Search results for: autologous blood injection
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3241

Search results for: autologous blood injection

1441 Effect of Ginger (Zingiber Officinal) Root Extract on Blood Glucose Level and Lipid Profile in Normal and Alloxan-Diabetic Rabbits

Authors: Khalil Abdullah Ahmed Khalil, Elsadig Mohamed Ahmed

Abstract:

Ginger is one of the most important medicinal plants, which is widely used in folk medicine. This study was designed to go further step and evaluate the hypoglycemic and hypolipidaemic effects of the aqueous ginger root extract in normal and alloxan diabetic rabbits. Results revealed that the aqueous ginger has a significant hypoglycemic effect (P<0.05) in diabetic rabbits but a non-significant hypoglycemic effect (P>0.05) in normal rabbits. There were also significant decreases in the concentrations (P<0.05) in serum cholesterol, triglycerides and LDL – cholesterol in both normal and diabetic rabbits. Although there was an elevation in serum HDL- cholesterol in both normal and diabetic rabbits, these elevations were non-significant (P>0.05). Our data suggest the aqueous ginger has a hypoglycemic effect in diabetic rabbits and lipid-lowering properties in both normal and diabetic rabbits.

Keywords: aqueous extract of ginger root (AEGR), hypoglycemic, cholesterol, triglyceride

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1440 Effects of Purslane Shoot and Seed Ethanolic Extracts on Doxorubicin-Induced Testicular Toxicity in Albino Rats

Authors: Walaa G. Hozayen, Osama M. Ahmed, Haidy T. Abo Sree

Abstract:

The clinical usefulness of anthracycline antineoplastic antibiotic, doxorubicin (DOX) is restricted since it has several acute and chronic side effects. The effect of doxorubicin (4 mg/kg b.w/week) without or with oral administration of purslane (Portulaca oleracea) shoot ethanolic extract (50mg/kg b.w./day) and purslane seed ethanolic extract (50mg/kg b.w./day) co-treatments for 6 weeks was evaluated in adult male rats. Serum testosterone luteinizing hormone (LH), follicle stimulating hormone (FSH) level were assayed. Testis lipid peroxidation (indexed by MDA) and antioxidants like glutathione (GSH), glutathione-S-transferase (GST), peroxidase (POX), superoxide dismutase (SOD), catalase (CAT) levels in testis were assessed. The data revealed a significant decrease in serum levels concentration of testosterone, LH and FSH levels in doxorubicin-injected rats. In addition, testis glutathione, glutathione transferase, peroxidase, SOD and CAT levels were decreased while lipid peroxidation concentration in the testis was increased as a result of doxorubicin injection. Co-administration of ethanolic purslane and seed extracts potentially improved the adverse changes in serum testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH) levels with an increase in testis antioxidants levels and reduction in lipid peroxidation. In conclusion, it can be suggested that dietary purslane extract supplementation may provide a cushion for a prolonged therapeutic option against DOX testicular toxicity without harmful side effects.

Keywords: doxorubicin, purslane, testis function, antioxidants

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1439 Antioxidant Activity of Germinated African Yam Bean (Sphenostylis Stenocarpa) in Alloxan Diabetic Rats

Authors: N. Uchegbu Nneka

Abstract:

This study was conducted to investigate the effect of the antioxidant activity of germinated African Yam Bean (AYB) on oxidative stress markers in alloxan-induced diabetic rat. Rats were randomized into three groups; control, diabetic and germinated AYB–treated diabetic rats. The Total phenol and flavonoid content and DPPH radical scavenging activity before and after germination were investigated. The glucose level, lipid peroxidation and reduced glutathione of the animals were also determined using the standard technique for four weeks. Germination increased the total phenol, flavonoid and antioxidant activity of AYB extract by 19.14%, 32.28%, and 57.25% respectively. The diabetic rats placed on germinated AYB diet had a significant decrease in the blood glucose and lipid peroxidation with a corresponding increase in glutathione (p<0.05). These results demonstrate that consumption of germinated AYB can be a good dietary supplement in inhibiting hyperglycemia/hyperlipidemia and the prevention of diabetic complication associated with oxidative stress.

Keywords: African yam bean, antioxidant, diabetes, total phenol

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1438 The Pomade for Treatment of Bovine Papilomavirus-Induced Warts in Teats

Authors: Mehmet Kale, Ramazan Sencan, Sibel Yavru, Ahmet Ak, Nuri Mamak, Sibel Hasırcıoglu, Mesih Kocamuftuoglu, Yakup Yıldırım, Hasbi Sait Saltık

Abstract:

Bovine Papilloma Virus (BPV)-induced warts can cause mastitis, teat blindness, reduction of milk yield, udder deformities, and a difficulty in getting the teats into the milking machine. Especially, surgical operations cannot be performed in BPV-induced teat warts because of the increased sensitivity of the breast region and small-sized papillomas. Thus, there is a need to find new topical treatment methods. We have developed a pomade for treatment of BPV in cattle. The pomade is consists of lanoline, snakeskin (two special kind of snake), alcohol, vaseline, and ether. Firstly, we determined 46 cattle with teat warts. In the study, BPV antigen was detected in 28 cattle blood samples (61%) by ELISA. The pomade was applied to all BPV infected animals. The regression and recovery of warts were 100% in all animals. We advised using the pomade for treatment of BPV-induced warts in teats.

Keywords: bovine papilloma virus, pomade, teat, udder

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1437 The Prevalence of X-Chromosome Aneuploidy in Recurrent Pregnancy Loss

Authors: Rim Frikha, Nouha Bouayed, Afifa Sellami, Nozha Chakroun, Salima Douad, Leila Keskes, Tarek Rebai

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Recurrent pregnancy loss (RPL), classically defined as the occurrence of two or more failed pregnancies, is a serious reproductive problem, in which, chromosomal rearrangements in either carrier are a major cause; mainly the chromosome aneuploidy. This study was conducted to determine the frequency and contribution of X-chromosome aneuploidy in recurrent pregnancy loss. A retrospective study was carried out among 100 couples with more than 2 miscarriages, referred to our genetic counseling. In all the cases the detailed reproductive histories were taken. Chromosomal analysis was performed using RHG banding in peripheral blood. Of a total of 100 couples; 3 patients with a detected X-chromosome aneuploidy were identified with an overall frequency of 3%. Chromosome abnormalities are as below: a Turner syndrome with 45, X/46, XX mosaicism, a 47, XXX, and a Klinefelter syndrome with 46, XY/47, XXY. These data show a high incidence of X-chromosome aneuploidy; mainly with mosaicism; in RPL. Thus, couples with such chromosomal abnormality should be referred to a clinical geneticist with whom the option of pre-implantation genetic diagnosis in subsequent pregnancy should be discussed.

Keywords: aneuploidy, genetic testing, recurrent pregnancy loss, X-chromosome

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1436 Estimation of Chronic Kidney Disease Using Artificial Neural Network

Authors: Ilker Ali Ozkan

Abstract:

In this study, an artificial neural network model has been developed to estimate chronic kidney failure which is a common disease. The patients’ age, their blood and biochemical values, and 24 input data which consists of various chronic diseases are used for the estimation process. The input data have been subjected to preprocessing because they contain both missing values and nominal values. 147 patient data which was obtained from the preprocessing have been divided into as 70% training and 30% testing data. As a result of the study, artificial neural network model with 25 neurons in the hidden layer has been found as the model with the lowest error value. Chronic kidney failure disease has been able to be estimated accurately at the rate of 99.3% using this artificial neural network model. The developed artificial neural network has been found successful for the estimation of chronic kidney failure disease using clinical data.

Keywords: estimation, artificial neural network, chronic kidney failure disease, disease diagnosis

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1435 Management of Hypoglycemia in Von Gierke’s Disease

Authors: Makda Aamir, Sood Aayushi, Syed Omar, Nihan Khuld, Iskander Peter, Ijaz Naeem, Sharma Nishant

Abstract:

Introduction:Glycogen Storage Disease Type-1 (GSD-1) is a rare phenomenon primarily affecting the liver and kidney. Excessive accumulation of glycogen and fat in liver, kidney, and intestinal mucosa is noted in patients with deficiency of Glucose-6-phosphatase deficiency. Patients with GSD-1 have a wide spectrum of symptoms, including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Age of onset, rate of disease progression and its severity is variable in this disease.Case:An 18-year-old male with GSD-1a, Von Gierke’s disease, hyperuricemia, and hypertension presented to the hospital with nausea and vomiting. The patient followed an hourly cornstarch regimen during the day and overnight through infusion via a PEG tube. The complaints started at work, where he was unable to tolerate oral cornstarch. He washemodynamically stable on arrival. ABG showed pH 7.372, PaCO2 30.3, and PaO2 92.2. WBC 16.80, K+ 5.8, HCO3 13, BUN 28, Cr 2.2, Glucose 60, AST 115, ALT 128, Cholesterol 352, Triglycerides >1000, Uric Acid 10.6, Lactic Acid 11.8 which trended down to 8.0. CT abdomen showed hepatomegaly and fatty infiltration with the PEG tube in place.He was admitted to the ICU and started on D5NS for hypoglycemia and lactic acidosis. Per request by the patient’s pediatrician, he was transitioned to IV D10/0.45NS at 110mL/Hr to maintain blood glucose above 75 mg/L. Frequent accuchecks were done till he could tolerate his dietary regimen with cornstarch. Lactic acid downtrend to 2.9, and accuchecks ranged between 100-110. Cr improved to 1.3, and his home medications (Allopurinol and Lisinopril) were resumed. He was discharged in stable condition with plans for further genetic therapy work up.Discussion:Mainstay therapy for Von Gierke’s Disease is the prevention of metabolic derangements for which dietary and lifestyle changes are recommended. A low fructose and sucrose diet is recommended by limiting the intake of galactose and lactose to one serving per day. Hypoglycemia treatment in such patients is two-fold, utilizing both quick and stable release sources. Cornstarch has been one such therapy since the 1980s; its slow digestion provides a steady release of glucose over a longer period of time as compared with other sources of carbohydrates. Dosing guidelines vary from age to age and person to person, but it is highly recommended to check BG levels frequently to maintain a BG > 70 mg/dL. Associated high levels of triglycerides and cholesterol can be treated with statins, fibrates, etc. Conclusion:The management of hypoglycemia in GSD 1 disease presents various obstacles which could prove to be fatal. Due to the deficiency of G6P, treatment with a specialized hypoglycemic regimen is warranted. A D10 ½ NS infusion can be used to maintain blood sugar levels as well as correct metabolic or lactate imbalances. Infusion should be gradually weaned off after the patient can tolerate oral feeds as this can help prevent the risk of hypoglycemia and other derangements. Further research is needed in regards to these patients for more sustainable regimens.

Keywords: von gierke, glycogen storage disease, hypoglycemia, genetic disease

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1434 Effect Of Selected Food And Nutrition Environments On Prevalence Of Cardio-Metabolic Risk Factors With Emphasis On Worksite Environment In Urban Delhi

Authors: Deepa Shokeen, Bani Tamber Aeri

Abstract:

Food choice is a complex process influenced by the interplay of multiple factors, including physical, socio-cultural and economic factors comprising macro or micro level food environments. While a clear understanding of the relationship between what we eat and the environmental context in which these food choices are made is still needed; it has however now been shown that food environments do play a significant role in the obesity epidemic and increasing cardio-metabolic risk factors. Evidence in other countries indicates that the food environment may strongly influence the prevalence of obesity and cardio-metabolic risk factors among young adults. Although in the Indian context, data does indicate the associations between sedentary lifestyle, stress, faulty diets but very little evidence supports the role of food environment in influencing cardio-metabolic health among employed adults. Thus, this research is required to establish how different environments affect different individuals as individuals interact with the environment on a number of levels. Methodology: The objective of the present study is to assess the effect of selected food and nutrition environments with emphasis on worksite environment and to analyse its impact on the food choices and dietary behaviour of the employees (25-45 years of age) of the organizations under study. In the proposed study an attempt will be made to randomly select various worksite environments from Delhi and NCR. The study will be conducted in two phases. In phase I, Information will be obtained on their socio-demographic profile and various factors influencing their food choices including most commonly consumed foods and most frequently visited eating outlets in and around the work place. Data will also be gathered on anthropometry (height, weight, waist circumference), biochemical parameters (lipid profile and fasting glucose), blood pressure and dietary intake. Based on the findings of phase I, a list of the most frequently visited eating outlets in and around the workplace will be prepared in Phase II. These outlets will then be subjected to nutrition environment assessment survey (NEMS). On the basis of the information gathered from phase I and phase II, influence of selected food and nutrition environments on food choice, dietary behaviour and prevalence of cardio-metabolic risk factors among employed adults will be assessed. Expected outcomes: The proposed study will try to ascertain the impact of selected food and nutrition environments on food choice and dietary intake of the working adults as it is important to learn how these food environments influence the eating perceptions and health behavior of the adults. In addition to this, anthropometry blood pressure and biochemical assessment of the subjects will be done to assess the prevalence of cardio-metabolic risk factors. If the findings indicate that the work environment, where most of these young adults spend their productive hours of the day, influence their health, than perhaps steps maybe needed to make these environments more conducive to health.

Keywords: food and nutrition environment, cardio-metabolic risk factors, India, worksite environment

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1433 Energy Trends in Rural South Africa: A Case Study of the Mnweni Rural Community in the Province of Kwazulu-Natal

Authors: Noel Chellan

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Energy is the life-blood of development. All human societies have been and still are dependent on energy – some societies more than others. With regard to energy in South Africa, previous policies of the apartheid regime neglected the energy needs of poor black communities in general – and rural communities in particular. Since South Africa’s first democratic elections in 1994 – whilst millions of South African households have received electricity from the national electricity grid, there are still many rural communities that are still experiencing challenges in relation to both electricity deprivation as well as provision. This paper looks at the energy-mix of the Mnweni rural community in South Africa and argues that understanding energy is key to understanding the nature and forms of development of any community or country, for that matter. The paper engages with the energy trends in the rural community of Mnweni from the days of apartheid until 2021. It also looks at agricultural practises from an energy perspective. Such an energy perspective will enable one to assess the pace and scale of development in rural Mnweni.

Keywords: rural, energy, development, apartheid

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1432 Sublethal Effects of Industrial Effluents on Fish Fingerlings (Clarias gariepinus) from Ologe Lagoon Environs, Lagos, Nigeria

Authors: Akintade O. Adeboyejo, Edwin O. Clarke, Oluwatoyin Aderinola

Abstract:

The present study is on the sub-lethal toxicity of industrial effluents (IE) from the environment of Ologe Lagoon, Lagos, Nigeria on the African catfish fingerlings Clarias gariepinus. The fish were cultured in varying concentrations of industrial effluents: 0% (control), 5%, 15%, 25%, and 35%. Trials were carried out in triplicates for twelve (12) weeks. The culture system was a static renewable bioassay and was carried out in the fisheries laboratory of the Lagos State University, Ojo-Lagos. Weekly physico-chemical parameters: Temperature (0C), pH, Conductivity (ppm) and Dissolved Oxygen (DO in mg/l) were measured in each treatment tank. Length (cm) and weight (g) data were obtained weekly and used to calculate various growth parameters: mean weight gain (MWG), percentage weight gain (PWG), daily weight gain (DWG), specific growth rate (SGR) and survival. Haematological (Packed Cell Volume (PCV), Red blood cells (RBC), White Blood Cell (WBC), Neutrophil and Lymphocytes etc) and histological alterations were measured after 12 weeks. The physico-chemical parameters showed that the pH ranged from 7.82±0.25–8.07±0.02. DO range from 1.92±0.66-4.43±1.24 mg/l. The conductivity values increased with increase in concentration of I.E. While the temperature remained stable with mean value range between 26.08±2.14–26.38±2.28. The DO showed significant differences at P<0.05. There was progressive increase in length and weight of fish during the culture period. The fish placed in the control had highest increase in both weight and length while fish in 35% had the least. MWG ranged from 16.59–35.96, DWG is from 0.3–0.48, SGR varied from 1.0–1.86 and survival was 100%. Haematological results showed that C. gariepinus had PCV ranging from 13.0±1.7-27.7±0.6, RBC ranged from 4.7±0.6–9.1±0.1, and Neutrophil ranged from 26.7±4.6–61.0±1.0 amongst others. The highest values of these parameters were obtained in the control and lowest at 35%. While the reverse effects were observed for WBC and lymphocytes. This study has shown that effluents may affect the health status of the test organism and impair vital processes if exposure continues for a long period of time. The histological examination revealed several lesions as expressed by the gills and livers. The histopathology of the gills in the control tanks had normal tissues with no visible lesion, but at higher concentrations, there were: lifting of epithelium, swollen lamellae and gill arch infiltration, necrosis and gill arch destruction. While in the liver: control (0%) show normal liver cells, at higher toxic level, there were: vacoulation, destruction of the hepatic parenchyma, tissue becoming eosinophilic (i.e. tending towards Carcinogenicity) and severe disruption of the hepatic cord architecture. The study has shown that industrial effluents from the study area may affect fish health status and impair vital processes if exposure continues for a long period of time even at lower concentrations (Sublethal).

Keywords: sublethal toxicity, industrial effluents, clarias gariepinus, ologe lagoon

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1431 Enhanced Functional Production of a Crucial Biomolecule Human Serum Albumin in Escherichia coli

Authors: Ashima Sharma

Abstract:

Human Serum Albumin (HSA)- one of the most demanded therapeutic proteins with immense biotechnological applications- is a large multidomain protein containing 17 disulfide bonds. The current source of HSA is human blood plasma which is a limited and unsafe source. Thus, there exists an indispensable need to promote non-animal derived recombinant HSA (rHSA) production. Escherichia coli is one of the most convenient hosts which had contributed to the production of more than 30% of the FDA approved recombinant pharmaceuticals. It grows rapidly and reaches high cell density using inexpensive and simple substrates. E. coli derived recombinant products have more economic potential as fermentation processes are cheaper compared to the other expression hosts. The major bottleneck in exploiting E. coli as a host for a disulfide-rich multidomain protein is the formation of aggregates of overexpressed protein. The majority of the expressed HSA forms inclusion bodies (more than 90% of the total expressed rHSA) in the E. coli cytosol. Recovery of functional rHSA from inclusion bodies is not preferred because it is difficult to obtain a large multidomain disulfide bond rich protein like rHSA in its functional native form. Purification is tedious, time-consuming, laborious and expensive. Because of such limitations, the E. coli host system was neglected for rHSA production for the past few decades despite its numerous advantages. In the present work, we have exploited the capabilities of E. coli as a host for the enhanced functional production of rHSA (~60% of the total expressed rHSA in the soluble fraction). Parameters like intracellular environment, temperature, induction type, duration of induction, cell lysis conditions etc. which play an important role in enhancing the level of production of the desired protein in its native form in vivo have been optimized. We have studied the effect of assistance of different types of exogenously employed chaperone systems on the functional expression of rHSA in the E. coli host system. Different aspects of cell growth parameters during the production of rHSA in presence and absence of molecular chaperones in E. coli have also been studied. Upon overcoming the difficulties to produce functional rHSA in E. coli, it has been possible to produce significant levels of functional protein through engineering the biological system of protein folding in the cell, the E. coli-derived rHSA has been purified to homogeneity. Its detailed physicochemical characterization has been performed by monitoring its conformational properties, secondary and tertiary structure elements, surface properties, ligand binding properties, stability issues etc. These parameters of the recombinant protein have been compared with the naturally occurring protein from the human source. The outcome of the comparison reveals that the recombinant protein resembles exactly the same as the natural one. Hence, we propose that the E. coli-derived rHSA is an ideal biosimilar for human blood plasma-derived serum albumin. Therefore, in the present study, we have introduced and promoted the E. coli- derived rHSA as an alternative to the preparation from a human source, pHSA.

Keywords: recombinant human serum albumin, Escherichia coli, biosimilar, chaperone assisted protein folding

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1430 Application of Laser Spectroscopy for Detection of Actinides and Lanthanides in Solutions

Authors: Igor Izosimov

Abstract:

This work is devoted to applications of the Time-resolved laser-induced luminescence (TRLIF) spectroscopy and time-resolved laser-induced chemiluminescence spectroscopy for detection of lanthanides and actinides. Results of the experiments on Eu, Sm, U, and Pu detection in solutions are presented. The limit of uranyl detection (LOD) in urine in our TRLIF experiments was up to 5 pg/ml. In blood plasma LOD was 0.1 ng/ml and after mineralization was up to 8pg/ml – 10pg/ml. In pure solution, the limit of detection of europium was 0.005ng/ml and samarium, 0.07ng/ml. After addition urine, the limit of detection of europium was 0.015 ng/ml and samarium, 0.2 ng/ml. Pu, Np, and some U compounds do not produce direct luminescence in solutions, but when excited by laser radiation, they can induce chemiluminescence of some chemiluminogen (luminol in our experiments). It is shown that multi-photon scheme of chemiluminescence excitation makes chemiluminescence not only a highly sensitive but also a highly selective tool for the detection of lanthanides/actinides in solutions.

Keywords: actinides/lanthanides detection, laser spectroscopy with time resolution, luminescence/chemiluminescence, solutions

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1429 Phorbol 12-Myristate 13-Acetate (PMA)-Differentiated THP-1 Monocytes as a Validated Microglial-Like Model in Vitro

Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

Abstract:

Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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1428 Effect of Solvents in the Extraction and Stability of Anthocyanin from the Petals of Caesalpinia pulcherrima for Natural Dye-Sensitized Solar Cell

Authors: N. Prabavathy, R. Balasundaraprabhu, S. Shalini, Dhayalan Velauthapillai, S. Prasanna, N. Muthukumarasamy

Abstract:

Dye sensitized solar cell (DSSC) has become a significant research area due to their fundamental and scientific importance in the area of energy conversion. Synthetic dyes as sensitizer in DSSC are efficient and durable but they are costlier, toxic and have the tendency to degrade. Natural sensitizers contain plant pigments such as anthocyanin, carotenoid, flavonoid, and chlorophyll which promote light absorption as well as injection of charges to the conduction band of TiO2 through the sensitizer. But, the efficiency of natural dyes is not up to the mark mainly due to instability of the pigment such as anthocyanin. The stability issues in vitro are mainly due to the effect of solvents on extraction of anthocyanins and their respective pH. Taking this factor into consideration, in the present work, the anthocyanins were extracted from the flower Caesalpinia pulcherrima (C. pulcherrimma) with various solvents and their respective stability and pH values are discussed. The usage of citric acid as solvent to extract anthocyanin has shown good stability than other solvents. It also helps in enhancing the sensitization properties of anthocyanins with Titanium dioxide (TiO2) nanorods. The IPCE spectra show higher photovoltaic performance for dye sensitized TiO2nanorods using citric acid as solvent. The natural DSSC using citric acid as solvent shows a higher efficiency compared to other solvents. Hence citric acid performs to be a safe solvent for natural DSSC in boosting the photovoltaic performance and maintaining the stability of anthocyanins.

Keywords: Caesalpinia pulcherrima, citric acid, dye sensitized solar cells, TiO₂ nanorods

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1427 Screening of Congenital Heart Diseases with Fetal Phonocardiography

Authors: F. Kovács, K. Kádár, G. Hosszú, Á. T. Balogh, T. Zsedrovits, N. Kersner, A. Nagy, Gy. Jeney

Abstract:

The paper presents a novel screening method to indicate congenital heart diseases (CHD), which otherwise could remain undetected because of their low level. Therefore, not belonging to the high-risk population, the pregnancies are not subject to the regular fetal monitoring with ultrasound echocardiography. Based on the fact that CHD is a morphological defect of the heart causing turbulent blood flow, the turbulence appears as a murmur, which can be detected by fetal phonocardiography (fPCG). The proposed method applies measurements on the maternal abdomen and from the recorded sound signal a sophisticated processing determines the fetal heart murmur. The paper describes the problems and the additional advantages of the fPCG method including the possibility of measurements at home and its combination with the prescribed regular cardiotocographic (CTG) monitoring. The proposed screening process implemented on a telemedicine system provides an enhanced safety against hidden cardiac diseases.

Keywords: cardiac murmurs, fetal phonocardiography, screening of CHDs, telemedicine system

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1426 An Efficient Tool for Mitigating Voltage Unbalance with Reactive Power Control of Distributed Grid-Connected Photovoltaic Systems

Authors: Malinwo Estone Ayikpa

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With the rapid increase of grid-connected PV systems over the last decades, genuine challenges have arisen for engineers and professionals of energy field in the planning and operation of existing distribution networks with the integration of new generation sources. However, the conventional distribution network, in its design was not expected to receive other generation outside the main power supply. The tools generally used to analyze the networks become inefficient and cannot take into account all the constraints related to the operation of grid-connected PV systems. Some of these constraints are voltage control difficulty, reverse power flow, and especially voltage unbalance which could be due to the poor distribution of single-phase PV systems in the network. In order to analyze the impact of the connection of small and large number of PV systems to the distribution networks, this paper presents an efficient optimization tool that minimizes voltage unbalance in three-phase distribution networks with active and reactive power injections from the allocation of single-phase and three-phase PV plants. Reactive power can be generated or absorbed using the available capacity and the adjustable power factor of the inverter. Good reduction of voltage unbalance can be achieved by reactive power control of the PV systems. The presented tool is based on the three-phase current injection method and the PV systems are modeled via an equivalent circuit. The primal-dual interior point method is used to obtain the optimal operating points for the systems.

Keywords: Photovoltaic system, Primal-dual interior point method, Three-phase optimal power flow, Voltage unbalance

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1425 Comparative Evaluation of Vanishing Interfacial Tension Approach for Minimum Miscibility Pressure Determination

Authors: Waqar Ahmad Butt, Gholamreza Vakili Nezhaad, Ali Soud Al Bemani, Yahya Al Wahaibi

Abstract:

Minimum miscibility pressure (MMP) plays a great role in determining the displacement efficiency of different gas injection processes. Experimental techniques for MMP determination include industrially recommended slim tube, vanishing interfacial tension (VIT) and rising bubble apparatus (RBA). In this paper, MMP measurement study using slim tube and VIT experimental techniques for two different crude oil samples (M and N) both in live and stock tank oil forms is being presented. VIT measured MMP values for both 'M' and 'N' live crude oils were close to slim tube determined MMP values with 6.4 and 5 % deviation respectively. Whereas for both oil samples in stock tank oil form, VIT measured MMP showed a higher unacceptable deviation from slim tube determined MMP. This higher difference appears to be related to high stabilized crude oil heavier fraction and lack of multiple contacts miscibility. None of the different nine deployed crude oil and CO2 MMP computing correlations could result in reliable MMP, close to slim tube determined MMP. Since VIT determined MMP values for both considered live crude oils are in close match with slim tube determined MMP values, it confirms reliable, reproducible, rapid and cheap alternative for live crude oil MMP determination. Whereas VIT MMP determination for stock tank oil case needed further investigation about stabilization / destabilization mechanism of oil heavier ends and multiple contacts miscibility development issues.

Keywords: minimum miscibility pressure, interfacial tension, multiple contacts miscibility, heavier ends

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1424 Comparison of the Effectiveness between Exosomes from Different Origins in Reversing Skin Aging

Authors: Iannello G., Coppa F., Pennisi S., Giuffrida G., Lo Faro R., Cartelli S., Ferruggia G., Brundo M. V.

Abstract:

Skin is the largest multifunctional human organ and possesses a complex, multilayered structure with the ability to regenerate and renew. The key role in skin regeneration is played by fibroblasts, which also occupy an important role in the wound healing process. Different methods, including dynamic light scattering, scanning electron microscopy, ELISA, and MTT assay, were employed to evaluate on fibroblasts the in vitro effects of plant-derived nanovesicles and cord blood stem cells‐derived exosomes. We compared the results with those of cells exposed to a technology called AMPLEX PLUS, containing a mixture of 20 different biologically active factors (GF20) and exosomes isolated and purified from bovine colostrum. AMPLEX PLUS was able to significantly enhance the cell proliferation status of cells at both 24 and 48 hours compared to untreated cells (control). The obtained results suggest how AMPLEX PLUS could be potentially effective in treating skin rejuvenation.

Keywords: AMPLEX PLUS, cell vitality, colostrum, nanovesicles

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1423 Hepatitis B Vaccination Status and Its Determinants among Primary Health Care Workers in Northwest Pakistan

Authors: Mohammad Tahir Yousafzai, Rubina Qasim

Abstract:

We assessed Hepatitis B vaccination and its determinants among health care workers (HCW) in Northwest Pakistan. HCWs from both public and private clinics were interviewed about hepatitis B vaccination, socio-demographic, hepatitis B virus transmission modes, disease threat and benefits of vaccination. Logistic regression was performed. Hepatitis B vaccination was 40% (Qualified Physicians: 86% and non-qualified Dispensers:16%). Being Qualified Physician (Adj. OR 26.6; 95%CI 9.3-73.2), Non-qualified Physician (Adj.OR 1.9; 95%CI 0.8-4.6), qualified Dispensers (Adj. OR 3.6; 95%CI 1.3-9.5) compared to non-qualified Dispensers, working in public clinics (Adj. OR 2.5; 95%CI 1.1-5.7) compared to private, perceived disease threat after exposure to blood and body fluids (Adj. OR 1.1; 95%CI 1.1-1.2) and perceived benefits of vaccination (Adj. OR 1.1; 95%CI 1.1-1.2) were significant predictors of hepatitis B vaccination. Improved perception of disease threat and benefits of vaccination and qualification of HCWs are associated with hepatitis B vaccination.

Keywords: Hepatitis B vaccine, immunization, healthcare workers, primary health

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1422 Development of Biosensor Chip for Detection of Specific Antibodies to HSV-1

Authors: Zatovska T. V., Nesterova N. V., Baranova G. V., Zagorodnya S. D.

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In recent years, biosensor technologies based on the phenomenon of surface plasmon resonance (SPR) are becoming increasingly used in biology and medicine. Their application facilitates exploration in real time progress of binding of biomolecules and identification of agents that specifically interact with biologically active substances immobilized on the biosensor surface (biochips). Special attention is paid to the use of Biosensor analysis in determining the antibody-antigen interaction in the diagnostics of diseases caused by viruses and bacteria. According to WHO, the diseases that are caused by the herpes simplex virus (HSV), take second place (15.8%) after influenza as a cause of death from viral infections. Current diagnostics of HSV infection include PCR and ELISA assays. The latter allows determination the degree of immune response to viral infection and respective stages of its progress. In this regard, the searches for new and available diagnostic methods are very important. This work was aimed to develop Biosensor chip for detection of specific antibodies to HSV-1 in the human blood serum. The proteins of HSV1 (strain US) were used as antigens. The viral particles were accumulated in cell culture MDBK and purified by differential centrifugation in cesium chloride density gradient. Analysis of the HSV1 proteins was performed by polyacrylamide gel electrophoresis and ELISA. The protein concentration was measured using De Novix DS-11 spectrophotometer. The device for detection of antigen-antibody interactions was an optoelectronic two-channel spectrometer ‘Plasmon-6’, using the SPR phenomenon in the Krechman optical configuration. It was developed at the Lashkarev Institute of Semiconductor Physics of NASU. The used carrier was a glass plate covered with 45 nm gold film. Screening of human blood serums was performed using the test system ‘HSV-1 IgG ELISA’ (GenWay, USA). Development of Biosensor chip included optimization of conditions of viral antigen sorption and analysis steps. For immobilization of viral proteins 0.2% solution of Dextran 17, 200 (Sigma, USA) was used. Sorption of antigen took place at 4-8°C within 18-24 hours. After washing of chip, three times with citrate buffer (pH 5,0) 1% solution of BSA was applied to block the sites not occupied by viral antigen. It was found direct dependence between the amount of immobilized HSV1 antigen and SPR response. Using obtained biochips, panels of 25 positive and 10 negative for the content of antibodies to HSV-1 human sera were analyzed. The average value of SPR response was 185 a.s. for negative sera and from 312 to. 1264 a.s. for positive sera. It was shown that SPR data were agreed with ELISA results in 96% of samples proving the great potential of SPR in such researches. It was investigated the possibility of biochip regeneration and it was shown that application of 10 mM NaOH solution leads to rupture of intermolecular bonds. This allows reuse the chip several times. Thus, in this study biosensor chip for detection of specific antibodies to HSV1 was successfully developed expanding a range of diagnostic methods for this pathogen.

Keywords: biochip, herpes virus, SPR

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1421 In vitro and in vivo Effects of 'Sonneratia alba' Extract against the Fish Pathogen 'Aphanomyces invadans'

Authors: S. F. Afzali, W. L. Wong

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The epizootic ulcerative syndrome (EUS) causes by the oomycete fungus, Aphanomyces invadans; known to be one of the infectious fish diseases for farmed and wild fishes in fresh and brackish-water from the Asia-pacific region, America and Africa. Although, EUS had been documented by the Office International des Epizooties (OIE) since 1995, hitherto, there is neither standard chemical agents that can be used for successful treatment of this destructive infection in the time of outbreak; nor available vaccine for prevention. Plant-based remedies in controlling fish diseases are gaining much attention recently as an alternative to chemical treatments, which possess negative effects to the environment and human. In present study, Sonneratia alba, a mangrove plant belongs to the Sonneratiaceae family, was screened in vitro and in vivo for its antifungal activity against A. invadans mycelium growth and its effects on fish innate immune system and disease resistant. The in vitro tests was performed using the disc diffusion methods with measurements of minimum inhibitory concentration (MIC) and inhibition zone. For in vivo study, the S. alba extract supplemented diets were administrated at 0.0, 1.0%, 3.0%, and 5.0% on healthy goldfish, Carassius auratus, which challenged with A. invadans zoospores (100 spores/ml). To compare the significant differences in the hematological and immunological parameters obtained from the experiments, the data were analysed using the SPSS. The methanol extract of S. alba effectively inhibited the mycelial growth of A. invadans at a minimum concentration of 1000 ppm for agar and filter paper diffusion experiments. In the agar diffusion test, 500 ppm of the extract inhibited the fungus mycelial growth up to 96 hours after exposure. The mycelial growth from the edge of the pre-inoculated A. invadans agar discs treated with S. alba extracts at concentrations of 100, 500 and 1000 ppm were 15, 8 and 0 mm respectively. The results of the filter paper disc test showed that the S. alba extract at its minimal inhibitory concentration (1000 ppm) has similar qualitative inhibitory effect as malachite green at 1 ppm and formalin at 250 ppm. According to the in vivo tests findings, in the infected fish fed with 3.0% and 5.0% supplementation diet, the numbers of white blood cell and myeloperoxidase activity significantly increased after the second week of treatment. Whilst the numbers of red blood cell significantly decreased in the infected fish fed with 0.0 and 1.0% supplementation diet. After the third week of feeding, significant increases in the total protein, albumin level, lysozyme activity were recorded in the infected fish fed with 3.0% and 5.0% supplementation diet. Also, the enriched diets increased the survival rate as compared to the untreated group that suffered from 90% mortality. The present study indicated that S. alba extract may inhibit the mycelial growth of A. invadans effectively, suggesting an alternative to other chemotherapeutic agents, which brought much environmental and health concerns to the public, for EUS treatment.

Keywords: fungal pathogen, goldfish, organic extract, treatment

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1420 Co-Culture of Neonate Mouse Spermatogonial Stem Cells with Sertoli Cells: Inductive Role of Melatonin following Transplantation: Adult Azoospermia Mouse Model

Authors: Mehdi Abbasi, Shadan Navid, Mohammad Pourahmadi, M. Majidi Zolbin

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We have recently reported that melatonin as antioxidant enhances the efficacy of colonization of spermatogonial stem cells (SSCs). Melatonin as an antioxidant plays a vital role in the development of SSCs in vitro. This study aimed to investigate evaluation of sertoli cells and melatonin simultaneously on SSC proliferation following transplantation to testis of adult mouse busulfan-treated azoospermia model. SSCs and sertoli cells were isolated from the testes of three to six-day old male mice.To determine the purity, Flow cytometry technique using PLZF antibody were evaluated. Isolated testicular cells were cultured in αMEM medium in the absence (control group) or presence (experimental group) of sertoli cells and melatonin extract for 2 weeks. We then transplanted SSCs by injection into the azoospermia mice model. Higher viability, proliferation, and Id4, Plzf, expression were observed in the presence of simultaneous sertoli cells and melatonin in vitro. Moreover, immunocytochemistry results showed higher Oct4 expression in this group. Eight weeks after transplantation, injected cells were localized at the base of seminiferous tubules in the recipient testes. The number of spermatogonia and the weight of testis were higher in the experimental group relative to control group. The results of our study suggest that this new protocol can increase the transplantation of these cells can be useful in the treatment of male infertility.

Keywords: colonization, melatonin, spermatogonial stem cell, transplantation

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1419 Gonadal Maturation in Pen Shells Pinna Rudis and Pinna Nobilis Stimulated by Reproductive Neuropeptides

Authors: Ntalamagka N., Sanchis-Benlloch P. J., Mayoral-Serrano R., Tena-Medialdea J., García-March J. R.

Abstract:

The pen shell Pinna nobilis population has declined dramatically since 2016 due to die-off events observed in the whole extent of the Mediterranean Sea associated with the protozoan Haplosporidium pinnae. As of 2019, it is considered a critically endangered species. Due to its ecological importance and its endangered status, several initiatives have been developed for its salvation and recovery. This research is an effort to understand and control its reproduction under captivity. As a limited number of Pinna nobilis individuals could be used for experimentation, the possibility of using the Pinna rudis as a model animal was explored. The molecular mechanism that regulates the reproduction of both species is unknown; consequently, transcriptomic analysis was performed to identify neuropeptides that are expressed in the key regulatory tissues of the visceral ganglia and gonads of both species. Neuropeptides form an important group of signaling peptides that regulate reproductive, behavioral and physiological functions in molluscs. In total, 17 neuropeptide precursors were identified in P. nobilis and 14 in P. rudis transcriptomes; 14 of them were identical in both species. This affinity verified the genetic similarity of these species at the reproduction level. APGWamide, buccalin, ELH and GnRH were tested in P. rudis and demonstrated their capacity to advance gonadal maturation and trigger spawning while spawning was recorded in P. nobilis after the usage of APGWamide and buccalin. The neuropeptides were administered using intramuscular injection and cholesterol implants following relative literature as well as a new method was developed for external administration without the use of anesthesia using a mathematical model. The know-how of this research will not only lead to the survival of the species but also will narrow the horizons of broodstock conditioning of other similar species.

Keywords: neuropeptides, Pinna nobilis, reproduction, transcriptomics

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1418 Computed Tomography Brain and Inpatient Falls: An Audit Evaluating the Indications and Outcomes

Authors: Zain Khan, Steve Ahn, Kathy Monypenny, James Fink

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In Australian public hospitals, there were approximately 34,000 reported inpatient falls between 2015 to 2016. The gold standard for diagnosing intracranial injury is non-contrast enhanced brain computed tomography (CTB). Over a three-month timeframe, a total of one hundred and eighty (180) falls were documented between the hours of 4pm and 8am at a large metro hospital. Only three (3) of these scans demonstrated a positive intra-cranial finding. The rationale for scanning varied. The common indications included a fall with head strike, the presence of blood thinning medication, loss of consciousness, reduced Glasgow Coma Scale (GCS), vomiting and new neurological findings. There are several validated tools to aid in decision-making around ordering CTB scans in the acute setting, but no such accepted tool exists for the inpatient space. With further data collection, spanning a greater length of time and through involving multiple centres, work can be done towards generating such a tool that can be utilized for inpatient falls.

Keywords: computed tomography, falls, inpatient, intracranial hemorrhage

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1417 Reactivity of Clay Minerals of the Hydrocarbon Reservoir Rocks and the Effect of Zeolites on Operation and Production Costs That the Oil Industry in the World Assumes

Authors: Carlos Alberto Ríos Reyes

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Traditionally, clays have been considered as one of the main problems in the flow of fluids in hydrocarbon reservoirs. However, there is not known the significance of zeolites formed from the reactivity of clays and their effect not only on the costs of operations carried out by the oil industry in the world but also on production. The present work focused on understanding the interaction between clay minerals with brines and alkaline solutions used in the oil industry. For this, a comparative study was conducted where the reaction of sedimentary rocks under laboratory conditions was examined. Original and treated rocks were examined by X-ray powder diffraction (XRPD) and Scanning Electron Microscopy (SEM) to determine the changes that these rocks underwent upon contact with fluids of variable chemical composition. As a result, zeolite Linde Type A (LTA), sodalite (SOD), and cancrinite (CAN) can be formed after experimental work, which coincided with the dissolution of kaolinite and smectite. Results reveal that the Oil Industry should invest efforts and focus its gaze to understand at the pore scale the problem that could arise as a consequence of the clay-fluid interaction in hydrocarbon reservoir rocks due to the presence of clays in their porous system, as well as the formation of zeolites, which are better hydrocarbon absorbents. These issues could be generating losses in world production. We conclude that there is a critical situation that may be occurring in the stimulation of hydrocarbon reservoirs, where real solutions are necessary not only for the formulation of more efficient and effective injection fluids but also to contribute to the improvement of production and avoid considerable losses in operating costs.

Keywords: clay minerals, zeolites, rock-fluid interaction, experimental work, reactivity

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1416 Prevalence and Risk Factors of Cardiovascular Diseases among Bangladeshi Adults: Findings from a Cross Sectional Study

Authors: Fouzia Khanam, Belal Hossain, Kaosar Afsana, Mahfuzar Rahman

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Aim: Although cardiovascular diseases (CVD) has already been recognized as a major cause of death in developed countries, its prevalence is rising in developing countries as well, and engendering a challenge for the health sector. Bangladesh has experienced an epidemiological transition from communicable to non-communicable diseases over the last few decades. So, the rising prevalence of CVD and its risk factors are imposing a major problem for the country. We aimed to examine the prevalence of CVDs and socioeconomic and lifestyle factors related to it from a population-based survey. Methods: The data used for this study were collected as a part of a large-scale cross-sectional study conducted to explore the overall health status of children, mothers and senior citizens of Bangladesh. Multistage cluster random sampling procedure was applied by considering unions as clusters and households as the primary sampling unit to select a total of 11,428 households for the base survey. Present analysis encompassed 12338 respondents of ≥ 35 years, selected from both rural areas and urban slums of the country. Socio-economic, demographic and lifestyle information were obtained through individual by a face-to-face interview which was noted in ODK platform. And height, weight, blood pressure and glycosuria were measured using standardized methods. Chi-square test, Univariate modified Poisson regression model, and multivariate modified Poisson regression model were done using STATA software (version 13.0) for analysis. Results: Overall, the prevalence of CVD was 4.51%, of which 1.78% had stroke and 3.17% suffered from heart diseases. Male had higher prevalence of stroke (2.20%) than their counterparts (1.37%). Notably, thirty percent of respondents had high blood pressure and 5% population had diabetes and more than half of the population was pre-hypertensive. Additionally, 20% were overweight, 77% were smoker or consumed smokeless tobacco and 28% of respondents were physically inactive. Eighty-two percent of respondents took extra salt while eating and 29% of respondents had deprived sleep. Furthermore, the prevalence of risk factor of CVD varied according to gender. Women had a higher prevalence of overweight, obesity and diabetes. Women were also less physically active compared to men and took more extra salt. Smoking was lower in women compared to men. Moreover, women slept less compared to their counterpart. After adjusting confounders in modified Poisson regression model, age, gender, occupation, wealth quintile, BMI, extra salt intake, daily sleep, tiredness, diabetes, and hypertension remained as risk factors for CVD. Conclusion: The prevalence of CVD is significant in Bangladesh, and there is an evidence of rising trend for its risk factors such as hypertension, diabetes especially in older population, women and high-income groups. Therefore, in this current epidemiological transition, immediate public health intervention is warranted to address the overwhelming CVD risk.

Keywords: cardiovascular diseases, diabetes, hypertension, stroke

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1415 Positioning Food Safety in Halal Assurance

Authors: Marin Neio Demirci, Jan Mei Soon, Carol A. Wallace

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Muslims follow the religion of Islam and the food they eat should be Halal, meaning lawful or permissible. Muslims are allowed to eat halal and wholesome food that has been provided for them. However, some of the main prohibitions are swine flesh, blood, carrion, animals not slaughtered according to Islamic laws and alcoholic drinks. At present Halal assurance is in a complicated state, with various Halal standards differing from each other without gaining mutual acceptance. The world is starting to understand the need for an influential globally accepted standard that would open doors to global markets and gain consumer confidence. This paper discusses issues mainly related to food safety in Halal assurance. The aim was to discover and describe the approach to food safety requirements in Halal food provision and how this is incorporated in the Halal assurance systems. The position of food safety regulation within Halal requirements or Halal standards’ requirements for food safety is still unclear. This review also considers whether current Halal standards include criteria in common with internationally accepted food hygiene standards and emphasizes the potential of using the HACCP system for Halal assurance.

Keywords: certification, GHP, HACCP, Halal standard

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1414 Distributed Generation Connection to the Network: Obtaining Stability Using Transient Behavior

Authors: A. Hadadi, M. Abdollahi, A. Dustmohammadi

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The growing use of DGs in distribution networks provide many advantages and also cause new problems which should be anticipated and be solved with appropriate solutions. One of the problems is transient voltage drop and short circuit in the electrical network, in the presence of distributed generation - which can lead to instability. The appearance of the short circuit will cause loss of generator synchronism, even though if it would be able to recover synchronizing mode after removing faulty generator, it will be stable. In order to increase system reliability and generator lifetime, some strategies should be planned to apply even in some situations which a fault prevent generators from separation. In this paper, one fault current limiter is installed due to prevent DGs separation from the grid when fault occurs. Furthermore, an innovative objective function is applied to determine the impedance optimal amount of fault current limiter in order to improve transient stability of distributed generation. Fault current limiter can prevent generator rotor's sudden acceleration after fault occurrence and thereby improve the network transient stability by reducing the current flow in a fast and effective manner. In fact, by applying created impedance by fault current limiter when a short circuit happens on the path of current injection DG to the fault location, the critical fault clearing time improve remarkably. Therefore, protective relay has more time to clear fault and isolate the fault zone without any instability. Finally, different transient scenarios of connection plan sustainability of small scale synchronous generators to the distribution network are presented.

Keywords: critical clearing time, fault current limiter, synchronous generator, transient stability, transient states

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1413 Pharmacokinetics and Safety of Pacritinib in Patients with Hepatic Impairment and Healthy Volunteers

Authors: Suliman Al-Fayoumi, Sherri Amberg, Huafeng Zhou, Jack W. Singer, James P. Dean

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Pacritinib is an oral kinase inhibitor with specificity for JAK2, FLT3, IRAK1, and CSF1R. In clinical studies, pacritinib was well tolerated with clinical activity in patients with myelofibrosis. The most frequent adverse events (AEs) observed with pacritinib are gastrointestinal (diarrhea, nausea, and vomiting; mostly grade 1-2 in severity) and typically resolve within 2 weeks. A human ADME mass balance study demonstrated that pacritinib is predominantly cleared via hepatic metabolism and biliary excretion (>85% of administered dose). The major hepatic metabolite identified, M1, is not thought to materially contribute to the pharmacological activity of pacritinib. Hepatic diseases are known to impair hepatic blood flow, drug-metabolizing enzymes, and biliary transport systems and may affect drug absorption, disposition, efficacy, and toxicity. This phase 1 study evaluated the pharmacokinetics (PK) and safety of pacritinib and the M1 metabolite in study subjects with mild, moderate, or severe hepatic impairment (HI) and matched healthy subjects with normal liver function to determine if pacritinib dosage adjustments are necessary for patients with varying degrees of hepatic insufficiency. Study participants (aged 18-85 y) were enrolled into 4 groups based on their degree of HI as defined by Child-Pugh Clinical Assessment Score: mild (n=8), moderate (n=8), severe (n=4), and healthy volunteers (n=8) matched for age, BMI, and sex. Individuals with concomitant renal dysfunction or progressive liver disease were excluded. A single 400 mg dose of pacritinib was administered to all participants. Blood samples were obtained for PK evaluation predose and at multiple time points postdose through 168 h. Key PK parameters evaluated included maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the plasma concentration time curve (AUC) from hour zero to last measurable concentration (AUC0-t), AUC extrapolated to infinity (AUC0-∞), and apparent terminal elimination half-life (t1/2). Following treatment, pacritinib was quantifiable for all study participants at 1 h through 168 h postdose. Systemic pacritinib exposure was similar between healthy volunteers and individuals with mild HI. However, there was a significant difference between those with moderate and severe HI and healthy volunteers with respect to peak concentration (Cmax) and plasma exposure (AUC0-t, AUC0-∞). Mean Cmax decreased by 47% and 57% respectively in participants with moderate and severe HI vs matched healthy volunteers. Similarly, mean AUC0-t decreased by 36% and 45% and mean AUC0-∞ decreased by 46% and 48%, respectively in individuals with moderate and severe HI vs healthy volunteers. Mean t1/2 ranged from 51.5 to 74.9 h across all groups. The variability on exposure ranged from 17.8% to 51.8% across all groups. Systemic exposure of M1 was also significantly decreased in study participants with moderate or severe HI vs. healthy participants and individuals with mild HI. These changes were not significantly dissimilar from the inter-patient variability in these parameters observed in healthy volunteers. All AEs were grade 1-2 in severity. Diarrhea and headache were the only AEs reported in >1 participant (n=4 each). Based on these observations, it is unlikely that dosage adjustments would be warranted in patients with mild, moderate, or severe HI treated with pacritinib.

Keywords: pacritinib, myelofibrosis, hepatic impairment, pharmacokinetics

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1412 Role of Inflammatory Markers in Arthritic Rats Treated with Ethanolic Bark Extract of Albizia procera

Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal

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Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.

Keywords: CFA-Complete Freund’s adjuvant, ETBE – ethanolic bark extract, IL- interleukins, RA-rheumatoid arthritis

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