Search results for: slow drug release

Authors: Pallavi Kishore, Mariam Aslam

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The sharp decline in oil prices that started in 2014 affected most economies in the world either positively or negatively. In some economies, particularly the oil exporting countries, the effects were felt immediately. The Gulf Cooperation Council’s (GCC henceforth) countries are oil and gas-dependent with the largest oil reserves in the world. UAE (United Arab Emirates) has been striving to diversify away from oil and expects higher non-oil growth in 2018. These two factors, falling oil prices and the economy strategizing away from oil dependence, make a compelling case to study the financial performance of various sectors in the economy. Among other sectors, the insurance sector is widely recognized as an important indicator of the health of the economy. An expanding population, surge in construction and infrastructure, increased life expectancy, greater expenditure on automobiles and other luxury goods translate to a booming insurance sector. A slow-down of the insurance sector, on the other hand, may indicate a general slow-down in the economy. Therefore, a study on the insurance sector will help understand the general nature of the current economy. This study involves calculations and comparisons of ratios pre and post the fall in oil prices in the insurance sector in the UAE. A sample of 33 companies listed on the official stock exchanges of UAE-Dubai Financial Market and Abu Dhabi Stock Exchange were collected and empirical analysis employed to study the financial performance pre and post fall in oil prices. Ratios were calculated in 5 categories: Profitability, Liquidity, Leverage, Efficiency, and Investment. The means pre- and post-fall are compared to conclude that the profitability ratios including ROSF (Return on Shareholder Funds), ROCE (Return on Capital Employed) and NPM (Net Profit Margin) have all taken a hit. Parametric tests, including paired t-test, concludes that while the fall in profitability ratios is statistically significant, the other ratios have been quite stable in the period. The efficiency, liquidity, gearing and investment ratios have not been severely affected by the fall in oil prices. This may be due to the implementation of stronger regulatory policies and is a testimony to the diversification into the non-oil economy. The regulatory authorities can use the findings of this study to ensure transparency in revealing financial information to the public and employ policies that will help further the health of the economy. The study will also help understand which areas within the sector could benefit from more regulations.

Keywords: UAE, insurance sector, ratio analysis, oil price, profitability, liquidity, gearing, investment, efficiency

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Authors: Thanh Phuong Doan, Narueporn Sutanthavibul

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The influence of freezing cycle on influenza haemagglutinin (HA) conformational stability was investigated in terms of freezing rates and formulation compositions. The results showed that appropriate HA conformation could be evaluated using circular dichroism (CD) spectroscopy with HA concentration of greater than 0.09 mg/ml. The intermediate freezing rate of approximately 1.0oC/min preserved the original HA conformation better than at slow freezing rate (0.5oC/min) and rapid freezing rate (2.6oC/min). The changes in CD spectra of the secondary HA structure were more pronounced than those of the tertiary HA structure during the evaluation. Additionally, the formulations, which resulted in the highest conformational stability were found to have sucrose present in the composition. As opposed to when only glycine was used, the stability of HA conformation was poor.

Keywords: freezing, haemagglutinin, influenza, circular dichroism

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Authors: Palanisamy Sivanandy, Tan Tyng Wei, Tan Wee Loon, Lim Chong Yee

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Background: Patient safety has become a major concern over recent years with elevated medication errors; particularly prescribing and dispensing errors. Meticulous prescription screening and diligent drug dispensing is therefore important to prevent drug-related adverse events from inflicting harm to patients. Hence, pharmacists play a significant role in this scenario. The evaluation of patient safety in a pharmacy setup is crucial to contemplate current practices, attitude and perception of pharmacists towards patient safety. Method: The questionnaire for Pharmacy Survey on Patient Safety Culture developed by the Agency for Healthcare and Research Quality (AHRQ) was used to assess patient safety. Main objectives of the study was to evaluate the attitude and perception of pharmacists towards patient safety in retail pharmacies setup in Malaysia. Results: 417 questionnaire were distributed via convenience sampling in three different states of Malaysia, where 390 participants were responded and the response rate was 93.52%. The overall positive response rate (PRR) was ranged from 31.20% to 87.43% and the average PRR was found to be 67%. The overall patient safety grade for our pharmacies was appreciable and it ranges from good to very good. The study found a significant difference in the perception of senior and junior pharmacists towards patient safety. The internal consistency of the questionnaire contents /dimensions was satisfactory (Cronbach’s alpha - 0.92). Conclusion: Our results reflect that there was positive attitude and perception of retail pharmacists towards patient safety. Despite this, various efforts can be implemented in the future to amplify patient safety in retail pharmacies setup.

Keywords: patient safety, attitude, perception, positive response rate, medication errors

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Authors: Hayley Boal, Chloe Bromley, John Fairfield

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Novel Psychoactive Substances (NPS) are synthetic compounds designed to reproduce effects of illicit drugs. Cheap, potent, and readily available on UK highstreets from so-called ‘head shops’, in recent years their use has surged and with it have emerged side effects including seizures, aggression, palpitations, coma, and death. Rapid development of new substances has vastly outpaced pre-existing drug legislation but the Psychoactive Substances Act 2016 rendered all but tobacco, alcohol, and amyl nitrates, illegal. Drug use has long been rife within prisons, but the absence of a reliable screening tool alongside the availability of NPS makes them ideal for prison use. Here we examine the occurrence of NPS-related adverse side effects within HMP Leeds, comparing May-September of 2015 and 2017 using daily reports distributed amongst prison staff summarising medical and behavioural incidents of the previous day. There was a statistically-significant rise of over 200% in the use of NPS between 2015 and 2017: 0.562 and 1.149 incidents per day respectively. In 2017, 38.46% incidents required ambulances, fallen from 51.02% in 2015. Although the most common descriptions in both years were ‘seizure’ and ‘unresponsive’, by 2017 ‘inhalation by staff’ had emerged. Patterns of NPS consumption mirrored the prison regime, peaking when cell doors opened, and prisoners could socialise. Despite limited data, the Psychoactive Substances Act has clearly been an insufficient deterrent to the prison population; more must be done to understand and address substance misuse in prison. NPS remains a significant risk to prisoners’ health and wellbeing.

Keywords: legislation, novel psychoactive substances, prison, spice

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Authors: N. Pitcheswara Rao

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In the process of conveying the information there may be a chance of signal being corrupted which leads to the erroneous bits in the message. The message may consist of single, double and multiple bit errors. In high-reliability applications, memory can sustain multiple soft errors due to single or multiple event upsets caused by environmental factors. The traditional hamming code with SEC-DED capability cannot be address these types of errors. It is possible to use powerful non-binary BCH code such as Reed-Solomon code to address multiple errors. However, it could take at least a couple dozen cycles of latency to complete first correction and run at a relatively slow speed. In order to overcome this drawback i.e., to increase speed and latency we are using reed-Muller code.

Keywords: SEC-DED, BCH code, Reed-Solomon code, Reed-Muller code

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Authors: Samashi Munaweera

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Cancer stem cells (CSC) are responsible for the initiation, extensive proliferation and metastasis of cancer. CSCs, including breast cancer stem cells (bCSCs) have a capacity to generate chemo and radiotherapy resistance heterogeneous population of cells. Over-expressed ABCB1 has been reported as a main reason for drug resistance of CSCs via activating drug efflux pumps by creating pores in the cell membrane. The overall efficiency of chemotherapeutic agents might be enhanced by blocking the ABCB protein efflux pump in the CSC membrane. There is an urgent need to search for persuasive natural drugs which can target CSCs. Anti-cancer properties of Hylocereus undatus on cancer CSCs have not yet been studied. In the present study, the anti-cancer effects of the peel and flesh of H. undatus fruit on bCSCs were evaluated with the aim of developing a marketable anti-cancer nutraceutical formulation. The flesh and peel of H. undatus were freeze-dried and sequentially extracted into four different solvents (hexane, chloroform, ethyl acetate and ethanol). All extracts (eight extracts) were dried under reduced pressure, and different concentrations (12.5-400 µg/mL) were treated on bCSCs isolated from a triple-negative chemo-resistant breast cancer phenotype (MDA-MB-231 cells). Anti-proliferative effects of all extracts and paclitaxel (positive control) were determined by a colorimetric assay (WST-1 based). Since peel-chloroform (IC50= 54.8 µg/mL) and flesh-ethyl acetate (IC50= 150.5 µg/mL) extras exerted a potent anti-proliferative effect at 72 h post-incubation, a combinatorial formulation (CF) was developed with the most active peel-chloroform extract and 20 µg/mL of verapamil (a known ABCB1 drug efflux pump blocker) first time in the world. Anti-proliferative effects and pro-apoptotic effects of CF were confirmed by estimating activated caspase3 and caspase7 levels and apoptotic morphological features in the CF-treated bCSCs compared to untreated and only verapamil (20 µg/mL) treated bCSCs, and CF treated normal mammary epithelial cells (MCF-10A). The antiproliferative effects of CF (16.4 µg/mL) are greater than paclitaxel (19.2 µg/mL) and three folds greater than peel-chloroform extract (IC50= 54.8 µg/mL) on bCSCs while exerting less effects on normal cells (> 400 µg/mL). Collectively, CF can be considered as a potential initiative of a nutraceutical formulation that can target CSCs.

Keywords: breast cancer stem cells (bCSCs), Hylocereus undatus, combinatorial formulation (CF), ABCB 1 protein, verapamil

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Authors: Laura Roe

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This study draws on twelve months of ethnographic fieldwork conducted in 2017 with heroin and poly-substance users in Scotland and explores experiences of time and temporality as factors in continuing drug use. The research largely took place over the year in which drug-related deaths in Scotland reached a record high, and were statistically recorded as the highest in Europe. This qualitative research is therefore significant in understanding both evolving patterns of drug use and the experiential lifeworlds of those who use heroin and other substances in high doses. Methodologies included participant observation, structured and semi-structured interviews, and unstructured conversations with twenty-two regular participants. The fieldwork was conducted in two needle exchanges, a community recovery group and in the community. The initial aim of the study was to assess evolving patterns of drug preferences in order to explore a clinical and user-reported rise in the use of novel psychoactive substances (NPS), which are typically considered to be highly potent, synthetic substances, often available at a low cost. It was found, however, that while most research participants had experimented with NPS with varying intensity, those who used every day regularly consumed heroin, methadone, and alcohol with benzodiazepines such as diazepam or anticonvulsants such as gabapentin. The research found that many participants deliberately pursued the non-fatal effects of overdose, aiming to induce states of dissociation, detachment and uneven consciousness, and did so by both mixing substances and experimenting with novel modes of consumption. Temporality was significant in the decision to consume cocktails of substances, as users described wishing to sever themselves from time; entering into states of ‘non-time’ and insensibility through specific modes of intoxication. Time and temporality similarly impacted other aspects of addicted life. Periods of attempted abstinence witnessed a slowing of time’s passage that was tied to affective states of boredom and melancholy, in addition to a disruptive return of distressing and difficult memories. Abject past memories frequently dominated and disrupted the present, which otherwise could be highly immersive due to the time and energy-consuming nature of seeking drugs while in financial difficulty. There was furthermore a discordance between individual user temporalities and the strict time-based regimes of recovery services and institutional bodies, and the study aims to highlight the impact of such a disjuncture on the efficacy of treatment programs. Many participants had difficulty in adhering to set appointments or temporal frameworks due to their specific temporal situatedness. Overall, exploring increasing tendencies of heroin users in Scotland towards poly-substance use, this study draws on experiences and perceptions of time, analysing how temporality comes to bear on the ways drugs are sought and consumed, and how recovery is imagined and enacted. The study attempts to outline the experiential, intimate and subjective worlds of heroin and poly-substance users while explicating the structural and historical factors that shape them.

Keywords: addiction, poly-substance use, temporality, timelessness

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Authors: Radek Novotny, Michal Novak, Daniela Marusakova, Monika Sipova, Hugo Fuentes, Peter Borst

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This research has been conducted within the European HORIZON 2020 project ECC-SMART. The main objective is to assess whether it is feasible to design and develop a small modular reactor (SMR) that would be cooled by supercritical water (SCW). One of the main objectives for material research concerns the corrosion of the candidate cladding materials. The experimental part has been conducted in support of the qualification procedure of the future SCW-SMR constructional materials. The last objective was to identify the gaps in current norms and guidelines. Apart from corrosion, resistance testing of candidate materials stresses corrosion cracking susceptibility tests have been performed in supercritical water. This paper describes part of these tests, in particular, those slow strain rate tensile loading applied for tangential ring shape specimens of two candidate materials, Alloy 800H and 310S stainless steel. These ring tensile tests are one the methods used for tensile testing of nuclear cladding. Here full circular heads with dimensions roughly equal to the inner diameter of the sample and the gage sections are placed in the parallel direction to the applied load. Slow strain rate tensile tests have been conducted in 380 or 500oC supercritical water applying two different elongation rates, 1x10-6 and 1x10-7 s-1. The effect of temperature and dissolved oxygen content on the SCC susceptibility of Alloy 800H and 310S stainless steel was investigated when two different temperatures and concentrations of dissolved oxygen were applied in supercritical water. The post-fracture analysis includes fractographic analysis of the fracture surfaces using SEM as well as cross-sectional analysis on the occurrence of secondary cracks. Assessment of the effect of environment and dissolved oxygen content was by comparing to the results of the reference tests performed in air and N2 gas overpressure. The effect of high temperature on creep and its role in the initiation of SCC was assessed as well. It has been concluded that the applied test method could be very useful for the investigation of stress corrosion cracking susceptibility of candidate cladding materials in supercritical water.

Keywords: stress corrosion cracking, ring tensile tests, super-critical water, alloy 800H, 310S stainless steel

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Authors: Mohan H., C. Elajchet Senni

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In the present of high energy consumption in every sphere of life, renewable energy sources are emerging as alternative to conventional fuels for energy security, mitigating green house gas emission and climate change. There has been a world wide interest in searching for alternatives to petroleum derived fuels due to their depletion as well as due to the concern for the environment. Vegetable oils have capability to solve this problem because they are renewable and lead to reduction in environmental pollution. But high smoke emission and lower thermal efficiency are the main problems associated with the use of neat vegetable oils in diesel engines. In the present work, performance, combustion and emission characteristics of CI engine fuelled with 20% by vol. methyl esters mixed with Karanja seed Oil, and Fuel injection pressures of 200 bar and 240 bar, injection timings (21°,23° and 25° BTDC) and Proportion B20 diesel respectively. Vegetable oils have capability to solve this problem because they are renewable and lead to reduction in environmental pollution. But, high smoke emission and lower thermal efficiency are the main problems associated with the use of neat vegetable oils in diesel engines. In the present work, performance, combustion and emission characteristics of CI engine fuelled with 20% by vol. methyl esters mixed with Karanja seed Oil, and Fuel injection pressures of 200 bar and 240 bar ,Injection timings (21°,23° and 25° BTDC) and Proportion B20 diesel respectively. Various performance, combustion and emission characteristics such as thermal efficiency, and brake specific fuel consumption, maximum cylinder pressure, instantaneous heat release, cumulative heat release with respect to crank angle, ignition lag, combustion duration, HC, NOx, CO, exhaust temperature and smoke intensity were measured.

Keywords: karanja oil, injection pressure, injection timing, karanja oil methyl ester

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Authors: Mohammad Zafar-ul Islam

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The breeding programme of Houbara bustard was started in Saudi Arabia in 1986 to undertake the restoration of native species such as Houbara through a programme of re-introduction, involving the release of captive-bred birds in the wild. Two sites were selected for houbara re-introduction, i.e., Mahazat as-Sayd and Saja Umm Ar-Rimth protected areas in 1988 and 1998 respectively. Both the areas are fenced fairly level, sandy plain with a few rock outcrops. Captive bred houbara have been released in Mahazat since 1992 by NWRC and those birds have been successfully breeding since then. The nesting season of the houbara at Mahazat recorded from February to May and on an average 20-25 nests are located each year but no nesting recorded in Saja. Houbara are monitored using radio transmitters through aerial tracking technique and also a vehicle for terrestrial tracking. Total population of houbara in Mahazat is roughly estimated around 300-400 birds, using the following: N = n1+n2+n3+n4+n5 (n1 = released or wild-born, radio, regularly monitored/checked; n2 = radio tagged missing; n3 = wild born chicks not recorded; n4 = wild born chicks, recorded but not tagged; n5 = immigrants). However, in Saja only 4-7 individuals of houbara have been survived since 2001 because most of the birds are predated immediately after the release. The mean annual home was also calculated using Kernel and Convex polygons methods with Range VII software. The minimum density of houbara was also calculated. In order to know the houbara movement or their migration to other regions, two captive-reared male houbara that were released into the wild and one wild born female were fitted with Platform Transmitter Terminals (PTT). The home range shows that wild-born female has larger movement than two males. More areas need to be selected for reintroduction programme to establish the network of sites to provide easy access to move these birds and mingle with the wild houbara. Some potential sites have been proposed which require more surveys to check the habitat suitability.

Keywords: re-introduction, survival rate, home range, Saudi Arabia

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Authors: Mukta Singh, Ratan Kumar Saha, Himadri Saha, Paramveer Singh

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The present study evaluated the effect of sub-lethal doses of antifungal drug miconazole nitrate (MCZ) on immunological responses including immune-related gene expression and its role as a prophylactic drug against S. parasitica in Labeo rohita fingerlings. Fish were fed with sub lethal doses of MCZ i.e., T1- 6.30 mg MCZ kgBW⁻¹, T2- 12.61 mg MCZ kgBW⁻¹ and T3- 25.22 mg MCZ kgBW⁻¹ and sampling was done at different time intervals for 240 h. Immunological parameters viz. lysozyme activity, oxygen radical production and plasma anti-protease activity showed significant enhancement (p < 0.05) in fish fed with T2 and T3 doses. Significant reduction in plasma protein content was observed in all the dietary groups as compared to control. Expression of immune-relevant genes like TLR-22 and β2-M showed significantly higher expression at six h and 24 h of sampling in both liver and head-kidney. However, these genes showed a down-regulation after 120 h of sampling in both the tissues. Preventive efficacy study showed that single dose of MCZ provides protection against oomycetes up to the fourth day of infection. Significantly higher mortality was observed in control diet-fed fish as compared to fish fed with MCZ medicated diet. Thus, from the study, it can be concluded that the MCZ can act as a potent antifungal agent for preventing oomycetes infection as well as to enhance the immune response.

Keywords: antifungal, immune gene, immunological, miconazole nitrate, prophylactic

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Authors: Rita Ghosh, Joykrishna Dey

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PEG-based amphiphiles are of tremendous importance for its widespread applications in pharmaceutics, household purposes, and drug delivery. Previously, a number of single PEG-tailed amphiphiles having significant applications have been reported from our group. Therefore, it was of immense interest to explore the properties and application potential of PEG-based double tailed amphiphiles. Herein, for the first time, two novel double PEG-tailed amphiphiles having different PEG chain lengths have been developed. The self-assembly behavior of the newly developed amphiphiles in aqueous buffer (pH 7.0) was thoroughly investigated at 25 oC by a number of techniques including, 1H-NMR, and steady-state and time-dependent fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy, and isothermal titration calorimetry. Despite having two polar PEG chains both molecules were found to have strong tendency to self-assemble in aqueous buffered solution above a very low concentration. Surprisingly, the amphiphiles were shown to form stable vesicles spontaneously at room temperature without any external stimuli. The results of calorimetric measurements showed that the vesicle formation is driven by the hydrophobic effect (positive entropy change) of the system, which is associated with the helix-to-random coil transition of the PEG chain. The spectroscopic data confirmed that the bilayer membrane of the vesicles is constituted by the PEG chains of the amphiphilic molecule. Interestingly, the vesicles were also found to exhibit structural transitions upon addition of salts in solution. These properties of the vesicles enable them as potential candidate for drug delivery.

Keywords: double-tailed amphiphiles, fluorescence, microscopy, PEG, vesicles

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Authors: Minjeoung Kim

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Since women obtained the right to vote in 1893 for the first time in New Zealand, they have tried to participate actively into politics but still the world has a few women in political leadership. The article asks which factors might influence the appearance of women leadership in politics. The article investigates two factors such as political context, personal factors. Countries where economic development is stable and political democracy is consolidated have a tendency of appearance of women political leadership but in less developed and politically unstable countries, women politicians can be in power with their own reasons. For the personal factor, their feminist propensity is studied but there is no relationship between the appearance of women leaders and their feminist propensity.

Keywords: women political leadership, political context, slow track, transitory countries, feminist propensity

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Authors: M. Doudi, M. H. Pazandeh, L. Rahimzadeh Torabi

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Bedsores are pressure ulcers that occur on the skin or tissue due to being immobile and lying in bed for extended periods. Bedsores have the potential to progress into open ulcers, increasing the possibility of a variety of bacterial infections. Acinetobacter baumannii, a pathogen of considerable clinical importance, exhibited a significant correlation with Bedsores (pressure ulcers) infections, thereby manifesting a wide spectrum of antibiotic resistance. The emergence of drug resistance has led researchers to focus on alternative methods, particularly phage therapy, for tackling bacterial infections. Phage therapy has emerged as a novel therapeutic approach to regulate the activity of these agents. The management of bacterial infections greatly benefits from the clinical utilization of bacteriophages as a valuable antimicrobial intervention. The primary objective of this investigation consisted of isolating and discerning potent bacteriophage capable of targeting multi-drug-resistant (MDR) and extensively drug-resistant (XDR) bacteria obtained from pressure ulcers. The present study analyzed and isolated A. baumannii strains obtained from a cohort of patients suffering from pressure ulcers at Taleghani Hospital in Ahvaz, Iran. An approach that included biochemical and molecular identification techniques was used to determine the taxonomic classification of bacterial isolates at the genus and species levels. The molecular identification process was facilitated by using the 16S rRNA gene in combination with universal primers 27 F and 1492 R. Bacteriophage was obtained through the isolation process conducted on treatment plant sewage located in Isfahan, Iran. The main goal of this study was to evaluate different characteristics of phage, such as their appearance, the range of hosts they can infect, how quickly they can enter a host, their stability at varying temperatures and pH levels, their effectiveness in killing bacteria, the growth pattern of a single phage stage, mapping of enzymatic digestion, and identification of proteomics patterns. The findings demonstrated that an examination was conducted on a sample of 50 specimens, wherein 15 instances of A. baumannii were identified. These microorganisms are the predominant Gram-negative agents known to cause wound infections in individuals suffering from bedsores. The study's findings indicated a high prevalence of antibiotic resistance in the strains isolated from pressure ulcers, excluding the clinical strains that exhibited responsiveness to colistin. According to the findings obtained from assessments of host range and morphological characteristics of bacteriophage VbɸAB-1, it can be concluded that this phage possesses specificity towards A. Baumannii BAH_Glau1001 was classified as a member of the Podoviridae family. The bacteriophage mentioned earlier showed the strongest antibacterial effect at a temperature of 18 °C and a pH of 6.5. Through the utilization of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis on protein fragments, it was established that the bacteriophage VbɸAB-1 exhibited a size range between 50 and 75 kilodaltons (KDa). The numerous research findings on the effectiveness of phages and the safety studies conducted suggest that the phages studied in this research can be considered as a practical solution and recommended approach for controlling and treating stubborn pathogens in burn wounds among hospitalized patients. The findings of our research indicated that isolated phages could be an effective antimicrobial and an appreciate candidate for prophylaxis against pressure ulcers.

Keywords: acinetobacter baumannii, extremely drug-resistant, phage therapy, surgery wound

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Authors: E. C. Mattos, V. S. M. G. Daros, R. Dal Col, A. L. Nascimento

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The aim of this study is to present the results of a retrospective survey on the foreign matter found in foods analyzed at the Adolfo Lutz Institute, from July 2001 to July 2015. All the analyses were conducted according to the official methods described on Association of Official Agricultural Chemists (AOAC) for the micro analytical procedures and Food and Drug Administration (FDA) for the macro analytical procedures. The results showed flours, cereals and derivatives such as baking and pasta products were the types of food where foreign matters were found more frequently followed by condiments and teas. Fragments of stored grains insects, its larvae, nets, excrement, dead mites and rodent excrement were the most foreign matter found in food. Besides, foreign matters that can cause a physical risk to the consumer’s health such as metal, stones, glass, wood were found but rarely. Miscellaneous (shell, sand, dirt and seeds) were also reported. There are a lot of extraneous materials that are considered unavoidable since are something inherent to the product itself, such as insect fragments in grains. In contrast, there are avoidable extraneous materials that are less tolerated because it is preventable with the Good Manufacturing Practice. The conclusion of this work is that although most extraneous materials found in food are considered unavoidable it is necessary to keep the Good Manufacturing Practice throughout the food processing as well as maintaining a constant surveillance of the production process in order to avoid accidents that may lead to occurrence of these extraneous materials in food.

Keywords: extraneous materials, food contamination, foreign matter, surveillance

Procedia PDF Downloads 355

Authors: Pitcheswara Rao Nelapati

Abstract:

In the process of conveying the information there may be a chance of signal being corrupted which leads to the erroneous bits in the message. The message may consist of single, double and multiple bit errors. In high-reliability applications, memory can sustain multiple soft errors due to single or multiple event upsets caused by environmental factors. The traditional hamming code with SEC-DED capability cannot be address these types of errors. It is possible to use powerful non-binary BCH code such as Reed-Solomon code to address multiple errors. However, it could take at least a couple dozen cycles of latency to complete first correction and run at a relatively slow speed. In order to overcome this drawback i.e., to increase speed and latency we are using reed-Muller code.

Keywords: SEC-DED, BCH code, Reed-Solomon code, Reed-Muller code

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Authors: Amelia R. Anshar, Dini Kurnia, Muh A. Bahar

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Nowadays, there are so many incidences had been reported in pet animals regarding drug overdose caused by incorrect doses of a non-steroidal anti-inflammatory drug (NSAID), for instance, meloxicam. As supporting treatment, the avocado is used in traditional medicine to treat or prevent some health cases. The study was aimed at providing the basis for the antioxidant activity of avocado puree in animal medicine. Experimental animals used in this study were 24 male rats that were randomly divided into 4 groups (n=6). Control Group I got 1 ml CMC 1% and control II got meloxicam 30 mg/kgBB and 1 ml CMC 1%. Treatment group I got meloxicam 30 mg/kgBB and avocado 5 g/kgBB/day and treatment II got meloxicam 30 mg/kgBB and avocado 10 g/kgBB/day. The study was conducted over 8 days, then the level of Blood Urea Nitrogen and creatinine of the white rats were examined in 1st day and 8th day. The results were analyzed by ANOVA Two Way With Replication, then followed by T-test (α = 0,05) if there were a difference. Comparison test among the four groups after treatment with avocado using Anova Two Way With Replication test showed that there were significant differences between the mean of the four groups either decreased levels of Blood Urea Nitrogen and creatinine with p < 0,05. Treatment group I and II received treatment showed remarkable (p < 0,05) decreases ini Blood Urea Nitrogen level by 27,17 mg/dl and 17,83 mg/dl respectively. There was also significant decrease in the values of creatinine in Treatment group I and treatment group II by 0,983 mg/dl and 0,713 mg/dl respectively. The conclusion of this study was that avocado decreases level of Blood Urea Nitrogen and creatinine in white rats which are exposed to toxic doses of meloxicam.

Keywords: avocado, blood urea nitrogen, creatinine, meloxicam

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Authors: Chi Wu, Dean Wu, Wen-Te Liu, Cheng-Yu Tsai, Shin-Mei Hsu, Yin-Tzu Lin, Ru-Yin Yang

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Background: The results of previous studies compared the benefits and risks of receiving insomnia medication. However, the effects between hypnotic drugs used and enhancement of sleep quality were still unclear. Objective: The aim of this study is to establish a prediction model for hypnotic drugs' dosage used for insomnia subjects and associated the relationship between sleep stage ratio change and drug types. Methodologies: According to American Academy of Sleep Medicine (AASM) guideline, sleep stages were classified and transformed to hypnogram via the polysomnography (PSG) in a hospital in New Taipei City (Taiwan). The subjects with diagnosis for insomnia without receiving hypnotic drugs treatment were be set as the comparison group. Conversely, hypnotic drugs dosage within the past three months was obtained from the clinical registration for each subject. Furthermore, the collecting subjects were divided into two groups for training and testing. After training convolution neuron network (CNN) to predict types of hypnotics used and dosages are taken, the test group was used to evaluate the accuracy of classification. Results: We recruited 76 subjects in this study, who had been done PSG for transforming hypnogram from their sleep stages. The accuracy of dosages obtained from confusion matrix on the test group by CNN is 81.94%, and accuracy of hypnotic drug types used is 74.22%. Moreover, the subjects with high ratio of wake stage were correctly classified as requiring medical treatment. Conclusion: CNN with hypnogram was potentially used for adjusting the dosage of hypnotic drugs and providing subjects to pre-screening the types of hypnotic drugs taken.

Keywords: convolution neuron network, hypnotic drugs, insomnia, polysomnography

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Authors: Emel Bayraktar, Gulengun Turk

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Introduction and Objective: Safe administration of medicines is one of the main responsibilities of nurses. Intramuscular drug administration is among the most common methods used by nurses among all drug applications. This study was carried out in order to determine determine the effect of education given on injection in ventrogluteal area on the level of knowledge of nurses on this subject. Methods: The sample of the study consisted of 20 nurses who agreed to participate in the study between 01 October and 31 December 2019. The research is a pretest-posttest comparative, quasi-experimental type pilot study. The nurses were given a 4-hour training prepared on injection into the ventrogluteal area. The training consisted of two hours of theoretical and two hours of laboratory practice. Before the training and 4 weeks after the training, a questionnaire form containing questions about their knowledge and practices regarding the injection of the ventrogluteal region was applied to the nurses. Results: The average age of the nurses is 26.55 ± 7.60, 35% (n = 7) of them are undergraduate and 30% (n = 6) of them work in intensive care units. Before the training, 35% (n = 7) of the nurses stated that the most frequently used intramuscular injection site was the ventrogluteal area, and 75% (n = 15) stated that the safest area was the rectus femoris muscle. After the training, 55% (n = 11) of the nurses stated that they most frequently used the ventrogluteal area and 100% (n = 20) of them stated that the ventrogluteal area was the safest area. The average score the nurses got from the premises before the training is 14.15 ± 6.63 (min = 0, max = 20), the total score is 184. The average score obtained after the training was determined as 18.69 ± 2.35 (min = 12, max = 20), and the total score was 243. Conclusion: As a result of the research, it was determined that the training given on the injection of ventrogluteal area increased the knowledge level of the nurses. It is recommended to organize in-service trainings for all nurses on the injection of ventrogluteal area.

Keywords: safe injection, knowledge level, nurse, intramuscular injection, ventrogluteal area

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

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

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

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Authors: Michio Kurosu

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Alterations in glycosylation not only directly impact cell growth and survival but also facilitate tumor-induced immunomodulation and eventual metastasis. Identification of cell type-specific glycoconjugates (tumor markers) has led to the discovery of new assay systems for certain cancers via immunodetection reagents. N- and O-linked glycans are the most abundant forms of glycoproteins. Recent studies of cancer immunotherapy are based on the immunogenicity of truncated O-glycan chains (e.g., Tn, sTn, T, and sLea/x). The prevalence of N-linked glycan changes in the development of tumor cells is known; however, therapeutic antibodies against N-glycans have not yet been developed. This is due to the lack of specificity of N-linked glycans between normal/healthy and cancer cells. Abnormal branching of N-linked glycans has been observed, particularly in solid cancer cells. While the discovery of drug-like glycosyltransferase inhibitors that block the biosynthesis of specific branching has a very low likelihood of success, altered glycosylation levels can be exploited by suppressing N-glycan biosynthesis through the inhibition of dolichyl-phosphate N-acetylglucosaminephosphotransferase1 (DPAGT1) activity. Inhibition of DPAGT1 function leads to changes of O-glycosylation on proteins associated with mitochondria and zinc finger binding proteins (indirect effects). On the basis of dynamic crosstalk between DPAGT1 and Snail/Slung/ZEB1 (a family of transcription factors that promote the repression of the adhesion molecules), we have developed pharmacologically acceptable selective DPAGT1 inhibitors. Tunicamycin kills a wide range of cancer and healthy cells in a non-selective manner. In sharp contrast, our DPAGT1 inhibitors display strong cytostatic effects against 16 solid cancers, which require the overexpression of DPAGT1 in their progression but do not affect the cell viability of healthy cells. The identified DPAGT1 inhibitors possess impressive anti-metastatic ability in various solid cancer cell lines and induce their mitochondrial structural changes, resulting in apoptosis. A prototype DPAGT1 inhibitor, APPB has already been proven to shrink solid tumors (e.g., pancreatic cancers, triple-negative breast cancers) in vivo while suppressing metastases and has strong synergistic effects when combined with current cytotoxic drugs (e.g., paclitaxel). At this conference, our discovery of selective DPAGT1 inhibitors with drug-like properties and proof-of-pharmaceutical concept studies of a novel DPAGT1 inhibitor are presented.

Keywords: DPAGT1 inhibitors, anti-metastatic drugs, natural product based drug designs, cytostatic effects

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Authors: Nuruddeen Usman, Usman Mohammed Gidado, Muhammad Ahmad Ibrahim

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Construction industry is one of the sectors that are eyeing adoption of ICT for its development due to the advancement in technology. Though, many manufacturing sectors had been using it, but construction industry was left behind, especially in the developing nation like Nigeria. On account of that, the objective of this study is to conceptually and quantitatively synthesise whether the slow adoption of ICT by the construction industries can be attributable to cybercrime threats. The result of the investigation found that, the risk of cybercrime, and lack of adequate cyber security policies that can enforce and punish defaulters are among the things that hinder ICT adoption of the Nigerian construction industries. Therefore, there is need for the nations to educate their citizens on cybercrime risk, and to establish cybercrime police units that can be monitoring and controlling all online communications.

Keywords: construction industry, cybercrime, information and communication technology adoption, risk

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Authors: Tivani Phosa Mashamba-Thompson, Mahmoud E. S. Soliman

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To date, the cause of neurodegeneration is not well understood and diseases that stem from neurodegeneration currently have no known cures. Cathepsin B (CB) enzyme is known to be involved in the production of peptide neurotransmitters and toxic peptides in neurodegenerative diseases (NDs). CA-074Me is a membrane-permeable irreversible selective cathepsin B (CB) inhibitor as confirmed by in vivo studies. Due to the lack of the crystal structure, the binding mode of CA-074Me with the human CB at molecular level has not been previously reported. The main aim of this study is to gain an insight into the binding mode of CB CA-074Me to human CB using various computational tools. Herein, molecular dynamics simulations, binding free energy calculations and per-residue energy decomposition analysis were employed to accomplish the aim of the study. Another objective was to identify novel CB inhibitors based on the structure of CA-074Me using fragment based drug design using scaffold hoping drug design approach. Results showed that two of the designed ligands (hit 1 and hit 2) were found to have better binding affinities than the prototype inhibitor, CA-074Me, by ~2-3 kcal/mol. Per-residue energy decomposition showed that amino acid residues Cys29, Gly196, His197 and Val174 contributed the most towards the binding. The Van der Waals binding forces were found to be the major component of the binding interactions. The findings of this study should assist medicinal chemist towards the design of potential irreversible CB inhibitors.

Keywords: cathepsin B, scaffold hopping, docking, molecular dynamics, binding-free energy, neurodegerative diseases

Procedia PDF Downloads 373

Authors: Jignasha Derasari, Patel Krishna M, Modi Jignasa G.

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Chemical stability of pharmaceutical molecules is a matter of great concern as it affects the safety and efficacy of the drug product.Stability testing data provides the basis to understand how the quality of a drug substance and drug product changes with time under the influence of various environmental factors. Besides this, it also helps in selecting proper formulation and package as well as providing proper storage conditions and shelf life, which is essential for regulatory documentation. The ICH guideline states that stress testing is intended to identify the likely degradation products which further help in determination of the intrinsic stability of the molecule and establishing degradation pathways, and to validate the stability indicating procedures. A simple, accurate and precise stability indicating RP- HPLC method was developed and validated for simultaneous estimation of Amiloride Hydrochloride and Furosemide in tablet dosage form. Separation was achieved on an Phenomenexluna ODS C18 (250 mm × 4.6 mm i.d., 5 µm particle size) by using a mobile phase consisting of Ortho phosphoric acid: Acetonitrile (50:50 %v/v) at a flow rate of 1.0 ml/min (pH 3.5 adjusted with 0.1 % TEA in Water) isocratic pump mode, Injection volume 20 µl and wavelength of detection was kept at 283 nm. Retention time for Amiloride Hydrochloride and Furosemide was 1.810 min and 4.269 min respectively. Linearity of the proposed method was obtained in the range of 40-60 µg/ml and 320-480 µg/ml and Correlation coefficient was 0.999 and 0.998 for Amiloride hydrochloride and Furosemide, respectively. Forced degradation study was carried out on combined dosage form with various stress conditions like hydrolysis (acid and base hydrolysis), oxidative and thermal conditions as per ICH guideline Q2 (R1). The RP- HPLC method has shown an adequate separation for Amiloride hydrochloride and Furosemide from its degradation products. Proposed method was validated as per ICH guidelines for specificity, linearity, accuracy; precision and robustness for estimation of Amiloride hydrochloride and Furosemide in commercially available tablet dosage form and results were found to be satisfactory and significant. The developed and validated stability indicating RP-HPLC method can be used successfully for marketed formulations. Forced degradation studies help in generating degradants in much shorter span of time, mostly a few weeks can be used to develop the stability indicating method which can be applied later for the analysis of samples generated from accelerated and long term stability studies. Further, kinetic study was also performed for different forced degradation parameters of the same combination, which help in determining order of reaction.

Keywords: amiloride hydrochloride, furosemide, kinetic study, stability indicating RP-HPLC method validation

Procedia PDF Downloads 458

Authors: Rodrigo De A. Ferrazza, Henry D. M. Garcia, Viviana H. V. Aristizabal, Camilla De S. Nogueira, Cecilia J. Verissimo, Jose Roberto Sartori, Roberto Sartori, Joao Carlos P. Ferreira

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Environmental factors adversely influence sustainability in livestock production system. Dairy herds are the most affected by heat stress among livestock industries. This clearly implies in development of new strategies for mitigating heat, which should be based on physiological and metabolic adaptations of the animal. In this study, we incorporated the effect of climate variables and heat exposure time on the thermoregulatory responses in order to clarify the adaptive mechanisms for bovine heat dissipation under intense thermal stress induced experimentally in climate chamber. Non-lactating Holstein cows were contemporaneously and randomly assigned to thermoneutral (TN; n=12) or heat stress (HS; n=12) treatments during 16 days. Vaginal temperature (VT) was measured every 15 min with a microprocessor-controlled data logger (HOBO®, Onset Computer Corporation, Bourne, MA, USA) attached to a modified vaginal controlled internal drug release insert (Sincrogest®, Ourofino, Brazil). Rectal temperature (RT), respiratory rate (RR) and heart rate (HR) were measured twice a day (0700 and 1500h) and dry matter intake (DMI) was estimated daily. The ambient temperature and air relative humidity were 25.9±0.2°C and 73.0±0.8%, respectively for TN, and 36.3± 0.3°C and 60.9±0.9%, respectively for HS. Respiratory rate of HS cows increased immediately after exposure to heat and was higher (76.02±1.70bpm; P<0.001) than TN (39.70±0.71bpm), followed by rising of RT (39.87°C±0.07 for HS versus 38.56±0.03°C for TN; P<0.001) and VT (39.82±0.10°C for HS versus 38.26±0.03°C for TN; P<0.001). A diurnal pattern was detected, with higher (P<0.01) afternoon temperatures than morning and this effect was aggravated for HS cows. There was decrease (P<0.05) of HR for HS cows (62.13±0.99bpm) compared to TN (66.23±0.79bpm), but the magnitude of the differences was not the same over time. From the third day, there was a decrease of DMI for HS in attempt to maintain homeothermy, while TN cows increased DMI (8.27kg±0.33kg d-1 for HS versus 14.03±0.29kg d-1 for TN; P<0.001). By regression analysis, RT and RR better reflected the response of cows to changes in the Temperature Humidity Index and the effect of climate variables from the previous day to influence the physiological parameters and DMI was more important than the current day, with ambient temperature the most important factor. Comparison between acute (0 to 3 days) and chronic (13 to 16 days) exposure to heat stress showed decreasing of the slope of the regression equations for RR and DMI, suggesting an adaptive adjustment, however with no change for RT. In conclusion, intense heat stress exerted strong influence on the thermoregulatory mechanisms, but the acclimation process was only partial.

Keywords: acclimation, bovine, climate chamber, hyperthermia, thermoregulation

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Authors: Keshari Shrestha, Philip Vatterott

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Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare and potentially fatal drug-related syndrome. DRESS classically presents with a diffuse maculopapular rash, fevers, and eosinophilia more than three weeks after drug exposure. DRESS can present with multi-organ involvement, with liver damage being the most common and severe. Pulmonary involvement is a less common manifestation and is associated with poor clinical outcomes. Chest imaging is often nonspecific, and symptoms can range from mild cough to acute respiratory distress syndrome (ARDS) . This is a case of a 49-year-old female with a history of recent clostridium difficile colitis status post treatment with oral vancomycin who presented with rash, acute liver and kidney failure, as well as diffuse nodular alveolar lung opacities concerning for DRESS syndrome with multi-organ involvement. Clinical Course: This patient initially presented to an outside hospital with clostridium difficile colitis, acute liver injury, and acute kidney injury. She developed a desquamating maculopapular rash in the setting of recent oral vancomycin, meloxicam, and furosemide initiation. She was hospitalized on two additional occasions with worsening altered mental status, liver injury, and acute kidney injury and was initiated on intermittent hemodialysis. Notably, she was found to have systemic eosinophilia (4100 cells/microliter) several weeks prior. She was transferred to this institution for further management where she was found to have encephalopathy, jaundice, lower extremity edema, and diffuse bilateral rhonchorous breath sounds on pulmonary examination. The patient was started on methylprednisolone for suspected DRESS syndrome. She underwent an evaluation for alternative causes of her organ failure. Her workup included a negative infectious, autoimmune, metabolic, toxic, and malignant work-up. Abdominal computed tomography (CT) and ultrasound were remarkable for evidence of hepatic steatosis and possible cirrhotic morphology. Additionally, a chest CT demonstrated diffuse and symmetric nodular alveolar lung opacities with peripheral sparing not consistent with acute respiratory distress syndrome or edema. Ultimately, her condition continued to decline, and she required intubation on several occasions. On hospital day 25 she succumbed to distributive shock in the setting of probable sepsis and multi-organ failure. Discussion: DRESS syndrome occurs in 1 in 1,000 to 10,000 patients with a mortality rate of around 10%. Anti-convulsant, anti-bacterial, anti-viral, and sulfonamide drugs are the most common drugs implicated in the development of DRESS syndrome; however, the list of offending agents is extensive . The diagnosis of DRESS syndrome is made after excluding other causes of disease such as infectious and autoimmune etiologies. The RegiSCAR scoring system is used to diagnose DRESS syndrome with 2-3 points indicating possible disease, 4-5 probable disease, and >5 definite disease. This patient scored a 7 on the RegiSCAR scale for eosinophilia, rash, organ involvement, and exclusion of other causes (infectious and autoimmune). While the pharmacologic trigger in this case is unknown, it is speculated to be caused by vancomycin, meloxicam, or furosemide due to the favorable timeline of initiation. Despite aggressive treatment, DRESS syndrome can often be fatal. Because of this, early diagnosis and treatment of patients with suspected DRESS syndrome is imperative.

Keywords: drug reaction with eosinophilia and systemic symptoms, multi-organ failure, pulmonary involvement, renal failure

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Authors: Sara Salehi, Ka Yu Cheng, Anna Heitz, Maneesha Ginige

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This study investigated the efficiency of granular sludge for phosphorous (P) recovery from wastewater. A laboratory scale sequencing batch reactor (SBR) was operated under alternating aerobic/anaerobic conditions to enrich a P accumulating granular biomass. This study showed that an overall 45-fold increase in P concentration could be achieved by reducing the volume of the P capturing liquor by 5-fold in the anaerobic P release phase. Moreover, different fractions of the granular biomass have different individual contributions towards generating a concentrated stream of P.

Keywords: granular sludge, PAOs, P recovery, SBR

Procedia PDF Downloads 474

Authors: Nagmani Lnu

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Test automation is a vital requirement of any organization to release products faster to their customers. In most cases, an organization has an approach to developing automation but struggles to maintain it. It results in an increased number of Flaky Tests, reducing return on investments and stakeholders’ confidence. Challenges grow in multiple folds when automation is for UI behaviors. This paper describes the approaches taken to identify the root cause of automation instability in an extensive payments application and the best practices to address that using processes, tools, and technologies, resulting in a 75% reduction of effort.

Keywords: automation stability, test stability, Flaky Test, test quality, test automation quality

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Authors: Zsanett Bahor, Cristina Nunes-Fonseca, Gillian L. Currie, Emily S. Sena, Lindsay D.G. Thomson, Malcolm R. Macleod

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Psychosis is ranked as the third most disabling medical condition in the world by the World Health Organization. Despite a substantial amount of research in recent years, available treatments are not universally effective and have a wide range of adverse side effects. Since many clinical drug candidates are identified through in vivo modelling, a deeper understanding of these models, and their strengths and limitations, might help us understand reasons for difficulties in psychosis drug development. To provide an unbiased summary of the preclinical psychosis literature we performed a systematic electronic search of PubMed for publications modelling a psychotic disorder in vivo, identifying 14,721 relevant studies. Double screening of 11,000 publications from this dataset so far established 2403 animal studies of psychosis, with the most common model being schizophrenia (95%). 61% of these models are induced using pharmacological agents. For all the models only 56% of publications test a therapeutic treatment. We propose a systematic review of these studies to assess the prevalence of reporting of measures to reduce risk of bias, and a meta-analysis to assess the internal and external validity of these animal models. Our findings are likely to be relevant to future preclinical studies of psychosis as this generation of strong empirical evidence has the potential to identify weaknesses, areas for improvement and make suggestions on refinement of experimental design. Such a detailed understanding of the data which inform what we think we know will help improve the current attrition rate between bench and bedside in psychosis research.

Keywords: animal models, psychosis, systematic review, schizophrenia

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Authors: Christopher R. Triggle, Hong Ding, Khaled Machaca, Gnanapragasam Arunachalam

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The antidiabetic drug, metformin, has been in clinical use for over 50 years and remains the first choice drug for the treatment of type two diabetes. In addition to its effectiveness as an oral anti-hyperglycaemic drug metformin also possesses vasculoprotective effects that are assumed to be secondary to its ability to reduce insulin resistance and control glycated hemoglobin levels; however, recent data from our laboratory indicate that metformin also has direct vasoprotective effects that are mediated, at least in part, via the anti-ageing gene, SIRT1. Diabetes is a major risk factor for the development of cardiovascular disease (CVD) and it is also well established that tobacco use further enhances the risk of CVD; however, it is not known whether treatment with metformin can offset the negative effects of diabetes and tobacco use on cardiac function. The current study was therefore designed to investigate 1: the effects of hyperglycaemia (HG) either alone or in the presence of elevated fatty acids (palmitate) and nicotine on the protein expression levels of the deacetylase sirtuin 1 (the protein product of SIRT1), anti-apoptotic Bcl-2, pro-apoptotic BIM and the pro-apoptotic, tumour suppressor protein, acetylated p53 in cardiomyocytes. 2: the ability of metformin to prevent the detrimental effects of HG, palmitate and nicotine on cardiomyocyte survival. Cell culture protocols were designed using a rat cardiomyocyte cell line, H9c2, either under normal glycaemic (NG) conditions of 5.5mM glucose, or hyperglycaemic conditions (HG) of 25mM glucose with, or without, added palmitate (250μM) or nicotine (1.0mM) for 24h. Immuno-blotting was used to detect the expression of sirtuin 1, Bcl-2, BIM, acetylated (Ac)-p53, p53 with β-actin used as the reference protein. Exposure to HG, palmitate, or nicotine alone significantly reduced expression of sirtuin1, Bcl-2 and raised the expression levels of acetylated p53 and BIM; however, the combination of HG, palmitate and nicotine had a synergistic effect to significantly suppress the expression levels of sirtuin 1 and Bcl-2, but further enhanced the expression of Ac-p53, and BIM. The inclusion of 1000μM, but not 50μM, metformin in the H9c2 cell culture protocol prevented the effects of HG, palmitate and nicotine on the pro-apoptotic pathways. Collectively these data indicate that metformin, in addition to its anti-hyperglycaemic and vasculoprotective properties, also has direct cardioprotective actions that offset the negative effects of hyerglycaemia, elevated free fatty acids and nicotine on cardiac cell survival. These data are of particular significance for the treatment of patients with diabetes who are also smokers as the inclusion of metformin in their therapeutic treatment plan should help reduce cardiac-related morbidity and mortality.

Keywords: apoptosis, cardiac muscle, diabetes, metformin, nicotine

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