor. To further understand how SOCE was modulating Ca2+ release we therefore monitored Ca2+ levels in the ER lumen by expressing the FRET sensor D1ER. After injection of IP3, D1ER imaging revealed the depletion/reloading of the ER stores by SOCE as a function of the membrane potential. Finally, during the long voltage jumps that are able to induce a Ca2+ wave, the D1ER signal revealed that the high Ca2+ in the ER outlasts the cytoplasmic Ca2+ event leaving the IP3R facing a low cytoplasmic Ca2+ concentration and a high luminal one. Together these findings shed a new light on the complex regulation of IP3R and their tuning by Ca2+ on both sides of the ER membrane.
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Biocompatible Graphene Oxide With Anchored Zwitterionic Moiety - Synthesis, Characterization And Application
المؤلفون: Marketa Ilcikova, Zuzana Kronekova, Anna Zahoranova and Peter KasakBiocompatible Graphene Oxide with Anchored Zwitterionic Moiety - Synthesis, Characterization and Application Markéta Ilčíková1, Zuzana Kroneková2, Anna Záhoranová2 and Peter Kasák1* 1 Center for Advanced Materials, Qatar University, P.O.Box 2713 Doha, Qatar 2 Polymer Institute, Slovak Academy of Sciences, Dubravska cesta 9, Bratislava, Slovakia *Corresponding author: [email protected] The novel biocompatible graphene oxide (GO) bearing zwitterionic moiety was synthesized and characterized. The zwitterionic structures have recently gained attention in biomedical applications as materials for development of ultra-low fouling surfaces. Generally, zwitterions contain both negative and positive charge in their structures; however the overall charge is neutral. That impart them highly hydrophilic performance; the adsorbed water then prevent the cells or bacteria to interact with surface. Graphene is two dimensional filler interesting predominantly due to high electrical conductivity. In oxidized form the electrical conductivity is compromised due to presence of hydroxyl, epoxy and carboxyl functional groups. In this work, the hydroxyl groups were utilized for anchoring the zwitterionic moiety onto the GO surface. The reaction was performed in two steps. First the silanization with (3-mercaptopropyl)trimethoxysilane was preformed to introduce the thiol functionality onto the GO surface that was reacted with sulfobetaine monomer (3-((2-methacrylamidoethyl)dimethylammonio)propane-1-sulfonate) through thiolene click reaction in the following step. The successful modification was confirmed by FTIR and TGA. Compared to neat graphene, the presence of sulfobetaine improved the graphene biotolerability for fibroblasts and pancreatic beta cells. Modification of GO surface with zwitterionic moiety prevents its negative effect on cell viability. Thus the adsorption of cells on the surface and the cell - GO surface interaction is effected. The modified GO will be used for modification of electrode at biochips construction, and the electrorheological response will be discussed as well. Acknowledgement: This publication was made possible by NPRP grant # NPRP-6-381-1- 078 from the Qatar National Research Fund (a member of Qatar Foundation). The statements made herein are solely the responsibility of the authors.
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Metastatic Cancer And Rna Editing: Brief Look At How Rna Editing Is Seen To Encourage Primary Cancer Cells To Metastasize
المؤلفون: Lisa Mathew, Binu George, Iman Al Azwani, Eman Al Dous, Yasmin A Mohamoud, Arash Rafii and Joel A MalekObjective: Information that is present in our DNA is transferred to RNA, which is in turn transcribed into proteins. This is a central principle of molecular biology. Over the years, there have been many attempts to document the thousands of places where transcribed RNA does not match the DNA template it was created from. This behavior is called RNA Editing, and is generally thought to be mainly an A->I change, that is, adenosine to inosine (read as guanine by DNA sequencers), with occasional cytosine to uracil changes as well. Cancer, with its volatility due to DNA base changes, gets more complex with the occurrences of RNA editing. To ensure a fair ground to study RNA editing, we have considered exome and RNASeq library pairs from the cancer-affected ovarian, lymph node and peritoneum tissues in three individual. This data set will help identify RNA editing locations in these tissues, and the role it plays in metastasis. Methods: The exome libraries were prepared using Illumina Paired End Sample Preparation kit and Agilent SureSelect Target Enrichment System kit. RNASeq libraries were prepared using Illumina paired-end protocol. Both the libraries were sequenced using the Illumina NextGen Sequencing platform. Exome libraries were aligned using bowtie2 and RNASeq using tophat2. SNPs were called using samtools. The RNAEditing database from Ensemble was used to filter out known editing sites. With the remaining editing locations, a blat was run against the surrounding sequence to check for similarity to other parts of the genome, to rule out editing sites being called as a result of incorrect alignment scoring. Results: From our preliminary analysis, we see that a majority of the RNA Editing positions represent A->I changes, with a few C->U changes as well. Some of these positional changes are seen across all tissues in an individual. There are few RNA edited sites that are mainly seen only in the metastatic locations, and not seen in the primary. Conclusions: By analyzing the initial results, we can identify the mutations and RNA edited sites that originate from the primary tumor tissue, and those that are acquired in the metastatic tissues.
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Remodeling Of Collagen-Fibers In Deformed Tissues
المؤلفون: Heiko Topol, Hasan Demirkoparan, Thomas J. Pence and Alan WinemanOne goal in the field of soft tissue biomechanics is to understand and to model the properties of collagen-fibers in biological tissues such as blood vessels, brain tissues, and skin which undergo growth and remodeling processes. Experimental studies of Bhole et al.\ [1] suggest that the mechanical properties of fibers in biological tissues depend not only on the current state of the deformation but also on the deformation history. Demirkoparan et al.\ [2] developed a hyperelasticity based framework taking this effect into account. The framework developed in [2] uses an additive hyperelastic material model for the strain energy density, $W = W_m + W_f$. The matrix contribution $W_m$ does not take time-dependent changes of the material properties into account yet the fiber contribution $W_f$ changes over time as it is modeled in terms of a constant creation rate and a deformation dependent dissolution rate of the fibers. Then Topol et al.\ [3] have investigated the predictions of such a model by studying the effect of fiber deformation state at the time of their creation on the overall mechanical properties of the material. This research investigates the relation between the change in the fiber density, the Cauchy stress development, and the deformation of the material.
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Quantitative Microbial Risk Assessment For Campylobacter Jejuni And C. Coli Associated With The Consumption Of Camel Milk Qatar
المؤلفون: Hussni Omar Mohammed, Kenlyn Peters, Ahmed Salem, Sanjay Doiphode and Ali SultanBackground and Introduction—According to the Food and Agricultural Organization that more than one-third of the population of the world is affected each year by food-borne diseases caused by chemical and biological hazards. Foodsafety has been identified as high priority in the Qatar National Food Security Master Plan. Campylobacter spp. are among the leading causes of foodborne illness and capable of triggering severe gastroenteritis with grave long-term sequelae and serious economic impact such as, Inflammatory Bowel Disease (IBD). The practice of drinking fresh camel milk, although is a tradition in Qatar, is increasing around the world because of the perceived medicinal value for health in general, diabetes, autism, and allergies. In addition to the fact that camel milk is the closest to human mother's milk, it contains high levels of antioxidants and iron. Being a fresh product it is exposed o foodborne pathogens including Campylobacter spp. Understanding the pathway by which this hazard enter the food chain and pose risk to human will help in developing risk mitigation strategies. We carried out a study to assess the potential risk of illness from the consumption of camel milk contaminated with Campylobacter spp. in Qatar and identify critical intervention points that would contribute to mitigating its associated risk. Methods—We used the quantitative risk assessment (QRA) methodology using a combination of deterministic and stochastic approaches to address the stated objectives. The QRA approach helps in identifying stages in the production system from farm-to-table that are likely to play role in mitigating or exacerbating the risk of illness associated with the consumption of contaminated camel milk with this pathogen. Data on the probability of either C. jejuni or C. coli in camel milk or in humans were obtained through repeat cross-sectional studies in these populations. Estimates of the adverse health effects were obtained using risk characterization which integrated data on hazard characterization and exposure assessment, including dose-response model. A Monte Carlo Simulation of inputs in the model was performed using @Risk software (Palisade Software, Newfield, NY, USA) and parameters were obtained using Latin Hypercube sampling. Sensitivity analyses were performed to capture the effect of uncertainty and variability of the different parameters used in the model on the predicted risk of illness. Results—Our preliminary analyses showed that the probability of illness for a healthy female from the consumption of camel milk contaminated with C. jejuni ranged from 5 x 10-3 to 24 x 10-2 depending on the amount of camel milk consumed. However, the risk for male is higher (13 x 10-3 to 30 x 10-2). The estimates of illness are three times higher for immune compromised females consumed fresh camel milk. We also evaluated the risk of illness for immune compromised males that consumed fresh camel milk and it was five-times higher in comparison to healthy men. The risk of illness due to the consumption of camel milk contaminated with either C. jejuni or C. coli could be significantly reduced for either gender by increasing the efficacy of sterilizing the milk by boiling or pasteurization.
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Docosahexaenoic Acid (DHA) Remedies Hyperglycemia-Induced Retinal Endothelial Dysfunction: A Potential Therapeutic Intervention For Diabetic Retinopathy
المؤلفون: Nasser Rizk, Isha Sharma, Amina Fadel and Mohamed Al-shabraweyDiabetic retinopathy (DR) is a leading cause of blindness among working diabetic patients worldwide. The current therapeutic strategies are limited by several side effects. Thus, it is important to investigate novel approaches for therapeutic intervention. Early inflammatory response and late neovascularization (NV) are cardinal clinical signs of the DR. We have previously demonstrated the involvement of bioactive lipids especially the products of omega-6 polyunsaturated fatty acids (PUFAs) such as arachidonic acids in the development of retinal hyperpermeability and NV during DR. Hyperglycemia is a major risk factor for endothelial cell activation and development of microvascular dysfunction during DR. Overwhelming evidences suggest that omega-3 PUFAs like DHA (C22:6n-3) are protective in proliferative DR. In the present study, we investigate the effect of exogenous supplementation of DHA on human retinal microvascular endothelial cells (HREC) under hyperglycemic conditions. Cells were treated with or without high glucose (HG, 25 mM) for 36 hrs in the presence or absence of the DHA (30 µM). To study the early inflammatory response, cells were analyzed for cell barrier function by measuring the changes in transcellular electrical resistance (TER) using the Electrical Cell-substrate Impedance Sensing (ECIS). Hyperglycemia resulted in a significant decline in TER while it was significantly improved by DHA. Furthermore, to investigate the effect of DHA on the proangiogenc properties of hyperglycemia in HREC a scratch-wound repair assay was carried out in cultured HREC cells treated with or without HG in the presence or absence of DHA. The migration and proliferation of cells induced by HG was reduced on supplementation of cells with DHA. Levels of apoptosis and oxidative stress were also monitored under the effect of hyperglycemia. While HG treatment did not result in any change in level of apoptosis, it resulted in sharp induction of oxidative stress in cells, which however was ameliorated under the effect of DHA treatment to hyperglycemic cells. Real-time PCR revealed significantly enhanced transcripts for the vascular endothelial growth factor (vegf) in hyperglycemic cells while reduced expression of the pigment epithelium derived factor (pedf) and the peroxisome proliferator activated receptor gamma (PPAR) was observed. These changes were prevented by DHA. Anti-inflammatory properties of DHA were further evinced by monitoring the levels of several inflammatory cytokines and angiogenic factors by multiplex enzyme-linked immunosorbent assay. Glucose treatment resulted in upregulation of various pro-angiogenic factors like angiogenin, angiopoietin, pdgf, pigf and this effect of HG was prevented by DHA treatment. Similarly, inflammatory cytokines like TNF-alpha and MCP1, which are involved in promotion of angiogenesis and inflammation were induced by HG and was attenuated in the presence of DHA. Interestingly, anti-inflammatory cytokines like IL-1 beta and IL-6 were markedly increased by DHA as compared to HG alone. These results suggest that DHA protects HREC against the pro-angiogenic, -inflammatory and -oxidative effects of HG and thus it can be proposed as alternative or supplementary treatment to the current therapeutic strategies of DR.
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Bicuspid Aortic Valve In Qatar
المؤلفون: Cornelia S Carr, Nizar Mohammed, Shady Mohammed, Madgi Yacoub, Sherif Helmy and Abdulaziz AlkhulaifiBicuspid Aortic Valve in Qatar N Mohammed, S Mohammed, M Yacoub, S Helmy, CS Carr, AM Alkhulaifi Objective Bicuspid Aortic Valve (BAV) is the commonest congenital cardiac anomaly with about 1% of the population being affected and can be divided into different phenotypes. The majority of BAV patients will require valve replacement surgery in their lifetime. We aimed to assess the BAV patients in Qatar in terms of demographics, valve phenotype, associated valve dysfunction, ejection fractions and aortic dilatation. Methods BAV patients were identified from an existing echocardiography database. The patients' demographics were recorded. The echocardiograms were assessed for phenotype (figure 1), aortic dilatation, as well as ejection fraction and degree of valvular dysfunction. Associated conditions such as coarctation were also noted. Results 128 BAV patients were identified over almost 3 years (September 2011 to August 2014). There were 108 males (84%) and 20 females (16%), with an age range of 16 to 74 years (median 47, mean 45), (figure 2). The phenotypes were evenly distributed with 64 horizontal (right-left) and 64 vertical (right-non coronary). Males had 50% horizontal and 50% vertical compared to females 40% horizontal and 60% vertical. Overall 25% had significant stenosis (moderate and above) and 50% had no evidence of stenosis. 21% had significant regurgitation (moderate and above) and 50% had no evidence of regurgitation. The left ventricular ejection fractions were 83% good, 14% moderate and 3% poor (figure 3). Overall 40% of the BAV patients had dilatation of the aorta, with a breakdown of vertical types - 44% dilated and 56% non-dilated and horizontal 37% dilated and 63% non-dilated. There were 8 coarctations in the group, 4 in the vertical group and 4 in the horizontal group. Conclusions There are more male BAV patients in Qatar than the normal 2-3:1 (male:female) quoted in the literature, but this may reflect the skewed population in Qatar. There are similar numbers of horizontal and vertical phenotypes, and similar degrees of stenosis and regurgitation. Overall 50% of patients had no vavular dysfuction demonstrated at this time. Poor left ventricular ejection fraction was rare at presentation. Aortic dilatation was slightly more common in the vertical group and 8 coarctations were seen giving an incidence of 8% in our BAV population. BAV is a common cardiac anomaly that is likely to require cardiac surgery at some point for most patients, and study in an Asian population has not previously been performed. We will continue to expand our cohort with our main areas of interest being the associated aortic dilatation and the high incidence of coarctation in our population.
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Measuring The Return On Investment For Research At Sidra
المؤلفون: Zeina Jamaleddine and Stefano BertuzziGeneral consensus exists that biomedical research is a key determinant of innovation, health, and economic wellbeing. However, the answer to the question how do we determine and quantify the value and the impact of research is apparently simple, while a thoughtful and analytical answer quickly becomes very probing and difficult to address. Qatar has dedicated itself to transitioning from a resource-based to a knowledge-based economy and Sidra Medical and Research Center is envisioned to become a beacon of learning and a world-class institution of its kind in the MENA region. A unique opportunity exists at Sidra for the development of a comprehensive system to capture the return on investment (ROI) for research on knowledge, the economy, and on health outcomes. This would enable Sidra to establish itself as a leader in the field of impact assessment, ahead of many other countries also grappling with this thorny problem. In fact, Sidra's status as a startup creates a rare situation where measurement and analysis of ROI can be initiated from a baseline. Work can then be done prospectively rather than trying to gather information retroactively, a difficult obstacle that institutions that have attempted to implement similar systems have had to try to overcome. In order to take advantage of this opportunity at Sidra, we propose creating a core system consisting of a smart, web-based, auto-populated "Sidra Biosketch". This system will interact with internal enterprise resource planning, grants and proposal management systems, as well as external publication, patent, startup and commercial license databases (e.g., PubMed). This system takes into consideration two critical factors. First, it minimizes the administrative burden on investigators and administrators. Second, it does not solely measure stochastically by counting numbers of publications, citations, etc. Rather, it focuses and relies heavily on content and contextual assessment to enable Sidra to fully understand exactly what research is being done, where it is being done, by whom, and with what collaborators. The impact on knowledge, economic and health outcomes can then be mapped through dynamic network analyses, natural language processing, and topic modeling approaches. This approach to measuring the impact of Sidra research will maximize efficiency of input and analysis as well as the quality of outputs and results. Meanwhile, this system will also enable Sidra to make decisions that will enhance resource allocation and allow for better assessment of its contribution to progress in science, the economy, and health outcomes in Qatar and worldwide.
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Influence Of Qatar Agricultural Products On Human Cell Redox Homeostasis
المؤلفون: Afnan Al-menhali, Safya Ali Jameela, Aishah A Latiff and Morana JaganjacReactive oxygen species (ROS) are generated ubiquitously by all mammalian cells and at small concentrations they act as physiological mediators of cellular response to various stimuli. Excessive ROS damages DNA, RNA, proteins and lipids triggering various diseases. Cellular redox homeostasis is thus, balanced by endogenous and exogenous antioxidant defense systems. Natural antioxidants have made a significant impact in the research area of exogenous antioxidants as they exhibit universal action in various redox systems. In the present work we have studied the effects of two Qatar grown vegetables (cucumber and zucchini) on cellular redox homeostasis of HaCaT (Human keratinocytes) and AGS (Human gastric adenocarcinoma) cell lines. Vegetables were collected from the farm in Qatar and their juice was extracted by a heavy-duty juicer, with a stone mill-like screw, using a low speed of 80 RPMs resulting in minimal heat build up and oxidation of samples. Copper sulphate was used to induce cellular oxidative damage to membranes and molecules altering redox homeostasis. The impact of extracts on cell proliferation in the presence or absence of copper sulphate was tested by MTT assay and High content screening assay while flow cytometry based Annexin V assay was used to detect apoptotic cells. Moreover, impact of extracts on cellular redox homeostasis was evaluated by dichlorodihydro fluorescein (DCFH) assay that measures the intracellular ROS production and by MitoSOX assay for the production of superoxide by mitochondria. The obtained results revealed strong protective role of cucumber and zucchini in both human keratinocytes and gastric adenocarcinoma cell lines indicating the importance of dietary antioxidants with a potentially significant impact on the health of individuals.
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Updated Lagrange Formulation Of Internally Balanced Compressible Hyperelastic Materials
المؤلفون: Ashraf Hadoush, Hasan Demirkoparan and Tom J. PenceNonlinear continuum mechanics is commonly used to study the response of highly de- formable materials. Nowadays, the proposed material models often include internal ma- terial variables in order to capture realistic engineering behavior. The theoretical back- ground is mature and its implementation in the frame of nite element method is well established. Solely, these material constitutive models are expressed in terms of defor- mation gradient F, its derived quantities, and various multiplicative decompositions such as F = ^F F (1) This multiplicative decomposition serves to pertain particular portions of F to specic parts of the material response. The usual scheme is then that ^F models elastic response and it is associated to the rules of variational calculus. The F portion then models inelastic response, usually by means of a time dependent evolution law. Recently, the arguments of variational calculus have been applied to both portions of the deformation gradient decomposition for incompressible hyperelastic material [1]. The decomposition itself is then determined by an additional internal balance equation that is generated by such a variational treatment. The internally balanced compressible hyperelastic material response is presented in [2]. Fundamental studies of this type are key to better physics-based modeling of complex biomechanical processes in soft tissue, including long time scale processes of growth, and short time scale processes of wound healing. The FE formulation of this internal balance multiplicative decomposition is naturally achieved by linearizing the weak form that is obtained by the variation with respect to both portions of the multiplicative decomposition. In this work, we would like to present the Updated Lagrange Formulation. This formulation will be implemented into com- mercial nite element package FEAP that will facilitate in future studying engineering application in the eld of biomechanics. The correctness of implementation will be ex- amined by simulating homogeneous deformations such as uniaxial loading, dilatation and simple shear. References [1] H. Demirkoparan, T. J. Pence, and H. Tsai. Hyperelastic internal balance by multi- plicative decomposition of the deformation gradient. Archive for Rational Mechanics and Analysis, 2014. DOI: 10.1007/s00205-014-0770-9. [2] A. Hadoush, H. Demirkoparan, and T.J. Pence. Modeling of soft materials via mul- tiplicative decomposition of deformation gradient. In USNCTAM, 2014.
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Antibacterial Modification Of Polyethylene By Multistage Process Utilizing Low-temperature Plasma
المؤلفون: Anton Popelka, Igor Novák, Marián Lehocký and Igor KrupaLimiting factor of PE application in healthcare is high susceptibility of polyethylene towards bacterial growth. For this reason, antibacterial treatment of PE foils using appropriate antibacterial agents was used in this work. Benzalkonium chloride and bronopol were selected due to their satisfactory antibacterial effect confirmed by applications in medical and cosmetic industry. These antibacterial agents were immobilized onto PE surface by a multistage approach via polyacrylic acid brushes grafting onto the PE surface pre-treated by low-temperature plasma. Measurements of surface energy, X-ray Photoelectron Spectroscopy (XPS), Fourier Transform Infrared Spectroscopy with Attenuated Total Reflectance (FTIR-ATR), Scanning Electron Microscopy (SEM), and Atomic Force Microscopy (AFM) were used for investigation of surface changes after antibacterial modification of PE. Moreover, the antibacterial effect was evaluated by inhibition zone measurements of Staphylococcus aureus and Escherichia coli bacterial strains.
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Non-coding RNA Biomarkers Of Diabetes And Metabolic Health
المؤلفون: Anandwardhan A HardikarBackground Islet cell death is a common feature of type 1 diabetes (T1D), including after islet cell transplantation, as well as of type 2 diabetes (T2D). As of today, we lack tools to quantitatively detect islet cell loss prior to the clinical onset of diabetes, or to predict the progression of established diabetes. Our preliminary data demonstrates that a signature of 20 different non-coding (nc) RNAs (including microRNAs) reflects beta cell death (RAPID: RNA-based Analysis for Prediction of Islet Death signature). Objectives 1)To identify a high-throughput platform for detection of ncRNAs/microRNAs 2)To validate the RAPID signature of 20 ncRNAs using this high-throughput platform 3)To test the suitability of these ncRNA biomarkers in predicting the progression to T1D Method Next Generation Sequencing (NGS) studies on developing human pancreas have led to the identification of specific ncRNAs that are found to be expressed specifically in the human pancreatic islets. We use combined FISH and immunostaining to confirm the localization of each miRNA in human islets. TaqMan-based real-time PCR on plasma from at-risk diabetic individuals and age/gender matched controls in a longitudinal study, is used to measure the abundance of specific ncRNAs in plasma-EDTA samples of individuals at risk of T1D. I will discuss the comparison of 2 different ultra-high-throughput TaqMan real-time PCR platforms that we use to analyze these samples and present the data demonstrating the suitability of these RNA-based biomarkers in predicting the progression to T1D. Results Present study has allowed us to validate a microRNA-based signature of islet cell death in diabetes. Using a cohort of kids at risk of T1D, we demonstrate the suitability and advantages of these ncRNA biomarkers over traditional / conventional antibody- and glucose-based detection. The development of an assay for early detection of islet injury and death has direct applications in clinical medicine. Hopefully, this study results will inform medical researchers as to how to predict the development of Type 1 diabetes, monitor response to interventions such as islet transplantation, vaccines and drugs that aim to retard beta cell loss or promote beta cell regeneration.
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RNA -seq Study Of Muscle And Adipose Tissue In Cancer Patients With Early Cachexia
المؤلفون: Iman Al-azwani, Amal Al Haddad, Yasmin Mohamoud, Farouk Safi, Haytham Salhat, Joel Malek and Thomas AdrianObjectives: Cancer cachexia is a syndrome characterized by weight loss resulting from a reduction of lean body mass and adipose mass. Although often associated with pre-terminal patients bearing disseminated disease, cachexia may be present in the early stages of tumor growth before any signs or symptoms of malignancy. Studies show that weight loss in cachexia is not caused by malnutrition or starvation but, rather, by inflammatory changes associated with the presence of the tumor and the production of cytokines. The purpose of this study is to investigate gene expression changes in muscle-adipose wasting and cachexia. Methods: RNA was extracted from 6 muscle and 6 adipose human tissue samples from 6 patients with cancer cachexia. 6 muscle and 6 adipose tissue samples from 12 controls were also collected. RNA-seq was performed on the samples to identify both genes and pathways that are affected by cachexia. Comparisons were made between muscle and adipose of cachectic and control patients. Results: Analysis of the RNA-seq data showed that 4 pathways are especially up regulated in cachectic muscle samples (Notch signaling pathway, Cell adhesion molecules..) and 11 pathways are down regulated (Hypertrophic cardiomyopathy, Insulin signaling pathway..). While in cachectic adipose samples, there are 5 pathways up regulated (Cytokine-cytokine receptor interaction, N-Glycan biosynthesis…) and only one pathway is down regulated (Neuroactive ligand-receptor interaction). Muscle samples were more clearly affected at the gene expression level than were adipose samples. Conclusion: For the first time we have identified consistent gene expression changes in cancer patients experiencing cachexia. These changes should lead to development of markers for early diagnosis and a better understanding of the conditions that lead to cachexia.
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Molecular Characterization Of White And Brown Adipocytes Reveals Complex Phenotypes
Over the last two decades the prevalence of obesity has reached epidemic levels worldwide. Secondary major health risks, such as hypertension, insulin resistance, type 2 diabetes and cardiovascular diseases, can be summarized as the metabolic syndrome and are highly associated with obesity. In cases in which energy intake e.g. through high caloric food intake exceeds energy expenditure the overall energy homeostasis is imbalanced. White adipose tissue depots mainly act as the body's main energy storage and additionally act as an endocrine organ by releasing adipokines and cytokines into the body. Additionally, functional brown adipose tissue (BAT) has been discovered through radiological detection in the last years in substantial amount in adults. Formerly overlooked BAT, which was thought to be absent in the human adult, has therefore recently become an interesting anti‐obesity target due to its ability to dissipate energy in form of heat. We extensively characterized human brown PAZ6 adipocytes in comparison with a white adipose cell line SW872. In addition, human SGBS adipocytes were included in the analysis. Brown and white adipocyte markers were tested by quantitative Real-time PCR. Fluorescent and Oil‐Red staining assessed the quantity and quality of the differentiation process. Next generation RNA sequencing of undifferentiated and mature SGBS and PAZ6 cells was performed in order to elucidate pathways distinctly activated in white vs. brown human adipocytes. Functional assessment of oxidative rates of each cell line was conducted using the Seahorse technology. Whereas PAZ6 and SW872 cells showed classical molecular and phenotypic markers of brown and white adipocytes, respectively, SGBS cells presented a versatile phenotype of adipocyte. 14 days after initiating the differentiation process the expression of classical brown marker such as UCP‐1 and PPARγ peaked and declined until day 28. The white adipocyte marker Tcf21 however, showed reciprocal behavior. Interestingly, Leptin levels peaked at day 28 whereas the highest adiponectin mRNA levels were monitored at day 14. Phenotypic analysis of the abundance and shape of lipid droplets were consistent with the molecular patterns. On day 14, SGBS cells showed multiple small droplets, however the number of droplets decreased and the size increased until day 28 as expected for a white adipocyte phenotype. Lastly, functional metabolic analysis showed the highest oxidative rate of mature SGBS cells on Day 14, which remained consistent or slightly decreased until day 28. SGBS cells are widely used as a model for white adipocytes. Our data suggest that the cell line harbors a versatile phenotype, which changes throughout their mature stage. Many reports suggest recently that the traditional classification of adipocytes is not exclusive and the existence of beige/brite adipocytes has been shown. We are presenting data derived from a human cell line model, which harbors characteristics of both distinct phenotypes. This knowledge will be of importance for studies aimed to increase brown fat depots in order to increase energy expenditure in obese subjects with the ultimate goal of weight reduction.
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Arabic Symbol Dictionary For Augmentative And Alternative Communication (AAC) Users
المؤلفون: Amal Idris Ahmad, Amatullah Kadous, Ea Draffan and Mike WaldThe Arabic Symbol Dictionary research project aims to develop a lexicon with symbols that are culturally appropriate for Qataris and the Arab world. This project focuses on symbol use for those who cannot communicate verbally such as those with Autism, Cerebral Palsy, Intellectual Disability and Aphasia. Symbols can be used to communicate wants and needs, provide a method for dialogue with others as well as actively learning and advancing literacy skills. This is an example of Alternative Augmentative Communication (AAC). AAC has opened the door for many with disabilities and/or communication deficits to become active participants in society and engage in everyday activities. Thus AAC has the ability to enhance one's quality of life, health and well-being to unprecedented levels. However, this potential is restricted in Qatar and other Arab countries. Currently, symbols used in Qatar are purely based on Western symbol sets. This poses great cultural and linguistic challenges. The need for symbols to be adapted to suit the Qatari culture are sentiments echoed by therapists and symbol users across Qatar. The Statistics Authority's Disability Survey of 2009 showed that the recorded number of people with disabilities grew 23% from 2007 to 2009. This means that services and resources for Qataris need to be accessible and suited to their needs to ensure that this growing portion of the Qatari population have equal opportunities, optimal quality of life and overall good health and well-being. The Arabic Symbol Dictionary research team has deemed user led research using a partcipitory and iterative approach the most effective method to develop a dictionary that will meet the needs of symbol users in Qatar. Action research with forums, interviews including quantative and qualitative methods for gathering data and working with AAC users, therapists, school teachers and carers has been employed. Guidance has also been sought from a group of advisors who are experts in this field. During the first six months of the project, it has become clear that many aspects of consistent symbol use by those belonging to Arabic speaking families is a great challenge. This is due to a lack of suitable symbols, their inappropriate cultural and linguistic features, a lack of Arabic speaking specialists and the time needed to adapt Western symbol sets. Simple word for symbol translation from English to Arabic and symbol sentence presentation from left to right (English) rather than right to left (Arabic) is the cause of much confusion. Encouraging literacy skills requires an in depth understanding of morphology and semantics undermined by current symbol sets. This presentation will explore the cultural and linguistic challenges of developing a symbol dictionary for Arabic and English speaking AAC users in Qatar. A rare insight from the view point of teachers, therapists, families, symbol users and evidence based literature. The concerning results from our online symbol voting system will be presented, a system that offers the AAC community participation in rating the acceptability of symbols. Solutions to these challenges and future directions for the development of the dictionary will be outlined.
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Identifying Novel Mutations In Familial Myeloproliferative Neoplasms Patients In The State Of Qatar Via Targeted Exome Sequencing Approach
Background: Polycythemia Vera (PV), Essential Thrombocytosis (ET) & Primary Myelofibrosis (PMF) are Philadelphia negative Myeloproliferative Neoplasms (MPNs) characterized by overproduction of one or more myeloid cell lineages. MPNs are associated with the presence JAK2 V617F mutation in 95% of PV & 50% of ET & PMF patients. Several molecular methods such as RQ-PCR, HRM & Sequencing are currently used to detect common mutations. However, there are still significant numbers of MPNs are negative to the most common genetic anomalies. The advent of Next Generation Sequencing (NGS) gives the opportunity to study relevant mutations in several genes. Aim: Utilizing NGS to identify potential genetic anomalies causing familial MPNs patients in Qatar. Methods: 6 MPNs patients from consanguineous families & 5 healthy individuals were consented into the study gDNA was extracted & used for multiplex amplification of amplicons targeting cancer associated mutations in 28 key genes using the Ion AmpliSeq Kit. NGS was performed via the Ion Torrent using the 318 chip & data was analyzed with the Torrent Suite. The confirmation of NGS data was done by RQ-PCR or Sequencing. Results: NGS identified novel deleterious mutations in MPNs patients. Out of 6 familial cases, 5 patients (P1- P5) were ET & 1 patient (P6) was PV. P1 had JAK2 V617F, ASXL1 T600P, CBFB G180S, THPO S184R & ITGA2 R76Q, P2 had JAK2 V617F, MPL A554G & ATM F582L, the other three Patients (P3, P4 & P5) had CLAR K385fs*47 & one PV patient (P6) had TYK2 E1163G, ASXL1 P808H, PDGFRB P4L TERT G300fs. In patients & healthy individuals, mutations/SNVs such as MPL P106L, K553N, SH2B3 L476F, ATM F1036F KIT N564S & TET2 T730R were also found Discussion & conclusion: In this study, several deleterious somatic/germ-line mutations/SNVs were identified using Targeted Exome Sequencing approach. A complex combination of mutations occurred in ET patients & coexistence of several oncogenic events occurred in PV patient. This finding may also suggest that the MPNs phenotype may depend on presence of other mutations. It is worth to mention that the presence of ATM variant in P2 is associated with increased risk of CLL. Somatic CALR type-2 mutation was identified in 3 ET (nonmutated JAK2 or MPL) patients. This mutation is 5-bp TTGTC insertion in exon 9 that generates a mutant protein with a novel C-terminal (p.K385fs*47). In patients & healthy individuals, a heterozygous germ-line mutation in exon 3 of the MPL gene (MPL P106L) has been observed and previously described as a rare autosomal-dominant disorder. However, this mutation is considered to be frequent in Arabic populations also several unreported variants of uncertain significance were identified. Our finding suggested that familial MPNs patients in Qatari tribes have several potential disease- associated variants/mutations which represent a unique interest for the scientific community worldwide and present an unprecedented opportunity for local and international collaborations to carry out WES in society with its unique coherence and genetic pool (founder effect), this would offer invaluable resources to unravel the genetic etiology and pathogenesis, delineate the mechanisms behind MPNs phenotypic diversity.
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