Search results for: in vivo/vitro exposure

Authors: Kitti Szoke, Laszlo Szoke, Attila Czompa, Arpad Tosaki, Istvan Lekli

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Autophagy plays an important role in cardiac hypertrophy, which is one of the most common causes of heart failure in the world. This self-degradative catabolic process, responsible for protein quality control, balancing sources of energy at critical times, and elimination of damaged organelles. The autophagic activity can be triggered by starvation, oxidative stress, or pharmacological agents, like rapamycin. This induced autophagy can promote cell survival during starvation or pathological stress. In this study, it is investigated the effect of the induced autophagic process on angiotensin induced hypertrophic H9c2 cells. In our study, it is used H9c2 cells as an in vitro model. To induce hypertrophy, cells were treated with 10000 nM angiotensin-II, and to activate autophagy, 100 nM rapamycin treatment was used. The following groups were formed: 1: control, 2: 10000 nM AT-II, 3: 100 nM rapamycin, 4: 100 nM rapamycin pretreatment then 10000 nM AT-II. The cell viability was examined via MTT (cell proliferation assay) assay. The cells were stained with rhodamine-conjugated phalloidin and DAPI to visualize F-actin filaments and cell nuclei then the cell size alteration was examined in a fluorescence microscope. Furthermore, the expression levels of autophagic and apoptotic proteins such as Beclin-1, p62, LC3B-II, Cleaved Caspase-3 were evaluated by Western blot. MTT assay result suggests that the used pharmaceutical agents in the tested concentrations did not have a toxic effect; however, at group 3, a slight decrement was detected in cell viability. In response to AT-II treatment, a significant increase was detected in the cell size; cells became hypertrophic. However, rapamycin pretreatment slightly reduced the cell size compared to group 2. Western blot results showed that AT-II treatment-induced autophagy, because the increased expression of Beclin-1, p62, LC3B-II were observed. However, due to the incomplete autophagy, the apoptotic Cleaved Caspase-3 expression also increased. Rapamycin pretreatment up-regulated Beclin-1 and LC3B-II, down-regulated p62 and Cleaved Caspase-3, indicating that rapamycin-induced autophagy can restore the normal autophagic flux. Taken together, our results suggest that rapamycin activated autophagy reduces angiotensin-II induced hypertrophy.

Keywords: angiotensin-II, autophagy, H9c2 cell line, hypertrophy, rapamycin

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Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

Procedia PDF Downloads 204

Authors: J. Vitku, L. Kolatorova, T. Chlupacova, J. Heracek, M. Hill, M. Duskova, L. Starka

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Background: 7β-hydroxy-epiandrosterone (7β–OH-EpiA) is an endogenous steroid, that has been shown to exert neuroprotective and anti-inflammatory effects in vitro as well as in animal models. However, to the best of our knowledge no information is available about concentration of this androgen metabolite in human population. The aim of the study was to measure and compare levels of 7β–OH-EpiA in men and pregnant women in different biological fluids and evaluate the relationship between 7β–OH-EpiA in men and their sperm quality. Methods: First, a sensitive isotope dilution high performance liquid chromatography-mass spectrometry method for measurement of 7β–OH-EpiA in different biological fluids was developed. Validation of the method met the requirements of FDA guidelines. Afterwards 7β–OH-EpiA in plasma and seminal plasma of 191 men with different degree of infertility (healthy men, lightly infertile men, moderately infertile men, severely infertile men) was analysed. Furthermore, the levels of 7β–OH-EpiA in plasma of 34 pregnant women in 37th week of gestation and corresponding cord plasma that reflects steroid levels in the fetus were measured. Results: Concentrations of 7β–OH-EpiA in seminal plasma were significantly higher in severely infertile men in comparison with healthy men and lightly infertile men. The same trend was observed when blood plasma was evaluated. Furthermore, plasmatic 7β –OH-EpiA negatively correlated with concentration (-0.215; p < 0.01) and total count (-0.15; p < 0.05). Seminal 7β–OH-EpiA was negatively associated with motility (-0.26; p < 0.01), progressively motile sperms (-0.233; p < 0.01) and nonprogressively motile sperms (-0.188; p < 0.05). Plasmatic 7β –OH-EpiA levels in men were generally higher in comparison with pregnant women. Levels 7β–OH-EpiA were under the lower limit of quantification (LLOQ) in majority of samples of pregnant women and cord plasma. Only 4 plasma samples of pregnant women and 7 cord blood plasma samples were above LLOQ and where in range of units of pg/ml. Conclusion: Based on available information, this is the first study measuring 7β–OH-EpiA in human samples. 7β–OH-EpiA is associated with lower sperm quality and certainly it is worth to explore its role in this field thoroughly. Interestingly, levels of 7β–OH-EpiA in pregnant women were extremely low despite the fact that steroid levels including androgens are generally higher during pregnancy. Acknowledgements: This work was supported by the project MH CR 17-30528 A from the Czech Health Research Council, MH CZ - DRO (Institute of Endocrinology - EU, 00023761) and by the MEYS CR (OP RDE, Excellent research - ENDO.CZ).

Keywords: 7β-hydroxy-epiandrosterone, steroid, sperm quality, pregnancy

Procedia PDF Downloads 255

Authors: Natalia Uribe Corrales, Carolina Cano Arroyave, Santiago Henao Villegas

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Introduction: Stunning is an important stage in the meat industry due to the repercussions on the characteristics of the carcass. It has been demonstrated that inadequate stun can lead to hematomas, fractures and promote the appearance of pale, soft and exudative meat due to the stress caused in animals. In Colombia, gas narcosis and electrical stunning are the two authorized methods in pigs. Objective: To describe the practices of stunning in the Valle de Aburrá and its relation with animal welfare. Methods: A descriptive cross - sectional study was carried out in Valle de Aburrá slaughterhouses, which were authorized by National Institute for Food and Medicine Surveillance (INVIMA). Variables such as stunning method, presence of vocalization, falls, slips, rhythmic breathing, corneal reflex and attempts to incorporate after stunning, stun time and time between stun and bleeding were analyzed. Results: 225 pigs were analyzed, finding that 50.2% had electrical stun, whose amperage and voltage were 1.23 (A) and 120 (V) respectively; 49.8% of the animals were stunned with CO2 chamber whose concentration was always above 95%, the mean desensitization time was 16.8 seconds (d.e.5.37); the mean time of stunning - bleeding was 47.9 seconds (d.e.13.9); similarly, it was found that 27.1% had vocalizations after stunning; 12% had falls; 10.7% showed rhythmic breathing; 33.3% exhibited corneal reflex; and 10.7% had reincorporation attempts. Conclusions: The methods of stunning used in the Valle de Aburrá, although performed with those permitted by law, are shortcomings in relation to the amperage and voltage used for each type of pig, as well, it is found that welfare animal is being violated to find signology of an inadequate desensitization. It is necessary to promote compliance with the principles of stunning according to Animal Welfare, and keep in mind that in electrical desensitization, the calibration of the equipment must be guaranteed (pressure according to the type of animal or current applied and the position where the electrodes are) and in the narcosis the equipment should be calibrated to ensure proper gas concentration and exposure time.

Keywords: animal welfare, pigs, quality of meat, stun methods

Procedia PDF Downloads 223

Authors: Aisha Khodijah Kholib Jati, Suharni Mohamad, Azlan Husin, Wan Suriana Wan Ab Rahman

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Introduction: Toxoplasmosis is caused by an obligate intracellular parasite, Toxoplasma gondii (T. gondii). It is commonly asymptomatic in normal individual, but it can be fatal to immunocompromised patients as it can lead to severe complications such as encephalitis, chorioetinitis and myocarditis. Objective: The aim of the study was to determine the seroprevalence of toxoplasmosis and its association with socio-demographic and behavioral characteristics among hemato-oncology patients in Hospital USM. Methods: In this cross-sectional study, 56 hemato-oncology patients were screened for immunoglobulin M (IgM) antibodies, immunoglobulin G (IgG) antibodies, and IgG avidity of T. gondii by using ELISA Kit (BioRad, USA). For anti-T. gondii IgG antibody, titer ≥ 9 IU/ml was considered as recent infection, while for IgM, ratio ≥ 1.00 was considered as reactive for the anti-T. gondii IgM antibodies. Low avidity index is considered as recent infection within 20 weeks while high avidity considered as past infection. T. gondii exposure, socio-demographic and behavioral characteristics was assessed by a questionnaire and interview. Results: A total of 28 (50.0%) hemato-oncology patients were seropositive for T. gondii antibodies. Out of that total, 27 (48.21%) patients were IgG+/IgM- and one patient (1.79%) was IgG+/IgM+ with high avidity index. Univariate analysis showed that age, gender, ethnicity, marital status, educational level, employment status, stem cell transplant, blood transfusion, close contact with cats, water supply, and consumption of undercooked meat were not significantly associated with Toxoplasma seropositivity rate. Discussion: The seropositivity rate of IgG anti-T. gondii was high among hemato-oncology patients in Hospital USM. With impaired immune system, these patients might have a severe consequence if the infection reactivated. Therefore, screening for anti-T. gondii may be considered in the future. Moreover, health programme towards healthy food and good hygiene practice need to be implemented.

Keywords: immunocompromised, seroprevalence, socio-demographic, toxoplasmosis

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Authors: Abd El-Aziz Khairy Abd El-Aal, Yuji Yagi, Heba Kamal

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In this study, an integrated multi-channel analysis of Surface Waves (MASW) technique is applied to explore the geotechnical parameters of subsurface layers at the Zafarana wind farm. Moreover, a seismic hazard procedure based on the extended deterministic technique is used to estimate the seismic hazard load for the investigated area. The study area includes many active fault systems along the Gulf of Suez that cause many moderate and large earthquakes. Overall, the seismic activity of the area has recently become better understood following the use of new waveform inversion methods and software to develop accurate focal mechanism solutions for recent recorded earthquakes around the studied area. These earthquakes resulted in major stress-drops in the Eastern desert and the Gulf of Suez area. These findings have helped to reshape the understanding of the seismotectonic environment of the Gulf of Suez area, which is a perplexing tectonic domain. Based on the collected new information and data, this study uses an extended deterministic approach to re-examine the seismic hazard for the Gulf of Suez region, particularly the wind turbine towers at Zafarana Wind Farm and its vicinity. Alternate seismic source and magnitude-frequency relationships were combined with various indigenous attenuation relationships, adapted within a logic tree formulation, to quantify and project the regional exposure on a set of hazard maps. We select two desired exceedance probabilities (10 and 20%) that any of the applied scenarios may exceed the largest median ground acceleration. The ground motion was calculated at 50th, 84th percentile levels.

Keywords: MASW, seismic hazard, wind turbine towers, Zafarana wind farm

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Authors: Maurício N. Kleinberg, Ana P. R. N. Barroso, Frederico R. Silva, Natasha l. Gomes, Rodrigo F. Guimarães, Marcelo M. V. Parente, Jackson Q. Malveira

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Increased production of biofuels, especially biodiesel, as an option to replace the diesel derived from oil is already a reality in countries seeking a renewable and environmentally friendly fuel, as is the case in Brazil. However, it is known that the use of fuels, renewable or not, implies that it is in contact with various metallic materials which may cause corrosion. In the search for more corrosion resistant materials has been experimentally observed that the addition of molybdenum in ferritic steels increases their protective character without significantly burdening the cost of production. In order to evaluate the effect of adding molybdenum, samples of commercial steel (austenitic, ferritic and carbon steel) and the experimental ferritic alloy with a high molybdenum content (5.3%) were immersed separately into biodiesel derived from transesterification of soy oil to monitor the corrosion process of these metal samples, and in parallel to analyze the oxidative degradation of biodiesel itself. During the immersion time of 258 days, biodiesel samples were taken for analysis of acidity, kinematic viscosity, density and refraction. Likewise, the metal samples were taken from the biodiesel to be weighed and microstructurally analyzed by light microscopy. The results obtained at the end of 258 days shown that biodiesel presented a considerable increase on the values of the studied parameters for all the samples. However, this increase was not able to produce significant mass loss in metallic samples. As regards the microstructural analysis, it showed the onset of surface oxidation on the carbon steel sample. As for the other samples, no significant surface changes were shown. These results are consistent with literature for short immersion times. It is concluded that the increase in the values of the studied parameters is not significant yet, probably due to the low time of immersion and exposure of the samples. Thus, it is necessary to continue the tests so that the objectives of this work are achieved.

Keywords: biodiesel, corrosion, immersion, experimental alloy

Procedia PDF Downloads 439

Authors: M. P. Dandekar, A. P. Bharne, P. T. Borkar, D. M. Kokare, N. K. Subhedar

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Ethanol ingestion by the mother ensue adverse consequences for her offspring. Herein, we examine the behavioral phenotype and neural substrate of the offspring of the mother on ethanol. Female rats were fed with ethanol-containing liquid diet from 8 days prior of conception and continued till 25 days post-parturition to coincide with weaning. Behavioral changes associated with anxiety, depression and learning and memory were assessed in the offspring, after they attained adulthood (day 85), using elevated plus maze (EPM), forced swim (FST) and novel object recognition tests (NORT), respectively. The offspring of the alcoholic mother, compared to those of the pair-fed mother, spent significantly more time in closed arms of EPM and showed more immobility time in FST. Offspring at the age of 25 and 85 days failed to discriminate between novel versus familiar object in NORT, thus reflecting anxiogenic, depressive and amnesic phenotypes. Neuropeptide cocaine- and amphetamine-regulated transcript peptide (CART) is known to be involved in central effects of ethanol and hence selected for the current study. Twenty-five days old pups of the alcoholic mother showed significant augmentation in CART-immunoreactivity in the cells of Edinger-Westphal (EW) nucleus and lateral hypothalamus. However, a significant decrease in CART-immunoreactivity was seen in nucleus accumbens shell (AcbSh), lateral part of bed nucleus of the stria terminalis (BNSTl), locus coeruleus (LC), hippocampus (CA1, CA2 and CA3), and arcuate nucleus (ARC) of the pups and/or adults offspring. While no change in the CART-immunoreactive fibers of AcbSh and BNSTl, CA2 and CA3 was noticed in the 25 days old pups, the CART-immunoreactive cells in EW and paraventricular nucleus (PVN), and fibers in the central nucleus of amygdala of 85 days old offspring remained unaffected. We suggest that the endogenous CART system in these discrete areas, among other factors, may be a causal to the abnormalities in the next generation of an alcoholic mother.

Keywords: anxiety, depression, CART, ethanol, immunocytochemistry

Procedia PDF Downloads 395

Authors: Jihoon Yang, Jeong II Choi

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Mincle is expressed in macrophages and is members of immunoreceptors induced after exposure to various stimuli and stresses. Mincle receptor activation promotes the production of these substances by increasing the transcription of inflammatory cytokines and chemokines. Cytokines, which play an important role in the initiation and maintenance of such inflammatory pain diseases, have a significant effect on sensory neurons in addition to their enhancement and inhibitory effects on immune and inflammatory cells as mediators of cell interaction. Glial cells in the central nervous system play a critical role in development and maintenance of chronic pain states. Microglia are tissue-resident macrophages in the central nervous system, and belong to a group of mononuclear phagocytes. In the central nervous system, mincle receptor is present in neurons and glial cells of the brain.This study was performed to identify the Mincle receptor in the spinal cord and to investigate the effect of Mincle receptor activation on nociception and the changes of microglia. Materials and Methods: C-type lectins(Mincle) was identified in spinal cord of Male Sprague–Dawley rats. Then, mincle receptor ligand (TDB), via an intrathecal catheter. Mechanical allodynia was measured using von Frey test to evaluate the effect of intrathecal injection of TDB. Result: The present investigation shows that the intrathecal administration of TDB in the rat produces a reliable and quantifiable mechanical hyperalgesia. In addition, The mechanical hyperalgesia after TDB injection gradually developed over time and remained until 10 days. Mincle receptor is identified in the spinal cord, mainly expressed in neuronal cells, but not in microglia or astrocyte. These results suggest that activation of mincle receptor pathway in neurons plays an important role in inducing activation of microglia and inducing mechanical allodynia.

Keywords: mincle, spinal cord, pain, microglia

Procedia PDF Downloads 159

Authors: Dipanshu Sur, Ratnabali Chakravorty, Rimi Pal, Siddhartha Chatterjee, Joyshree Chaterjee, Amal Mallik

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Background: Polycystic ovary syndrome (PCOS) is a common endocrine disease in reproductive women with a complex hormonal disturbance that affects the menstrual cycle and leads to metabolic consequences in later life. Hyperandrogenaemia is noticeable features of PCOS and influence the process of folliculogenesis in women. The levels of Antimüllerian Hormone (AMH) reflect the number of pre-antral follicles and thus are a marker of oocyte pool – germinal reserve of the ovary for reproduction. Besides its utilization in IVF (In-vitro fertilization), determination of AMH may serve as an additional marker in the diagnostics of PCOS, where increased AMH levels reflect the severity of the disease. The positive correlation of serum AMH with the number of antral follicles was found also in patients with PCOS. Objective: The objective of this study was to investigate the relationship between AMH androgens and whether AMH contributes to altered folliculogenesis in non-obese women with PCOS. Methods: We designed a prospective study which included a total of 65 IVF individuals. It enrolled 26 cases of PCOS based on 2003 Rotterdam criteria and 39 ovulatory normal- non PCOS, healthy, age-matched controls. AMH levels and ovarian morphology were assessed. The relationships between AMH and androgenaemia in patients with and without PCOS were studied. Results: Mean age of PCOS patients were slightly higher than controls (32±4 and 28±3 years, respectively). AMH generally increased with antral follicle count (AFC) [P=0.001], testosterone, and luteinising hormone, and decreased with age, and serum sex hormone binding globulin (SHBG). No significant relationships were found between circulating AMH levels and BMI between PCOS and non-PCOS patients. The calculation of AMH production per antral follicle (AMH/AF) showed that there was a significant difference in median AMH/AF between PCOS and non-PCOS (P =0.001). Both PCOS and non-PCOS groups showed a very similar increase in AMH with increases in AFC, but the PCOS patients had consistently higher AMH across all AFC levels. Conclusions: These observations indicate that there is a connection between AMH and androgens levels between PCOS and non-PCOS East Indian women. Excessive granulosa cell activity may be implicated in the abnormal follicular dynamic of the syndrome. They are higher in women with PCOS and, on the other hand, very low in women with an ovarian failure.

Keywords: anti-Mullerian hormone, polycystic ovary syndrome, antral follicle count, androgens

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Authors: G. Medkour Ishak-Boushaki, A. Taibi, M. Allab

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Quantitative environmental radioactivity measurements are needed to determine the level of exposure of a population to ionizing radiations and for the assessment of the associated risks. Gamma spectrometry remains a very powerful tool for the analysis of radionuclides present in an environmental sample but the basic problem in such measurements is the low rate of detected events. Using large environmental samples could help to get around this difficulty but, unfortunately, new issues are raised by gamma rays attenuation and self-absorption. Recently, a new method has been suggested, to detect and identify without quantification, in a short time, a gamma ray of a low count source. This method does not require, as usually adopted in gamma spectrometry measurements, a pulse height spectrum acquisition. It is based on a chronological record of each detected photon by simultaneous measurements of its energy ε and its arrival time τ on the detector, the pair parameters [ε,τ] defining an event mode sequence (EMS). The EMS serials are analyzed sequentially by a Bayesian approach to detect the presence of a given radioactive source. The main object of the present work is to test the applicability of this sequential approach in radioactive environmental materials detection. Moreover, for an appropriate health oversight of the public and of the concerned workers, the analysis has been extended to get a reliable quantification of the radionuclides present in environmental samples. For illustration, we consider as an example, the problem of detection and quantification of 238U. Monte Carlo simulated experience is carried out consisting in the detection, by a Ge(Hp) semiconductor junction, of gamma rays of 63 keV emitted by 234Th (progeny of 238U). The generated EMS serials are analyzed by a Bayesian inference. The application of the sequential Bayesian approach, in environmental radioactivity analysis, offers the possibility of reducing the measurements time without requiring large environmental samples and consequently avoids the attached inconvenient. The work is still in progress.

Keywords: Bayesian approach, event mode sequence, gamma spectrometry, Monte Carlo method

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Authors: Nandhakumar Elumalai, Purushothaman Ayyakannu, Sachidanandam T. Panchanatham

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Background: Understanding the basic mechanisms and factors underlying the tumor growth and invasion has gained attention in recent times. The processes of angiogenesis and apoptosis are known to play a vital role in various stages of cancer. The vascular endothelial growth factor (VEGF) is well established as one of the key regulators of tumor angiogenesis while MMPs are known for their exclusive ability to degrade ECM. Objective: The present study was designed to evaluate the pro apoptotic and anti angiogenic activity of the herbal formulation Shemamruthaa. The anticancer activity of Shemamruthaa was tested in breast cancer cell line (MCF-7). Results of MTT, trypan blue and flow cytometric analysis of apoptotis suggested that Shemamruthaa can induce cytotoxicity in cancer cells, in a concentration- and time dependent manner and induce apoptosis. With these results, we further evaluated the antiangiogenic and pro-apoptotic activities of Shemamruthaa in DMBA induced mammary carcinoma in Sprague Dawley rats. Flavono tumour was induced in 8-week-old Sprague-Dawley rats by gastric intubation of 25 mg DMBA in 1ml olive oil. After 90 days of induction period, the rats were orally administered with Shemamruthaa (400 mg/kg body wt) for 45 days. Treatment with the drug SM significantly modulated the expression of p53, MMP-2, MMP-3, MMP-9 and VEGF by means of its anti angiogenic and protease inhibiting activity. Conclusion: Based on these results, it might be concluded that the formulation, Shemamruthaa, constituted of dried flowers of Hibiscus rosa-sinensis, fruits of Emblica officinalis, and honey has been found to exhibit pronounced antiproliferative and apoptotic effects. This enhanced anticancer effect of Shemamruthaa might be attributed to the synergistic action of polyphenols such as flavonoids, tannins, alkaloids, glycosides, saponins, steroids, terpenoids, vitamin C, niacin, pyrogallol, hydroxymethylfurfural, trilinolein, and other compounds present in the formulation. Collectively, these results demonstrate that Shemamruthaa holds potential to be developed as a potent chemotherapeutic agent against mammary carcinoma.

Keywords: Shemamruthaa, flavonoids, MCF-7 cell line, mammary cancer

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Authors: Nacer Hamza

Abstract:

Naturally radiation exposure that present due to the cosmic ray or the naturel occurring radioactives materials(NORMs) that originated in the earth's crust and are present everywhere in the environment(1) , a significant concentration of NORMs reported in the produced water which comes out during the oil extraction process, so that the management of this produced water is a challenge for oil and gas companies which include either minimization of produced water which considered as the best way in the term of environment based in the fact that ,the lower water produced the lower cost in treating this water , recycling and reuse by reinjected produced water that fulfills some requirements to enhance oil recovery or disposal in the case that the produced water cannot be minimize or reuse. In the purpose of produced water management, the investigation of NORMs activity concentration present in it considered as the main step for more understanding of the radionuclide’s distribution. Many studies reported the present of NORMs in produced water and investigated the correlation between 〖Ra〗^226and the different metals present in produced water(2) including Cations and anions〖Na〗^+,〖Cl〗^-, 〖Fe〗^(2+), 〖Ca〗^(2+) . and lead, nickel, zinc, cadmium, and copper commonly exist as heavy metal in oil and gas field produced water(3). However, there are no real interesting to investigate the correlation between 〖Rn〗^222and the different metals exist in produced water. methods using, in first to measure the radon concentration activity in produced water samples is a RAD7 .RAD7 is a radiometer instrument based on the solid state detectors(4) which is a type of semi-conductor detector for alpha particles emitting from Rn and their progenies, in second the concentration of different metals presents in produced water measure using an atomic absorption spectrometry AAS. Then to investigate the correlation between the 〖Rn〗^222concentration activity and the metals concentration in produced water a statistical method is Pearson correlation analysis which based in the correlation coefficient obtained between the 〖Rn〗^222 and metals. Such investigation is important to more understanding how the radionuclides act in produced water based on this correlation with metals , in first due to the fact that 〖Rn〗^222decays through the sequence 〖Po〗^218, 〖Pb〗^214, 〖Bi〗^214, 〖Po〗^214, and〖Pb〗^210, those daughters are metals thus they will precipitate with metals present in produced water, secondly the short half-life of 〖Rn〗^222 (3.82 days) lead to faster precipitation of its progenies with metals in produced water.

Keywords: norms, radon concentration, produced water, heavy metals

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Authors: J. D. Villanueva, N. Peyraube, I. Allan, G. D. Salvosa, M. Reid, C. Harman, K. D. Salvosa, J. M. V. Castro, M. V. O. Espaldon, J. B. Sevilla-Nastor, P. Le Coustumer

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The main objectives of this research are to (1) assess the occurrence of the pharmaceutical compounds and (2) present the environmental challenges posed by the existence of these pharmaceutical compounds in the surface water. These pharmaceuticals were measured in Napindan Lake, Philippines. This lake is not only a major tributary of the Pasig River (an estuary) and Laguna Lake (freshwater). It also joins these two important surface waters of the National Capital Region. Pharmaceutical compounds such as Atenolol, Carbamazepine, and two other over the counter medicines: Cetirizine, and Ibuprofen were measured in Napindan Lake. Atenolol is a beta blocker that helps in lowering hypertensions. Carbamazepine is an anticonvulsant used as treatment for epilepsy and neuropathic pain. Cetirizine is an antihistamine that can relieve allergies. Ibuprofen is a non-steroidal anti-inflammatory drug normally used to relieve pains. Three different climatological conditions with corresponding hydro physico chemical characteristics were considered. First, was during a dry season with a simultaneous dredging. Second was during a transition period from dry to wet season. Finally, the third was during a continuous wet event. Based from the results of the study, most of these pharmaceuticals can be found in Napindan Lake. This is a proof that these pharmaceutical compounds are being released to a natural surface water. Even though climatological conditions were different, concentrations of these pharmaceuticals can still be detected. This implies that there is an incessant supply of these pharmaceutical compounds in Napindan Lake. Chronic exposure to these compounds even at low concentrations can lead to possible environmental and health risks. Given this information and since consistent occurrence of these compounds can be expected, the main challenge, at present, is on how to control the sources of these pharmaceutical compounds. Primarily, there is a need to manage the disposal of the pharmaceutical compounds. Yet, the main question is how to? This study would like to present the challenges and institutional roles in helping manage the pharmaceutical disposals in a developing country like the Philippines.

Keywords: atenolol, carbamazepine, cetirizine, ibuprofen, institutional roles, Napindan lake, pharmaceutical compound disposal management, surface water, urban lake

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Authors: Obafemi Akinwotu, Aylin Tas, Tony Taylor, Bukola Onarinde

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The study was conducted to explore the methods and tools to improve texture and preserve the total phenolic and antioxidant compounds of dysphagia foods produced from carrot-based puree with decolourised Chlorella algae. Textural properties (Texture profile analysis [TPA]; the International Dysphagia Diet Standardization Initiative, particle size test [PST]) and rheological properties (viscosity and viscoelastic properties) of carrot puree defrosted by different treatments (microwave, steamer, oven), were characterised using hydrocolloids (guar gum, k. carrageenan, and xanthan gum), and the results were compared to a level 4 commercial sample. DPPH (2,2-diphenyl-1-picrylhydrazyl) antiradical scavenging radicals and total phenolic contents were employed to evaluate the total phenolics, and radical scavenging properties of defrosted carrot puree sonicated carrot puree (20 Hz, 30 min, 60 oC), and vacuum-dried carrot powder with the addition of algae. Results show that the viscosity, viscoelasticity test, TPA, and PST of the commercial sample were comparable to those of guar gum and xanthan gum containing puree, suggesting that they could be used as dysphagia diets. There was no noticeable decolourisation of the Chlorella pigment. Additionally, the use of the microwave, stemmer, and oven for defrosting treatment had an impact on the textural characteristics of the moulded samples upon cooling and also contributed to the reduction in the total phenolic and antioxidant properties of the samples. Sonication treatments of algae exposure reduced the cloudiness of the green pigment and lightened the colour of the samples containing algae, and they also reduced the drying time from 2.5 to 1.5 hours during the preliminary work. The low-temperature vacuum- and freeze-dried samples increased the concentration of the powder and resulted in an increase in the total phenolic content of the dry samples. The dried products may therefore have the potential to become more nutrient-dense to benefit the health of individuals with dysphagia.

Keywords: dysphagia, elderly, hydrocolloids, carrot puree

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Authors: Dona Pamoda W. Jayatunga, Veer Bala Gupta, Eugene Hone, Ralph N. Martins

Abstract:

Being a neurodegenerative disorder, Alzheimer’s disease (AD) affects a majority of the elderly demented worldwide. The key risk factors for AD are age, metabolic syndrome, allele status of APOE gene, head injuries and lifestyle. The progressive nature of AD is characterized by symptoms of multiple cognitive deficits exacerbated over time, leading to death within a decade from clinical diagnosis. However, it is revealed that AD originates via a prodromal phase that spans from one to few decades before symptoms first manifest. The key pathological hallmarks of AD brains are deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT). However, the yet unknown etiology of the disease fails to distinguish mitochondrial dysfunction between a cause or an outcome. The absence of early diagnosis tools and definite therapies for AD have permitted recruits of nutraceutical-based approaches aimed at reducing the risk of AD by modulating lifestyle or be used as preventive tools during AD prodromal state before widespread neurodegeneration begins. The objective of the present study was to investigate beneficial effects of luteolin, a plant-based flavone compound, against AD. The neuroprotective effects of luteolin on amyloid beta (Aβ) (1-42)-induced neurotoxicity was measured using cultured human neuroblastoma BE(2)-M17 cells. After exposure to 20μM Aβ (1-42) for 48 h, the neuroblastoma cells exhibited marked apoptotic death. Co-treatment of 20μM Aβ (1-42) with luteolin (0.5-5μM) significantly protected the cells against Aβ (1-42)-induced toxicity, as assessed by the MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2(4sulfophenyl)-2H-tetrazolium, inner salt; MTS] reduction assay and the lactate dehydrogenase (LDH) cell death assay. The results suggest that luteolin prevents Aβ (1-42)-induced apoptotic neuronal death. However, further studies are underway to determine its protective mechanisms in AD including the activity against tau hyperphosphorylation and mitochondrial dysfunction.

Keywords: Aβ (1-42)-induced toxicity, Alzheimer’s disease, luteolin, neuroblastoma cells

Procedia PDF Downloads 150

Authors: Jitendra Pratap, Jonathan Sivyer

Abstract:

Introduction: Dual energy/Spectral CT scanning permits simultaneous acquisition of two x-ray spectra datasets and can complement radiological diagnosis by allowing tissue characterisation (e.g., uric acid vs. non-uric acid renal stones), enhancing structures (e.g. boost iodine signal to improve contrast resolution), and quantifying substances (e.g. iodine density). However, the latter showed inconsistent results between the 2 main modes of dual energy scanning (i.e. dual source vs. dual layer). Therefore, the present study aimed to determine which technology is more accurate in quantifying iodine density. Methods: Twenty vials with known concentrations of iodine solutions were made using Optiray 350 contrast media diluted in sterile water. The concentration of iodine utilised ranged from 0.1 mg/ml to 1.0mg/ml in 0.1mg/ml increments, 1.5 mg/ml to 4.5 mg/ml in 0.5mg/ml increments followed by further concentrations at 5.0 mg/ml, 7mg/ml, 10 mg/ml and 15mg/ml. The vials were scanned using Dual Energy scan mode on a Siemens Somatom Force at 80kV/Sn150kV and 100kV/Sn150kV kilovoltage pairing. The same vials were scanned using Spectral scan mode on a Philips iQon at 120kVp and 140kVp. The images were reconstructed at 5mm thickness and 5mm increment using Br40 kernel on the Siemens Force and B Filter on Philips iQon. Post-processing of the Dual Energy data was performed on vendor-specific Siemens Syngo VIA (VB40) and Philips Intellispace Portal (Ver. 12) for the Spectral data. For each vial and scan mode, the iodine concentration was measured by placing an ROI in the coronal plane. Intraclass correlation analysis was performed on both datasets. Results: The iodine concentrations were reproduced with a high degree of accuracy for Dual Layer CT scanner. Although the Dual Source images showed a greater degree of deviation in measured iodine density for all vials, the dataset acquired at 80kV/Sn150kV had a higher accuracy. Conclusion: Spectral CT scanning by the dual layer technique has higher accuracy for quantitative measurements of iodine density compared to the dual source technique.

Keywords: CT, iodine density, spectral, dual-energy

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Authors: Zsolt Szucs, Viktor Kelemen, Son Le Thai, Magdolna Csavas, Erzsebet Roth, Gyula Batta, Annelies Stevaert, Evelien Vanderlinden, Aniko Borbas, Lieve Naesens, Pal Herczegh

Abstract:

The approval of modern glycopeptide antibiotics such as dalbavancin and oritavancin which have excellent activity against Gram-positive bacteria, encouraged our research group to prepare semisynthetic compounds from several members of glycopeptides by various chemical methods. Derivatives from the aglycone of ristocetin, eremomycin, vancomycin and a pseudoaglycon of teicoplanin have been synthesized in a systematic manner. Interestingly, some of the aglycoristocetin derivatives displayed noteworthy anti-influenza activity. More recently our group has been focusing on the modifications of one of the pseudoaglycons of teicoplanin. The reaction of N-ethoxycarbonyl maleimide derivatives with the primary amino function, the copper-catalysed azide-alkyne click reaction and the sulfonylation of the N-terminus were utilized to obtain systematic series of compounds. All substituents provide a more lipophilic character to the new molecules compared to the parent antibiotics, which is known to be favourable for activity against resistant bacteria. Lipoglycopeptides are also known to have antiviral properties, which has been predominantly studied on HIV by others. The structure-activity relationship study of our compounds revealed the influence of a few structural elements on biological activity. In many cases, minimal changes in lipophilicity and structure produced great differences in efficacy and cytotoxicity. In vitro experiments showed that these compounds are not only active against glycopeptide resistant Gram-positive bacteria but in several cases they prevent the infection of cell cultures by different strains of influenza viruses. This is probably related to the inhibition of the viral entry into the host cell nucleus, of which the exact mechanism is unknown. In some instances, reasonably low concentrations were sufficient to observe this effect. Several derivatives were highly cytotoxic at the same time, but some of them displayed a good selectivity index. The antiviral properties of the compounds are not restricted to influenza viruses e.g., some of them showed good activity against Human Coronavirus 229E. This work could potentially lead to the development of antiviral drugs which possess the crucial structural motifs that are needed for antiviral activity, while missing those which contribute to the antibacterial effect.

Keywords: antiviral, glycopeptide, semisynthetic, teicoplanin

Procedia PDF Downloads 157

Authors: Farhad Reyazat, Richard Werner

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This paper contributes to the existent literature by developing a framework that explains how to monitor potential threats to banking sector stability. The study explores structural vulnerabilities at the country level, but also look at bilateral exposures within a network context. The study contributes in analysing of the European banking systemic risk at aggregated level, which integrates the characteristics of bank size, and interconnectedness relative to the size of the economy which ultimate risk belong to, taking to account the concentration ratio of the banking industry within the whole economy. The nature of the systemic risk depends on the interplay of the network topology with the nature of financial transactions over the network, assets and buffer stemming from bank size, correlations, and the nature of the shocks to the financial system. The study’s results illustrate the contribution of banks’ size, size of economy and concentration of counterparty exposures to a given country’s banks in explaining its systemic importance, how much the banking network depends on a few traditional hubs activities and the changes of this dependencies over the last 9 years. The role of few of traditional hubs such as Swiss banks and British Banks and also Irish banks- where the financial sector is fairly new and grew strongly between 1990s till 2008- take the fourth position on 2014 reducing the relative size since 2006 where they had the first position. In-degree concentration index analysis in the study shows concentration index of banking network was not changed since financial crisis 2007-8. In-degree concentration index on first quarter of 2014 indicates that US, UK and Germany together, getting over 70% of the network exposures. The result of comparing the in-degree concentration index with 2007-4Q, shows the same group having over 70% of the network exposure, however the UK getting more important role in the hub and the market share of US and Germany are slightly diminished.

Keywords: systemic risk, counterparty risk, financial stability, interconnectedness, banking concentration, european banks risk, network effect on systemic risk, concentration risk

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Authors: Nobuyuki Takemoto, Ai Koyanagi, Masanori Yasuda, Hiroshi Yamamoto

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Background: Fluorescence imaging (FI) is one of the methods to identify sentinel lymph nodes (SLNs). However, the procedure is technically complicated and requires procedural skills, as SLN biopsy must be conducted in dim light conditions. As an improved version of this method, we introduced a combined method (Combined mixed dye and fluorescence; CMF) consisting of indigo carmine blue dye and FI. The direct visualization of SLNs under shadowless surgical light conditions is facilitated by the addition of the blue dye. We compared the SLN detection rates of CMF with that of the indocyanine green (ICG) dye method (ICG-D). Methods: A total of 202 patients with stage ≤ IIA breast cancer who underwent breast conservative therapy with separate incision from January 2004 to February 2017 were reviewed. Details of the two methods are as follows: (1) ICG-D: 2ml of ICG (10mg) was used and the green-stained SLNs were resected via a 3-4cm axillary incision; (2) CMF: A combination of 1ml of ICG (5mg) and 1-3ml of indigo carmine (4-12mg) was used. Using Photodynamic Eye (PDE), a 1.5-2 cm incision was made near the point of disappearance of the fluorescence and SLNs with intermediate color of blue and green were resected. Results: There were 92 ICG-D and 110 CMF cases. CMF resulted in a significantly higher detection rate than ICG-D (96.4% vs. 83.7%; p=0.003). This difference was particularly notable in those aged ≥ 60 years (98.3% vs. 74.3%) and individuals with BMI ≥ 25kg/m2 (90.3% vs. 58.3%). Conclusion: CMF is an effective method to identify SLNs which is safe, efficient, and cost-effective. Furthermore, radiation exposure can be avoided, and it can be performed in institutes without nuclear medicine facilities. CMF achieves a high SLN identification rate, and most of this procedure is feasible under shadowless surgical light conditions. CMF can reliably perform SLN biopsy even in those aged ≥ 60 years and individuals with BMI ≥ 25 kg/m2.

Keywords: sentinel lymph node biopsy, identification rate, indocyanine green (ICG), indigocarmine, fluorescence

Procedia PDF Downloads 171

Authors: Susmita Goswami, Joyeeta Mitra, Indu Gaur, Neha Bhadauria, Shilpi Shilpi, Prabir K. Paul

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'Malbhog’, an indigenous banana variety, much prized for its flavour and delicacy suffers production losses due to Fusarium oxysporum f.sp. cubense. The pathogen enters young plants through feeder roots causing wilting of plants ultimately leading to death of plants. The pathogen spreads rapidly to other plants in the field. In eastern part of India, this variety escapes the onslaught of the pathogen when either co-cultivated or rotated with Amorphophallus campanulatus (yam). The present study provides an insight into the physiological aspect of the biocontrol by yam. In vitro application of sterile aqueous extract of yam tuber (100gm/100ml distilled water and its 1:10 and 1:100 dilutions) were mixed with PDA media which was substantially inoculated with spores of Fusarium oxysporum f.sp. cubense. The extract could significantly reduce germination of pathogen spores. Banana variety susceptible to Fusarium sp was raised in soil rite under aseptic conditions. Spores of the pathogen (106 spores/ml) were inoculated into the soil rite. The plants were spread with aqueous extract of yam. The control plants were treated with sterilized distilled water. The activity of phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO) and peroxidase (POX) were estimated in leaves and roots at interval of 24 hours for 5 days after treatment. The incidence of wilt disease was recorded after two weeks. The results demonstrated that yam extract could induce significant activity of PAL, PPO and POX along with accumulation of phenols in both roots and leaves of banana plants. However, significantly high activity of enzymes and phenol accumulation was observed in roots. The disease incidence was significantly low in yam treated plants. The results clearly demonstrated the control of the pathogen due to induction of defense mechanism in the host by the extract. The observed control of the pathogen in the field could possibly be due to induction of such defense responses in host by exudates leached into the soil from yam tubers. Yam extract could be a potential source of environment-friendly biocide against Panama wilt of banana.

Keywords: Amorphophallus campanulatus, banana, Fusarium oxysporum f.sp. cubense, phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), peroxidase (POX)

Procedia PDF Downloads 262

Authors: Stefanache Stefania, Ioana R. Podina

Abstract:

Background: Embodied Conversational Agents (ECAs) are revolutionizing education and healthcare by offering cost-effective, adaptable, and portable solutions. Research on the Uncanny Valley effect (UVE) involves various embodied agents, including ECAs. Achieving the optimal level of anthropomorphism, no consensus on how to overcome the uncanniness problem. Objectives: This systematic review aims to identify the user characteristics, agent features, and context factors that influence the UVE. Additionally, this review provides recommendations for creating effective ECAs and conducting proper experimental studies. Methods: We conducted a systematic review following the PRISMA 2020 guidelines. We included quantitative, peer-reviewed studies that examined human-ECA interaction. We identified 17,122 relevant records from ACM Digital Library, IEE Explore, Scopus, ProQuest, and Web of Science. The quality of the predictors, mediators, and moderators adheres to the guidelines set by prior systematic reviews. Results: Based on the included studies, it can be concluded that females and younger people perceive the ECA as more attractive. However, inconsistent findings exist in the literature. ECAs characterized by extraversion, emotional stability, and agreeableness are considered more attractive. Facial expressions also play a role in the UVE, with some studies indicating that ECAs with more facial expressions are considered more attractive, although this effect is not consistent across all studies. Few studies have explored contextual factors, but they are nonetheless crucial. The interaction scenario and exposure time are important circumstances in human-ECA interaction. Conclusions: The findings highlight a growing interest in ECAs, which have seen significant developments in recent years. Given this evolving landscape, investigating the risk of the UVE can be a promising line of research.

Keywords: human-computer interaction, uncanny valley effect, embodied conversational agent, systematic review

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Authors: Saule Shazhanbayeva, Denise van der Merwe

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Study hypothesis: Nazarbayev Intellectual School of Kyzylorda’s Biology teachers can use STEM-integrated learning to improve students' problem-solving ability and responsibility as global citizens. The significance of this study is to indicate how the use of STEM integrative learning during Biology lessons could contribute to forming globally-minded students who are responsible community members. For the purposes of this study, worldview is defined as a view that is broader than the country of Kazakhstan, allowing students to see the significance of their scientific contributions to the world as global citizens. The context of worldview specifically indicates that most students have never traveled outside of their city or region within Kazakhstan. In order to broaden student understanding, it is imperative that students are exposed to different world views and contrasting ideas within the educational setting of Biology as the science being used for the research. This exposure promulgates students understanding of the significance they have as global citizens alongside the obligations which would rest on them as scientifically minded global citizens. Integrative learning should be Biological Science - with Technology and engineering in the form of problem-solving, and Mathematics to allow improved problem-solving skills to develop within the students of Nazarbayev Intellectual School (NIS) of Kyzylorda. The school's vision is to allow students to realise their role as global citizens and become responsible community members. STEM allows integrations by combining four subject skills to solve topical problems designed by educators. The methods used are based on qualitative analysis: for students’ performance during a problem-solution scenario; and Biology teacher interviews to ascertain their understanding of STEM implementation and willingness to integrate it into current lessons. The research indicated that NIS is ready for a shift into STEM lessons to promote globally responsible students. The only additional need is for proper STEM integrative lesson method training for teachers.

Keywords: global citizen, STEM, Biology, high-school

Procedia PDF Downloads 72

Authors: Julie Connelly, Tanvi Toprani, Xin Xie, Dhinoth Kumar Bangarusamy, Kris C. Gunsalus

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The overuse of antibiotics worldwide has contributed to the development of multi-drug resistant (MDR) pathogenic bacterial strains. There is an increasing urgency to discover antibiotics to combat MDR pathogens. The microbiome of the Arabian Gulf is a largely unexplored and potentially rich source of novel bioactive compounds. Microbes that inhabit the Abu Dhabi coastal regions adapt to extreme environments with high salinity, hot temperatures, large temperature fluctuations, and acute exposure to solar energy. The microbes native to this region may produce unique metabolites with therapeutic potential as antibiotics and antifungals. We have isolated 200 pure bacterial strains from mangrove sediments, cyanobacterial mats, and coral reefs of the Abu Dhabi region. In this project, we aim to screen the marine bacterial strains to identify antibiotics, in particular undocumented compounds that show activity against existing antibiotic-resistant strains. We have acquired the ESKAPE pathogen panel, which consists of six antibiotic-resistant gram-positive and gram-negative bacterial pathogens that collectively cause most clinical infections. Our initial efforts of the primary screen using colony-picking co-culture assay have identified several candidate marine strains producing potential antibiotic compounds. We will next apply different assays, including disk-diffusion and broth turbidity growth assay, to confirm the results. This will be followed by bioactivity-guided purification and characterization of target compounds from the scaled-up volume of candidate strains, including SPE fraction, HPLC fraction, LC-MS, and NMR. For antimicrobial compounds with unknown structures, our final goal is to investigate their mode of action by identifying the molecular target.

Keywords: marine bacteria, natural products, drug discovery, ESKAPE panel

Procedia PDF Downloads 75

Authors: Sakshi Piplani, Ajit Kumar

Abstract:

Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.

Keywords: HDAC8, docking, molecular dynamics simulation, valproic acid

Procedia PDF Downloads 250

Authors: Richard Ren

Abstract:

Air pollution is a serious danger to international well-being and economies - it will kill an estimated 7 million people every year, costing world economies $2.6 trillion by 2060 due to sick days, healthcare costs, and reduced productivity. In the United States alone, 60,000 premature deaths are caused by poor air quality. For this reason, there is a crucial need to develop effective methods to forecast air quality, which can mitigate air pollution’s detrimental public health effects and associated costs by helping people plan ahead and avoid exposure. The goal of this study is to propose an artificial intelligence framework for predicting future air quality based on timing variables (i.e. season, weekday/weekend), future weather forecasts, as well as past pollutant and air quality measurements. The proposed framework utilizes multiple machine learning algorithms (logistic regression, random forest, neural network) with different specifications and averages the results of the three top-performing models to eliminate inaccuracies, weaknesses, and biases from any one individual model. Over time, the proposed framework uses new data to self-adjust model parameters and increase prediction accuracy. To demonstrate its applicability, a prototype of this framework was created to forecast air quality in Los Angeles, California using datasets from the RP4 weather data repository and EPA pollutant measurement data. The results showed good agreement between the framework’s predictions and real-life observations, with an overall 92% model accuracy. The combined model is able to predict more accurately than any of the individual models, and it is able to reliably forecast season-based variations in air quality levels. Top air quality predictor variables were identified through the measurement of mean decrease in accuracy. This study proposed and demonstrated the efficacy of a comprehensive air quality prediction framework leveraging multiple machine learning algorithms to overcome individual algorithm shortcomings. Future enhancements should focus on expanding and testing a greater variety of modeling techniques within the proposed framework, testing the framework in different locations, and developing a platform to automatically publish future predictions in the form of a web or mobile application. Accurate predictions from this artificial intelligence framework can in turn be used to save and improve lives by allowing individuals to protect their health and allowing governments to implement effective pollution control measures.Air pollution is a serious danger to international wellbeing and economies - it will kill an estimated 7 million people every year, costing world economies $2.6 trillion by 2060 due to sick days, healthcare costs, and reduced productivity. In the United States alone, 60,000 premature deaths are caused by poor air quality. For this reason, there is a crucial need to develop effective methods to forecast air quality, which can mitigate air pollution’s detrimental public health effects and associated costs by helping people plan ahead and avoid exposure. The goal of this study is to propose an artificial intelligence framework for predicting future air quality based on timing variables (i.e. season, weekday/weekend), future weather forecasts, as well as past pollutant and air quality measurements. The proposed framework utilizes multiple machine learning algorithms (logistic regression, random forest, neural network) with different specifications and averages the results of the three top-performing models to eliminate inaccuracies, weaknesses, and biases from any one individual model. Over time, the proposed framework uses new data to self-adjust model parameters and increase prediction accuracy. To demonstrate its applicability, a prototype of this framework was created to forecast air quality in Los Angeles, California using datasets from the RP4 weather data repository and EPA pollutant measurement data. The results showed good agreement between the framework’s predictions and real-life observations, with an overall 92% model accuracy. The combined model is able to predict more accurately than any of the individual models, and it is able to reliably forecast season-based variations in air quality levels. Top air quality predictor variables were identified through the measurement of mean decrease in accuracy. This study proposed and demonstrated the efficacy of a comprehensive air quality prediction framework leveraging multiple machine learning algorithms to overcome individual algorithm shortcomings. Future enhancements should focus on expanding and testing a greater variety of modeling techniques within the proposed framework, testing the framework in different locations, and developing a platform to automatically publish future predictions in the form of a web or mobile application. Accurate predictions from this artificial intelligence framework can in turn be used to save and improve lives by allowing individuals to protect their health and allowing governments to implement effective pollution control measures.Air pollution is a serious danger to international wellbeing and economies - it will kill an estimated 7 million people every year, costing world economies $2.6 trillion by 2060 due to sick days, healthcare costs, and reduced productivity. In the United States alone, 60,000 premature deaths are caused by poor air quality. For this reason, there is a crucial need to develop effective methods to forecast air quality, which can mitigate air pollution’s detrimental public health effects and associated costs by helping people plan ahead and avoid exposure. The goal of this study is to propose an artificial intelligence framework for predicting future air quality based on timing variables (i.e. season, weekday/weekend), future weather forecasts, as well as past pollutant and air quality measurements. The proposed framework utilizes multiple machine learning algorithms (logistic regression, random forest, neural network) with different specifications and averages the results of the three top-performing models to eliminate inaccuracies, weaknesses, and biases from any one individual model. Over time, the proposed framework uses new data to self-adjust model parameters and increase prediction accuracy. To demonstrate its applicability, a prototype of this framework was created to forecast air quality in Los Angeles, California using datasets from the RP4 weather data repository and EPA pollutant measurement data. The results showed good agreement between the framework’s predictions and real-life observations, with an overall 92% model accuracy. The combined model is able to predict more accurately than any of the individual models, and it is able to reliably forecast season-based variations in air quality levels. Top air quality predictor variables were identified through the measurement of mean decrease in accuracy. This study proposed and demonstrated the efficacy of a comprehensive air quality prediction framework leveraging multiple machine learning algorithms to overcome individual algorithm shortcomings. Future enhancements should focus on expanding and testing a greater variety of modeling techniques within the proposed framework, testing the framework in different locations, and developing a platform to automatically publish future predictions in the form of a web or mobile application. Accurate predictions from this artificial intelligence framework can in turn be used to save and improve lives by allowing individuals to protect their health and allowing governments to implement effective pollution control measures.

Keywords: air quality prediction, air pollution, artificial intelligence, machine learning algorithms

Procedia PDF Downloads 127

Authors: Umamaheswari Shanmugam, Silvia Ronchi, Radu Vornicu

Abstract:

Software, artificial intelligence, and machine learning can improve healthcare through innovative and advanced technologies that are able to use the large amount and variety of data generated during healthcare services every day. As we read the news, over 500 machine learning or other artificial intelligence medical devices have now received FDA clearance or approval, the first ones even preceding the year 2000. One of the big advantages of these new technologies is the ability to get experience and knowledge from real-world use and to continuously improve their performance. Healthcare systems and institutions can have a great benefit because the use of advanced technologies improves the same time efficiency and efficacy of healthcare. Software-defined as a medical device, is stand-alone software that is intended to be used for patients for one or more of these specific medical intended uses: - diagnosis, prevention, monitoring, prediction, prognosis, treatment or alleviation of a disease, any other health conditions, replacing or modifying any part of a physiological or pathological process–manage the received information from in vitro specimens derived from the human samples (body) and without principal main action of its principal intended use by pharmacological, immunological or metabolic definition. Software qualified as medical devices must comply with the general safety and performance requirements applicable to medical devices. These requirements are necessary to ensure high performance and quality and also to protect patients’ safety. The evolution and the continuous improvement of software used in healthcare must take into consideration the increase in regulatory requirements, which are becoming more complex in each market. The gap between these advanced technologies and the new regulations is the biggest challenge for medical device manufacturers. Regulatory requirements can be considered a market barrier, as they can delay or obstacle the device approval, but they are necessary to ensure performance, quality, and safety, and at the same time, they can be a business opportunity if the manufacturer is able to define in advance the appropriate regulatory strategy. The abstract will provide an overview of the current regulatory framework, the evolution of the international requirements, and the standards applicable to medical device software in the potential market all over the world.

Keywords: artificial intelligence, machine learning, SaMD, regulatory, clinical evaluation, classification, international requirements, MDR, 510k, PMA, IMDRF, cyber security, health care systems.

Procedia PDF Downloads 89

Authors: Zahra Abdi, Roghayeh Alipour, Babak Farahi Ghasraboonasr

Abstract:

Introduction: Diabetes is a serious medical condition that requires constant care. People with type 2 diabetes may also be likely to experience dry, itchy skin and poor wound healing. Some people with diabetes will have a skin problems at some time in their lives and for those not yet diagnosed with diabetes, a skin problem can be an indication of the disease. our purpose was to assess the capability and knowledge of students of Shiraz University of Medical Sciences about prevent from skin complications in diabetes type 2. Methods: In this descriptive cross-sectional study, knowledge of 360 students of Shiraz University of Medical Sciences was evaluated about different ways to avoid skin complications in diabetes type 2. Data were analyzed by spss19.(P<0.05) was considered significant. Results: 360 students of Shiraz University of Medical Sciences participated in this study. 45% of students agree with the effect of Moisturize skin daily, If Diabetics have sensitive skin, choose a fragrance-free, dye-free moisturizer that won’t irritate skin. 52% believe that Protect skin from sun can be so useful, Sun exposure is drying and aging. Use sunscreen with SPF 30 or higher whenever you’re outside. Wear gloves when doing yardwork to protect the skin on your hands. 62% of students strongly agree with Carefully clean any cuts and scrapes, If diabetics notice any sign of infection skin that’s red, swollen, or warm to the touch, or has a foul-smelling drainage or pus should consulting with a doctor immediately. Diabetics should be careful about any injury that takes longer than normal to heal and they should consulting with doctor about them too. 72% of students believe that diabetics should be diligent about daily foot care. Clean and moisturize feet each day and check each foot closely, top and bottom, for wounds even a tiny cut, blisters, or cracked skin. Conclusions: The risk of getting these diabetes complications can be lessened by controlling blood sugar. Skin complications can cause serious consequences. Taking care of skin is so important and using these tips are remarkable effective and help diabetics to look after their skin easier.

Keywords: skin complications, diabetes type 2, Shiraz University of Medical Sciences, diabetics

Procedia PDF Downloads 355

Authors: Sara R. Knigge, Sugat R. Tuladhar, Alexander Becker, Tobias Schilling, Birgit Glasmacher

Abstract:

Commercially available mechanical or biological heart valve prostheses both tend to fail long-term due to thrombosis, calcific degeneration, infection, or immunogenic rejection. Moreover, these prostheses are non-viable and do not grow with the patients, which is a problem for young patients. As a result, patients often need to undergo redo-operations. Tissue-engineered (TE) heart valves based on degradable electrospun fiber scaffolds represent a promising approach to overcome these limitations. Such scaffolds need sufficient mechanical properties to withstand the hydrodynamic stress of intracardiac hemodynamics. Additionally, the scaffolds should be colonized by autologous or homologous cells to facilitate the in vivo remodeling of the scaffolds to a viable structure. This study investigates how process parameters of electrospinning and degradation affect the mechanical properties of electrospun scaffolds made of FDA-approved, biodegradable polymer polycaprolactone (PCL). Fiber mats were produced from a PCL/tetrafluoroethylene solution by electrospinning. The e-spinning process was varied in terms of scaffold thickness, fiber diameter, fiber orientation, and fiber interconnectivity. The morphology of the fiber mats was characterized with a scanning electron microscope (SEM). The mats were degraded in different solutions (cell culture media, SBF, PBS and 10 M NaOH-Solution). At different time points of degradation (2, 4 and 6 weeks), tensile and cyclic loading tests were performed. Fresh porcine pericardium and heart valves served as a control for the mechanical assessment. The progression of polymer degradation was quantified by SEM and differential scanning calorimetry (DSC). Primary Human aortic endothelial cells (HAECs) and Human induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) were seeded on the fiber mats to investigate the cell colonization potential. The results showed that both the electrospinning parameters and the degradation significantly influenced the mechanical properties. Especially the fiber orientation has a considerable impact and leads to a pronounced anisotropic behavior of the scaffold. Preliminary results showed that the polymer became strongly more brittle over time. However, the embrittlement can initially only be detected in the mechanical test. In the SEM and DSC investigations, neither morphological nor thermodynamic changes are significantly detectable. Live/Dead staining and SEM imaging of the cell-seeded scaffolds showed that HAECs and iPSC-ECs were able to grow on the surface of the polymer. In summary, this study's results indicate a promising approach to the development of a TE aortic heart valve based on an electrospun scaffold.

Keywords: electrospun scaffolds, long-term polymer degradation, mechanical behavior of electrospun PCL, tissue engineered aortic heart valve

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Authors: Rajkumar Ghosh

Abstract:

The study focuses on the tectonics of out-of-sequence thrusting (OOST) in the NW region of the Himalaya, particularly in Himachal Pradesh. The research aims to identify the features and nature of OOST in the field and the associated rock types and lithological boundaries in the field of NW Himalaya, Himachal Pradesh, India. The research employs fieldwork and micro-structure observations, correlations, and analyses to identify and analyze the OOST features and associated rock types. The study reveals the presence of three OOSTs, namely Jhakri Thrust (JT), Sarahan Thrust (ST), and Chaura Thrust (CT), which consist of several branches, some of which are still active. The thrust system exhibits varying internal geometry, including box folds, boudins, scar folds, crenulation cleavages, kink folds, and tension gashes. The CT, which is concealed beneath Jutogh Thrust sheet, represents a steepened downward thrust, while the JT has a western dip and is south-westward verging. The research provides crucial information on the tectonics of OOST in the NW region of the Himalaya, particularly in Himachal Pradesh, which is crucial in understanding the regional geological evolution and associated hazards. The data were collected through fieldwork and micro-structure observations, correlations, and analyses of rock samples. The data were analyzed using tectonic and geochronological techniques to identify the nature and characteristics of OOST. The research addressed the question of identifying Higher Himalayan OOST in the field of NW Himalaya, Himachal Pradesh, India, and the associated rock types and lithological boundaries. The study concludes that there is minimal documentation and a lack of suitable exposure of rocks to generalize the features of OOST in the field in NW Higher Himalaya, Himachal Pradesh. The study recommends more extensive mapping and fieldwork to improve understanding of OOST in the region.

Keywords: out-of-sequence thrust (OOST), main central thrust (MCT), jhakri thrust (JT), sarahan thrust (ST), chaura thrust (CT), higher himalaya (HH)

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