Search results for: efflux pump inhibitors

Authors: Md. Mizanur Rahman, Anquan Liu, Anna Frostegård, Johan Frostegård

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The role of the human immune system is essential in cardiovascular diseases and atherosclerosis. Activated cells in atherosclerosis produce abundant amounts of cytokines, but the exact mechanisms involved in the effects of these inflammatory cytokines are not clear in atherosclerosis. In a large clinical cohort, we have previously determined that antibodies against phosphorylcholine (anti-PC) are negatively and independently associated with both development of atherosclerosis and also a low risk of cardiovascular disease. Further, we reported that rheumatoid arthritis patients who were non-responders to TNF-inhibitors, where those with low anti-PC levels. Upon anti-TNF treatment, anti-PC levels increased. We, therefore, hypothesised that proinflammatory cytokines such as TNF could play a role in anti-PC regulation. Peripheral blood mononuclear cells (PBMC) were cultured with or without TNF and anti-TNF. The cell supernatants were collected after six days for ELISA measurements. In separate experiments, cells were cultured for 24 hours in both polystyrene plates and ELISPOT plates under a similar condition for ELISA and ELISPOT assays respectively. Total RNA was extracted after 6 hours of cell culture to perform RT-qPCR. Cell viability was confirmed by trypan blue staining and MTT assays. ELISA measurements detected less than 40% of anti-PC in TNF-treated cells, in comparison to control cells, whereas anti-PC production was recovered by anti-TNF treatment. ELISPOT assays showed that TNF suppresses anti-PC production by inhibiting anti-PC producing B-cells. In addition, RT-qPCR and ELISA showed that TNF also has effects also on B-cell activation as BAFF expression was inhibited by TNF treatment. Atherosclerosis is a major cause of cardiovascular diseases, but anti-PC is a protection marker for atherosclerosis development. Our findings show that TNF is a negative regulator of anti-PC production. Immune modulation and rising of anti-PC could be of major significance for the patients.

Keywords: anti-PC, Anti-TNF, atherosclerosis, cardiovascular diseases, phosphorylecholine

Procedia PDF Downloads 240

Authors: Mohamed H. Khalifa, Fikry I. El-Shahawi, Nabil A. Mansour

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The cotton leafworm, Spodoptera littoralis (Boisduval) is a major insect pest of vegetables and cotton crops in Egypt, and exhibits different levels of tolerance to certain insecticides. Chlorantraniliprole has been registered recently in Egypt for control this insect. The susceptibilities of three S. littoralis populations collected from El Behaira governorate, north Egypt to chlorantraniliprole were determined by leaf-dipping technique on 4^th instar larvae. Obvious variation of toxicity was observed among the laboratory susceptible, and three field populations with LC₅₀ values ranged between 1.53 µg/ml and 6.22 µg/ml. However, all the three field populations were less susceptible to chlorantraniliprole than a laboratory susceptible population. The most tolerant populations were sampled from El Delengat (ED) Province where S. littoralis had been frequently challenged by insecticides. Certain enzyme activity assays were carried out to be correlated with the mechanism of the observed field population tolerance. All field populations showed significantly enhanced activities of detoxification enzymes compared with the susceptible strain. The regression analysis between chlorantraniliprole toxicities and enzyme activities revealed that the highest correlation is between α-esterase or β-esterase (α-β-EST) activity and collected field strains susceptibility, otherwise this correlation is not significant (P > 0.05). Synergism assays showed the ED and susceptible strains could be synergized by known detoxification inhibitors such as piperonyl butoxide (PBO), triphenyl phosphate (TPP) and diethyl-maleate (DEM) at different levels (1.01-8.76-fold and 1.09-2.94 fold, respectively), TPP showed the maximum synergism in both strains. The results show that there is a correlation between the enzyme activity and tolerance, and carboxylic-esterase (Car-EST) is likely the main detoxification mechanism responsible for tolerance of S. littoralis to chlorantraniliprole.

Keywords: chlorantraniliprole, detoxification enzymes, Egypt, Spodoptera littoralis

Procedia PDF Downloads 272

Authors: Przemyslaw Nogly, Tobias Weinert, Daniel James, Sergio Carbajo, Dmitry Ozerov, Antonia Furrer, Dardan Gashi, Veniamin Borin, Petr Skopintsev, Kathrin Jaeger, Karol Nass, Petra Bath, Robert Bosman, Jason Koglin, Matthew Seaberg, Thomas Lane, Demet Kekilli, Steffen Brünle, Tomoyuki Tanaka, Wenting Wu, Christopher Milne, Thomas A. White, Anton Barty, Uwe Weierstall, Valerie Panneels, Eriko Nango, So Iwata, Mark Hunter, Igor Schapiro, Gebhard Schertler, Richard Neutze, Jörg Standfuss

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Ultrafast isomerization of retinal is the primary step in a range of photoresponsive biological functions including vision in humans and ion-transport across bacterial membranes. We studied the sub-picosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin using an X-ray laser. Twenty snapshots with near-atomic spatial and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket prior to passing through a highly-twisted geometry and emerging in the 13-cis conformation. The aspartic acid residues and functional water molecules in proximity of the retinal Schiff base respond collectively to formation and decay of the initial excited state and retinal isomerization. These observations reveal how the protein scaffold guides this remarkably efficient photochemical reaction.

Keywords: bacteriorhodopsin, free-electron laser, retinal isomerization mechanism, time-resolved crystallography

Procedia PDF Downloads 245

Authors: Amando A. Radomes Jr., LLoyd Jun Benjamin T. Embernatre, Cherssy Kaye F. Eviota, Krizia Allyn L. Nunez, Jose Thaddeus B. Roble III

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Sitio Kantaling is one of the 34 villages in Danao City, Cebu, in the central Philippines. As of 2015, the eight households in the mountainous village extending over 40 hectares of land area, including 12 hectares of arable land, are the source of over a fifth of the agricultural products that go into the city. Over the years, however, the local government had been concerned with the decline in agricultural productivity because increasing number of residents are migrating into the urban areas of the region to look for better employment opportunities. One of the major reasons for the agricultural productivity decline is underdeveloped irrigation infrastructure. The local government had partnered with the University of San Carlos to conduct research on developing an irrigation system that could sustainably meet both agricultural and household consumption needs. From a macro-perspective, a dynamic simulation model was developed to understand the long-term behavior of the status quo and proposed the system. Data on population, water supply and demand, household income, and urban migration were incorporated in the 20-year horizon model. The study also developed a smart irrigation system design. Instead of using electricity to pump water, a network of aqueducts with three main nodes had been designed and strategically located to take advantage of gravity to transport water from a spring. Simulation results showed that implementing a sustainable irrigation system would be able to significantly contribute to the socio-economic progress of the local community.

Keywords: agriculture, aqueduct, simulation, sustainable irrigation system

Procedia PDF Downloads 164

Authors: Svitlana Antonenko, Gennady Telegeev

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Introductive statement: The development of chronic myeloid leukemia (CML) is caused by Bcr-Abl oncoprotein. Modern treatments with tyrosine kinase inhibitors are greatly complicated by the mutational variability of the Bcr-Abl oncoprotein, which causes drug resistance. Therefore, there is an urgent need to develop new approaches to the treatment of the disease, which will allow modeling the level of Bcr-Abl oncoprotein in the cell. Promising in this direction is the identification of proteases that can selectively promote cellular proteolysis of oncoproteins. The aim of the study was to study the effect of the interaction of Bcr-Abl with deubiquitinase USP1 on the level of oncoprotein in CML cells. Methodology: K562 cells were selected for the experiment. Сells were incubated with ML323 inhibitor for 24 hours. Precipitation of endogenous proteins from K562 cell lysate was performed using anti-Bcr-Abl antibodies. Cell lysates and precipitation results were studied by Western blot. Subcellular localization of proteins was studied by immunofluorescence analysis followed by confocal microscopy. The results were analyzed quantitatively and statistically. Major findings: The Bcr-Abl/USP1 protein complex was detected in CML cells, and it was found that inhibition of USP1 deubiquitinating activity by the compound ML323 leads to disruption of this protein complex and a decrease in the level of Bcr-Abl oncoprotein in cells. The interaction of Bcr-Abl with USP1 may result in deubiquitination of the oncoprotein, which disrupts its proteasomal degradation and leads to the accumulation of CML in cells. Conclusion: We believe that the interaction of oncoprotein with USP1 may be one of the prerequisites that contribute to malignant cell transformation due to the deubiquitination of oncoprotein, which leads to its accumulation and disease progression. A correlation was found between the deubiquitinating activity of USP1 and the level of oncoprotein in CML cells. Thus, we identify deubiquitinase USP1 as a promising therapeutic target for the development of a new strategy for the treatment of CML by modulating the level of Bcr-Abl in the cell.

Keywords: chronic myeloid leukemia, Bcr-Abl, USP1, deubiquitination Bcr-Abl, K562 cell

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Authors: Zahra Dehghani, Hoda Dehghani, Elham Zarenezhad

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1,2,3-Triazole derivatives are important compounds in medicinal chemistry owing to their wide applications in drug discovery. They can readily associate with biologically targets through the hydrogen bonding and dipole interactions. The 1,2,3-triazole core is a key structural motif in many bioactive compounds, exhibiting a broad spectrum of biological activities, such as antiviral, anticancer, anti-HIV, antibiotic, antibacterial, and antimicrobial. Additionally, they have found significant industrial applications as dyes, agrochemicals, corrosion inhibitors, photo stabilizers, and photographic materials. we disclose the synthesis and characterization of 1-azido-3-(aryl-2-yloxy)propan-2-ol drivatives. The chemistry works well with various ß-azido alcohols involving aryloxy, alkoxy and alkyl residues, and also tolerates a wide spectrum of electron-donating and electron-withdrawing functional groups in both alkyne and azide molecules. Most of ß-azidoalcohols used in these experiments were pre-synthesized by the regioselective ring opening reaction of corresponded epoxides with sodium azide, whereas the majority of terminal alkynes were prepared via SN2-type reaction of propargyl bromide and corresponded nucleophiles. To evaluate the bioactivity of title compounds, the in vitro antifungal activity of all compound was investigated against several pathogenic fungi including Candida albicans, Candida krusei, Aspergillus niger, and Trichophyton rubrum , clotrimazole and fluconazole was used as standard antifungal drugs, also To understand the antibacterial activity of synthesized compounds, they were in vitro screened against E. coli and S. aureus as Gram-negative and Gram-positive bacteria, respectively. The in vitro tests have shown the promising antifungal but marginal antibacterial activity against tested fungi and bacteria.

Keywords: biological activities, antibacterial, antifungal, 1, 2, 3-Triazole

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Authors: Linda Blümel, Bettina Bert, Jan Brosda, Heidrun Fink, Melanie Hamann

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Age-related cognitive decline can eventually lead to dementia, the most common mental illness in elderly people and an immense challenge for patients, their families and caregivers. Cholinesterase inhibitors constitute the most commonly used antidementia prescription medication. The standardized Ginkgo biloba leaf extract EGb 761® is approved for treating age-associated cognitive impairment and has been shown to improve the quality of life in patients suffering from mild dementia. A clinical trial with 96 Alzheimer´s disease patients indicated that the combined treatment with donepezil and EGb 761® had fewer side effects than donepezil alone. In an animal model of cognitive aging, we compared the effect of combined treatment with EGb 761® or donepezil monotherapy and vehicle. We compared the effect of chronic treatment (15 days of pretreatment) with donepezil (1.5 mg/kg p. o.), EGb 761® (100 mg/kg p. o.), or the combination of the two drugs, or vehicle in 18 – 20 month old male OFA rats. Learning and memory performance were assessed by Morris water maze testing, motor behavior in an open field paradigm. In addition to chronic treatment, the substances were administered orally 30 minutes before testing. Compared to the first day and to the control group, only the combination group showed a significant reduction in latency to reach the hidden platform on the second day of testing. Moreover, from the second day of testing onwards, the donepezil, the EGb 761® and the combination group required less time to reach the hidden platform compared to the first day. The control group did not reach the same latency reduction until day three. There were no effects on motor behavior. These results suggest a superiority of the combined treatment of donepezil with EGb 761® compared to monotherapy.

Keywords: age-related cognitive decline, dementia, ginkgo biloba leaf extract EGb 761®, learning and memory, old rats

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Authors: Rukia Yosuf

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Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.

Keywords: diabetes, kidney disease, nephrology, prediabetes

Procedia PDF Downloads 185

Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Memoona Ramzan, Bushra Tabassum, Anwar Khan, Muhammad Tariq, Mudassar Fareed Awan, Idrees Ahmad Nasir, Zahida Qamar, Naila Shahid, Tayyab Husnain

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Biological control is a novel approach being used in crop protection nowadays. Bacteria like Bacillus and Pseudomonas are reported for this purpose and few of their products are commercially available too. Rhizosphere and phyllosphere of healthy cotton plants were used as a source to isolate bacteria capable of exhibiting properties worthy for selection as biocontrol agent. For this purpose all isolated strains were screened for the activities like phosphate solubilization, Indole acetic acid (IAA) production and biocontrol against fungi. Two strains S1HL3 and S1HL4 showed phosphate solubilization and IAA production simultaneously while two other JS2HR4 and JS3HR2 were good inhibitors of fungal pathogens. Through biochemical and molecular characterization these bacteria were identified as P. aeruginosa, Burkholderia and Bacillus respectively. In green house trials of these isolates against Cotton leaf curl virus (CLCuV), seven treatments including individual bacterial isolate and consortia were included. Treated plants were healthy as compared to control plants in which upto 74% CLCuV symptomatic plants exist. Maximum inhibition of CLCuV was observed in T7 treated plants where viral load was only 0.4% as compared to control where viral load was upto 74%. This treatment consortium included Bacillus and Pseudomonas isolates; S1HL3, S1HL4, JS2HR4 and JS3HR2. Principal Component Biplot depicted highly significant correlation between percentage viral load and the disease incidence.

Keywords: cotton leaf curl virus, biological control, bacillus, pseudomonas

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Authors: Dina Atmani-Kilani, Farah Yous, Djebbar Atmani

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The etiology of peptic ulcer is closely related to stress, excessive consumption of nonsteroidal anti-inflammatory drugs, or ethanol. Clematis flammula (Ranunculaceae) is a medicinal plant widely used by rural populations to treat inflammatory disorders. This study was designed to assess the gastroprotective potential of C. flammula extracts. Gastric ulcer was induced by stress, indomethacin, HCl / ethanol, and absolute ethanol on NMRI-type mice. The antioxidant potency of the ethanolic extract of Clematis flammula (EECF) was evaluated on catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities. Glutathione (GSH) and malonaldehyde (MDA) levels were also quantified. The anti-inflammatory potential was evaluated through the effect of EECF on myeloperoxidase activity (MPO) and vascular permeability. Complementary tests concerning the quantification of mucus levels, gastric motility, inhibition of ATPase H+/K+activity, as well as a histopathological study were also undertaken to explore the mechanism of action of the EECF. The EECF exhibited a significant (p <0.001) and optimal (100 mg/kg) gastroprotective effect by elevating SOD, CAT, and GSH levels, thereby minimizing the production of MDA and lowering the activity of MPO and vascular permeability. EECF also increased the rate of mucus production, decreased gastric motility, and completely suppressed the H+/K+ ATPase activity. Histopathological study confirmed the effectiveness of the extract in the prevention of peptic ulcer. The results obtained in this study demonstrated the gastro-protective effect of EECF via acidic antioxidant, anti-inflammatory, cytoprotective and anti-secretory mechanisms, which may justify its use as a substitute in peptic ulcer treatment.

Keywords: clematis flammula, superoxide dismutase, myeloperoxidase, ATPase, pump

Procedia PDF Downloads 196

Authors: Pragathi Gurumurthy, Christina Hagen, Patricia Ulloa, Martin A. Koch, Thorsten M. Buzug

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Obstructive sleep apnea (OSA) is a sleep disorder where the patient suffers a disturbed airflow during sleep due to partial or complete occlusion of the pharyngeal airway. Recently, numerical simulations have been used to better understand the mechanism of pharyngeal collapse. However, to gain confidence in the solutions so obtained, an experimental validation is required. Therefore, in this study an experimental validation of computational fluid dynamics (CFD) used for the study of human pharyngeal flow patterns during OSA is performed. A stationary incompressible Navier-Stokes equation solved using the finite element method was used to numerically study the flow patterns in a computed tomography-based human pharynx model. The inlet flow rate was set to 250 ml/s and such that a flat profile was maintained at the inlet. The outlet pressure was set to 0 Pa. The experimental technique used for the validation of CFD of fluid flow patterns is phase contrast-MRI (PC-MRI). Using the same computed tomography data of the human pharynx as in the simulations, a phantom for the experiment was 3 D printed. Glycerol (55.27% weight) in water was used as a test fluid at 25°C. Inflow conditions similar to the CFD study were simulated using an MRI compatible flow pump (CardioFlow-5000MR, Shelley Medical Imaging Technologies). The entire experiment was done on a 3 T MR system (Ingenia, Philips) with 108 channel body coil using an RF-spoiled, gradient echo sequence. A comparison of the axial velocity obtained in the pharynx from the numerical simulations and PC-MRI shows good agreement. The region of jet impingement and recirculation also coincide, therefore validating the numerical simulations. Hence, the experimental validation proves the reliability and correctness of the numerical simulations.

Keywords: computational fluid dynamics, experimental validation, phase contrast-MRI, obstructive sleep apnea

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Authors: A. K. R. Gobinath, He Jianzhong, Kun-Lin Yang

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Fruit waste was used as a feedstock to produce biohydrogen in this study. Fruit waste used in this study was collected from several fruit juice stalls in Singapore. Based on our observation, the fruit waste contained 35-40% orange, 10-20% watermelon, 10-15% apple, 10-15% pineapple, 1-5% mango. They were mixed with water (1:1 ratio based on wet biomass) and blended to attain homogenous mixtures. Later, fruit waste was subjected to one of the following pretreatments: autoclave (121 °C for 20min), microwave (20min) or both. After pretreatment, the total sugar concentration in the hydrolysate was high (>12g/l) when both autoclave and microwave were applied. In contrast, samples without pretreatment measured only less than 2g/l of sugar. While using these hydrolysates as carbon sources, Clostridium strain BOH3 produces 2526-3126 ml/l of hydrogen after 72h of anaerobic fermentation. The hydrogen yield was 295-300 ml/g of sugar which is close to the hydrogen yields from glucose (338 ml/gm) and xylose (330 ml/gm). Our HPLC analysis showed that fruit waste hydrolysate contained oligosugars (25-27%), sucrose (18-23%), fructose (25-30%), glucose (10-15%) and mannose (2-5%). Additionally, pretreatment led to the release of free amino acids (160-512 mg/l), calcium (7.8-12.9 ppm), magnesium (4.32-6.55 ppm), potassium (5.4-65.1 ppm) and sodium (0.4-0.5 ppm) into the hydrolysate. These nutrients were able to support strain-BOH3 to grow and produce high level of hydrogen. Notably, unlike other pretreatment methods (with strong acids and bases), these pretreatment techniques did not generate any inhibitors (e.g. furfural and phenolic acids) to suppress the hydrogen production. Interestingly, strain BOH3 can also ferment pretreated fruit waste slurry and produce hydrogen with a high yield (156-343 ml/gm fruit waste). While fermenting pretreated fruit waste slurry, strain-BOH3 excreted several saccharolytic enzymes majorly xylanase (1.84U/ml), amylase (1.10U/ml), pectinase (0.36U/ml) and cellulase (0.43U/ml). Due to expressions of these enzymes, strain BOH3 was able to directly utilize pretreated fruit waste hydrolysate and produces high-level of hydrogen.

Keywords: autoclave pretreatment, biohydrogen production, clostridial fermentation, fruit waste, and microwave pretreatment

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Authors: Xinxiu Li, Chuqian Zheng, Yanyan Qian, Hong Fan

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Objectives: In hepatocellular carcinoma (HCC), oncogenes are continuously and robustly transcribed due to aberrant expression of essential components of the trans-acting super-enhancers (SE) complex. Preclinical and clinical trials are now being conducted on small-molecule inhibitors that target core-transcriptional components, including as transcriptional bromodomain protein 4 (BRD4) and cyclin-dependent kinase 7 (CDK7), in a number of malignant tumors. This study aims to explore whether co-overexpression of BRD4 and CDK7 is a potential marker of worse prognosis and a combined therapeutic target in HCC. Methods: The expression pattern of BRD4 and CDK7 and their correlation with prognosis in HCC were analyzed by RNA sequencing data and survival data of HCC patients from TCGA and GEO datasets. The protein levels of BRD4 and CDK7 were determined by immunohistochemistry (IHC), and survival data of patients were analyzed using the Kaplan-Meier method. The mRNA expression levels of genes in HCC cell lines were evaluated by quantitative PCR (q-PCR). CCK-8 and colony formation assays were conducted to assess cell proliferation of HCC upon treatment with BRD4 inhibitor JQ1 or/and CDK7 inhibitor THZ1. Results: It was shown that BRD4 and CDK7 were often overexpressed in HCCs and were associated with poor prognosis of HCC by analyzing the TCGA and GEO datasets. BRD4 or CDK7 overexpression was related to a lower survival rate. It's interesting to note that co-overexpression of CDK7 and BRD4 was a worse prognostic factor in HCC. Treatment with JQ1 or THZ1 alone had an inhibitory effect on cell proliferation; however, when JQ1 and THZ1 were combined, there was a more notable suppression of cell growth. At the same time, the combined use of JQ1 and THZ1 synergistically suppresses the expression of HCC driver genes. Conclusion: Our research revealed that BRD4 and CDK7 coupled can be a useful biomarker in HCC prognosis and the combination of JQ1 and THZ1 can be a promising therapeutic therapy against HCC.

Keywords: BRD4, CDK7, cell proliferation, combined inhibition

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Authors: Ibrahim Mohammed

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Background: Diabetes mellitus is a chronic disease that can cause devastating secondary complications, reducing the quality and length of life as well as increasing medical costs for the patient and society. The guidelines recommend both clinical and preventive strategies for diabetes management and are regularly updated. The aim of the study is to assess the level of adherence of physicians to American Diabetes Association Guidelines. Method: Observational multicenter retrospective study will be conducted among different hospitals in the central region. Patient data will be collected from the records of the last three years (2017- 2020). Records will be selected randomly after a complete randomized design. The study focuses on the management of type 2 according to ADA not changed in the last three updating; those standards; all patients should be taking Metformin 1500 to 2000 mg/day as recommended dose and should be received a high dose of statin if the high risk to ASCVD or moderate statin if not at risk, patients with hypertension and diabetes should taking ACE or ARBS. Result: The study aimed to evaluate the commitment of physicians in the central region to the ADA. Out of the 153 selected patients, only 17 % were able to control their diabetes with an average A1c below 7. ADA stated that to reach the minimum benefit of using Metformin, the daily dose should be between 1500 and 2000 mg. Results showed that 110 patients were on Metformin, where 68% of them were on the recommended dose. ADA recommended the intake of high statin for diabetic patients with ASCVD risk, while diabetic patients without ASCVD risk should be on a moderate statin. Results showed that 61.5% of patients with ASCVD risk were at high statin while only 36% of patients without ASCVD risk were at moderate statin. Results showed that 89 patients have hypertension, and 80% of them are getting ACE/ARBs as recommended by the ADA. Recommendation: It is necessary to implement periodic training courses for some physicians to enhance and update their knowledge.

Keywords: American Diabetic Association, diabetes mellitus, atherosclerotic cardiovascular disease, ACE inhibitors

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Authors: Sani Ismaila, Shafiu Yau, Abubakar Salisu, Buhari Salisu, Sharifat Balogun, Mustapha Abubakar, Biobaku Khalid, Agaie Bello

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Over the years, Japanese quail egg has been in use in the management of diseases. The objective of this study was to evaluate the analgesic, anti-inflammatory and gastroprotective effects of raw Quail egg (yolk + albumin) in rats. Pain was assessed in rats by recording the latent period and writing reflex, anti-inflammatory effect was determined using both motility and compression test, while the gastro-protective effects were assessed by observing the histology of the stomach after diclofenac-induced gastric ulcers and subsequent treatment with the quail egg, Rats were randomly assigned into 4 groups; Groups I: were the control non-treated (NT), Group II were treated with Tramadol 50 mg/kg/Os (TMD) or Indomethacin (IND) 5mg/kg/Os (positive control for the writhing reflex determination), while group III and IV were treated with 3 and 6g/kg of raw quail egg respectively). Groups treated with quail egg in both doses showed a significant increase in the latent period (p <0 .05) when compared to the control NT, but lower than the group treated with tramadol at 20mins interval (p<0.05). Writing reflexes decrease in groups II, III, and IV compared to the NT group (p < 0.05). While motility increases significantly (p < 0.05) in groups II, compared to I (p<0.05). Control non-treated rats showed a quicker and extensive response to compression using the Vanier calliper on the inflamed paw compared to groups II-IV (p < 0.05). Histological studies of the stomach revealed sloughing of the epithelia, cellular infiltration with micro abscesses in the non-treated, while groups treated concurrently with quail egg showed proliferation of the glandular epithelia and goblet cells, and those treated 30 minutes before diclofenac administration showed proliferation of glands and thickening of the squamous epithelia. This study showed that quail egg has analgesic, anti-inflammatory and gastro-protective potentials and can be used as adjuvant treatment whenever COX-2 enzymes inhibitors are indicated.

Keywords: analgesia, anti-inflammatory, gastroprotective effect, japanese quail egg

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Authors: Jin Hwa Yang, Hwang Bae, Sung Uk Ryu, Byong Guk Jeon, Sung Jae Yi, Hyun Sik Park

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Experimental studies using a large-scale thermal-hydraulic integral test facility, System–integrated Modular Advanced Reactor Integral Test Loop (SMART-ITL), have been carried out to validate the performance of the prototype, SMART. After Fukushima accident, the passive safety systems have been dealt as important designs for retaining of nuclear safety. One of the concerned scenarios for evaluating the passive safety system is a Complete Loss of Coolant Flow (CLOF). The flowrate of coolant in the primary system is maintained by Reactor Coolant Pump (RCP). When the supply of electric power of RCP is shut off, the flowrate of coolant decreases sharply, and the temperature of the coolant increases rapidly. Therefore, the reactor trip signal is activated to prevent the over-heating of the core. In this situation, Passive Residual Heat Removal System (PRHRS) plays a significant role to assure the soundness of the SMART. The PRHRS using a two-phase natural circulation is a passive safety system in the SMART to eliminate the heat of steam generator in the secondary system with heat exchanger submarined in the Emergency Cooling Tank (ECT). As the RCPs continue to coast down, inherent natural circulation in the primary system transfers heat to the secondary system. The transferred heat is removed by PRHRS in the secondary system. In this paper, the progress of the CLOF accident is described with experimental data of transient condition performed by SMART-ITL. Finally, the capability of passive safety system and inherent natural circulation will be evaluated.

Keywords: CLOF, natural circulation, PRHRS, SMART-ITL

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Authors: A. Aljohani, D. Burke, D. Clarke, M. Gormally, M. Byrne, G. Fleming

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Introduction: House Dust Mites (HDMs) are a source of allergen particles embedded in textiles and furnishings. Vacuum sampling is commonly used to recover and determine the abundance of HDMs but the efficiency of this method is less than standardized. Here, the efficiency of recovery of HDMs was evaluated from home-associated textiles using vacuum sampling protocols.Methods/Approach: Living Mites (LMs) or dead Mites (DMs) House Dust Mites (Dermatophagoides pteronyssinus: FERA, UK) were separately seeded onto the surfaces of Smooth Cotton, Denim and Fleece (25 mites/10x10cm2 squares) and left for 10 minutes before vacuuming. Fabrics were vacuumed (SKC Flite 2 pump) at a flow rate of 14 L/min for 60, 90 or 120 seconds and the number of mites retained by the filter (0.4μm x 37mm) unit was determined. Vacuuming was carried out in a linear direction (Protocol 1) or in a multidirectional pattern (Protocol 2). Additional fabrics with LMs were also frozen and then thawed, thereby euthanizing live mites (now termed EMs). Results/Findings: While there was significantly greater (p=0.000) recovery of mites (76% greater) in fabrics seeded with DMs than LMs irrespective of vacuuming protocol or fabric type, the efficiency of recovery of DMs (72%-76%) did not vary significantly between fabrics. For fabrics containing EMs, recovery was greatest for Smooth Cotton and Denim (65-73% recovered) and least for Fleece (15% recovered). There was no significant difference (p=0.99) between the recovery of mites across all three mite categories from Smooth Cotton and Denim but significantly fewer (p=0.000) mites were recovered from Fleece. Scanning Electron Microscopy images of HMD-seeded fabrics showed that live mites burrowed deeply into the Fleece weave which reduced their efficiency of recovery by vacuuming. Research Implications: Results presented here have implications for the recovery of HDMs by vacuuming and the choice of fabric to ameliorate HDM-dust sensitization.

Keywords: allergy, asthma, dead, fabric, fleece, live mites, sampling

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Authors: Abdolamir Allameh, Seyyed Mortaza Haghgoo, Adnan Khosravi, Esmaeil Mortaz, Mihan Pourabdollah-Toutkaboni, Sharareh Seifi

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Non-Small Cell Lung Carcinoma (NSCLC) is associated with a number of gene mutations in epidermal growth factor receptor (EGFR). The prognostic significance of mutations in exons 19 and 21, together with serum levels of EGFR, amphiregulin (AR), and Transforming Growth Factor-alpha (TGF-α) are implicated in diagnosis and treatment. The aim of this study was to examine the relationship of EGFR mutations in selected exons with the expression of relevant ligands in sera samples of NSCLC patients. For this, a group of NSCLC patients (n=98) referred to the hospital for lung surgery with a mean age of 59±10.5 were enrolled (M/F: 75/23). Blood specimen was collected from each patient. Besides, formalin fixed paraffin embedded tissues were processed for DNA extraction. Gene mutations in exons 19 and 21 were detected by direct sequencing, following DNA amplification which was done by PCR (Polymerase Chain Reaction). Also, serum levels of EGFR, AR, and TGF-α were measured by ELISA. The results of our study show that EGFR mutations were present in 37% of Iranian NSCLC patients. The most frequently identified mutations were deletions in exon 19 (72.2%) and substitutions in exon 21 (27.8%). The most frequently identified alteration, which is considered as a rare mutation, was the E872K mutation in exon 21, which was found in 90% (9 out of 10) cases. EGFR mutation detected in exon 21 was significantly (P<0.05) correlated with the levels of its ligands, EGFR and TGF-α in serum samples. Furthermore, it was found that increased serum AR (>3pg/ml) and TGF-α (>10.5 pg/ml) were associated with shorter overall survival (P<0.05). The results clearly showed a close relationship between EGFR mutations and serum EGFR and serum TGF-α. Increased serum EGFR was associated with TGF-α and AR and linked to poor prognosis of NSCLC. These findings are implicated in clinical decision-making related to EGFR-Tyrosine kinase inhibitors (TKIs).

Keywords: lung cancer, Iranian patients, epidermal growth factor, mutation, prognosis

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Authors: Lahaina U. Dilangalen

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Using descriptive-experimental research methods, this study aimed to identify the main resources of water, assessed the water quality, sanitation and hygiene practices, and extent of implementation. Complete enumeration was done in 28 elementary public schools of Datu Odin Sinsuat Municipality. Questionnaires were given to the school advisers. Water samples were obtained from the same schools and were submitted to the Department of Science and Technology (DOST) Region XII for microbial analysis, specifically the presence of fecal coliform bacteria. Four water resources such as hand pump, faucet, deep well and spring were found being used in the 28 schools. Of water resources, the only treated was from the faucet. Most of the schools used the water for drinking and washing. Two schools strongly agreed, nine schools agreed and seventeen schools disagreed that they implemented DepEd Order no.56 s. 2009. In addition, two schools strongly agreed and twenty six agreed that they implemented DepEd Order No. 65 s. 2009. Five schools had water supply that were safe to drink while sixteen schools had water supply that were not safe to drink due to high fecal coliform count and did not undergo chemical treatment. The only safe for drinking were water resources that came from faucet because they were chemically treated. Seven out of 28 schools did not have water supply due to their location in mountainous areas. More than half of the schools did not comply with the DepEd Order No. 56 s. 2009 due to the lack of funds and support from the PTA and LGU. It is recommended that the Department of Education must have an urgent assessment of implementing both DepEd Orders No.56 and 65, to assure that the schoolchildren be protected from water and sanitation related ailments. Also, all water resources that are not treated must be used for washing only. Ideally, all the water resources must be treated to assure the safety of all school constituents. Moreover, the school administrators and teachers in the municipality must be provided copies of the results of this study for reference in implementing the said programs.

Keywords: assessment, drinking water, fecal coliform, groundwater

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Authors: Rebecca J. Hafner, Daniel Read, David Elmes

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The current research applies decision making theory in order to address the problem of increasing uptake of energy-efficient technologies in the market place, where uptake is currently slower than one might predict following rational choice models. Specifically, in two studies we apply the alignable/non-alignable features effect and explore the impact of varying information structure on the consumers’ preference for standard versus energy efficient technologies. As researchers in the Interdisciplinary centre for Storage, Transformation and Upgrading of Thermal Energy (i-STUTE) are currently developing energy efficient heating systems for homes and businesses, we focus on the context of home heating choice, and compare preference for a standard condensing boiler versus an energy efficient heat pump, according to experimental manipulations in the structure of prior information. In Study 1, we find that people prefer stronger alignable features when options are similar; an effect which is mediated by an increased tendency to infer missing information is the same. Yet, in contrast to previous research, we find no effects of alignability on option preference when options differ. The advanced methodological approach used here, which is the first study of its kind to randomly allocate features as either alignable or non-alignable, highlights potential design effects in previous work. Study 2 is designed to explore the interaction between alignability and construal level as an explanation for the shift in attentional focus when options differ. Theoretical and applied implications for promoting energy efficient technologies are discussed.

Keywords: energy-efficient technologies, decision-making, alignability effects, construal level theory, CO2 reduction

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Authors: Shanmugasundaram Selvadurai, Amal Chandran

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Small satellites have become an alternative low-cost solution for several missions to accomplish specific missions such as Earth imaging, Technology demonstration, Education, and other commercial purposes. Small satellite missions focusing on Infrared imaging applications require lower temperature for scientific instruments and such low temperature can be achieved only using external cryocoolers but the disadvantage is that they generate a large amount of waste heat. Existing passive thermal control techniques are not capable to handle such large thermal loads and hence one of the traditional active Thermal Control System (TCS) is studied for a small satellite configuration. This work aims to downscale the existing Mechanically Pumped Fluid Loop (MPFL) TCS to a 27U CubeSat platform for an imaginary scientific instrument. The temperature-sensitive detector in the instrument considered to be maintained between 130K and 150K to reduce dark current noise and increase the data quality. A Single-Phase fluid based MPFL is chosen for this system-level study and this TCS consists of a microfluid pump, a micro-cryocooler, a fluid accumulator, external heaters, flow regulators, and sensors. This work also explains the thermal control system architecture with a conceptual design, arrangement of all the components, and thermal analysis for different low orbit conditions. Sizing and extensive trade studies for the components are conducted and the results have shown that the Single-phase MPFL system is able to handle the given thermal loads and maintain the satellite’s interface temperature within the desired limit.

Keywords: active thermal control system, satellite thermal, mechanically pumped fluid loop system, cryogenics, cryocooler

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Authors: L. Meksem Amara, M. Ferfar, N. Meksem, M. R. Djebar

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The wheat is the cereal the most consumed in the world. In Algeria, the production of this cereal covers only 20 in 25 % of the needs for the country, the rest being imported. To improve the efficiency and the productivity of the durum wheat, the farmers turn to the use of pesticides: weed-killers, fungicides and insecticides. However this use often entrains losses of products more at least important contaminating the environment and all the food chain. Weed-killers are substances developed to control or destroy plants considered unwanted. That they are natural or produced by the human being (molecule of synthesis), the absorption and the metabolization of weed-killers by plants cause the death of these plants. In this work, we set as goal the evaluation of the effect of a weed-killer sulfonylurea, the CossackOD with various concentrations (0, 2, 4 and 9 µg) on variety of Triticum durum: Cirta. We evaluated the plant growth by measuring the leaves and root length, compared with the witness as well as the content of proline and analyze the level of one of the antioxydative enzymes: catalase, after 14 days of treatment. Sulfonylurea is foliar and root weed-killers inhibiting the acetolactate synthase: a vegetable enzyme essential to the development of the plant. This inhibition causes the ruling of the growth then the death. The obtained results show a diminution of the average length of leaves and roots this can be explained by the fact that the ALS inhibitors are more active in the young and increasing regions of the plant, what inhibits the cellular division and talks a limitation of the foliar and root’s growth. We also recorded a highly significant increase in the proline levels and a stimulation of the catalase activity. As a response to increasing the herbicide concentrations a particular increases in antioxidative mechanisms in wheat cultivar Cirta suggest that the high sensitivity of Cirta to this sulfonylurea herbicide is related to the enhanced production and oxidative damage of reactive oxygen species.

Keywords: sulfonylurea, triticum durum, oxydative stress, toxicity

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Authors: Aly Kassem, Eman Sapet, Eman Abdelbaset, Hosam Mahmoud

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Objective: Hypertension is an important public health challenge being one of the most common worldwide disease-affecting human. Our aim is to study the clinical characteristics, therapeutic regimens, treatment compliance, and risk factors in a sector of of hypertensive patients at Sohag City. Subject and Methods: A cross sectional study; conducted in Sohag city; it involved 520 patients; males (45.7 %) and females (54.3 %). Their ages ranged between 35-85 years. BP measurements, BMI, blood glucose, Serum creatinine, urine analysis, serum Lipids, blood picture and ECG were done all the studied patients. Results: Hypertension presented more between non-smokers (72.55%), females (54.3%), educated patients (50.99%) and patients with low SES (54.9%). CAD presented in (51.63%) of patients, while laboratory investigations showed hyperglycaemia in (28.7%), anemia in (18.3%), high serum creatinine level in (8.49%) and proteinuria in (10.45%) of patient. Adequate BP control was achieved in (49.67%); older patients had lower adequacy of BP control in spite of the extensive use of multiple-drug therapy. Most hypertensive patients had more than one coexistent CV risk factor. Aging, being a female (54.3%), DM (32.3%), family history of hypertension (28.7%), family history of CAD (25.4%), and obesity (10%) were the common contributing risk factors. ACE-inhibitors were prescribed in (58.16%), Beta-blockers in (34.64%) of the patients. Monotherapy was prescribed for (41.17%) of the patients. (75.81%) of patients had regular use of their drug regimens. (49.67%) only of patients had their condition under control, the number of drugs was inversely related to BP control. Conclusion: Hypertensive patients in Sohag city had a profile of high CV risks, and poor blood pressure control particularly in the elderly. A multidisciplinary approach for routine clinical check-up, follow-up, physicians and patients training, prescribing simple once-daily regimens and encouraging life style modifications are recommended. Anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance.

Keywords: anti hypertensives, hypertension, elderly patients, risk factors, treatment compliance

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Authors: Abdullah Alnutayfat, Alexander Sutin

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One of the most important types of renewable energy resources is wind energy which can be produced by wind turbines. The blades of the wind turbine are exposed to the pressure of the harsh environment, which causes a significant issue for the wind power industry in terms of the maintenance cost and failure of blades. One of the reliable methods for blade inspection is the vibroacoustic structural health monitoring (SHM) method which examines information obtained from the structural vibrations of the blade. However, all vibroacoustic SHM techniques are based on comparing the structural vibration of intact and damaged structures, which places a practical limit on their use. Methods for nonlinear vibroacoustic SHM are more sensitive to damage and cracking and do not need to be compared to data from the intact structure. This paper presents the Vibro-Acoustic Modulation (VAM) method based on the modulation of high-frequency (probe wave) by low-frequency loads (pump wave) produced by the blade rotation. The blade rotation alternates bending stress due to gravity, leading to crack size variations and variations in the blade resonance frequency. This method can be used with the classical SHM vibration method in which the blade is excited by piezoceramic actuator patches bonded to the blade and receives the vibration response from another piezoceramic sensor. The VAM modification of this method analyzes the spectra of the detected signal and their sideband components. We suggest the VAM model as the simple mechanical oscillator, where the parameters of the oscillator (resonance frequency and damping) are varied due to low-frequency blade rotation. This model uses the blade vibration parameters and crack influence on the blade resonance properties from previous research papers to predict the modulation index (MI).

Keywords: wind turbine blades, damaged detection, vibro-acoustic structural health monitoring, vibro-acoustic modulation

Procedia PDF Downloads 78

Authors: Oleg Sapelnikov, Ruslan Latypov, Darina Ardus, Samvel Aivazian, Andrey Shiryaev, Renat Akchurin

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OBJECTIVE: MAZE procedure is one of the most effective surgical methods in atrial fibrillation (AF) treatment. Nowadays we are all aware of its modifications. In our study we conducted clinical analysis of “Box lesion+” approach during MAZE procedure in two-year follow-up. METHODS: We studied the results of the open-heart on-pump procedures performed in our hospital from 2017 to 2018 years. Thirty-two (32) patients with atrial fibrillation (AF) were included in this study. Fifteen (15) patients had concomitant coronary bypass grafting and seventeen (17) patients had mitral valve repair. Mean age was 62.3±8.7 years; prevalence of men was admitted (56.1%). Mean duration of AF was 4.75±5.44 and 7.07±8.14 years. In all cases, we performed endocardial Cryo-MAZE procedure with one-time myocardium revascularization or mitral-valve surgery. All patients of this study underwent pulmonary vein (PV) isolation and ablation of mitral isthmus with additional isolation of LA posterior wall (Box-lesion+ procedure). Mean follow-up was 2 years. RESULTS: All cases were performed without any complications. Additional isolation of posterior wall did not prolong the operative time and artificial circulation significantly. Cryo-MAZE procedure directly lasted 20±2.1 min, the whole operation time was 192±24 min and artificial circulation time was 103±12 min. According to design of the study, we performed clinical investigation of the patients in 12 months and in 2 years from the initial procedure. In 12 months, the number of AF free patients 81.8% and 75.8% in two years of follow-up. CONCLUSIONS: Isolation of the left atrial posterior wall and perimitral area may considerably improve the efficacy of surgical treatment, which was demonstrated in significant decrease of AF recurrences during the whole period of follow-up.

Keywords: atrial fibrillation, cryoablation, left atrium isolation, open heart procedure

Procedia PDF Downloads 123

Authors: Zahra R. Almansoor

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Background: Selective serotonin reuptake inhibitors (SSRI’s) and cognitive behavioural therapy (CBT) are the main treatment methods used for patients with obsessive compulsive disorder (OCD) under the National Institute of Health and Care Excellence (NICE) guidelines. Yet many patients are left with residual symptoms or remit, so several other therapeutic approaches have been explored. Objective: The objective was to systematically review the available literature regarding the treatment efficacy of current and potential approaches and diagnostic strategies. Method: First, studies were examined concerning diagnosis, prognosis, and influencing factors. Then, one reviewer conducted a systematic search of six databases using stringent search terms. Results of studies exploring the efficacy of treatment interventions were analysed and compared separately for adults and children. This review was limited to randomised controlled trials (RCT’s) conducted from 2016 onwards, and an improved Y-BOCS (Yale- Brown obsessive compulsive scale) score was the primary outcome measure. Results: Technology-based interventions including internet-based cognitive behavioural therapy (iCBT) were deemed as potentially effective. Discrepancy remains about the benefits of SSRI use past one year, but potential medication adjuncts include amantadine. Treatments such as association splitting and family and mindfulness strategies also have future potential. Conclusion: A range of potential therapies exist, either as treatment adjuncts to current interventions or as sole therapies. To further improve efficacy, it may be necessary to remodel the current NICE stepped-care model, especially regarding the potential use of lower intensity, cheaper treatments, including iCBT. Although many interventions show promise, further research is warranted to confirm this.

Keywords: family and group treatment, mindfulness strategies, novel treatment approaches, standard treatment, technology-based interventions

Procedia PDF Downloads 117

Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Galih Imaduddin

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Knowledge has been viewed as one of the most important resources in organizations, including those that operate in the healthcare sector. On that basis, Knowledge Management (KM) is crucial for healthcare organizations to improve their productivity and ensure effective utilization of their resources. Despite the growing interests to understand how KM might work for healthcare organizations, there is only a modest amount of empirical inquiries which have specifically focused on the tools and initiatives to share knowledge. Hence, the main purpose of this paper is to investigate the way healthcare organizations, particularly public sector ones, utilize knowledge sharing tools and initiatives for the benefit of patient-care. Employing a qualitative method, 13 (thirteen) Community Health Centers (CHCs) from a high-performing district health setting in Indonesia were observed. Data collection and analysis involved a repetition of document retrievals and interviews (n=41) with multidisciplinary health professionals who work in these CHCs. A single case study was cultivated reflecting on the means that were used to share knowledge, along with the factors that inhibited the exchange of knowledge among those health professionals. The study discovers that all of the thirteen CHCs exhibited and applied knowledge sharing means which included knowledge documents, virtual communication channels (i.e. emails and chatting applications), and social learning forums such as staff meetings, morning briefings, and communities of practices. However, the intensity of utilization was different among these CHCs, in which organizational culture, leadership, professional boundaries, and employees’ technological aptitude were presumed to be the factors that inhibit knowledge sharing processes. Making a distance with the KM literature of other sectors, this study denounces the primacy of technology-based tools, suggesting that socially-based initiatives could be more reliable for sharing knowledge. This suggestion is largely due to the nature of healthcare work which is still predominantly based on the tacit form of knowledge.

Keywords: knowledge management, knowledge sharing, knowledge sharing tools and initiatives, knowledge sharing inhibitors, primary health care organizations

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Authors: Abhishek Pandey

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Ibuprofen and Acetaminophen is widely used as prescription & non-prescription medicine. Ibuprofen mainly used in the treatment of mild to moderate pain related to headache, migraine, postoperative condition and in the management of spondylitis, osteoarthritis and rheumatoid arthritis. Acetaminophen is used as an analgesic and antipyretic drug. Ibuprofen having high tendency of sticking to punches of tablet punching machine while Acetaminophen is not ordinarily compressible to tablet formulation because Acetaminophen crystals are very hard and brittle in nature and fracture very easily when compressed producing capping and laminating tablet defects therefore wet granulation method is used to make them compressible. The aim of study was to prepare Ibuprofen and Acetaminophen tablets by direct compression and top spray granulation technique. In this Investigation tablets were prepared by using directly compressible grade excipients. Dibasic calcium phosphate, lactose anhydrous (DCL21), microcrystalline cellulose (Avicel PH 101). In order to obtain best or optimized formulation, nine different formulations were generated among them batch F7, F8, F9 shows good results and within the acceptable limit. Formulation (F7) selected as optimize product on the basis of dissolution study. Furtherly, directly compressible granules of both drugs were prepared by using top spray granulation technique in fluidized bed processor equipment and compressed .In order to obtain best product process optimization was carried out by performing four trials in which various parameters like inlet air temperature, spray rate, peristaltic pump rpm, % LOD, properties of granules, blending time and hardness were optimized. Batch T3 coined as optimized batch on the basis physical & chemical evaluation. Finally formulations prepared by both techniques were compared.

Keywords: direct compression, top spray granulation, process optimization, blending time

Procedia PDF Downloads 355