Search results for: host transcriptome and drug repurposing

Authors: Oktavia Eka Puspita

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The possibility of using Solid Lipid Nanoparticles (SLN) for topical use is an interesting feature concerning this system has occlusive properties on the skin surface therefore enhance the penetration of drugs through the stratum corneum by increased hydration. This advantage can be used to enhance the drug penetration of topical delivery such as Diclofenac sodium for the relief of signs and symptoms of osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. The purpose of this study was focused on the preparation and physical characterization of Diclofenac sodium loaded SLN (D-SLN). D loaded SLN were prepared by hot homogenization followed by ultrasonication technique. Since the occlusion factor of SLN is related to its particle size the formulation of D-SLN in present study two formulations different in its surfactant contents were prepared to investigate the difference of the particle size resulted. Surfactants selected for preparation of formulation A (FA) were lecithin soya and Tween 80 whereas formulation B (FB) were lecithin soya, Tween 80, and Sodium Lauryl Sulphate. D-SLN were characterized for particle size and distribution, polydispersity index (PI), zeta potential using Beckman-Coulter Delsa™ Nano. Overall, the particle size obtained from FA was larger than FB. FA has 90% of the particles were above 1000 nm, while FB has 90% were below 100 nm.

Keywords: solid lipid nanoparticles, hot homogenization technique, particle size analysis, topical administration

Procedia PDF Downloads 478

Authors: Dilek Ozturk, Narin Ozturk, Zeliha Pala Kara, Engin Kaptan, Serap Sancar Bas, Nurten Ozsoy, Alper Okyar

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Most physiological processes oscillate in a rhythmic manner in mammals including metabolism and energy homeostasis, locomotor activity, hormone secretion, immune and endocrine system functions. Endocrine body rhythms are tightly regulated by the circadian timing system. The hypothalamic-pituitary-thyroid (HPT) axis is under circadian control at multiple levels from hypothalamus to thyroid gland. Since circadian timing system controls a variety of biological functions in mammals, circadian rhythms of biological functions may modify the drug tolerability/toxicity depending on the dosing time. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer agent that is active against many cancers. It was also found to be active in medullary thyroid cancer. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus on the thyroid gland and hormones in mice. Healthy C57BL/6J mice were synchronized with 12h:12h Light-Dark cycle (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding to Light onset). Everolimus was administered to male (5 mg/kg/day) and female mice (15 mg/kg/day) orally at ZT1-rest period- and ZT13-activity period- for 4 weeks; body weight loss, clinical signs and possible changes in serum thyroid hormone levels (TSH and free T4) were examined. Histological alterations in the thyroid gland were evaluated according to the following criteria: follicular size, colloid density and viscidity, height of the follicular epithelium and the presence of necrotic cells. The statistical significance between differences was analyzed with ANOVA. Study findings included everolimus-related diarrhea, decreased activity, decreased body weight gains, alterations in serum TSH levels, and histopathological changes in thyroid gland. Decreases in mean body weight gains were more evident in mice treated at ZT1 as compared to ZT13 (p < 0.001, for both sexes). Control tissue sections of thyroid glands exhibited well-organized histoarchitecture when compared to everolimus-treated groups. Everolimus caused histopathological alterations in thyroid glands in male (5 mg/kg, slightly) and female mice (15 mg/kg; p < 0.01 for both ZT as compared to their controls) irrespective of dosing-time. TSH levels were slightly decreased upon everolimus treatment at ZT13 in both males and females. Conversely, increases in TSH levels were observed when everolimus treated at ZT1 in both males (5 mg/kg; p < 0.05) and females (15 mg/kg; slightly). No statistically significant alterations in serum free T4 levels were observed. TSH and free T4 is clinically important thyroid hormones since a number of disease states have been linked to alterations in these hormones. Serum free T4 levels within the normal ranges in the presence of abnormal serum TSH levels in everolimus treated mice may suggest subclinical thyroid disease which may have repercussions on the cardiovascular system, as well as on other organs and systems. Our study has revealed the histological damage on thyroid gland induced by subacute everolimus administration, this effect was irrespective of dosing time. However, based on the body weight changes and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13 in both male and females. Yet, effects of everolimus on thyroid functions may deserve further studies regarding their clinical importance and chronotoxicity.

Keywords: circadian rhythm, chronotoxicity, everolimus, thyroid gland, thyroid hormones

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Authors: Veronica Barragan, Ligia Luna, Maria Patricia Zambrano, Carlos Bulnes, Eduardo Diaz, Talima Pearson

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Leptospirosis impacts animal production and is responsible for important economic losses in the pig industry. Infection is associated with reproductive failures that lead to abortions, stillbirth, and perinatal mortality. The leptospira serogroups that have been traditionally linked to disease in pigs are Pomona, Australis, and Tarassovi. Unfortunately, knowledge about pig leptospirosis is biased towards infection in large-scale commercial farms from developed countries, where exposure is usually limited to host-specific serotypes. The aim of our study is to describe leptospirosis in pigs from rural communities located in the coast of Ecuador-South America, where leptospirosis is endemic. A particularity of these pigs is that, because they are usually raised in the backyard of their owner’s houses, exposure to other leptospira excreted by other animals is likely to occur. Therefore, we collected 420 kidney samples from pigs sacrificed at a local slaughterhouse, and Leptospira positivity was tested in all samples by amplifying the Lipl32 gen. Our results show pathogenic Leptospira positivity in 19.3% (81/420) of pigs. Microaglutination test was performed in 60 PCR positive samples with titers >1:100 in 17 pigs, titers of 1:50 in 28 pigs, and no MAT titers in 15 pigs even though Leptospira DNA was found in their kidneys. Interestingly, reacting serovars were very diverse, with 18.3% of pig sera reacting with two or more serovars. Additionally, serovar Canicola was found in 16.7% of pigs followed by Tarassovi (10%), Australis (6.7%), Pyogenes (5%), Icterohaemorrhageae (1.7%), and Grippotyphosa (1.7%). It is also important to highlight that most of the analyzed animals came from small-scale farms where pigs may be exposed to the pathogen by exposure to other domestic and peridomestic animals such as rats, dogs, horses, donkeys, and even wildlife. This would explain the finding of non-pig adapted Leptospira serovars such as Canicola, which is commonly reported in dogs.

Keywords: Leptospira, Lipl32, peridomestic, pig, serovar

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Authors: Mubashra Shaheen

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The conflict over the South China Sea (SCS) is a complex imbroglio spanning over several territorial and maritime claims involving two major island groups, the Paracels and the Spratlys. It has become a major source of geopolitical competition between the United States and China. The study's overall objective is to understand China's land reclamations and assertive behavior in the South China Sea, which lies between both the Western Pacific and the Indian Ocean. Over half of global commerce passes through these waterways, which host a great amount of marine life and hydrocarbon deposits. China's sand-filling and island-building strategy in the South China Sea is motivated by its goal of privatizing all these riches as well as the routes. It would raise China to the pinnacle of world power status as well as allow it to threaten the dominance of the U.S. The study will examine China's assertive behavior and modernization plans as well as the United States' quest for supremacy through the lens of realists. While using a qualitative method of analysis, the study will examine China's nine-dash line claims and Exclusive Economic Zones (EEZs), UNCLOS, and U.S.-China divergence over international law considerations to pacify the tensions in the South China Sea. This paper is intended to explore the possible answers to the following questions: (1) Why does China’s rise necessitate the US's efforts to contain and encircle it through the lending of a hand to strategic partners and allies in the South China Sea? (2) Why South China Sea dispute is so complex imbroglio? (3) What are US-China international law considerations regarding the South China Sea? The study will further follow the bellow research procedure: 1: Comparative Legal Method: This method simply chalk-outs the follow of few steps that discarnate the positive and negative effects of the great power competitions. 2: Conceptualization: The conceptualization of the policies of containment defines and differentiates two different problems behind the persuasive means of hegemony and dominance in the strategic milieu.

Keywords: us, china, south china sea, unclos

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Authors: Włodzimierz Przewodowski, Agnieszka Przewodowska

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Colloidal metal nanoparticles have drawn increasing attention in the field of phytopathology because of their unique properties and possibilities of applications. Their antibacterial activity, no induction of the development of pathogen resistance and the ability to penetrate most of biological barriers make them potentially useful in the fighting against dangerous pathogens. These properties are very important in the case of protection of strategic crops in the world, like potato - fourth crop in the world - which is host to numerous pathogenic microorganisms causing serious diseases, significantly affecting yield and causing the economic losses. One of the most important and difficult to reduce pathogen of potato plant is quarantine bacterium Clavibacter michiganensis ssp. sepedonicus (Cms) responsible for ring rot disease. Control and detection of these pathogens is very complicated. Application of healthy, certified seed material as well as hygiene in potato production and storage are the most efficient ways of preventing of ring rot disease. Currently used disinfectants and pesticides, have many disadvantages, such as toxicity, low efficiency, selectivity, corrosiveness, and the inability to eliminate the pathogens in potato tissue. In this situation, it becomes important to search for new formulations based on components harmful to health, yet efficient, stable during prolonged period of time and a with wide range of biocide activity. Such capabilities are offered by the latest generation of biocidal nanoparticles such as colloidal metals. Therefore the aim of the presented research was to develop newly antibacterial preparation based on colloidal metal nanoparticles and checking their influence on the Cms bacteria. Our preliminary results confirmed high efficacy of the nano-colloids in controlling the this selected pathogen.

Keywords: clavibacter michiganensis ssp. sepedonicus, colloidal metal nanoparticles, phytopathology, bacteria

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Authors: Farhan Nayyar, A. Batool

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The red palm weevil (RPW), being the most invasive insect pest of palm family, is considered as the most dangerous pest around the globe. As three out of four life stages of weevils are concealed inside the host plants, leaving only the adult stage for controlling it. The use of sex pheromone (Ferrugineol) for the management of red palm weevil is considered as the most rewarding technique of IPM. The current studies were conducted to find the relative potential of four different treatments including Sex pheromone, sex pheromone + date fruit + sugarcane pieces, sex pheromone + ethyl acetate and sex pheromone + jaggary water applied on the attraction behavior of weevils. The treatments were applied randomly at two different locations of Dera Ismail Khan, Khyber Pakhtunkhwa, Pakistan including Germ Plasm Unit (GPU) and fruit nursery farm having date palm plants of different ages of four varieties of date palm. The treatments were applied for three consecutive months, including February, March, and April 2022. The pheromone traps were installed at the height of two feet under shade on the western side of date palm plants. The results revealed that among the treatments, T4 consisting of Jaggary water and sex pheromone was found as the most effective treatment and attracted the maximum number of 127 weevils followed by T3 consisting of ethyl acetate and sex pheromone, attracting 53 weevils. In contrast to this, T2 consisting of sex pheromone and date fruit was found as the least effective treatment in attracting red palm weevil and attracted only 15 adult weevils. Among the two selected locations, the population of red palm weevil was found comparatively higher at GPU compared to the nursery farm, Dera Ismail Khan. In conclusion, T4 may be used for the effective and safer management of red palm weevil.

Keywords: red palm weevil, integrated management, sex pheromones, Jaggary water

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Authors: Mulue Girmay Gebreslasie

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Entomopathogenic fungi are naturally safe and eco-friendly biological agents. Their potential of host specificity and ease handling made them appealing options to substitute synthetic pesticides in pest control programs. However, they are highly delicate and unstable under field conditions. Therefore, the current experiment was held to search out persistent fungal strains by defining the relationship between invitro heat tolerance and field persistence. Current results on leaf and soil persistence assay revealed that strains of Metarhizium species, M. pingshaense (F2685), M. pingshaense (MS2) and M. brunneum (F709) exhibit maximum cumulative CFUs count, relative survival rate and least percent of CFUs reductions showed significant difference at 7 days and 28 days post inoculations (dpi) in hot seasons from sampled soils and leaves and in cold season from soil samples. Whereas relative survival of B. brongniartii (TNO6) found significantly higher in cold weather leaf treatment application as compared to hot season and found as persistent as other fungal strains, while higher deterioration of fungal conidia seen with M. pingshaense (MS2). In the current study, strains of Beauveria brongniartii (TNO6) and Cordyceps javanica (Czy-LP) were relatively vulnerable in field condition with utmost colony forming units (CFUs) reduction and least survival rates. Further, the relationship of the two parameters (heat tolerance and field persistence) was seen with strong linear positive correlations elucidated that heat test could be used in selection of field persistent fungal strains for hot season applications.

Keywords: integrated pest management, biopesticides, Insect pathology and microbial control, entomology

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Authors: Helen K. Buteme, Rebecca Axelsson-Robertson, Moses L. Joloba, Henry W. Boom, Gunilla Kallenius, Markus Maeurer

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Background: The Ugandan population is heavily affected by infectious diseases and Human leukocyte antigen (HLA) diversity plays a crucial role in the host-pathogen interaction and affects the rates of disease acquisition and outcome. The identification of HLA class 1 alleles and determining which alleles are associated with tuberculosis (TB) outcomes would help in screening individuals in TB endemic areas for susceptibility to TB and to predict resistance or progression to TB which would inevitably lead to better clinical management of TB. Aims: To be able to determine the HLA class 1 phenotype distribution in a Ugandan TB cohort and to establish the relationship between these phenotypes and active and latent TB. Methods: Blood samples were drawn from 32 HIV negative individuals with active TB and 45 HIV negative individuals with latent MTB infection. DNA was extracted from the blood samples and the DNA samples HLA typed by the polymerase chain reaction-sequence specific primer method. The allelic frequencies were determined by direct count. Results: HLA-A*02, A*01, A*74, A*30, B*15, B*58, C*07, C*03 and C*04 were the dominant phenotypes in this Ugandan cohort. There were differences in the distribution of HLA types between the individuals with active TB and the individuals with LTBI with only HLA-A*03 allele showing a statistically significant difference (p=0.0136). However, after FDR computation the corresponding q-value is above the expected proportion of false discoveries (q-value 0.2176). Key findings: We identified a number of HLA class I alleles in a population from Central Uganda which will enable us to carry out a functional characterization of CD8+ T-cell mediated immune responses to MTB. Our results also suggest that there may be a positive association between the HLA-A*03 allele and TB implying that individuals with the HLA-A*03 allele are at a higher risk of developing active TB.

Keywords: HLA, phenotype, tuberculosis, Uganda

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Authors: Pear-Rarin Leelakunakorn, Patompong Satapornpong

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Introduction: Dapsone is an anti-inflammatory and antibiotic drug that was widely used for the treatment of leprosy, acne fulminans, and dermatitis herpetiformis (DH). However, dapsone is the main cause that triggers severe cutaneous adverse reactions (SCARs), with a possibility of 0.4 to 3.6% of patients after initiating treatment. In fact, the mortality rate of dapsone-induced SCARs is approximately 9.9%. In previous studies, HLA-B*13:01 was strongly associated with dapsone-induced SCARs in Han Chinese, Thais, and Koreans. Nevertheless, the distribution of HLA-B*13:01 marker in each population might differ. Moreover, there were found that the association between HLA-C*03:04 and dapsone hypersensitivity syndrome in Han Chinese leprosy patients by OR = 9.00 and p-value = 2.23×10⁻¹⁹. Objective: The aim of this study was to investigate the distribution of HLA-C* 03:04 in Thailand's healthy population. Method: A total of 350 participants were HLA-C genotyping used sequence-specific oligonucleotides (PCR-SSOs). This study was approved by the Ethics Committee of Rangsit University Result : The most frequency of HLA -C alleles in Thais, consist of HLA -C* 01:02 (17.00 %), -C*08:01 (11.00%) , -C*07:02 (10.70%) , -C* 03:04 ( 9.10%) , -C* 03:02 (8.00%) , -C* 07:01 (6.30%), -C* 07:04 (4.60%), -C* 04:01 (4.40%) ,-C* 12:02 ( 4.30% ) ,and -C* 04:03(3.90%). Interestingly, HLA -C* 03:04 allele was similar to the distribution among Thais and other populations such as Eastern Europe (6.09%), Vietnam (7.42% ), East Croatia (2.25%), and Han Chinese (11.70%). Conclusion: Consequently, HLA-C*03:04 might serve as a pharmacogenetic marker for screening prior to initiation therapy with dapsone for prevention of dapsone-induced SCARs in Thai population.

Keywords: HLA-C*03:04, SCARs, thai population, allele frequency

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Authors: Sevda Ddras, Fariba Mehrkhou, Remzi Atlihan, Maryam Fourouzan

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The greenhouse whitefly, Trialeurodes vaporariorum Westwood (Hemiptera: Aleyrodidae), is one of the most important pest on vegetables and ornamental host plants. In this research, the sub-lethal concentration (LC30) of thiamethoxam-lambda cyhalothrin (TLC) on the biological properties, life table parameters and population projection of T. vaporarium and its parasitoid, Encarsia formosa Gahan, were studied at controlled condition (25 ±5 ℃, R.H. 60 ±10 % and a photoperiod of 16:8 h (L:D). Bioassays were conducted by dipping tomato leaves containing third instar nymphs of the whitefly T. vaporariorum, in the obtained LC30 concentration of eforia. The life table data were analyzed using the computer program TWOSEX–MSChart based on the age-stage, two-sex life table theory. The results showed that, usage of sublethal concentration of TLC effected the biological properties and population growth parameters of greenhouse whitefly by shortening the developmentl time, adult longevity, decreasing the fecundity and population growth paramters. Also, the LC30 concentration of TLC had negative effects on life history and life table parameters of E.formosa. The obtained results illustrated that the sublethal concentration of TLC resulted in prolonging of developmental time, decreasing of adult longevity, survival rate and population growth parameters of E.formosa. Additionally, the population projection results were accordance with the population growth rate of either greenhouse whitefly or E.formosa. We conclude that, TLC should not be used in integrated pest management programs where E. formosa exists.

Keywords: greenhouse whitefly, Encarsia formosa, thiamethoxam-lambda cyhalothrin, population projection, life table parameters

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Authors: Abdulsalam A. Al-Tamimi, Chris Peach, Paulo Rui Fernandes, Paulo J. Bartolo

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Bone fixation implants currently used to treat traumatic fractured bones and to promote fracture healing are built with biocompatible metallic materials such as stainless steel, cobalt chromium and titanium and its alloys (e.g., CoCrMo and Ti6Al4V). The noticeable stiffness mismatch between current metallic implants and host bone associates with negative outcomes such as stress shielding which causes bone loss and implant loosening leading to deficient fracture treatment. This paper, part of a major research program to design the next generation of bone fixation implants, describes the combined use of three-dimensional (3D) topology optimization (TO) and additive manufacturing powder bed technology (Electron Beam Melting) to redesign and fabricate the plates based on the current standard one (i.e., locking compression plate). Topology optimization is applied with an objective function to maximize the stiffness and constraint by volume reductions (i.e., 25-75%) in order to obtain optimized implant designs with reduced stress shielding phenomenon, under different boundary conditions (i.e., tension, bending, torsion and combined loads). The stiffness of the original and optimised plates are assessed through a finite-element study. The TO results showed actual reduction in the stiffness for most of the plates due to the critical values of volume reduction. Additionally, the optimized plates fabricated using powder bed techniques proved that the integration between the TO and additive manufacturing presents the capability of producing stiff reduced plates with acceptable tolerances.

Keywords: additive manufacturing, locking compression plate, finite element, topology optimization

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Authors: Kalin Ivanov, Stanislava Ivanova

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Actoprotectors are substances with hight performance enchasing potential and hight antioxidant activity. Most of these drugs have been developed in USSR for military medicine purposes. Based on their chemical composition actoprotectors could be classified into three categories: benzimidazole derivatives (ethomersol, bemitil); adamantane derivatives (bromantane), other chemical classes. First data for intake of actoprotectors from professional athletes is from 1980. The daily intake of actoprotectors demonstrate many benefits for athletes like: positive effect on the efficiency of physical work, antihypoxic effects, antioxidant effects, nootropic effects, rapid recovery. Since 1997, bromantane is considered as doping. This is a result of Summer Olympic Games in Athlanta (1996) when several Russian athletes tested positive for bramantane. Even the drug is safe for athletes health its use is considered as violation of anti- doping rules. More than 37 years bemetil has been used by professional athletes with no risk but currently it is included in WADA monitoring programme for 2018. Current perspectives are that most used actoprotectors would be considered as doping. Many clinical studies have confirmed that intake of bemitil and bromantan demonstrate positive influence on the physical work capacity but data for other actoprotectors like chlodantane, ademol, ethomersol is limited.

Keywords: actoprotector, sport, doping, bemitil

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Authors: Martins Y. Otache, John J. Musa, Abayomi I. Kuti, Mustapha Mohammed

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The performance of an artificial neural network (ANN) is contingent on a host of factors, for instance, the network optimisation scheme. In view of this, the study examined the general implications of the ANN training optimisation algorithm on its forecast performance. To this end, the Bayesian regularisation (Br), Levenberg-Marquardt (LM), and the adaptive learning gradient descent: GDM (with momentum) algorithms were employed under different ANN structural configurations: (1) single-hidden layer, and (2) double-hidden layer feedforward back propagation network. Results obtained revealed generally that the gradient descent with momentum (GDM) optimisation algorithm, with its adaptive learning capability, used a relatively shorter time in both training and validation phases as compared to the Levenberg- Marquardt (LM) and Bayesian Regularisation (Br) algorithms though learning may not be consummated; i.e., in all instances considering also the prediction of extreme flow conditions for 1-day and 5-day ahead, respectively especially using the ANN model. In specific statistical terms on the average, model performance efficiency using the coefficient of efficiency (CE) statistic were Br: 98%, 94%; LM: 98 %, 95 %, and GDM: 96 %, 96% respectively for training and validation phases. However, on the basis of relative error distribution statistics (MAE, MAPE, and MSRE), GDM performed better than the others overall. Based on the findings, it is imperative to state that the adoption of ANN for real-time forecasting should employ training algorithms that do not have computational overhead like the case of LM that requires the computation of the Hessian matrix, protracted time, and sensitivity to initial conditions; to this end, Br and other forms of the gradient descent with momentum should be adopted considering overall time expenditure and quality of the forecast as well as mitigation of network overfitting. On the whole, it is recommended that evaluation should consider implications of (i) data quality and quantity and (ii) transfer functions on the overall network forecast performance.

Keywords: streamflow, neural network, optimisation, algorithm

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Authors: Bhenjamin Jordan L. Ona

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Weather modification is an act of altering weather systems that catches interest on scientific studies. Cloud seeding is a common form of weather alteration. On the same principle, tropical cyclone mitigation experiment follows the methods of cloud seeding with intensity to account for. This study will present the effects of aerosol to tropical cyclone cloud microphysics and intensity. The framework of Weather Research and Forecasting (WRF) model incorporated with Thompson aerosol-aware scheme is the prime host to support the aerosol-cloud microphysics calculations of cloud condensation nuclei (CCN) ingested into the tropical cyclones before making landfall over the Philippine coast. The coupled microphysical and radiative effects of aerosols will be analyzed using numerical data conditions of Tropical Storm Ketsana (2009), Tropical Storm Washi (2011), and Typhoon Haiyan (2013) associated with varying CCN number concentrations per simulation per typhoon: clean maritime, polluted, and very polluted having 300 cm-3, 1000 cm-3, and 2000 cm-3 aerosol number initial concentrations, respectively. Aerosol species like sulphates, sea salts, black carbon, and organic carbon will be used as cloud nuclei and mineral dust as ice nuclei (IN). To make the study as realistic as possible, investigation during the biomass burning due to forest fire in Indonesia starting October 2015 as Typhoons Mujigae/Kabayan and Koppu/Lando had been seeded with aerosol emissions mainly comprises with black carbon and organic carbon, will be considered. Emission data that will be used is from NASA's Moderate Resolution Imaging Spectroradiometer (MODIS). The physical mechanism/s of intensification or deintensification of tropical cyclones will be determined after the seeding experiment analyses.

Keywords: aerosol, CCN, IN, tropical cylone

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Authors: Sachin Saxena, Manju Srivastava

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The present study describes a stable, highly sensitive and selective analytical sensor. Fe-BTC was synthesized at room temperature using the noble Iron-trimesate system. The high surface area of as synthesized Fe-BTC proved MOFs as ideal modifiers for glassy carbon electrode. The characterization techniques such as TGA, XRD, FT-IR, BET (BET surface area= 1125 m2/gm) analysis explained the electrocatalytic behaviour of Fe-BTC towards these two drugs. The material formed is cost effective and exhibit higher catalytic behaviour towards analyte systems. The synergism between synthesized Fe-BTC and electroanalytical techniques helped in developing a highly sensitive analytical method for studying the redox fate of ARP and RZ, respectively. Cyclic voltammetry of ferricyanide system proved Fe-BTC/GCE with an increase in 132% enhancement in peak current value as compared to that of GCE. The response characteristics of cyclic voltammetry (CV) and square wave voltammetry (SWV) revealed that the ARP and RZ could be effectively accumulated at Fe-BTC/GCE. On the basis of the electrochemical measurements, electrode dynamics parameters have been evaluated. Present study opens up new field of applications of MOFs modified GCE for drug sensing.

Keywords: MOFs, anti-psychotic, electrochemical sensor, anti-migraine drugs

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Authors: Mina Rahmani Pour

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Negative consequences of unemployment are: increasing age at marriage, addiction, depression, drug trafficking, divorce, immigration, elite, frustration, delinquency, theft, murder, etc., has led to addressing the issue of employment by economic planners, public authorities, chief executive economic conditions in different countries and different time is important. All countries are faced with the problem of unemployment. By identifying the influential factors of occupational employment and employing strengths in the basic steps can be taken to reduce unemployment. In this study, the most significant factors affecting employment has identified 12 variables based on interviews conducted Choose Vtasyrafzaysh engaged in three main business is discussed. DRGAM next question the 8 expert ministry to respond to it is distributed and for weight Horns AZFN Shannon entropy and the ranking criteria of the (SAW, TOPSIS) used. According to the results of the above methods are not compatible with each other, to reach a general consensus on the rating criteria of the technique of integrating (POSET) involving average, Borda, copeland is used. Ultimately, there is no difference between the employments in the economic sector jobs of increased employment.

Keywords: employment, effective techniques, SAW, TOPSIS

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Authors: Pratibha Goyal, Nupur Mathur, Anuradha Singh

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Antibiotic resistance is the worldwide threat to human health in this century. Excessive use of antibiotic after their discovery in 1940 makes certain bacteria to become resistant against antibiotics. Most common antibiotic-resistant bacteria include Staphylococcus aureus, Salmonella typhi, E.coli, Klebsiella pneumonia, and Streptococcus pneumonia. Among all Staphylococcus resistant strain called Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for several lives threatening infection in human commonly found in the hospital environment. Our study aimed to isolate bacteriophage against MRSA from the hospital sewage treatment plant and to analyze its efficiency In Vivo in Swiss albino mice model. Sewage sample for the isolation of bacteriophages was collected from SDMH hospital sewage treatment plant in Jaipur. Bacteriophages isolated by the use of enrichment technique and after characterization, isolated phages used to determine phage treatment efficiency in mice. Mice model used to check the safety and suitability of phage application in human need which in turn directly support the use of natural bacteriophage rather than synthetic chemical to kill pathogens. Results show the plaque formation in-vitro and recovery of MRSA infected mice during the experiment. Favorable lytic efficiency determination of MRSA and Salmonella presents a natural way to treat lethal infections caused by Multidrug-resistant bacteria by using their natural host-pathogen relationship.

Keywords: antibiotic resistance, bacteriophages, methicillin resistance Staphylococcus aureus, pathogens, phage therapy, Salmonella typhi

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Authors: Donna M. Morrison, Lambert Chester, Coretta A. N. Samuels, David R. Ledoux

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A survey was conducted in the five rice-growing regions in Guyana to determine the presence of aflatoxins in multiple fractions of rice in June/October 2015 growing season. The fractions were paddy, steamed paddy, cargo rice, white rice and parboiled rice. Samples were analyzed by High Performance Liquid Chromatography. A subset of the samples was further analyzed by enzyme-linked immunosorbent assay (ELISA) for concurrence. All analyses were conducted at the University of Missouri, USA. Of the 186 samples tested, 16 had aflatoxin concentrations greater than 20 ppb the recommended limit for aflatoxins in food according to the United States Food and Drug Administration. An additional three samples had aflatoxin B₁ concentrations greater than the European Union Commission maximum levels for aflatoxin B₁ in rice at 5 µg/kg and total aflatoxins (B₁, B₂, G₁ and G₂) at 10 µg/kg. The survey indicates that there is no widespread aflatoxin problem in rice in Guyana. The incidence of aflatoxins appears to be localized.

Keywords: aflatoxin, enzyme-linked immunosorbent assay (ELISA), high-performance liquid chromatography (HPLC), rice fractions

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Authors: Mekni Sabrine, Nouira Mariem

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Background and aim: Allogeneic hematopoietic stem cell transplantation is a curative treatment for several hematological diseases; however, it has a non-negligible morbidity and mortality depending on several prognostic factors, including pre-transplant hyperferritinemia. The aim of our study was to estimate the impact of hyperferritinemia on survivals and on the occurrence of post-transplant complications. Methods: It was a longitudinal study conducted over 8 years and including all patients who had a first allograft. The impact of pretransplant hyperferritinemia (ferritinemia ≥1500) on survivals was studied using the Kaplan Meier method and the COX model for uni- and multivariate analysis. The Khi-deux test and binary logistic regression were used to study the association between pretransplant ferritinemia and post-transplant complications. Results: One hundred forty patients were included with an average age of 26.6 years and a sex ratio (M/F)=1.4. Hyperferritinemia was found in 33% of patients. It had no significant impact on either overall survival (p=0.9) or event -free survival (p=0.6). In multivariate analysis, only the type of disease was independently associated with overall survival (p=0.04) and event-free survival (p=0.002). For post-allograft complications: The occurrence of early documented infections was independently associated with pretransplant hyperferritinemia (p=0.02) and the presence of acute graft versus host disease( GVHD) (p<10-3). The occurrence of acute GVHD was associated with early documented infection (p=0.002) and Cytomegalovirus reactivation (p<10-3). The occurrence of chronic GVHD was associated with the presence of Cytomegalovirus reactivation (p=0.006) and graft source (p=0.009). Conclusion: Our study showed the significant impact of pre-transplant hyperferritinemia on the occurrence of early infections but not on survivals. Early and more accurate assessment iron overload by other tests such as liver magnetic resonance imaging with initiation of chelating treatment could prevent the occurrence of such complications after transplantation.

Keywords: allogeneic, transplants, ferritin, survival

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Authors: Jyh-Cheng Chen, Tai-Jing Wang, Yun-Wei Lin

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Astaxanthin has been demonstrated to exhibit a wide range of beneficial effects including anti-inflammatory and anti-cancer properties. However, the molecular mechanism of astaxanthin-induced cytotoxicity in non-small cell lung cancer (NSCLC) cells has not been identified. Rad51 plays a central role in homologous recombination and high levels of Rad51 expression are observed in chemo- or radioresistant carcinomas. In this study, astaxanthin treatment inhibited cell viability and proliferation of two NSCLC cells, A549 and H1703. Treatment with astaxanthin decreased Rad51 expression and phospho-AKT protein level in a time and dose-dependent manner. Furthermore, expression of constitutively active AKT (AKT-CA) vector significantly rescued the decreased Rad51 protein and mRNA levels in astaxanthin-treated NSCLC cells. Combined treatment with PI3K inhibitors (LY294002 or wortmannin) and astaxanthin further decreased the Rad51 expression in NSCLC cells. Knockdown of Rad51 enhanced astaxanthin-induced cytotoxicity and growth inhibition in NSCLC cells. These findings may have implications for the rational design of future drug regimens incorporating astaxanthin for the treatment of NSCLC.

Keywords: astaxanthin, cytotoxicity, AKT, non-small cell lung cancer, PI3K

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Authors: Mariya Dzhyoyeva

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In the present paper, I examine manifestations of toxic masculinity in the novels by Tomás Eloy Martínez, a post-Boom author, journalist, literary critic, and one of the representatives of the Argentine writing diaspora. I focus on the analysis of Martínez´s characters that display hypermasculine traits to define the relationship between toxic masculinity and power, including the power of authorship and violence as they are represented in his novels. The analysis reveals a complex network in which gender, power, and violence are intertwined and influence and modify each other. As the author exposes toxic masculine behaviors that generate violence, he looks to undermine them. Departing from M. Kimmel´s idea of masculinity as homophobia, I examine how Martínez “outs” his characters by incorporating into the narrative some secret, privileged sources that provide alternative accounts of their otherwise hypermasculine lives. These background stories expose their “weaknesses,” both physical and mental, and thereby feminize them in their own eyes. In a similar way, the toxic masculinity of the fictional male author that wields his power by abusing the written word as he abuses the female character in the story is exposed as a complex of insecurities accumulated by the character due to his childhood trauma. The artistic technique that Martínez uses to condemn the authoritarian male behavior is accessing his subjectivity and subverting it through a multiplicity of identities. Martínez takes over the character’s “I” and turns it into a host of pronouns with a constantly shifting point of reference that distorts not only the notions of gender but also the very notion of identity. In doing so, he takes the character´s affirmation of masculinity to the limit where the very idea of it becomes unsustainable. Viewed in the context of Martínez´s own exilic story, the condemnation of toxic masculine power turns into the condemnation of dictatorship and authoritarianism.

Keywords: gender, masculinity., toxic masculinity, authoritarian, Argentine literature, Martínez

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

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

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

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Authors: Laxman H. Surwase, Lalit V. Sonawane, Bhagwat N. Poul

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A simple stability indicating high performance liquid chromatographic method has been developed for the simultaneous determination of Levosalbutamol Sulphate and Ipratropium Bromide in bulk and pharmaceutical dosage form using reverse phase Zorbax Eclipse Plus C8 column (250mm×4.6mm), with mobile phase phosphate buffer (0.05M KH2PO4): acetonitrile (55:45v/v) pH 3.5 adjusted with ortho-phosphoric acid, the flow rate was 1.0 mL/min and the detection was carried at 212 nm. The retention times of Levosalbutamol Sulphate and Ipratropium Bromide were 2.2007 and 2.6611 min respectively. The correlation coefficient of Levosalbutamol Sulphate and Ipratropium Bromide was found to be 0.997 and 0.998.Calibration plots were linear over the concentration ranges 10-100µg/mL for both Levosalbutamol Sulphate and Ipratropium Bromide. The LOD and LOQ of Levosalbutamol Sulphate were 2.520µg/mL and 7.638µg/mL while for Ipratropium Bromide was 1.201µg/mL and 3.640 µg/mL. The accuracy of the proposed method was determined by recovery studies and found to be 100.15% for Levosalbutamol Sulphate and 100.19% for Ipratropium Bromide respectively. The method was validated for accuracy, linearity, sensitivity, precision, robustness, system suitability. The proposed method could be utilized for routine analysis of Levosalbutamol Sulphate and Ipratropium Bromide in bulk and pharmaceutical capsule dosage form.

Keywords: levosalbutamol sulphate, ipratropium bromide, RP-HPLC, phosphate buffer, acetonitrile

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Authors: Milica Z. Karadzic, Lidija R. Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Z. Kovacevic, Anamarija I. Mandic, Katarina Penov-Gasi, Andrea R. Nikolic, Aleksandar M. Okljesa

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In this study, a set of 29 newly synthesized steroid derivatives were investigated using reversed-phase high-performance liquid chromatography (RP-HPLC) as a first step in preselection of drug candidates. This analysis presents an experimental determination of chromatographic lipophilicity, and it was conducted to obtain physicochemical characterization of these molecules. As the most widely used bonded phases in RP-HPLC, octadecyl (C18) and octyl (C8) were used. Binary mixtures of water and acetonitrile or methanol were used as mobile phases. Obtained results were expressed as retention factor values logk and they were correlated with logP values. The results showed that both columns provide good estimations of the chromatographic lipophilicity of the molecules included in this study. This analysis was conducted in order to characterize newly synthesized steroid derivatives for further investigation regarding their antiproliferative and antimicrobial activity. This article is based upon work from COST Action (CM1306), supported by COST (European Cooperation in Science and Technology).

Keywords: antiproliferative activity, chromatographic lipophilicity, liquid chromatography, steroids

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Authors: Lakhminandan Kakati, Merenjungla Jamir

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Rearing of six strains of Samia ricini (eri silk worm) i.e. Yellow plain (YP), Yellow spotted (YS), Yellow Zebra (YZ), Greenish blue plain (GBP), Greenish blue spotted (GBS) and Greenish blue zebra (GBZ) was conducted on Ricinus communis (Castor), Heteropanax fragrans (Kesseru), Evodia fraxinifolia (Payam) and Manihot utilissima (Tapioca) to evaluate the effect of seasonal pattern on larval duration and cocoon parameters in Nagaland, India. Larval duration during spring season was maximum in all strains in all food plants; however minimum for all strains was recorded during summer season on Castor, Kesseru and Tapioca. Cocoon weight was recorded to be minimum (2.8 ± 2 0.55 gm) in YP on Kesseru and maximum (4.06 ± 0.68 gm) in GBZ on Castor during spring season; shell weight fluctuated between 0.34 ± 0.08 gm during spring in GBS on Kesseru and 0.58 ± 0.09 gm during summer in YZ on Castor and percentage of silk ratio was found to be minimum and maximum in YP on Payam during spring (11.37 ± 1.29) and in GBS on Castor during summer (16.05 ± 1.59) respectively. The variation in larval duration and cocoon parameters reflected variation in nutrient composition of food plants and dynamic environment conditions prevailing in different seasons of the year. Payam and Tapioca plants could be fed either singly or alternately with Castor or Kesseru to attain the commercial advantage to ensure more value added production. While there were differences in the productivity parameters with respect to strains and seasons, the present study shows that all the strains on four host plants expressed adaptability and suitability for commercial rearing under Nagaland climatic condition.

Keywords: alternative food plants, Larval and cocoon parameters, Nagaland Inia, six strains of Samia ricini

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Authors: Rufai Yakubu And Suleiman Kabiru

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Triterpenoids are a diverse class of secondary metabolites with potential antimicrobial properties. In this study, the crude extracts from ethyl acetate was obtained with ultrasonic extraction method. Using a combined chromatographic separation method to isolate squalene (1) stigmasterol (2), stigmasta-5,22-diene-3-ol acetate (3), γ-sitosterol (4), lupeol (5), taraxasterol (6), and betulinic acid (7) from ethyl acetate extracts. Ethyl acetate crude extracts and isolated compounds were both screened for antimicrobial activity and minimum inhibitory concentration (MIC). For ethyl acetate crude extracts with concentrations of (1.5, 0.75, 0.35, & 0.168 mg/mL) indicated marginal antibacterial activity with a range of 17, 20 and 14 mm zone of inhibition for Staphylococcus aureus, Escherichia coli and Candida albicans and lower minimum inhibitory concentrations ranges from 18.75 µg/ml to 150 µg/mL. Butulinic acid showed the highest activity against E. coli and C. albicans at 15 mm and 15 mm followed by Lupeol against S. aureus, E. coli and C. albicans at 13, 12, 12 mm. Moreso, no antimicrobial activity for both S. aureus and C. albicans with squalene except for E. coli which showed activity at 11 mm with 300 µg/mL (MIC). Thus, abundant triterpenoids in Deinbollia pinnata will be another centered area for antimicrobial drug discovery.

Keywords: triterpenoid, antimicrobial potentials, deinbollia pinnata, aerial parts

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Authors: Jaomai Tungsiripat, Patompong Satapornpong

Abstract:

Allopurinol have been used to treat diseases that relating with the reduction of uric acid and be a treatment preventing the severity of, including gout, chronic kidney disease, chronic heart failure, and diabetes mellitus (type 2). However, allopurinol metabolites can cause a severe cutaneous adverse reaction (SCARs) consist of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Stevens-Johnson Syndrome(SJS)/Toxic Epidermal Necrolysis (TEN). Previous studies, we found only HLA-B*58:01 allele has a strongly association with allopurinol-induced SCARs in many populations: Han Chinese [P value = 4.7 x 10−24], European [P value <10−6], and Thai [P value <0.001].However, there was no update the frequency of HLA-B alleles and pharmacogenetics markers distribution in healthy Thais and support for screening before the initiation of treatment. The aim of this study was to investigate the prevalence of HLA-B*58:01 allele associated with allopurinol-induced SCARs in healthy Thai population. A retrospective study of 260 individual healthy subjects who living in Thailand. HLA-B were genotyped using sequence-specific oligonucleotides (PCR-SSOs).In this study, we identified the prevalence of HLA-B alleles consist ofHLA-B*46:01 (12.69%), HLA-B*15:02 (8.85%), HLA-B*13:01 (6.35%), HLA-B*40:01 (6.35%), HLA-B*38:02 (5.00%), HLA-B*51:01 (5.00%), HLA-B*58:01 (4.81%), HLA-B*44:03 (4.62%), HLA-B*18:01 (3.85%) and HLA-B*15:25 (3.08%). Therefore, the distribution of HLA-B*58:01 will support the clinical implementation and screening usage of allopurinol in Thai population.

Keywords: allopurinol, HLA-B*58: 01, Thai population, SCARs

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Authors: Sandeep Pandey, Nimra Habib, Ranjana Singh, Abbas Ali Mahdi

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Leukemia is a malignancy of blood that mainly affects children and young adults; while advancement in the early diagnosis will have the potential to improve the outcome of diseases. A wide range of disease including leukemia shows inflammatory signals in their pathogenesis. In a pilot study conducted in our laboratory, 52 people were screened, of which 26 had leukemia and 26 were free from any kind of malignancy. We performed the estimation of the inflammatory cytokine Interleukin-8 and it was found significantly raised in all the leukemia patients concerning healthy volunteers who participated in the study. Flow cytometry had been performed for the confirmation of leukemia and further genomic, and proteomic, analyses of the sample revealed that IL-8 levels showed a positive correlation in patients with leukemia. The results had shown constitutive secretion of interleukin-8 by leukemia cells. So, our finding demonstrated that IL-8 is considered to have a role in the pathogenesis of leukemia, and quantification of IL-8 levels in leukemia conditions might be more useful and feasible in the clinical setting for the prediction of drug responses where it may represent a putative target for innovative diagnostic toward effective therapeutic approaches. However, further research explorations in this area are needed that include a greater number of patients with all different forms of leukemia, and estimating their IL-8 levels may hold the key for the additional predictive values on the recurrence of leukemia and its prognosis.

Keywords: T-ALL, IL-8, leukemia pathogenesis, cancer therapeutics

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Authors: T. A. Ajiboye

Abstract:

This study examines the effects of health education programme on knowledge and prevention of cerebrovascular disease among hypertensive patients in University College Hospital, Ibadan. A quasi-experimental design was adopted for the study. 100 hypertensive patients were conveniently selected from general outpatient department in UCH. Data generated were analyzed using ANOVA at 0.05 alpha levels. The findings of the study revealed that health education programme significantly influenced both the knowledge of hypertensive patients (F=22.70; DF=1/99; p < .05) and their attitude (F=10.377; DF=1/99; p < .05) on cerebrovascular disease. Findings also discovered that health education programme significantly reduce the complication of hypertension to cerebrovascular disease (F= 16.41; DF=7/286; p < 0.05) among the hypertensive patients at UCH. Based on the findings, it is recommended that hypertensive patients should relieve themselves from stress, engage themselves on regular exercises, compliance with drug and diet regimes coupled with keeping up of regular appointment. Government should design health information that will center on hypertension and cerebrovascular disease so as to keep health and community development problems to the barest minimum. Finally, there should be provision of social amenities and recreational centers, as this will prevents hypertension problems.

Keywords: cerebrovascular disease, effectiveness, health education, hypertension, knowledge, prevention

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Authors: Daniel C. Bonzo

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Practical considerations lead to the use of unit of analysis within subjects, e.g., bleeding episodes or treatment-related adverse events, in rare disease settings. This is coupled with data augmentation techniques such as extrapolation to enlarge the subject base. In general, one can think about extrapolation of data as extending information and conclusions from one estimand to another estimand. This approach induces hierarchichal clustered data with varying cluster sizes. Extrapolation of clinical trial data is being accepted increasingly by regulatory agencies as a means of generating data in diverse situations during drug development process. Under certain circumstances, data can be extrapolated to a different population, a different but related indication, and different but similar product. We consider here the problem of estimation (point and interval) using a mixed-models approach under an extrapolation. It is proposed that estimators (point and interval) be constructed using weighting schemes for the clusters, e.g., equally weighted and with weights proportional to cluster size. Simulated data generated under varying scenarios are then used to evaluate the performance of this approach. In conclusion, the evaluation result showed that the approach is a useful means for improving statistical inference in rare disease settings and thus aids not only signal detection but risk-benefit evaluation as well.

Keywords: clustered data, estimand, extrapolation, mixed model

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