Search results for: adverse drug effects

Authors: Leandra Prempeh, Emily Malugen

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Prenatal drug exposure can have a molecular impact on the hypothalamic and reward genes that regulate feeding behavior. This can impact feeding regulation, resulting in feeding difficulties and growth failure. This was potentially seen in “McKayla,” a 19- month old girl with a history of in-utero drug exposure, patent ductus arteriosus, and gastroesophageal reflux disease who presented for intensive day treatment feeding therapy. She was diagnosed with Avoidant Restrictive Food Intake Disorder, described as total food refusal and meeting 100% of her caloric needs from a gastrostomy tube. The primary goals during intensive feeding therapy were to increase her oral intake and decrease her reliance on supplementation with formula. Several behavioral antecedent manipulations were implemented to establish consistent responding and make progress towards treatment goals. This included multiple modified bolus placements (using underloaded and Nuk brush), reinforcement contingencies, and variety fading before stability was finally achieved. Following, increasing retention of bites then increasing volume and variety were goals targeted. From treatment onset to the last 3 days of treatment, McKayla's rate of rapid acceptance of bite presentations increased significantly from 33.33% to 93.13%, rapid swallowing went from 0.00% to 92.32%, and her percentage of inappropriate mealtime behavior and expels decreased from 58.33% and 100% to 2.31% and 7.68%, respectively. Overall, the treatment team successfully introduced and increased the bite size of 7 pureed foods, generalize the treatment to caregivers with high integrity, and began facilitating tube weaning. She was receiving about 33.42% of her needs by mouth at the time of discharge. Other nutritional concerns addressed during treatment included drinking a nutritionally complete drink out of an open cup and age appropriate growth. McKayla continued to have emesis almost daily, as was her baseline before starting treatment; however, the frequency during mealtime decreased. Overall, McKayla responded well to treatment. She had a very slow response to treatment and required a lot of antecedent manipulations to establish consistent responding. As the literature suggests, [drug]-exposed neonates, like McKayla, may be at increased risk for nutritional and growth challenges that may persist throughout development. This supports the need for longterm follow-up of infant growth.

Keywords: behavioral intervention, feeding problems, in-utero drug exposure, intensive multidisciplinary intervention

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Authors: Maryam Beiranvand

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Multi-drug resistance in various microorganisms has increased globally in many healthcare facilities. Less effective antimicrobial activity of drug therapies for infection control becomes trouble. Since 1980, no new type of antimicrobial drug has been identified, even though combinations of antibiotic drugs have been discovered almost every decade. Between 1981 and 2006, over 70% of novel pharmaceuticals and chemical agents came from natural sources. Microorganisms have yielded almost 22,000 natural compounds. The identification of antimicrobial components from endophytes bacteria could help overcome the threat posed by multi-drug resistant strains. The project aims to analyze and identify antimicrobial peptides isolated from entophytic bacteria and their activity against multidrug-resistant Gram-negative bacteria in South Korea. Endophytic Paenibacillus polymyxa. 4G3 isolated from the plant, Gynura procumbery exhibited considerable antimicrobial activity against Methicillin-resistant Staphylococcus aureus, and Escherichia coli. The Rapid Annotations using Subsystems Technology showed that the total size of the draft genome was 5,739,603bp, containing 5178 genes with 45.8% G+C content. Genome annotation using antiSMASH version 6.0.0 was performed, which predicted the most common types of non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS). In this study, diethyl aminoethyl cellulose (DEAEC) resin was used as the first step in purifying for unknown peptides, and then the target protein was identified using hydrophilic and hydrophobic solutions, optimal pH, and step-by-step tests for antimicrobial activity. This crude was subjected to C18 chromatography and elution with 0, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% methanol, respectively. Only the fraction eluted with 20% -60% methanol demonstrated good antimicrobial activity against MDR E. coli. The concentration of the active fragment was measured by the Brad-ford test, and Protein A280 - Thermo Fisher Scientific at the end by examining the SDS PAGE Resolving Gel, 10% Acrylamide and purity were confirmed. Our study showed that, based on the combined results of the analysis and purification. P polymyxa. 4G3 has a high potential exists for producing novel functions of polymyxin E and bacitracin against bacterial pathogens.

Keywords: endophytic bacteria, antimicrobial activity, antimicrobial peptide, whole genome sequencing analysis, multi -drug resistance gram negative bacteria

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Authors: Salma A. El-Marasy, Reham M. Abd-Elsalam, Omar A. Ahmed-Farid

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Dementia is characterized by impairments in memory and other cognitive abilities. This study aims to elucidate the possible ameliorative effect of silymarin on scopolamine-induced dementia using the object recognition test (ORT). The study was extended to demonstrate the role of cholinergic activity, oxidative stress, neuroinflammation, brain neurotransmitters and histopathological changes in the anti-amnestic effect of silymarin in demented rats. Wistar rats were pretreated with silymarin (200, 400, 800 mg/kg) or donepezil (10 mg/kg) orally for 14 consecutive days. Dementia was induced after the last drug administration by a single intraperitoneal dose of scopolamine (16 mg/kg). Then behavioral, biochemical, histopathological, and immunohistochemical analyses were then performed. Rats pretreated with silymarin counteracted scopolamine-induced non-spatial working memory impairment in the ORT and decreased acetylcholinesterase (AChE) activity, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), restored gamma-aminobutyric acid (GABA) and dopamine (DA) contents in the cortical and hippocampal brain homogenates. Silymarin dose-dependently reversed scopolamine-induced histopathological changes. Immunohistochemical analysis showed that silymarin dose-dependently mitigated protein expression of a glial fibrillary acidic protein (GFAP) and nuclear factor kappa-B (NF-κB) in the brain cortex and hippocampus. All these effects of silymarin were similar to that of the standard anti-amnestic drug, donepezil. This study reveals that the ameliorative effect of silymarin on scopolamine-induced dementia in rats using the ORT maybe in part mediated by, enhancement of cholinergic activity, anti-oxidant and anti-inflammatory activities as well as mitigation in brain neurotransmitters and histopathological changes.

Keywords: dementia, donepezil, object recognition test, rats, silymarin, scopolamine

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Authors: Francesco Berald, Yunhui Zhao

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The COVID-19 pandemic further extended the multi-year housing boom in advanced economies and emerging markets alike against massive monetary easing during the pandemic. In this paper, we analyze the pricing-out phenomenon in the U.S. residential housing market due to higher house prices associated with monetary easing. We first set up a stylized general equilibrium model and show that although monetary easing decreases the mortgage payment burden, it would raise house prices and lower housing affordability for first-time homebuyers (through the initial housing wealth channel and the liquidity constraint channel that increases repeat buyers’ housing demand), and increase housing wealth inequality between first-time and repeat homebuyers. We then use the U.S. household-level data to quantify the effect of the house price change on housing affordability relative to that of the interest rate change. We find evidence of the pricing-out effect for all homebuyers; moreover, we find that the pricing-out effect is stronger for first-time homebuyers than for repeat homebuyers. The paper highlights the importance of accounting for general equilibrium effects and distributional implications of monetary policy while assessing housing affordability. It also calls for complementing monetary easing with well-targeted policy measures that can boost housing affordability, particularly for first-time and lower-income households. Such measures are also needed during aggressive monetary tightening, given that the fall in house prices may be insufficient or too slow to fully offset the immediate adverse impact of higher rates on housing affordability.

Keywords: pricing-out, U.S. housing market, housing affordability, distributional effects, monetary policy

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Authors: Nashwa A. Mohamed

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Introduction: Omeprazole is a proton pump inhibitor used commonly in the treatment of acid-peptic disorders. Although omeprazole is generally well tolerated, serious adverse effects such as renal failure have been reported. Ginger is an antioxidant that could play a protective role in models of experimentally induced nephropathies. Aim of the work: The aim of this work was to study the possible histological changes induced by omeprazole on renal cortex and evaluate the possible protective effect of ginger on omeprazole-induced renal damage in adult male albino rats. Materials and methods: Twenty-four adult male albino rats divided into four groups (six rats each) were used in this study. Group I served as the control group. Rats of group II received only an aqueous extract of ginger daily for 3 months through a gastric tube. Rats of group III were received omeprazole orally through a gastric tube for 3 months. Rats of group IV were given both ginger and omeprazole at the same doses and through the same routes as the previous two groups. At the end of the experiment, the rats were sacrificed. Renal tissue samples were processed for light, immunohistochemical and electron microscopic examination. The obtained results were analysed morphometrically and statistically. Results: Omeprazole caused several histological changes in the form of loss of normal appearance of renal cortex with degenerative changes in the renal corpuscle and tubules. Cellular infilteration was also observed. The filteration barrier was markedly affected. Ginger ameliorated the omeprazole-induced histological changes. Conclusion: Omeprazole induced injurious effects on renal cortex. Coadministration of ginger can ameliorate the histological changes induced by omeprazole.

Keywords: ginger, kidney, omeprazole, rat

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Authors: S. Kudlacik-Kramarczyk, M. Kedzierska, B. Tyliszczak

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Recently, the continuous development of medicine and related sciences has been observed. Particular emphasis is directed on the development of biomaterials, i.e., non-toxic, biocompatible and biodegradable materials that may improve the effectiveness of treatment as well as the comfort of patients. This is particularly important in the case of cancer treatment. Currently, there are many methods of cancer treatment based primarily on chemotherapy and the surgical removal of the tumor, but it is worth noting that these therapies also cause many side effects. Among women, the most common cancer is breast cancer. It may be completely cured, but the consequence of treatment is partial or complete breast mastectomy and radiation therapy, which results in severe skin burns. The skin of the patient after radiation therapy is very burned, and therefore requires intensive care and high frequency of dressing changes. The traditional dressing adheres to the burn wounds and does not absorb adequate amount of exudate from injuries and the patient is forced to change the dressing every 2 hours. Therefore, the main purpose was to develop an innovative combination of dressing material with drug carriers that may be used in anti-cancer therapy. The innovation of this solution is the combination of these two products into one system, i.e., a transdermal system with the possibility of a controlled release of the drug- cytostatic. Besides, the possibility of modifying the hydrogel matrix with aloe vera juice provides this material with new features favorable from the point of view of healing processes of burn wounds resulting from the radiation therapy. In this study, hydrogel materials containing protein spheres with the active substance have been obtained as a result of photopolymerization process. The reaction mixture consisting of the protein (albumin) spheres incorporated with cytostatic, chitosan, adequate crosslinking agent and photoinitiator has been subjected to the UV radiation for 2 minutes. Prepared materials have been subjected to the numerous studies including the analysis of cytotoxicity using murine fibroblasts L929. Analysis was conducted based on the mitochondrial activity test (MTT reduction assay) which involves the determining the number of cells characterized by proper metabolism. Hydrogel materials obtained using different amount of crosslinking agents have been subjected to the cytotoxicity analysis. According to the standards, tested material is defined as cytotoxic when the viability of cells after 24 h incubation with this material is lower than 70%. In the research, hydrogel polymer materials containing protein spheres incorporated with the active substance, i.e. a cytostatic, have been developed. Such a dressing may support the treatment of cancer due to the content of the anti-cancer drug - cytostatic, and may also provide a soothing effect on the healing of the burn wounds resulted from the radiation therapy due to the content of aloe vera juice in the hydrogel matrix. Based on the conducted cytotoxicity studies, it may be concluded that the obtained materials do not adversely affect the tested cell lines, therefore they can be subjected to more advanced analyzes.

Keywords: hydrogel polymers, cytostatics, drug carriers, cytotoxicity

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Authors: Sudhir Kumar, V. R. Sinha

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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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Authors: Audrius Dedele, Aukse Miskinyte

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Air pollution is a major problem, especially in large cities, causing a variety of environmental issues and a risk to human health effects. In order to observe air quality, to reduce and control air pollution in the city, municipalities are responsible for the creation of air quality management plans, air quality monitoring and emission inventories. Atmospheric dispersion modelling systems, along with monitoring, are powerful tools, which can be used not only for air quality management, but for the assessment of human exposure to air pollution. These models are widely used in epidemiological studies, which try to determine the associations between exposure to air pollution and the adverse health effects. The purpose of this study was to determine the concentration of particulate matter smaller than 10 μm (PM10) in different districts of Kaunas city during winter season. ADMS-Urban dispersion model was used for the simulation of PM10 pollution. The inputs of the model were the characteristics of stationary, traffic and domestic sources, emission data, meteorology and background concentrations were entered in the model. To assess the modelled concentrations of PM10 in Kaunas districts, geographic information system (GIS) was used. More detailed analysis was made using Spatial Analyst tools. The modelling results showed that the average concentration of PM10 during winter season in Kaunas city was 24.8 µg/m3. The highest PM10 levels were determined in Zaliakalnis and Aleksotas districts with are the highest number of individual residential properties, 32.0±5.2 and 28.7±8.2 µg/m3, respectively. The lowest pollution of PM10 was modelled in Petrasiunai district (18.4 µg/m3), which is characterized as commercial and industrial neighbourhood.

Keywords: air pollution, dispersion model, GIS, Particulate matter

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Authors: Josiah Damisa, Michelle Louise Richardson, Morenike Adewuyi

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Lower back pain is a significant cause of disability worldwide and associated with great implications in terms of the well-being of affected individuals and society as a whole due to its undeniable socio-economic impact. With its prevalence on the increase as a result of an aging global population, the need for novel forms of pain management is ever paramount. This review aims to provide further insight into current research regarding a role for the endocannabinoid signaling pathway as a target in the treatment of chronic pain, with particular emphasis on its potential use as part of the treatment of lower back pain. Potential advantages and limitations of cannabis-based medicines over other forms of analgesia currently licensed for medical use are discussed in addition to areas that require ongoing consideration and research. To evaluate the efficacy of cannabis-based medicines in chronic pain, studies pertaining to the role of medical cannabis in chronic disease were reviewed. Standard searches of PubMed, Google Scholar and Web of Science databases were undertaken with peer-reviewed journal articles reviewed based on the indication for pain management, cannabis treatment modality used and study outcomes. Multiple studies suggest an emerging role for cannabis-based medicines as therapeutic agents in the treatment of chronic back pain. A potential synergistic effect has also been purported if these medicines are co-administered with opiate analgesia due to the similarity of the opiate and endocannabinoid signaling pathways. However, whilst recent changes to legislation in the United Kingdom mean that cannabis is now licensed for medicinal use on NHS prescription for a number of chronic health conditions, concerns remain as to the efficacy and safety of cannabis-based medicines. Research is lacking into both their side effect profiles and the long-term effects of cannabis use. Legal and ethical considerations to the use of these products in standardized medical practice also persist due to the notoriety of cannabis as a drug of abuse. Despite this, cannabis is beginning to gain traction as an alternative or even complementary drug to opiates, with some preclinical studies showing opiate-sparing effects. Whilst there is a paucity of clinical trials in this field, there is scope for cannabinoids to be successful anti-nociceptive agents in managing chronic back pain. The ultimate aim would be to utilize cannabis-based medicines as alternative or complementary therapies, thereby reducing opiate over-reliance and providing hope to individuals who have exhausted all other forms of standard treatment.

Keywords: endocannabinoids, cannabis-based medicines, chronic pain, lower back pain

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Authors: Gopal Lamichhane, Biswash Sapkota, Grinsun Sharma, Mahendra Adhikari

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Urolithiasis is a condition in which insoluble or less soluble salts like oxalate, phosphate etc. precipitate in urinary tract and causes obstruction in ureter resulting renal colic or sometimes haematuria. It is the third most common disorder of urinary tract affecting nearly 2% of world’s population. Poor urinary drainage, microbial infection, oxalate and calcium containing diet, calciferol, hyperparathyroidism, cysteine in urine, gout, dysfunction of intestine, drought environment, lifestyle, exercise, stress etc. are risk factors for urolithiasis. Wide ranges of treatments are available in allopathic system of medicine but reoccurrence is unpreventable even with the surgical removal of stone or lithotripsy. So, people prefer alternative medicinal systems such as Unani, homeopathic, ayurvedic etc. systems of medicine due to their fewer side effects over allopathic counterpart. Different plants based ethnomedicines are being well established by their continuous effective use in human since long time in treatment of urinary problem. Many studies have scientifically proved those ethnomedicines for antiurolithiatic effect in animal and in vitro model. Plant-based remedies were found to be therapeutically effective for both prevention as well as cure of calcium oxalate urolithiasis. Plants were known to show these effects through a combination of many effects such as antioxidant, diuretic, hypocalciuric, urine alkalinizing effect in them. Berberine, triterpenoids, lupeol are the phytochemicals established for antiurolithiatic effect. Hence, plant-based medicine can be the effective herbal alternative as well as means of discovery of novel drug molecule for curing urolithiatic disorder and should be focused on further research to discover their value in coming future.

Keywords: urolithiasis, herbal medicine, ethnomedicine, kidney stone, calcium oxalate

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Authors: Innocent Pangapanga, Eric Mungatana

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Tropical cyclones–related floods (TCRFs) in Malawi have devastating effects on smallholder agriculture, thereby threatening the food security agenda, which is already constrained by poor agricultural innovations, low use of improved varieties, and unaffordable inorganic fertilizers, and fragmenting landholding sizes. Accordingly, households have engineered and indigenously implemented sustainable landscape management (SLM) innovations to contain the adverse effects of TCRFs on farm productivity. This study, therefore, interrogated the efficacy of SLM adoption on farm productivity under varying TCRFs, while controlling for the potential selection bias and unobservable heterogeneity through the application of the Endogenous Switching Regression Model. In this study, we further investigated factors driving SLM adoption. Substantively, we found TCRFs reducing farm productivity by 31 percent, on the one hand, and influencing the adoption of SLM innovations by 27 percent, on the other hand. The study also observed that households that interacted SLM with TCRFs were more likely to enhance farm productivity by 24 percent than their counterparts. Interestingly, the study results further demonstrated that multiple adoptions of SLM-related innovations, including intercropping, agroforestry, and organic manure, enhanced farm productivity by 126 percent, suggesting promoting SLM adoption as a package to appropriately inform existing sustainable development goals’ agricultural productivity initiatives under intensifying TCRFs in the country.

Keywords: tropical cyclones–related floods, sustainable landscape management innovations, farm productivity, endogeneity, endogenous switching regression model, panel data, smallholder agriculture

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Authors: Po-Chen Chen, Tsung-Han Yang, Zhi-Wei Zheng, Shih-Tsang Tang

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Falls are the most common accidents during mountain hiking, especially in high-altitude environments with unstable terrain or adverse weather. Balance ability is a crucial factor in hiking, effectively ensuring hiking safety and reducing the risk of injuries. If balance ability can be assessed simply and effectively, hikers can identify their weaknesses and conduct targeted training to improve their balance ability, thereby reducing injury risks. With the widespread use of smartphones and their built-in inertial sensors, this project aims to develop a simple Inertial Measurement Unit (IMU) balance measurement technique based on smartphones. This will provide hikers with an easy-to-use, low-cost tool for assessing balance ability, monitoring training effects in real-time, and continuously tracking balance ability through uploading cloud data uploads, facilitating personal athletic performance.

Keywords: balance, IMU, smartphone, wearable devices

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Authors: Robin Anderson, Elizabeth Latham, David Nisbet

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Propagation and dissemination of antimicrobial resistant and pathogenic microbes from spoiled silages and composts represents a serious public health threat to humans and animals. In the present study, the antimicrobial activity of the short chain nitro-compound, 2-nitro-1-propanol (9 mM) as well as the medium chain fatty acid, lauric acid, and its glycerol monoester, monolaurin, (each at 25 and 17 µmol/mL, respectfully) were investigated against select pathogenic and multi-drug resistant antimicrobial resistant Gram-positive bacteria common to spoiled silages and composts. In an initial study, we found that growth rates of a multi-resistant Enterococcus faecalis (expressing resistance against erythromycin, quinupristin/dalfopristin and tetracycline) and Staphylococcus aureus strain 12600 (expressing resistance against erythromycin, linezolid, penicillin, quinupristin/dalfopristin and vancomycin) were more than 78% slower (P < 0.05) by 2-nitro-1-propanol treatment during culture (n = 3/treatment) in anaerobically prepared ½ strength Brain Heart Infusion broth at 37oC when compared to untreated controls (0.332 ± 0.04 and 0.108 ± 0.03 h-1, respectively). The growth rate of 2-nitro-1-propanol-treated Listeria monocytogenes was also decreased by 96% (P < 0.05) when compared to untreated controls cultured similarly (0.171 ± 0.01 h-1). Maximum optical densities measured at 600 nm were lower (P < 0.05) in 2-nitro-1-propanol-treated cultures (0.053 ± 0.01, 0.205 ± 0.02 and 0.041 ± 0.01, respectively) than in untreated controls (0.483 ± 0.02, 0.523 ± 0.01 and 0.427 ± 0.01, respectively) for E. faecalis, S. aureus and L. monocytogenes, respectively. When tested against mixed microbial populations during anaerobic 24 h incubation of spoiled silage, significant effects of treatment with 1 mg 2-nitro-1-propanol (approximately 9.5 µmol/g) or 5 mg lauric acid/g (approximately 25 µmol/g) on populations of wildtype Enterococcus and Listeria were not observed. Mixed populations treated with 5 mg monolaurin/g (approximately 17 µmol/g) had lower (P < 0.05) viable cell counts of wildtype enterococci than untreated controls after 6 h incubation (2.87 ± 1.03 versus 5.20 ± 0.25 log10 colony forming units/g, respectively) but otherwise significant effects of monolaurin were not observed. These results reveal differential susceptibility of multi-drug resistant enterococci and staphylococci as well as L. monocytogenes to the inhibitory activity of 2-nitro-1-propanol and the medium chain fatty acid, lauric acid and its glycerol monoester, monolaurin. Ultimately, these results may lead to improved treatment technologies to preserve the microbiological safety of silages and composts.

Keywords: 2-nitro-1-propanol, lauric acid, monolaurin, gram positive bacteria

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Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

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Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

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Authors: Rosa Tsegaye Aga, Xuan Jiang, Pavel Vazquez Faci, Siqing Liu, Simon Rayner, Endalkachew Alemu, Markos Abebe

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Tuberculosis (TB) is a major cause of disease globally. In most cases, TB is treatable and curable, but only with the proper treatment. There is a time when drug-resistant TB occurs when bacteria become resistant to the drugs that are used to treat TB. Current strategies to identify drug-resistant TB bacteria are laboratory-based, and it takes a longer time to identify the drug-resistant bacteria and treat the patient accordingly. But machine learning (ML) and data science approaches can offer new approaches to the problem. In this study, we propose to develop an ML-based model to predict the antibiotic resistance phenotypes of TB isolates in minutes and give the right treatment to the patient immediately. The study has been using the whole genome sequence (WGS) of TB isolates as training data that have been extracted from the NCBI repository and contain different countries’ samples to build the ML models. The reason that different countries’ samples have been included is to generalize the large group of TB isolates from different regions in the world. This supports the model to train different behaviors of the TB bacteria and makes the model robust. The model training has been considering three pieces of information that have been extracted from the WGS data to train the model. These are all variants that have been found within the candidate genes (F1), predetermined resistance-associated variants (F2), and only resistance-associated gene information for the particular drug. Two major datasets have been constructed using these three information. F1 and F2 information have been considered as two independent datasets, and the third information is used as a class to label the two datasets. Five machine learning algorithms have been considered to train the model. These are Support Vector Machine (SVM), Random forest (RF), Logistic regression (LR), Gradient Boosting, and Ada boost algorithms. The models have been trained on the datasets F1, F2, and F1F2 that is the F1 and the F2 dataset merged. Additionally, an ensemble approach has been used to train the model. The ensemble approach has been considered to run F1 and F2 datasets on gradient boosting algorithm and use the output as one dataset that is called F1F2 ensemble dataset and train a model using this dataset on the five algorithms. As the experiment shows, the ensemble approach model that has been trained on the Gradient Boosting algorithm outperformed the rest of the models. In conclusion, this study suggests the ensemble approach, that is, the RF + Gradient boosting model, to predict the antibiotic resistance phenotypes of TB isolates by outperforming the rest of the models.

Keywords: machine learning, MTB, WGS, drug resistant TB

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Authors: Mostafa Sefidgar, Sohrab Zendehboudi, Hossein Bazmara, Madjid Soltani

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Based on findings from clinical applications, most drug treatments fail to eliminate malignant tumors completely even though drug delivery through systemic administration may inhibit their growth. Therefore, better understanding of tumor formation is crucial in developing more effective therapeutics. For this purpose, nowadays, solid tumor modeling and simulation results are used to predict how therapeutic drugs are transported to tumor cells by blood flow through capillaries and tissues. A solid tumor is investigated as a porous media for fluid flow simulation. Most of the studies use Darcy model for porous media. In Darcy model, the fluid friction is neglected and a few simplified assumptions are implemented. In this study, the effect of these assumptions is studied by considering Brinkman model. A multi scale mathematical method which calculates fluid flow to a solid tumor is used in this study to investigate how neglecting fluid friction affects the solid tumor simulation. In this work, the mathematical model in our previous studies is developed by considering two model of momentum equation for porous media: Darcy and Brinkman. The mathematical method involves processes such as fluid flow through solid tumor as porous media, extravasation of blood flow from vessels, blood flow through vessels and solute diffusion, convective transport in extracellular matrix. The sprouting angiogenesis model is used for generating capillary network and then fluid flow governing equations are implemented to calculate blood flow through the tumor-induced capillary network. Finally, the two models of porous media are used for modeling fluid flow in normal and tumor tissues in three different shapes of tumors. Simulations of interstitial fluid transport in a solid tumor demonstrate that the simplifications used in Darcy model affect the interstitial velocity and Brinkman model predicts a lower value for interstitial velocity than the values that Darcy model does.

Keywords: solid tumor, porous media, Darcy model, Brinkman model, drug delivery

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Authors: Anna Strąkowska, Marian Zaborski

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The studies were focused on POSS application with methylvinylsilicone rubber (MVQ). The obtained results indicate that they can be successfully incorporated into silica-filled rubbers as modifying agents since they enhance cross-link density and improve most properties of the resulting network. It is also worth noting that the incorporation of POSS molecules resulted in stabilizing effect against adverse changes induced by the climatic, ozone or UV ageing of the rubbers. Furthermore, we obtained interesting results of rubbers surface modification using POSS functionalised with halogen groups (Cl, F, and Br). As the results, surface energy of the elastomeric composites and their hydrophobicity increased, barrier properties improved and thermal stability increased as well. Additionally, the studies with silicone rubber and POSS containing acidic and alkaline groups revealed composites with self-healing properties. The observed effects strictly depend on a kind and quantity of functional groups present in angles of POSS cages.

Keywords: elastomeric composites, POSS, properties modyfication, silicone rubber

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Authors: Ravi Patel, Ravisinh Solanki, Dignesh Khunt

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A stability-indicating reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for estimating Nirmatrelvir in its self-emulsifying drug delivery system (SEDDS). The separation of Nirmatrelvir and its degradation products was accomplished by employing an Agilent Zorbax Eclipse plus C18 (250 mm x 4.6 mm, 5 µm) column, through which the mobile phase 5 mM phosphate buffer (pH 4.0) as mobile phase A and Acetonitrile as mobile phase B in a ratio of (40:60 % v/v) was pumped at a flow rate of 1.0 mL/min, through the HPLC system. Chromatographic separation and elution were monitored by a photo-diode array detector at 210 nm. Stress studies have been employed to evaluate this method's ability to indicate stability. Nirmatrelvir was exposed to several stress conditions, such as acid, alkali, oxidative, photolytic, and thermal degradations. Significant degradation was observed during acid and alkali hydrolysis, and the resulting degradation product was successfully separated from the Nirmatrelvir peak, preventing any interference. Furthermore, the primary degradant produced under alkali degradation conditions was identified using UPLC-ESI-TQ-MS/MS. The method was validated in accordance with the International Council on Harmonization (ICH) and found to be selective, precise, accurate, linear, and robust. The apparent permeability of Nirmatrelvir SEDDS was 4.20 ± 0.21×10-6 cm/sec, and the average proportion of free drug recovered was 0.5%. The method developed in this study was feasible and accurate for routine quality control evaluation of Nirmatrelvir SEDDS.

Keywords: Nirmatrelvir, SEDDS, degradation study, HPLC, LC-MS/MS

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Authors: Pawan Kumar Gupta, Sumana Ghosh

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Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

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Authors: Magno Enrique Mendoza Meza

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This paper deals with the comparison of three control techniques: the hysteresis on-off control (HyOOC), the hybrid on-off control (HOOC) and the simple Structured Treatment Interruptions (sSTI). These techniques are applied to the mathematical model developed by Kirschner and Webb. To compare these techniques we use a cost functional that minimize the wild-type virus population and the mutant virus population, but the main objective is to minimize the systemic cost of treatment and maximize levels of healthy CD4+ T cells. HyOOC, HOOC, and sSTI are applied to the drug therapies using a reverse transcriptase and protease inhibitors; simulations show that these controls maintain the uninfected cells in a small, bounded neighborhood of a pre-specified level. The controller HyOOC and HOOC are designed by appropriate choice of virtual equilibrium points.

Keywords: virus dynamics, on-off control, hysteresis, multi-drug therapies

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Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.

Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa

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Authors: Jean Paul M. Milambo

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Purpose: Aromatase inhibitors (AIs) are indicated in the treatment of hormone-receptive breast cancer in postmenopausal women in various settings. Studies have shown cardiovascular events in some developed countries. To date the data is sparce for evidence-based recommendations in African clinical settings due to lack of cancer registries, capacity building and surveillance systems. Therefore, this study was conducted to assess the feasibility of HyBeacon® probe genotyping adjunctive to standard care for timely prediction and diagnosis of Aromatase inhibitors (AIs) associated adverse events in breast cancer survivors in Africa. Methods: Cross sectional study was conducted to assess the knowledge of POCT among six African countries using online survey and telephonically contacted. Incremental cost effectiveness ratio (ICER) was calculated, using diagnostic accuracy study. This was based on mathematical modeling. Results: One hundred twenty-six participants were considered for analysis (mean age = 61 years; SD = 7.11 years; 95%CI: 60-62 years). Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that sensitivity was reported at 99% (95% CI: 94.55% to 99.97%), specificity at 89.44% (95% CI: 87.25 to 91.38%), PPV at 51% (95%: 43.77 to 58.26%), and NPV at 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that ICER was R7 044.55. Conclusion: POCT using HyBeacon® probe genotyping for AI-associated adverse events maybe cost effective in many African clinical settings. Integration of preventive measures for early detection and prevention guided by different subtype of breast cancer diagnosis with specific clinical, biomedical and genetic screenings may improve cancer survivorship. Feasibility of POCT was demonstrated but the implementation could be achieved by improving the integration of POCT within primary health cares, referral cancer hospitals with capacity building activities at different level of health systems. This finding is pertinent for a future envisioned implementation and global scale-up of POCT-based initiative as part of risk communication strategies with clear management pathways.

Keywords: breast cancer, diagnosis, point of care, South Africa, aromatase inhibitors

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Authors: Murali Aarthy, Sanjeev Kumar Singh

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High risk human papillomaviruses are highly associated with the carcinoma of the cervix and the other genital tumors. Cervical cancer develops through the multistep process in which increasingly severe premalignant dysplastic lesions called cervical intraepithelial neoplastic progress to invasive cancer. The oncoprotein E7 of human papillomavirus expressed in the lower epithelial layers drives the cells into S-phase creating an environment conducive for viral genome replication and cell proliferation. The replication of the virus occurs in the terminally differentiating epithelium and requires the activation of cellular DNA replication proteins. To date, no suitable drug molecule is available to treat HPV infection whereas identification of potential drug targets and development of novel anti-HPV chemotherapies with unique mode of actions are expected. Hence, our present study aimed to identify the potential inhibitors analogous to EGCG, a green tea molecule which is considered to be safe to use for mammalian systems. A 3D similarity search on the natural small molecule library from natural product database using EGCG identified 11 potential hits based on their similarity score. The structure based docking strategies were implemented in the potential hits and the key interacting residues of protein with compounds were identified through simulation studies and binding free energy calculations. The conformational changes between the apoprotein and the complex were analyzed with the simulation and the results demonstrated that the dynamical and structural effects observed in the protein were induced by the compounds and indicated the dominance to the oncoprotein. Overall, our study provides the basis for the structural insights of the identified potential hits and EGCG and hence, the analogous compounds identified can be potent inhibitors against the HPV 16 E7 oncoprotein.

Keywords: EGCG, oncoprotein, molecular dynamics simulation, analogues

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Authors: Therese Scali

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Couple separations and divorces seem to be commonplace events. However, their frequency does not reduce their impact. Indeed, the adverse effects of parental divorce on children have been well documented. Thus, supporting the children from divorced families is a key concern. Several preventive interventions have been developed for children of divorced parents, such as Children’s Support Group. The present paper aims at presenting the program that has been created in Liege (Belgium). The setting and the tools will be presented. This Children’s Support Group is based on psychoeducational and systemic principles, art-therapy, and aims at acquiring coping skills and seeking social support. Also, the effectiveness of the program will be discussed. Results show that after parental divorce, a group intervention for children can be efficacious in promoting children’s well-being and parent-child communication. This paper contributes to enrich the understanding of children’s needs and to highlight the existence and efficacy of a program that helps them overcome the difficulties of divorce.

Keywords: art-therapy, children’s support group, divorce, efficacy, separation

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Authors: Md. Lutfor Rahman, Shaikh Md. Mominul Alam

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Sometimes it causes external bleeding when human skin gets seriously injured. Natural source-based blood-clotting bandages are rarely used. The available chemically treated blood clotting materials sometimes show adverse effects and are not effective in quick recovery. Considering these facts, a new blood clotting woven wound dressing product has been developed which is a combination of Micania micrantha extract with woven fabric by absorption process. This product can be represented as an important addition to medical textiles. To develop a dressing material, Micania micrantha leaf juice was applied on bleached woven fabric, followed by sun drying. The effectiveness of this woven sample was tested on volunteers. It was observed that Micania micrantha containing woven sample has a tremendous effect over conventional wound dressing materials. This result is a milestone for the textile and medical sector.

Keywords: blood clotting, Micania micrantha, medical textiles, woven fabric

Procedia PDF Downloads 133

Authors: Keiwoma Mark Yila, Mathew Lamrana Siaffa Gboku, Mohamed Sahr Lebbie, Lamin Ibrahim Kamara

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Rainfall and temperature are the important variables which are often used to trace climate variability and change. A perception study and analysis of climatic data were conducted to assess the changes in rainfall and temperature and their impact on crop production in Moyamba district, Sierra Leone. For the perception study, 400 farmers were randomly selected from farmer-based organizations (FBOs) in 4 chiefdoms, and 30 agricultural extension workers (AWEs) in the Moyamba district were purposely selected as respondents. Descriptive statistics and Kendall’s test of concordance was used to analyze the data collected from the farmers and AEWs. Data for the analysis of variability and trends of rainfall and temperature from 1991 to 2020 were obtained from the Sierra Leone Meteorological Agency and Njala University and grouped into monthly, seasonal and annual time series. Regression analysis was used to determine the statistical values and trend lines for the seasonal and annual time series data. The Mann-Kendall test and Sen’s Slope Estimator were used to analyze the trends' significance and magnitude, respectively. The results of both studies show evidence of climate change in the Moyamba district. A substantial number of farmers and AEWs perceived a decrease in the annual rainfall amount, length of the rainy season, a late start and end of the rainy season, an increase in the temperature during the day and night, and a shortened harmattan period over the last 30 years. Analysis of the meteorological data shows evidence of variability in the seasonal and annual distribution of rainfall and temperature, a decreasing and non-significant trend in the rainy season and annual rainfall, and an increasing and significant trend in seasonal and annual temperature from 1991 to 2020. However, the observed changes in rainfall and temperature by the farmers and AEWs partially agree with the results of the analyzed meteorological data. The majority of the farmers perceived that; adverse weather conditions have negatively affected crop production in the district. Droughts, high temperatures, and irregular rainfall are the three major adverse weather events that farmers perceived to have contributed to a substantial loss in the yields of the major crops cultivated in the district. In response to the negative effects of adverse weather events, a substantial number of farmers take no action due to their lack of knowledge and technical or financial capacity to implement climate-sensitive agricultural (CSA) practices. Even though few farmers are practising some CSA practices in their farms, there is an urgent need to build the capacity of farmers and AEWs to adapt to and mitigate the negative impacts of climate change. The most priority support needed by farmers is the provision of climate-resilient crop varieties, whilst the AEWs need training on CSA practices.

Keywords: climate change, crop productivity, farmer’s perception, rainfall, temperature, Sierra Leone

Procedia PDF Downloads 74

Authors: Kylie Mueller, Nijole Bernaitis, Shailendra Anoopkumar-Dukie

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Background: Vitamin K antagonists particularly warfarin is the most frequently used oral medication for deep vein thrombosis (DVT) treatment and prophylaxis. Time in therapeutic range (TITR) of the international normalised ratio (INR) is widely accepted as a measure to assess the quality of warfarin therapy. Multiple factors can affect warfarin control and the subsequent adverse outcomes including thromboembolic and bleeding events. Predictor models have been developed to assess potential contributing factors and measure the individual risk of these adverse events. These predictive models have been validated in atrial fibrillation (AF) patients, however, there is a lack of literature on whether these can be successfully applied to other warfarin users including DVT patients. Therefore, the aim of the study was to assess the ability of these risk models (HAS BLED and CHADS2) to predict haemorrhagic and ischaemic incidences in DVT patients treated with warfarin. Methods: A retrospective analysis of DVT patients receiving warfarin management by a private pathology clinic was conducted. Data was collected from November 2007 to September 2014 and included demographics, medical and drug history, INR targets and test results. Patients receiving continuous warfarin therapy with an INR reference range between 2.0 and 3.0 were included in the study with mean TITR calculated using the Rosendaal method. Bleeding and thromboembolic events were recorded and reported as incidences per patient. The haemorrhagic risk model HAS BLED and ischaemic risk model CHADS2 were applied to the data. Patients were then stratified into either the low, moderate, or high-risk categories. The analysis was conducted to determine if a correlation existed between risk assessment tool and patient outcomes. Data was analysed using GraphPad Instat Version 3 with a p value of <0.05 considered to be statistically significant. Patient characteristics were reported as mean and standard deviation for continuous data and categorical data reported as number and percentage. Results: Of the 533 patients included in the study, there were 268 (50.2%) female and 265 (49.8%) male patients with a mean age of 62.5 years (±16.4). The overall mean TITR was 78.3% (±12.7) with an overall haemorrhagic incidence of 0.41 events per patient. For the HAS BLED model, there was a haemorrhagic incidence of 0.08, 0.53, and 0.54 per patient in the low, moderate and high-risk categories respectively showing a statistically significant increase in incidence with increasing risk category. The CHADS2 model showed an increase in ischaemic events according to risk category with no ischaemic events in the low category, and an ischaemic incidence of 0.03 in the moderate category and 0.47 high-risk categories. Conclusion: An increasing haemorrhagic incidence correlated to an increase in the HAS BLED risk score in DVT patients treated with warfarin. Furthermore, a greater incidence of ischaemic events occurred in patients with an increase in CHADS2 category. In an Australian population of DVT patients, the HAS BLED and CHADS2 accurately predicts incidences of haemorrhage and ischaemic events respectively.

Keywords: anticoagulant agent, deep vein thrombosis, risk assessment, warfarin

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Authors: Shekoufeh Behdad, Sahar Yadegari, Alireza Ghehrazad, Amirhossein Yadegari

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Background: In this study, we compared the effect of intravenous dexamethasone with placebo on hemodynamic variables and hypotension in patients undergoing cesarean section under spinal anesthesia. Materials and methods: This double-blind, randomized clinical trial was conducted with the approval of the university ethics committee. Written informed consent was obtained from all participating patients. Before spinal anesthesia, patients were randomly assigned to receive either dexamethasone (8 mg IV) or placebo (normal saline). Hemodynamic variables, including systolic, diastolic, and mean arterial blood pressures, as well as heart rate, were measured before drug administration and every 3 minutes until the birth of the neonate and then every 5 minutes until the end of surgery. Side effects such as hypotension, bradycardia, nausea, and vomiting were assessed and recorded for all the patients. Results: There were no significant differences in mean systolic, diastolic, and mean arterial blood pressures before and after administration of the studied drugs in both groups (P.Value>0.05), but heart rate and the incidence of hypotension in the dexamethasone group were less than placebo significantly. Conclusions: Intravenous administration of 8 mg dexamethasone before spinal anesthesia in females undergoing cesarean section can reduce the incidence of post-spinal hypotension without causing serious side effects.

Keywords: cesarean section, hypotension, spinal anesthesia, dexamethasone

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Authors: Archana Sharma, Vijayashree Nayak, Ashok Kumar

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Three-dimensional matrices were fabricated from blend of natural-natural polymers like carrageenan-gelatin and synthetic -natural polymers such as PEG- gelatin (PEG of different molecular weights (2,000 and 6,000) using two different crosslinkers; glutaraldehyde and EDC-NHS by cryogelation technique. Blends represented a feasible approach to design 3-D scaffolds with controllable mechanical, physical and biochemical properties without compromising biocompatibility and biodegradability. These matrices possessed interconnected porous structure, good mechanical strength, biodegradable nature, constant swelling kinetics, ability to withstand high temperature and visco-elastic behavior. Hemocompatibility of cryogel matrices was determined by coagulation assays and hemolytic activity assay which demonstrated that these cryogels have negligible effects on coagulation time and have excellent blood compatibility. In vitro biocompatibility (cell-matrix interaction) inferred good cell adhesion, proliferation, and secretion of ECM on matrices. These matrices provide a microenvironment for the growth, proliferation, differentiation and secretion of ECM of different cell types such as IMR-32, C2C12, Cos-7, rat bone marrow derived MSCs and human bone marrow MSCs. Hoechst 33342 and PI staining also confirmed that the cells were uniformly distributed, adhered and proliferated properly on the cryogel matrix. An ideal scaffold used for tissue engineering application should allow the cells to adhere, proliferate and maintain their functionality. Neurotransmitter analysis has been done which indicated that IMR-32 cells adhered, proliferated and secreted neurotransmitters when they interacted with these matrices which showed restoration of their functionality. The cell-matrix interaction up to molecular level was also evaluated so to check genotoxicity and protein expression profile which indicated that these cryogel matrices are non-genotoxic and maintained biofunctionality of cells growing on these matrices. All these cryogels, when implanted subcutaneously in balb/c mice, showed no adverse systemic or local toxicity effects at implantation site. There was no significant increase in inflammatory cell count has otherwise been observed after scaffold implantation. These cryogels are supermacroporous and this porous structure allows cell infiltration and proliferation of host cells. This showed the integration and presence of infiltrated cells into the cryogel implants. Histological analysis confirmed that the implanted cryogels do not have any adverse effect in spite of host immune system recognition at the site of implantation, on its surrounding tissues and other vital host organs. In vivo biocompatibility study after in vitro biocompatibility analysis has also concluded that these synthesized cryogels act as important biological substitutes, more adaptable and appropriate for transplantation. Thus, these cryogels showed their potential for soft tissue engineering applications.

Keywords: cryogelation, hemocompatibility, in vitro biocompatibility, in vivo biocompatibility, soft tissue engineering applications

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Authors: Jiji Jose, R. Narayanacharyulu, Molly Mathew, Jisha Prems

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Introduction: Lercanidipine hydrochloride (LD), an effective calcium channel blocker, widely used for the treatment of chronic stable angina and hypertension seems to be potential transdermal therapeutic system candidate, mainly due to its low oral bio availability, short half life and high first-pass metabolism. Objective: To develop transdermal therapeutic systems for LD and to evaluate its in vivo performance in rabbits. Methodology: Transdermal patches of LD were formulated using the polymer blend of eudragit RL100 (ERL) and polyvinyl pyrolidone (PVP) by casting method Propylene glycol (PG) and tween 80 were used as plasticizer and permeation enhancer respectively. The pharmaco kinetic parameters of LD after the administration of transdermal patches was compared with that of oral administration. The study was carried out in a two way crossover design in male New Zealand albino rabbits. Results: The formulation with ERL: PVP ratio 1:4 with 15% w/w PG as plasticizer and 4% w/w tween 80 as permeation enhancer showed the best drug release results. The pharmacokinetic parameters such as Cmax, tmax, mean residence time (MRT) and area under the curve (AUC 0-∞) were significantly different following transdermal administration compared to oral administration. The terminal half life of transdermally administered LD was found to similar that of oral administration. A sustained drug release over a period of 24 hrs was observed after transdermal administration. Conclusion: The fabricated transdermal delivery system have the potential to provide controlled and extended drug release, better bio availability and thus, this may improve the patient compliance.

Keywords: transdermal therapeutic system, lercanidipine hydrochloride, eudragit, skinpermeation

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