Search results for: extremely drug- resistant
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 3686

Search results for: extremely drug- resistant

2996 Mathematical Modeling on Capturing of Magnetic Nanoparticles in an Implant Assisted Channel for Magnetic Drug Targeting

Authors: Shashi Sharma, V. K. Katiyar, Uaday Singh

Abstract:

The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.

Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling

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2995 The Efficacy of Andrographis paniculata and Chromolaena odorata Plant Extract against Malaria Parasite

Authors: Funmilola O. Omoya, Abdul O. Momoh

Abstract:

Malaria constitutes one of the major health problems in Nigeria. One of the reasons attributed for the upsurge was the development of resistance of Plasmodium falciparum and the emergence of multi-resistant strains of the parasite to anti-malaria drugs. A continued search for other effective, safe and cheap plant-based anti-malaria agents thus becomes imperative in the face of these difficulties. The objective of this study is therefore to evaluate the in vivo anti-malarial efficacy of ethanolic extracts of Chromolaena odorata and Androgaphis paniculata leaves. The two plants were evaluated for their anti-malaria efficacy in vivo in a 4-day curative test assay against Plasmodium berghei strain in mice. The group treated with 500mg/ml dose of ethanolic extract of A. paniculata plant showed parasite suppression with increase in Packed Cell Volume (PCV) value except day 3 which showed a slight decrease in PCV value. During the 4-day curative test, an increase in the PCV values, weight measurement and zero count of Plasmodium berghei parasite values was recorded after day 3 of drug administration. These results obtained in group treated with A. paniculata extract showed anti-malarial efficacy with higher mortality rate in parasitaemia count when compared with Chromolaena odorata group. These results justify the use of ethanolic extracts of A. paniculata plant as medicinal herb used in folklore medicine in the treatment of malaria.

Keywords: anti-malaria, curative, plant-based anti-malaria agents, biology

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2994 The Bloom of 3D Printing in the Health Care Industry

Authors: Mihika Shivkumar, Krishna Kumar, C. Perisamy

Abstract:

3D printing is a method of manufacturing wherein materials, such as plastic or metal, are deposited in layers one on top of the other to produce a three dimensional object. 3D printing is most commonly associated with creating engineering prototypes. However, its applications in the field of human health care have been frequently disregarded. Medical applications for 3D printing are expanding rapidly and are envisaged to revolutionize health care. Medical applications for 3D printing, both present and its potential, can be categorized broadly, including: creation of customized prosthetics tissue and organ fabrication; creation of implants, and anatomical models and pharmaceutical research regarding drug dosage forms. This piece breaks down bioprinting in the healthcare sector. It focuses on the better subtle elements of every particular point, including how 3D printing functions in the present, its impediments, and future applications in the health care sector.

Keywords: bio-printing, prototype, drug delivery, organ regeneration

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2993 Targeting Calcium Dysregulation for Treatment of Dementia in Alzheimer's Disease

Authors: Huafeng Wei

Abstract:

Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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2992 Inclusion Complexes of Some Imidazoline Drugs with Cucurbit[N]Uril (N=7,8): Preparation, Characterization and Theoretical Calculations

Authors: Fakhreldin O. Suliman, Alia H. Al-Battashi

Abstract:

This work explored the interaction of three different imidazoline drugs, naphazoline nitrate (NPH), oxymetazoline hydrochloride (OXY) and xylometazoline hydrochloride (XYL) with two different synthesized cucurbit[n]urils CB[n], cucurbit[7]uril (CB[7]) and cucuribit[8]uril (CB[8]). Three binary inclusion complexes have been investigated in solution and in the solid state. The solid complexes were obtained by lyophilization, whereas the physical mixtures of guests and hosts at a stoichiometric ratio of 1:1 were obtained for each drug. 1HNMR, electrospray ionization mass spectrometry (ESI-MS), and matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF) mass spectrometry was used to study the complexes prepared in aqueous media. The lyophilized solid complexes were characterized by Fourier transform-infrared spectroscopy (FT-IR), powder X-ray diffractometry (PXRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). MS, FT-IR and PXRD experimental results established in this work reveal that NPH, OXY and XYL molecules form stable inclusion complexes with the two hosts. The TGA and DSC confirmed the enhancement of the thermal stability of each drug and the production of a thermally stable solid complex. The 1HNMR has shown that the protons of the guests faced shifting in ppm and broadening of their peaks upon the formation of inclusion complexes with the selected CB[n]. The aromatic protons of the guest exhibited the highest changes in the chemical shifts and shape of the NMR peaks, suggesting their inclusion into the cavity of the CB[n]. The diffusion coefficients (D), developed from the diffusion-controlled NMR Spectroscopy (DOSY) measurements, for the complexation of the selected imidazoline drugs with CB[7] and CB[8], were decreased in the presence of hosts compared to the free guests indicating the formation of the guest-host adduct. Furthermore, we conducted molecular dynamic simulations and quantum mechanics calculations on these complexes. The results of the theoretical study corroborate the experimental findings and have also shed light on the mechanism of inclusion of the guests into the two hosts. This study generates initial data for potential drug delivery or drug formulation systems for these three selected imidazoline drug compounds based on their inclusion into the CB[n] cavities.

Keywords: cucurbit[n]urils, imidazoline, inclusion complexes, molecular dynamics, DFT calculations, mass spectrometry

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2991 Enzymatic Activities of Two Iranian Wheat Cultivars Infected with Fusarium Culmorum

Authors: Parastoo Motallebi, Vahid Niknam, Hassan Ebrahimzadeh, Majid Hashemi

Abstract:

Wheat, the most strategically important worldwide crop, is widely grown in various countries. Based on international wheat production statistics (FAOSTAT database), the total production of wheat in 2012 was 13.8 in Iran. Fusarium culmorum is one of the principal causative agents of Fusarium crown rot (FCR), an overwhelming disease of wheat and barley which is in the early stages causing yield losses, stand reductions and rotting of root and lower stem tissues. In this study inoculation of two wheat seedlings of the susceptible cultivar Falat and the partially field-resistant cultivar Pishtaz were carried out in greenhouse conditions and root samples were taken for 6 days. The activity of peroxidase (POX) and polyphenoloxidase (PPO) enzymes were analyzed to identify possible relations between resistance and enzymatic activities. Although the POX and PPO activities in both geno types increased, this significant increase was more dominant in Pishtaz. The results showed an earlier elevation in the activity of these defense related enzymes in semi-resistant cv. Pishtaz after inoculation, suggested that the activities of POX and PPO in wheat geno types play an important role in the induction of resistance to this disease.

Keywords: Defense responses, Fusarium culmorum, Wheat

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2990 Formulation of Famotidine Solid Lipid Nanoparticles (SLN): Preparation, Evaluation and Release Study

Authors: Rachmat Mauludin, Nurmazidah

Abstract:

Background and purpose: Famotidine is an H2 receptor blocker. Absorption orally is rapid enough, but famotidine can be degraded by stomach acid causing dose reduction until 35.8% after 50 minutes. This drug also undergoes first-pass metabolism which reduced its bio availability only until 40-50%. To overcome these problems, Solid Lipid Nano particles (SLNs) as alternative delivery systems can be formulated. SLNs is a lipid-based drug delivery technology with 50-1000 nm particle size, where the drug incorporated into the bio compatible lipids and the lipid particles are stabilized using appropriate stabilizers. When the particle size is 200 nm or below, lipid containing famotidine can be absorbed through the lymphatic vessels to the subclavian vein, so first-pass metabolism can be avoided. Method: Famotidine SLNs with various compositions of stabilizer was prepared using a high-speed homogenization and sonication method. Then, the particle size distribution, zeta potential, entrapment efficiency, particle morphology and in vitro release profiles were evaluated. Optimization of sonication time also carried out. Result: Particle size of SLN by Particle Size Analyzer was in range 114.6 up to 455.267 nm. Ultrasonicated SLNs within 5 minutes generated smaller particle size than SLNs which was ultrasonicated for 10 and 15 minutes. Entrapment efficiency of SLNs were 74.17 up to 79.45%. Particle morphology of the SLNs was spherical and distributed individually. Release study of Famotidine revealed that in acid medium, 28.89 up to 80.55% of famotidine could be released after 2 hours. Nevertheless in basic medium, famotidine was released 40.5 up to 86.88% in the same period. Conclusion: The best formula was SLNs which stabilized by 4% Poloxamer 188 and 1 % Span 20, that had particle size 114.6 nm in diameter, 77.14% famotidine entrapped, and the particle morphology was spherical and distributed individually. SLNs with the best drug release profile was SLNs which stabilized by 4% Eudragit L 100-55 and 1% Tween 80 which had released 36.34 % in pH 1.2 solution, and 74.13% in pH 7.4 solution after 2 hours. The optimum sonication time was 5 minutes.

Keywords: famotodine, SLN, high speed homogenization, particle size, release study

Procedia PDF Downloads 842
2989 Magnetic Navigation of Nanoparticles inside a 3D Carotid Model

Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis

Abstract:

Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.

Keywords: artery, drug, nanoparticles, navigation

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2988 Systematic Formulation Development and Evaluation of Self-Nanoemulsifying Systems of Rosuvastatin Employing QbD Approach and Chemometric Techniques

Authors: Sarwar Beg, Gajanand Sharma, O. P. Katare, Bhupinder Singh

Abstract:

The current studies entail development of self-nano emulsifying drug delivery systems (SNEDDS) of rosuvastatin, employing rational QbD-based approach for enhancing its oral bioavailability. SNEDDS were prepared using the blend of lipidic and emulsifying excipients, i.e., Peceol, Tween 80, and Transcutol HP. The prepared formulations evaluated for in vitro drug release, ex vivo permeation, in situ perfusion studies and in vivo pharmacokinetic studies in rats, which demonstrated 3-4 fold improvement in biopharmaceutical performance of the developed formulations. Cytotoxicity studies using MTT assay and histopathological studies in intestinal cells revealed the lack of cytotoxicity and thereby safety and efficacy of the developed formulations.

Keywords: SNEDDS, bioavailability, solubility, Quality by Design (QbD)

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2987 Phytochemical Screening, Anticancer, Antibacterial and Antioxidant Activities of the Leaf Extracts of Mabolo (Diospyros philippinensis A. DC.)

Authors: Jarel Elgin Tolentino, Arby Denise Nera, Mary Rose Roco, Angela Vianca Aspa, Nikko Beltran, Else Dapat

Abstract:

Drug resistance by cells has been the problem in the medical field for decades now. The use of medicinal plants as a source of creating powerful drugs has been nowadays recognized worldwide to treat such resistant diseases. In the present study, the potential for Diospyros philippinensis A. DC. to inhibit growth of both bacteria and cancer cell line was conducted. The leaf crude extracts were screened for the presence of phytochemicals and examined for potential bioactivities by employing several assays like Kirby-Bauer disc diffusion method, DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay and MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay for the antibacterial, antioxidant and cytotoxic activities of the extract, respectively. Phytochemical test results of the extracts revealed the presence of alkaloids, flavonoids, saponins, phenols, quinones, cardiac glycosides, phlobatannins, carbohydrate, cardenolides and proteins. The leaf extracts were found to exhibit antibacterial activity against gram-positive bacteria, high antioxidant activity (99.22% ± 0.005) but did not show any sign of cytotoxicity towards HCT116 (ATCC CCL-247). The study therefore concludes that D. philippinensis A. DC. leaf extract can be a source of antibacterial and chemopreventive agents. This claim may be used as basis for future investigation.

Keywords: bioassay, medicinal plants, plant crude extracts, phytochemical screening

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2986 Akt: Isoform-Specific Regulation of Cellular Signaling in Cancer

Authors: Bhumika Wadhwa, Fayaz Malik

Abstract:

The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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2985 Development of capsaicin-loaded nanostructured lipid carriers for topical application

Authors: Kwanputtha Arunprasert, Chaiyakarn Pornpitchanarong, Praneet Opanasopit, , Prasopchai Patrojanasophon

Abstract:

Capsaicin, a recently FDA-approved drug for the topical treatment of neuropathic pain, is associated with several side effects like burning sensation and erythema leading to severe skin irritation and poor patient compliance. These unwanted side effects are due to the rapid penetration of capsaicin into the epidermis and low permeation to the dermis layer. The purpose of this study was to develop nanostructured lipid carriers (NLCs) that entrapped capsaicin for reducing dermal irritation. Solid lipid (glyceryl monostearate (GM), cetyl palmitate (CP), cetyl alcohol (COH), stearic acid (SA), and stearyl alcohol (SOH)) and surfactant (Tween®80, Tween®20, and Span®20) were varied to obtained optimal capsaicin-loaded NLCs. The formulation using CP as solid lipid and Tween®80 as a surfactant (F2) demonstrated the smallest size, excellent colloidal stability, and narrow range distribution of the particles as being analyzed using Zetasizer. The obtained capsaicin-loaded NLCs were then characterized by entrapment efficiency (EE) and loading capacity (LC). The release characteristics followed Higuchi kinetics, and the prolonged capsaicin release may result in the reduction in skin irritation. These results could demonstrate the potentials of capsaicinloaded lipid-based nanoparticles for topical drug delivery.

Keywords: capsaicin, lipid-based nanoparticles, nanostructured lipid carriers, topical drug delivery system

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2984 The Impact of Intelligent Control Systems on Biomedical Engineering and Research

Authors: Melkamu Tadesse Getachew

Abstract:

Intelligent control systems have revolutionized biomedical engineering, advancing research and enhancing medical practice. This review paper examines the impact of intelligent control on various aspects of biomedical engineering. It analyzes how these systems enhance precision and accuracy in biomedical instrumentation, improving diagnostics, monitoring, and treatment. Integration challenges are addressed, and potential solutions are proposed. The paper also investigates the optimization of drug delivery systems through intelligent control. It explores how intelligent systems contribute to precise dosing, targeted drug release, and personalized medicine. Challenges related to controlled drug release and patient variability are discussed, along with potential avenues for overcoming them. The comparison of algorithms used in intelligent control systems in biomedical control is also reviewed. The implications of intelligent control in computational and systems biology are explored, showcasing how these systems enable enhanced analysis and prediction of complex biological processes. Challenges such as interpretability, human-machine interaction, and machine reliability are examined, along with potential solutions. Intelligent control in biomedical engineering also plays a crucial role in risk management during surgical operations. This section demonstrates how intelligent systems improve patient safety and surgical outcomes when integrated into surgical robots, augmented reality, and preoperative planning. The challenges associated with these implementations and potential solutions are discussed in detail. In summary, this review paper comprehensively explores the widespread impact of intelligent control on biomedical engineering, showing the future of human health issues promising. It discusses application areas, challenges, and potential solutions, highlighting the transformative potential of these systems in advancing research and improving medical practice.

Keywords: Intelligent control systems, biomedical instrumentation, drug delivery systems, robotic surgical instruments, Computational monitoring and modeling

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2983 Studies On Triazole Resistant Candida Albicans Expressing ERG11 Gene Among Adult Females In Abakaliki; Nigeria

Authors: Agumah N. B. Orji, M. U., Oru C. M., Ugbo, E. N., Onwuliri E. A Nwakaeze, E. A.,

Abstract:

ERG11 gene has been reported to be one of the genes whose expression is responsible for resistance of Candida to various triazole drugs, which are first line treatment for candidiasis. This study was carried out to determine the prevalence of Triazole (Fluconazole and voriconazole) resistant Candida albicans expressing ERG11 gene from adult females in Abakaliki. Urine and vaginal swab samples were randomly collected from volunteers after obtaining their consent to participate in the study. A total of 565 adult females participated in the study. A total of 340 urine specimens and 288 vaginal swab specimens were collected. Direct wet mount technique, as well as culture in Trichomonas broth, were used to examine the urine and vaginal swab specimens for the presence of motile Trichomonads. The Trichomonas broth used was selective for both T. vaginalis and C. albicans. Broths that yielded budding yeast cells after microscopy were subcultured on to Sabouraud dextrose agar, after which Germ tube test was carried out to confirm the presence of C. albicans. Biochemical tests, including carbohydrate fermentation and urease utilization, were also performed. Antibiogram of C. albicans isolates obtained from this study was carried out using commercially available azole drugs. Fluconazole and voriconazole were selected as Triazole drugs used for this study. Nystatin was used as a tangential control. An MIC test was carried out with E-strips on some of the resistant C. albicans isolates A total of 6 isolates that resisted all the azole drugs were selected and screened for the presence of ERG11 gene using Reverse transcriptase polymerase chain reaction technique. The total prevalence recorded for C. albicans was 13.0%. Frequency was statistically higher in Pregnant (7.96%) than non pregnant (5.09%) volunteers (X2=0.94 at P=0.05). With respect to clinical samples, frequency was higher in vaginal swabs samples (7.96%) than Urine samples (5.09%) (X2=9.05 at P=0.05). Volunteers within the age group 26-30 years recorded the highest prevalence (4.46%), while those within the age group 36-40 years recorded the lowest at 1.27%(X2=4.34 at P=0.05). In pregnant female participants, the highest frequency was recorded with those in their 3rd trimester (4.14%), while lowest incidence was recorded for those in their first trimester (0.80%). Antibiogram results from this study showed that C. albicans isolates obtained from this study resisted Fluconazole (72%) more than Voriconazole (57%). Only one out of the six selected isolates yielded resistance in the MIC test. Results obtained from the RT-PCR showed that there was no expression of ERG11 gene among the fluconazole resistant isolates of C. albicans. Observed resistance may be due to other factors other than expression of ERG11 gene.

Keywords: candida, ERG11, triazole, nigeria

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2982 Antibiotic Potential of Bioactive Compounds from a Marine Streptomyces Isolated from South Pacific Sediments

Authors: Ilaisa Kacivakanadina, Samson Viulu, Brad Carte, Katy Soapi

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Two bioactive compounds namely Vulgamycin (also known as enterocin A) and 5-deoxyenterocin were purified from a marine bacterial strain 1903. Strain 1903 was isolated from marine sediments collected from the Solomon Islands. Morphological features of strain 1903 showed that it belongs to the genus Streptomyces. The two secondary metabolites were extracted using EtOAc and purified by chromatographic methods using EtOAc and hexane solvents. Mass spectrum and NMR data of pure compounds were used to elucidate the chemical structures. In this study, results showed that both compounds were strongly active against Wild Type Staphylococcus aureus (WTSA) (MIC < 1 µg/mL) and in Brine shrimp assays (BSA) (MIC < 1 µg/mL). 5-deoxyenterocin was also active against Rifamycin resistant Staphylococcus aureus (RRSA) (MIC, 250 µg/mL) while vulgamycin showed bioactivity against Methicillin resistant Staphylococcus aureus (MRSA) (MIC 250 µg/mL). To the best of our knowledge, this is the first study that showed the bio-activity of 5-deoxyenterocin. This is also the first time that Vulgamycin has been reported to be active in a BSA. There has not been any mechanism of action studies for these two compounds against pathogens. This warrants further studies on their mechanism of action against microbial pathogens.

Keywords: 5-deoxyenterocin, bioactivity, brine shrimp assay (BSA), vulgamycin

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2981 Antidiabetic and Admet Pharmacokinetic Properties of Grewia Lasiocarpa E. Mey. Ex Harv. Stem Bark Extracts: An in Vitro and in Silico Study

Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.

Abstract:

Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.

Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET

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2980 Projects and Limits of Memory Engineering: A Case of Lithuanian Partisan War

Authors: Mingaile Jurkute, Vilnius University

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The memory of the Lithuanian partisan war (1944-1953) underwent extremely dramatic transformations. During this war, the image of the resistance and a partisan was one of the key elements of Lithuanian identity. Its importance is evidenced by the extremely large legacy of songs about partisans, no other topic has collected so much folklore in Lithuania. In the Soviet years, this resistance was practically forced to be forgotten. Terror and Soviet laws have forced people to stop talking about the events, even in the family circle. In addition, the Soviets created their own propaganda story, reinterpreting the Lithuanian partisan war, presenting partisans as bandits who brutally tortured and murdered locals. But even in the Soviet years, the memory could neither be completely suppressed, nor completely transformed into wishful shape. The analysis of fiction and cinema shows that the traumatic memory of real events rushed to the surface, thus transforming the very propagandistic narrative. After the restoration of the Republic of Lithuania in 1990, the Lithuanian partisan war was gradually returned to the central place of Lithuanian history. After 2014 the nationalist heroic narrative about Lithuanian partisans became the central narrative of modern Lithuanian history. Nevertheless, interviews I conducted in Lithuanian villages reveal that the memory of local communities and families preserves quite different experiences that do not fit into neither the Soviet narrative nor the heroic one. Such experiences include, for example, partisan violence against local families. This paper is about the efforts of two political ideologies (the Soviet and the Lithuanian patriotic) to use the history of the Lithuanian partisans for their own needs, and the attempts of small communities (mostly families) to resist these efforts. The research reveals that family memory, even when opposed to aggressive state memory policies, can preserve counter-narratives by exploiting unexpected objects beyond the control of the state, such as nature and wildlife. Basically, the paper analyses the limits of the instrumentalization of memory, even by extremely aggressive political regimes.

Keywords: collective memory, post-memory, violence, military conflict, family memory

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2979 In vitro Disaggregation and Dissolution of Four IR Lamotrigine Solid Dosage Forms

Authors: Ilaria Manca, Ilaria Manca, Francesca Pettinau, Ignazia Mocci, Elisabetta M. Usai, Barbara Pittau

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Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to test and compare various solid forms of immediate release (IR) lamotrigine products, at different strenghts, in order to study their disaggregation and dissolution behavior. IR products are designed to release their active substance promptly after administration. Concentration of hydrochloric acid in gastric juice is about 0.1-0.001 M, so FDA (Food and Drug Administration) recommends, for lamotrigine regular tablets, dissolution tests in HCl 0.1 M.Toinvestigate the pH dependency of drug release in the entire gastrointestinal tract, we worked at two additional media with different pH values (4.5 and 6.8), that reflect conditions in it. To afford acceptable dissolution rates, tablets must disintegrate. Disaggregation of constituent particles increases the surface area and substantially increases the dissolution rate. For this reason availability of an active substance from tablets depends on its ability to disintegrate fast in dissolution media. pH of gastrointestinal fluid affects drug absorption by conditioning its solubility and dissolution, but also tablet disintegration may be influenced by it. To obtain information about the quantitative relationship between different mixture components, Nuclear Magnetic Resonance (NMR) spectroscopy was used. We also investigate tablet hardness. The investigation carried out confirms pH 1.2 as the ideal environment for the immediate availability of the active substance.

Keywords: dissolution, disaggregation, Lamotrigine, bioequivalence

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2978 Combating Malaria: A Drug Discovery Approach Using Thiazole Derivatives Against Prolific Parasite Enzyme PfPKG

Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

Abstract:

Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

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2977 Stability and Rheology of Sodium Diclofenac-Loaded and Unloaded Palm Kernel Oil Esters Nanoemulsion Systems

Authors: Malahat Rezaee, Mahiran Basri, Raja Noor Zaliha Raja Abdul Rahman, Abu Bakar Salleh

Abstract:

Sodium diclofenac is one of the most commonly used drugs of nonsteroidal anti-inflammatory drugs (NSAIDs). It is especially effective in the controlling the severe conditions of inflammation and pain, musculoskeletal disorders, arthritis, and dysmenorrhea. Formulation as nanoemulsions is one of the nanoscience approaches that have been progressively considered in pharmaceutical science for transdermal delivery of drug. Nanoemulsions are a type of emulsion with particle sizes ranging from 20 nm to 200 nm. An emulsion is formed by the dispersion of one liquid, usually the oil phase in another immiscible liquid, water phase that is stabilized using surfactant. Palm kernel oil esters (PKOEs), in comparison to other oils; contain higher amounts of shorter chain esters, which suitable to be applied in micro and nanoemulsion systems as a carrier for actives, with excellent wetting behavior without the oily feeling. This research was aimed to study the effect of O/S ratio on stability and rheological behavior of sodium diclofenac loaded and unloaded palm kernel oil esters nanoemulsion systems. The effect of different O/S ratio of 0.25, 0.50, 0.75, 1.00 and 1.25 on stability of the drug-loaded and unloaded nanoemulsion formulations was evaluated by centrifugation, freeze-thaw cycle and storage stability tests. Lecithin and cremophor EL were used as surfactant. The stability of the prepared nanoemulsion formulations was assessed based on the change in zeta potential and droplet size as a function of time. Instability mechanisms including coalescence and Ostwald ripening for the nanoemulsion system were discussed. In comparison between drug-loaded and unloaded nanoemulsion formulations, drug-loaded formulations represented smaller particle size and higher stability. In addition, the O/S ratio of 0.5 was found to be the best ratio of oil and surfactant for production of a nanoemulsion with the highest stability. The effect of O/S ratio on rheological properties of drug-loaded and unloaded nanoemulsion systems was studied by plotting the flow curves of shear stress (τ) and viscosity (η) as a function of shear rate (γ). The data were fitted to the Power Law model. The results showed that all nanoemulsion formulations exhibited non-Newtonian flow behaviour by displaying shear thinning behaviour. Viscosity and yield stress were also evaluated. The nanoemulsion formulation with the O/S ratio of 0.5 represented higher viscosity and K values. In addition, the sodium diclofenac loaded formulations had more viscosity and higher yield stress than drug-unloaded formulations.

Keywords: nanoemulsions, palm kernel oil esters, sodium diclofenac, rheoligy, stability

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2976 Exploring Fluoroquinolone-Resistance Dynamics Using a Distinct in Vitro Fermentation Chicken Caeca Model

Authors: Bello Gonzalez T. D. J., Setten Van M., Essen Van A., Brouwer M., Veldman K. T.

Abstract:

Resistance to fluoroquinolones (FQ) has evolved increasingly over the years, posing a significant challenge for the treatment of human infections, particularly gastrointestinal tract infections caused by zoonotic bacteria transmitted through the food chain and environment. In broiler chickens, a relatively high proportion of FQ resistance has been observed in Escherichia coli indicator, Salmonella and Campylobacter isolates. We hypothesize that flumequine (Flu), used as a secondary choice for the treatment of poultry infections, could potentially be associated with a high proportion of FQ resistance. To evaluate this hypothesis, we used an in vitro fermentation chicken caeca model. Two continuous single-stage fermenters were used to simulate in real time the physiological conditions of the chicken caeca microbial content (temperature, pH, caecal content mixing, and anoxic environment). A pool of chicken caecal content containing FQ-resistant E. coli obtained from chickens at slaughter age was used as inoculum along with a spiked FQ-susceptible Campylobacter jejuni strain isolated from broilers. Flu was added to one of the fermenters (Flu-fermenter) every 24 hours for two days to evaluate the selection and maintenance of FQ resistance over time, while the other served as a control (C-Fermenter). The experiment duration was 5 days. Samples were collected at three different time points: before, during and after Flu administration. Serial dilutions were plated on Butzler culture media with and without Flu (8mg/L) and enrofloxacin (4mg/L) and on MacConkey culture media with and without Flu (4mg/L) and enrofloxacin (1mg/L) to determine the proportion of resistant strains over time. Positive cultures were identified by mass spectrometry and matrix-assisted laser desorption/ionization (MALDI). A subset of the obtained isolates were used for Whole Genome Sequencing analysis. Over time, E. coli exhibited positive growth in both fermenters, while C. jejuni growth was detected up to day 3. The proportion of Flu-resistant E. coli strains recovered remained consistent over time after antibiotic selective pressure, while in the C-fermenter, a decrease was observed at day 5; a similar pattern was observed in the enrofloxacin-resistant E. coli strains. This suggests that Flu might play a role in the selection and persistence of enrofloxacin resistance, compared to C-fermenter, where enrofloxacin-resistant E. coli strains appear at a later time. Furthermore, positive growth was detected from both fermenters only on Butzler plates without antibiotics. A subset of C. jejuni strains from the Flu-fermenter revealed that those strains were susceptible to ciprofloxacin (MIC < 0.12 μg/mL). A selection of E. coli strains from both fermenters revealed the presence of plasmid-mediated quinolone resistance (PMQR) (qnr-B19) in only one strain from the C-fermenter belonging to sequence type (ST) 48, and in all from Flu-fermenter belonged to ST189. Our results showed that Flu selective impact on PMQR-positive E. coli strains, while no effect was observed in C. jejuni. Maintenance of Flu-resistance was correlated with antibiotic selective pressure. Further studies into antibiotic resistance gene transfer among commensal and zoonotic bacteria in the chicken caeca content may help to elucidate the resistance spread mechanisms.

Keywords: fluoroquinolone-resistance, escherichia coli, campylobacter jejuni, in vitro model

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2975 Antihyperlipidemic Activity of Butea Monosperma in Triton WR 1339 Induced Hyperlipidemic Rats

Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

Abstract:

The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

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2974 Development of a New Method for the Evaluation of Heat Tolerant Wheat Genotypes for Genetic Studies and Wheat Breeding

Authors: Hameed Alsamadany, Nader Aryamanesh, Guijun Yan

Abstract:

Heat is one of the major abiotic stresses limiting wheat production worldwide. To identify heat tolerant genotypes, a newly designed system involving a large plastic box holding many layers of filter papers positioned vertically with wheat seeds sown in between for the ease of screening large number of wheat geno types was developed and used to study heat tolerance. A collection of 499 wheat geno types were screened under heat stress (35ºC) and non-stress (25ºC) conditions using the new method. Compared with those under non-stress conditions, a substantial and very significant reduction in seedling length (SL) under heat stress was observed with an average reduction of 11.7 cm (P<0.01). A damage index (DI) of each geno type based on SL under the two temperatures was calculated and used to rank the genotypes. Three hexaploid geno types of Triticum aestivum [Perenjori (DI= -0.09), Pakistan W 20B (-0.18) and SST16 (-0.28)], all growing better at 35ºC than at 25ºC were identified as extremely heat tolerant (EHT). Two hexaploid genotypes of T. aestivum [Synthetic wheat (0.93) and Stiletto (0.92)] and two tetraploid genotypes of T. turgidum ssp dicoccoides [G3211 (0.98) and G3100 (0.93)] were identified as extremely heat susceptible (EHS). Another 14 geno types were classified as heat tolerant (HT) and 478 as heat susceptible (HS). Extremely heat tolerant and heat susceptible geno types were used to develop re combinant inbreeding line populations for genetic studies. Four major QTLs, HTI4D, HTI3B.1, HTI3B.2 and HTI3A located on wheat chromosomes 4D, 3B (x2) and 3A, explaining up to 34.67 %, 28.93 %, 13.46% % and 11.34% phenotypic variation, respectively, were detected. The four QTLs together accounted for 88.40% of the total phenotypic variation. Random wheat geno types possessing the four heat tolerant alleles performed significantly better under the heat condition than those lacking the heat tolerant alleles indicating the importance of the four QTLs in conferring heat tolerance in wheat. Molecular markers are being developed for marker assisted breeding of heat tolerant wheat.

Keywords: bread wheat, heat tolerance, screening, RILs, QTL mapping, association analysis

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2973 Affordable and Sustainable Housing Construction: Case Studies

Authors: Tony Rizk

Abstract:

Recent material advances and cost efficiencies are transforming the housing industry away from traditional lumber and gypsum material to alternate fiberboard material that is workable and resistant to fire, mold, and pest infestation. The use of these materials may add to the initial cost of construction. However, the life cycle (cradle to grave) cost of houses using these construction materials and methods are lower than the life cycle costs using traditional housing construction materials and methods. This paper will present four (4) case studies of sustainable house projects. Each project was designed and constructed using earthen-based, sustainable fiberboard material that is resistant to fire, mold, and infestation and fabricated at a very low material calorific value. These house projects have a living space ranging from 625 sq. ft. for an accessory dwelling unit and up to 3,200 sq. ft. 1-story and 2-story homes. For each case study, we will present the house engineering design and construction method, the initial construction costs, a summary of the life cycle costs, and a comparison to the life cycle cost of traditional housing available in the literature.

Keywords: residential housing, sustainable housing, life cycle cost, fire resistance, mold, infestation resistance

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2972 Development of selective human matrix metalloproteinases-9 (hMMP-9) inhibitors as potent diabetic wound healing agents

Authors: Geetakshi Arora, Danish Malhotra

Abstract:

Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

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2971 Research on Sensitivity of Geological Disasters in Road Area Based on Analytic Hierarchy Process

Authors: Li Yongyi

Abstract:

In order to explore the distribution of geological disasters within the expressway area of Shaanxi Province, the Analytic Hierarchy Process theory is applied based on the geographic information system technology platform, and the ground elevation, rainfall, vegetation coverage and other indicators are selected for analysis, and the expressway area is sensitive Sexual evaluation. The results show that the highway area disasters in Shaanxi Province are mainly distributed in the southern mountainous areas and are dominated by landslides; the disaster area ratio basically increases with the increase in ground elevation, surface slope, surface undulation, rainfall, and vegetation coverage. The increase in the distance from the river shows a decreasing trend; after grading the disaster sensitivity within 5km of the expressway, the extremely sensitive area, the highly sensitive area, the medium sensitive area, the low sensitive area, and the extremely low sensitive area respectively account for 8.17%、15.80%、22.99%、26.22%、26.82%. Highly sensitive road areas are mainly distributed in southern Shaanxi.

Keywords: highway engineering, sensitivity, analytic hierarchy process, geological hazard, road area

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2970 The Mechanical and Comfort Properties of Cotton/Micro-Tencel Lawn Fabrics

Authors: Abdul Basit, Shahid Latif, Shah Mehmood

Abstract:

Lawn fabric was usually prepared from originally of linen but at present chiefly cotton. Lawn fabric is worn in summer. Cotton Lawn is a lightweight pure cloth which is heavier than voile. It is so fine that it is somewhat transparent. It is soft and superb to wear thus it is perfect for summer clothes or for regular wear in hotter climates. Tencel (Lyocell) fiber is considered as the fiber of the future as Tencel fibers are absorbent, soft, and extremely strong when wet or dry, and resistant to wrinkles. Fibers are more absorbent than cotton, softer than silk and cooler than linen. High water absorption and water vapor absorption give more heat capacity and heat balancing effect for thermo-regulation. This thermo-regulation is analogous with the action of phase-change-materials. The thermal wear properties result in cool and dry touch that gives cooling effect in sportswear, and the warmth properties (when used as an insulation layer). These cooling and warming effects are adaptive to the environment giving comfort in a broad range of climatic conditions. In this work, single yarns of Ne 80s were made. Yarns were made from conventional ring spinning. Different yarns of 100% cotton, 100% micro-Tencel and Cotton:micro-Tencel blends (67:33, 50:50:33:67) were made. The mechanical and comfort properties of the woven fabrics were compared. The mechanical properties include the tensile and tear strength, bending length, pilling and abrasion resistance whereas comfort properties include the air permeability, moisture management and thermal resistance. It is found that as the content of the micro-Tencel is increased, the mechanical and comfort properties of the woven fabric are also increased.

Keywords: combed cotton, comfort properties , mechanical properties, micro-Tencel

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2969 Pathogenic Escherichia Coli Strains and Their Antibiotic Susceptibility Profiles in Cases of Child Diarrhea at Addis Ababa University, College of Health Sciences, Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

Authors: Benyam Zenebe, Tesfaye Sisay, Gurja Belay, Workabeba Abebe

Abstract:

Background: The prevalence and antibiogram of pathogenic E. coli strains, which cause diarrhea vary from region to region, and even within countries in the same geographical area. In Ethiopia, diagnostic approaches to E. coli induced diarrhea in children less than five years of age are not standardized. The aim of this study was to determine the involvement of pathogenic E. coli strains in child diarrhea and determine the antibiograms of the isolates in children less than 5 years of age with diarrhea at Addis Ababa University College of Health Sciences TikurAnbessa Specialized Hospital, Addis Ababa, Ethiopia. Methods: A purposive study that included 98 diarrheic children less than five years of age was conducted at Addis Ababa University College of Health Sciences, TikurAnbessa Specialized Hospital, Addis Ababa, Ethiopia to detect pathogenic E. coli biotypes. Stool culture was used to identify presumptive E. coliisolates. Presumptive isolates were confirmed by biochemical tests, and antimicrobial susceptibility tests were performed on confirmed E. coli isolates by the disk diffusion method. DNA was extracted from confirmed isolates by a heating method and subjected to Polymerase Chain Reaction or the presence of virulence genes. Amplified PCR products were analyzed by agarose gel electrophoresis. Data were collected on child demographics and clinical conditions using administered questionnaires. The prevalence of E. coli strains from the total diarrheic children, and the prevalence of pathogenic strains from total E. coli isolates along with their susceptibility profiles; the distribution of pathogenic E.coli biotypes among different age groups and between the sexes were determined by using descriptive statistics. Result: Out of 98 stool specimens collected from diarrheic children less than 5 years of age, 75 presumptive E. coli isolates were identified by culture; further confirmation by biochemical tests showed that only 56 of the isolates were E. coli; 29 of the isolates were found in male children and 27 of them in female children. Out of the 58 isolates of E. coli, 25 pathotypes belonging to different classes of pathogenic strains: STEC, EPEC, EHEC, EAEC were detected by using the PCR technique. Pathogenic E. coli exhibited high rates of antibiotic resistance to many of the antibiotics tested. Moreover, they exhibited multiple drug resistance. Conclusion: This study found that the isolation rate of E. coli and the involvement of antibiotic-resistant pathogenic E. coli in diarrheic children is prominent, and hence focus should be given on the diagnosis and antimicrobial sensitivity testing of pathogenic E. coli at Addis Ababa University College of Health Sciences TikurAnbessa Specialized Hospital. Among antibiotics tested, Cefotitan could be a drug of choice to treat E. coli.

Keywords: antibiotic susceptibility profile, children, diarrhea, E. coli, pathogenic

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2968 A Benchtop Experiment to Study Changes in Tracer Distribution in the Subarachnoid Space

Authors: Smruti Mahapatra, Dipankar Biswas, Richard Um, Michael Meggyesy, Riccardo Serra, Noah Gorelick, Steven Marra, Amir Manbachi, Mark G. Luciano

Abstract:

Intracranial pressure (ICP) is profoundly regulated by the effects of cardiac pulsation and the volume of the incoming blood. Furthermore, these effects on ICP are incremented by the presence of a rigid skull that does not allow for changes in total volume during the cardiac cycle. These factors play a pivotal role in cerebrospinal fluid (CSF) dynamics and distribution, with consequences that are not well understood to this date and that may have a deep effect on the Central Nervous System (CNS) functioning. We designed this study with two specific aims: (a) To study how pulsatility influences local CSF flow, and (b) To study how modulating intracranial pressure affects drug distribution throughout the SAS globally. In order to achieve these aims, we built an elaborate in-vitro model of the SAS closely mimicking the dimensions and flow rates of physiological systems. To modulate intracranial pressure, we used an intracranially implanted, cardiac-gated, volume-oscillating balloon (CADENCE device). Commercially available dye was used to visualize changes in CSF flow. We first implemented two control cases, seeing how the tracer behaves in the presence of pulsations from the brain phantom and the balloon individually. After establishing the controls, we tested 2 cases, having the brain and the balloon pulsate together in sync and out of sync. We then analyzed the distribution area using image processing software. The in-sync case produced a significant increase, 5x times, in the tracer distribution area relative to the out-of-sync case. Assuming that the tracer fluid would mimic blood flow movement, a drug introduced in the SAS with such a system in place would enhance drug distribution and increase the bioavailability of therapeutic drugs to a wider spectrum of brain tissue.

Keywords: blood-brain barrier, cardiac-gated, cerebrospinal fluid, drug delivery, neurosurgery

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2967 An Assessment of Adverse Events Following Immunization Reporting Pattern of Selected Vaccines in VigiAccess

Authors: Peter Yamoah, Frasia Oosthuizen

Abstract:

Introduction: Reporting of Adverse Events Following Immunization continues to be a challenge. Pharmacovigilance centers throughout the world are mandated by the WHO to submit AEFI reports from various countries to a large pool of adverse drug reaction electronic database called Vigibase. Despite the relevant information of AEFI in Vigibase, it is unavailable to the general public. However, the WHO has an alternative website called VigiAccess which is an open access website serving as a repository of reported adverse drug reactions and AEFIs. The aim of the study was to ascertain the reporting pattern of a number of commonly used vaccines in VigiAccess. Methods: VigiAccess was thoroughly searched on the 5th of February 2018 for AEFI reports of measles vaccine, oral polio vaccine (OPV), yellow fever vaccine, pneumococcal vaccine, rotavirus vaccine, meningococcal vaccine, tetanus vaccine and tuberculosis (BCG) vaccine. These were reports from all pharmacovigilance centers in the world from the time they joined the WHO drug monitoring program. Results: After a thorough search in VigiAccess, there were 9,062 measles vaccine AEFIs, 185,829 OPV AEFIs, 24,577 yellow fever vaccine AEFIs, 317,208 pneumococcal vaccine AEFIs, 73,513 rotavirus vaccine AEFIs, 145,447 meningococcal vaccine AEFIs, 22,781 tetanus vaccine AEFIs and 35,556 BCG vaccine AEFIs. Conclusion: The study revealed that out of the eight vaccines studied, pneumococcal vaccines are associated with the highest number of AEFIs whilst measles vaccines were associated with the least AEFIs.

Keywords: vaccines, adverse reactions, VigiAccess, adverse event reporting

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