Search results for: common drug combinations
7189 The Voiceless Dental- Alveolar Common Augment in Arabic and Other Semitic Languages, a Morphophonemic Comparison
Authors: Tarek Soliman Mostafa Soliman Al-Nana'i
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There are non-steady voiced augments in the Semitic languages, and in the morphological and structural augmentation, two sounds were augments in all Semitic languages at the level of the spoken language and two letters at the level of the written language, which are the hamza and the ta’. This research studies only the second of them; Therefore, we defined it as “The Voiceless Dental- alveolar common augment” (VDACA) to distinguish it from the glottal sound “Hamza”, first, middle, or last, in a noun or in a verb, in Arabic and its equivalent in the Semitic languages. What is meant by “VDACA” is the ta’ that is in addition to the root of the word at the morphological level: the word “voiceless” takes out the voiced sounds that we studied before, and the “dental- alveolar common augment” takes out the laryngeal sound of them, which is the “Hamza”: and the word “common” brings out the uncommon voiceless sounds, which are sīn, shīn, and hā’. The study is limited to the ta' alone among the Arabic sounds, and this title faced a problem in identifying it with the ta'. Because the designation of the ta is not the same in most Semitic languages. Hebrew, for example, has “tav” and is pronounced with the voiced fa (v), which is not in Arabic. It is called different names in other Semitic languages, such as “taw” or “tAu” in old Syriac. And so on. This goes hand in hand with the insistence on distance from the written level and the reference to the phonetic aspect in this study that is closely and closely linked to the morphological level. Therefore, the study is “morphophonemic”. What is meant by Semitic languages in this study are the following: Akkadian, Ugaritic, Hebrew, Syriac, Mandaean, Ge'ez, and Amharic. The problem of the study is the agreement or difference between these languages in the position of that augment, first, middle, or last. And in determining the distinguishing characteristics of each language from the other. As for the study methodology, it is determined by the comparative approach in Semitic languages, which is based on the descriptive approach for each language. The study is divided into an introduction, four sections, and a conclusion: Introduction: It included the subject of the study, its importance, motives, problem, methodology, and division. The first section: VDACA as a non-common phoneme. The second: VDACA as a common phoneme. The third: VDACA as a functional morpheme. The fourth section: Commentary and conclusion with the most important results. The positions of VDACA in Arabic and other Semitic languages, and in nouns and verbs, were limited to first, middle, and last. The research identified the individual addition, which is common with other augments, and the research proved that this augmentation is constant in all Semitic languages, but there are characteristics that distinguish each language from the other.Keywords: voiceless -, dental- alveolar, augment, Arabic - semitic languages
Procedia PDF Downloads 737188 The Increasing Importance of CFC Rules: An OECD+ Country Overview
Authors: Axel Prettl
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This paper provides an overview of the different CFC rule settings in the OECD and 22 additional countries for the years 2004 to 2014 and compares them. In order to do so, it gives a summary of law amendments for every country, provides a comparison and afterwards all CFC rules are rated in their ”power of anti-avoidance” over time. For that rating of CFC rules, the largest common denominator of rule characteristics is used to keep it as abstract as necessary and possible. The paper points out that the CFC rules in the considered countries are very different in their specifications and they reach from very strict to very low binding. All in all these rules get more and more common and important; more countries implement a CFC legislation and the strictness of most of them rises over time.Keywords: CFC rules, international taxation, corporate taxation, country comparison
Procedia PDF Downloads 3107187 Differences in Production of Knowledge between Internationally Mobile versus Nationally Mobile and Non-Mobile Scientists
Authors: Valeria Aman
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The presented study examines the impact of international mobility on knowledge production among mobile scientists and within the sending and receiving research groups. Scientists are relevant to the dynamics of knowledge production because scientific knowledge is mainly characterized by embeddedness and tacitness. International mobility enables the dissemination of scientific knowledge to other places and encourages new combinations of knowledge. It can also increase the interdisciplinarity of research by forming synergetic combinations of knowledge. Particularly innovative ideas can have their roots in related research domains and are sometimes transferred only through the physical mobility of scientists. Diversity among scientists with respect to their knowledge base can act as an engine for the creation of knowledge. It is therefore relevant to study how knowledge acquired through international mobility affects the knowledge production process. In certain research domains, international mobility may be essential to contextualize knowledge and to gain access to knowledge located at distant places. The knowledge production process contingent on the type of international mobility and the epistemic culture of a research field is examined. The production of scientific knowledge is a multi-faceted process, the output of which is mainly published in scholarly journals. Therefore, the study builds upon publication and citation data covered in Elsevier’s Scopus database for the period of 1996 to 2015. To analyse these data, bibliometric and social network analysis techniques are used. A basic analysis of scientific output using publication data, citation data and data on co-authored publications is combined with a content map analysis. Abstracts of publications indicate whether a research stay abroad makes an original contribution methodologically, theoretically or empirically. Moreover, co-citations are analysed to map linkages among scientists and emerging research domains. Finally, acknowledgements are studied that can function as channels of formal and informal communication between the actors involved in the process of knowledge production. The results provide better understanding of how the international mobility of scientists contributes to the production of knowledge, by contrasting the knowledge production dynamics of internationally mobile scientists with those being nationally mobile or immobile. Findings also allow indicating whether international mobility accelerates the production of knowledge and the emergence of new research fields.Keywords: bibliometrics, diversity, interdisciplinarity, international mobility, knowledge production
Procedia PDF Downloads 2937186 Emotion Recognition in Video and Images in the Wild
Authors: Faizan Tariq, Moayid Ali Zaidi
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Facial emotion recognition algorithms are expanding rapidly now a day. People are using different algorithms with different combinations to generate best results. There are six basic emotions which are being studied in this area. Author tried to recognize the facial expressions using object detector algorithms instead of traditional algorithms. Two object detection algorithms were chosen which are Faster R-CNN and YOLO. For pre-processing we used image rotation and batch normalization. The dataset I have chosen for the experiments is Static Facial Expression in Wild (SFEW). Our approach worked well but there is still a lot of room to improve it, which will be a future direction.Keywords: face recognition, emotion recognition, deep learning, CNN
Procedia PDF Downloads 1877185 Simultaneous Targeting of MYD88 and Nur77 as an Effective Approach for the Treatment of Inflammatory Diseases
Authors: Uzma Saqib, Mirza S. Baig
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Myeloid differentiation primary response protein 88 (MYD88) has long been considered a central player in the inflammatory pathway. Recent studies clearly suggest that it is an important therapeutic target in inflammation. On the other hand, a recent study on the interaction between the orphan nuclear receptor (Nur77) and p38α, leading to increased lipopolysaccharide-induced hyperinflammatory response, suggests this binary complex as a therapeutic target. In this study, we have designed inhibitors that can inhibit both MYD88 and Nur77 at the same time. Since both MYD88 and Nur77 are an integral part of the pathways involving lipopolysaccharide-induced activation of NF-κB-mediated inflammation, we tried to target both proteins with the same library in order to retrieve compounds having dual inhibitory properties. To perform this, we developed a homodimeric model of MYD88 and, along with the crystal structure of Nur77, screened a virtual library of compounds from the traditional Chinese medicine database containing ~61,000 compounds. We analyzed the resulting hits for their efficacy for dual binding and probed them for developing a common pharmacophore model that could be used as a prototype to screen compound libraries as well as to guide combinatorial library design to search for ideal dual-target inhibitors. Thus, our study explores the identification of novel leads having dual inhibiting effects due to binding to both MYD88 and Nur77 targets.Keywords: drug design, Nur77, MYD88, inflammation
Procedia PDF Downloads 3057184 Upconversion Nanoparticle-Mediated Carbon Monoxide Prodrug Delivery System for Cancer Therapy
Authors: Yaw Opoku-Damoah, Run Zhang, Hang Thu Ta, Zhi Ping Xu
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Gas therapy is still at an early stage of research and development. Even though most gasotransmitters have proven their therapeutic potential, their handling, delivery, and controlled release have been extremely challenging. This research work employs a versatile nanosystem that is capable of delivering a gasotransmitter in the form of a photo-responsive carbon monoxide-releasing molecule (CORM) for targeted cancer therapy. The therapeutic action was mediated by upconversion nanoparticles (UCNPs) designed to transfer bio-friendly low energy near-infrared (NIR) light to ultraviolet (UV) light capable of triggering carbon monoxide (CO) from a water-soluble amphiphilic manganese carbonyl complex CORM incorporated into a carefully designed lipid drug delivery system. Herein, gaseous CO that plays a role as a gasotransmitter with cytotoxic and homeostatic properties was investigated to instigate cellular apoptosis. After successfully synthesizing the drug delivery system, the ability of the system to encapsulate and mediate the sustained release of CO after light excitation was demonstrated. CO fluorescence probe (COFP) was successfully employed to determine the in vitro drug release profile upon NIR light irradiation. The uptake of nanoparticles enhanced by folates and its receptor interaction was also studied for cellular uptake purposes. The anticancer potential of the final lipid nanoparticle Lipid/UCNPs/CORM/FA (LUCF) was also determined by cell viability assay. Intracellular CO release and a subsequent therapeutic action involving ROS production, mitochondrial damage, and CO production was also evaluated. In all, this current project aims to use in vitro studies to determine the potency and efficiency of a NIR-mediated CORM prodrug delivery system.Keywords: carbon monoxide-releasing molecule, upconversion nanoparticles, site-specific delivery, amphiphilic manganese carbonyl complex, prodrug delivery system.
Procedia PDF Downloads 1127183 Discrimination of Bio-Analytes by Using Two-Dimensional Nano Sensor Array
Authors: P. Behera, K. K. Singh, D. K. Saini, M. De
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Implementation of 2D materials in the detection of bio analytes is highly advantageous in the field of sensing because of its high surface to volume ratio. We have designed our sensor array with different cationic two-dimensional MoS₂, where surface modification was achieved by cationic thiol ligands with different functionality. Green fluorescent protein (GFP) was chosen as signal transducers for its biocompatibility and anionic nature, which can bind to the cationic MoS₂ surface easily, followed by fluorescence quenching. The addition of bio-analyte to the sensor can decomplex the cationic MoS₂ and GFP conjugates, followed by the regeneration of GFP fluorescence. The fluorescence response pattern belongs to various analytes collected and transformed to linear discriminant analysis (LDA) for classification. At first, 15 different proteins having wide range of molecular weight and isoelectric points were successfully discriminated at 50 nM with detection limit of 1 nM. The sensor system was also executed in biofluids such as serum, where 10 different proteins at 2.5 μM were well separated. After successful discrimination of protein analytes, the sensor array was implemented for bacteria sensing. Six different bacteria were successfully classified at OD = 0.05 with a detection limit corresponding to OD = 0.005. The optimized sensor array was able to classify uropathogens from non-uropathogens in urine medium. Further, the technique was applied for discrimination of bacteria possessing resistance to different types and amounts of drugs. We found out the mechanism of sensing through optical and electrodynamic studies, which indicates the interaction between bacteria with the sensor system was mainly due to electrostatic force of interactions, but the separation of native bacteria from their drug resistant variant was due to Van der Waals forces. There are two ways bacteria can be detected, i.e., through bacterial cells and lysates. The bacterial lysates contain intracellular information and also safe to analysis as it does not contain live cells. Lysates of different drug resistant bacteria were patterned effectively from the native strain. From unknown sample analysis, we found that discrimination of bacterial cells is more sensitive than that of lysates. But the analyst can prefer bacterial lysates over live cells for safer analysis.Keywords: array-based sensing, drug resistant bacteria, linear discriminant analysis, two-dimensional MoS₂
Procedia PDF Downloads 1437182 Screening of Four Malaysian Isolated Endophytes with Candesartan in a Microtiter Plate
Authors: Rasha Saad, Jean Frederic Weber, Fatimah Bebe, Sadia Sultan
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The goal of study was to screen the effects of candesartan and four endophytic fungi for their potential in microbial biotransformation. In this experiment, four types of unidentified fungi with the codes of TH2L1, TH2R10, TH1P35 and TH1S46 were used in screening process by MECFUS (Microtiter plate, Elicitors, Combination, Freeze-drying, UHPLC, Statistical analysis) protocol. The experiment was carried out by using 96-well microtiter plate (MTP) with different media and elicitors. Various media with two concentrations of Potato Dextrose Broth (PDB) and elicitors used were to induce the production of secondary metabolites from the fungi as well as the biotransformation of the drug compound. After incubation, cultures were extracted by freeze drying method and finally analyzed by ultra-High performance Liquid Chromatography (uHPLC). The extracts analyzed by uHPLC followed by LC/Ms, demonstrated the presence of biotransformation products from the drug compound and elicitation of the secondary metabolism from the fungi by the occurrence of the additional peaks. From the four fungi, TH1S46 showed highly potential produced secondary metabolites as well as the biotransformation of candesartan. For other fungi, they responded when candesartan was introduced. Moreover, the additional peaks produced in uHPLC need to be further investigation by using LC-MS or NMR.Keywords: biotransformation, candesartan, endophytes, secondary metabolites
Procedia PDF Downloads 2637181 New Coating Materials Based on Mixtures of Shellac and Pectin for Pharmaceutical Products
Authors: M. Kumpugdee-Vollrath, M. Tabatabaeifar, M. Helmis
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Shellac is a natural polyester resin secreted by insects. Pectins are natural, non-toxic and water-soluble polysaccharides extracted from the peels of citrus fruits or the leftovers of apples. Both polymers are allowed for the use in the pharmaceutical industry and as a food additive. SSB Aquagold® is the aqueous solution of shellac and can be used for a coating process as an enteric or controlled drug release polymer. In this study, tablets containing 10 mg methylene blue as a model drug were prepared with a rotary press. Those tablets were coated with mixtures of shellac and one of the pectin different types (i.e. CU 201, CU 501, CU 701 and CU 020) mostly in a 2:1 ratio or with pure shellac in a small scale fluidized bed apparatus. A stable, simple and reproducible three-stage coating process was successfully developed. The drug contents of the coated tablets were determined using UV-VIS spectrophotometer. The characterization of the surface and the film thickness were performed with the scanning electron microscopy (SEM) and the light microscopy. Release studies were performed in a dissolution apparatus with a basket. Most of the formulations were enteric coated. The dissolution profiles showed a delayed or sustained release with a lagtime of at least 4 h. Dissolution profiles of coated tablets with pure shellac had a very long lagtime ranging from 13 to 17.5 h and the slopes were quite high. The duration of the lagtime and the slope of the dissolution profiles could be adjusted by adding the proper type of pectin to the shellac formulation and by variation of the coating amount. In order to apply a coating formulation as a colon delivery system, the prepared film should be resistant against gastric fluid for at least 2 h and against intestinal fluid for 4-6 h. The required delay time was gained with most of the shellac-pectin polymer mixtures. The release profiles were fitted with the modified model of the Korsmeyer-Peppas equation and the Hixson-Crowell model. A correlation coefficient (R²) > 0.99 was obtained by Korsmeyer-Peppas equation.Keywords: shellac, pectin, coating, fluidized bed, release, colon delivery system, kinetic, SEM, methylene blue
Procedia PDF Downloads 4077180 Numerical and Experimental Comparison of Surface Pressures around a Scaled Ship Wind-Assisted Propulsion System
Authors: James Cairns, Marco Vezza, Richard Green, Donald MacVicar
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Significant legislative changes are set to revolutionise the commercial shipping industry. Upcoming emissions restrictions will force operators to look at technologies that can improve the efficiency of their vessels -reducing fuel consumption and emissions. A device which may help in this challenge is the Ship Wind-Assisted Propulsion system (SWAP), an actively controlled aerofoil mounted vertically on the deck of a ship. The device functions in a similar manner to a sail on a yacht, whereby the aerodynamic forces generated by the sail reach an equilibrium with the hydrodynamic forces on the hull and a forward velocity results. Numerical and experimental testing of the SWAP device is presented in this study. Circulation control takes the form of a co-flow jet aerofoil, utilising both blowing from the leading edge and suction from the trailing edge. A jet at the leading edge uses the Coanda effect to energise the boundary layer in order to delay flow separation and create high lift with low drag. The SWAP concept has been originated by the research and development team at SMAR Azure Ltd. The device will be retrofitted to existing ships so that a component of the aerodynamic forces acts forward and partially reduces the reliance on existing propulsion systems. Wind tunnel tests have been carried out at the de Havilland wind tunnel at the University of Glasgow on a 1:20 scale model of this system. The tests aim to understand the airflow characteristics around the aerofoil and investigate the approximate lift and drag coefficients that an early iteration of the SWAP device may produce. The data exhibits clear trends of increasing lift as injection momentum increases, with critical flow attachment points being identified at specific combinations of jet momentum coefficient, Cµ, and angle of attack, AOA. Various combinations of flow conditions were tested, with the jet momentum coefficient ranging from 0 to 0.7 and the AOA ranging from 0° to 35°. The Reynolds number across the tested conditions ranged from 80,000 to 240,000. Comparisons between 2D computational fluid dynamics (CFD) simulations and the experimental data are presented for multiple Reynolds-Averaged Navier-Stokes (RANS) turbulence models in the form of normalised surface pressure comparisons. These show good agreement for most of the tested cases. However, certain simulation conditions exhibited a well-documented shortcoming of RANS-based turbulence models for circulation control flows and over-predicted surface pressures and lift coefficient for fully attached flow cases. Work must be continued in finding an all-encompassing modelling approach which predicts surface pressures well for all combinations of jet injection momentum and AOA.Keywords: CFD, circulation control, Coanda, turbo wing sail, wind tunnel
Procedia PDF Downloads 1357179 Synthesis, Molecular Modeling and Study of 2-Substituted-4-(Benzo[D][1,3]Dioxol-5-Yl)-6-Phenylpyridazin-3(2H)-One Derivatives as Potential Analgesic and Anti-Inflammatory Agents
Authors: Jyoti Singh, Ranju Bansal
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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors
Procedia PDF Downloads 2007178 An Update on Linezolid against Methicillin-Resistant Staphylococcus Aureus Clinical Isolates from Pakistan
Authors: Tayaba Dastgeer, Farhan Rasheed, Muhammad Saeed, Maqsood Ahmad, Zia Ashraf, Abdul Waheed, Muhammad Kamran, Mohsin Khurshid
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Objectives: The study aimed to determine the efficacy of linezolid against clinical isolates of methicillin-resistant staphylococcus aureus (MRSA). Methodology: This cross-sectional study was conducted in the microbiology department of Allama Iqbal Medical College Lahore from August 2017 to September 2019. Isolates were confirmed as MRSA via the presence of the mec-A gene. Confirmed MRSA isolates were processed for susceptibility testing against different antimicrobials, especially linezolid, via the disc diffusion method. Zone sizes were interpreted according to CLSI guidelines. Results: Various types of clinical samples were included in the study; however, the highest frequency of MRSA isolates was found in pus samples, followed by other clinical samples. Among hospitalized patients, most MRSA isolates were obtained from patients in the surgical ward. Of 243 mec-A gene detected isolates, Vancomycin and linezolid showed 100% susceptibility, chloramphenicol showed declining resistance 78 (32.09%), and emerging sensitivity 165 (67.90%) against MRSA. Conclusion: Linezolid is a very efficient drug against MRSA, but the use of this novel drug must be conserved for vancomycin-resistant Staphylococcus aureus or when more resistant pathogens are suspected.Keywords: MRSA, chloramphenicol, linezolid, nosocomial infections
Procedia PDF Downloads 977177 Development of Trigger Tool to Identify Adverse Drug Events From Warfarin Administered to Patient Admitted in Medical Wards of Chumphae Hospital
Authors: Puntarikorn Rungrattanakasin
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Objectives: To develop the trigger tool to warn about the risk of bleeding as an adverse event from warfarin drug usage during admission in Medical Wards of Chumphae Hospital. Methods: A retrospective study was performed by reviewing the medical records for the patients admitted between June 1st,2020- May 31st, 2021. ADEs were evaluated by Naranjo’s algorithm. The international normalized ratio (INR) and events of bleeding during admissions were collected. Statistical analyses, including Chi-square test and Reciever Operating Characteristic (ROC) curve for optimal INR threshold, were used for the study. Results: Among the 139 admissions, the INR range was found to vary between 0.86-14.91, there was a total of 15 bleeding events, out of which 9 were mild, and 6 were severe. The occurrence of bleeding started whenever the INR was greater than 2.5 and reached the statistical significance (p <0.05), which was in concordance with the ROC curve and yielded 100 % sensitivity and 60% specificity in the detection of a bleeding event. In this regard, the INR greater than 2.5 was considered to be an optimal threshold to alert promptly for bleeding tendency. Conclusions: The INR value of greater than 2.5 (>2.5) would be an appropriate trigger tool to warn of the risk of bleeding for patients taking warfarin in Chumphae Hospital.Keywords: trigger tool, warfarin, risk of bleeding, medical wards
Procedia PDF Downloads 1487176 Incorporation of Safety into Design by Safety Cube
Authors: Mohammad Rajabalinejad
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Safety is often seen as a requirement or a performance indicator through the design process, and this does not always result in optimally safe products or systems. This paper suggests integrating the best safety practices with the design process to enrich the exploration experience for designers and add extra values for customers. For this purpose, the commonly practiced safety standards and design methods have been reviewed and their common blocks have been merged forming Safety Cube. Safety Cube combines common blocks for design, hazard identification, risk assessment and risk reduction through an integral approach. An example application presents the use of Safety Cube for design of machinery.Keywords: safety, safety cube, product, system, machinery, design
Procedia PDF Downloads 2467175 Curcumin Nanomedicine: A Breakthrough Approach for Enhanced Lung Cancer Therapy
Authors: Shiva Shakori Poshteh
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Lung cancer is a highly prevalent and devastating disease, representing a significant global health concern with profound implications for healthcare systems and society. Its high incidence, mortality rates, and late-stage diagnosis contribute to its formidable nature. To address these challenges, nanoparticle-based drug delivery has emerged as a promising therapeutic strategy. Curcumin (CUR), a natural compound derived from turmeric, has garnered attention as a potential nanomedicine for lung cancer treatment. Nanoparticle formulations of CUR offer several advantages, including improved drug delivery efficiency, enhanced stability, controlled release kinetics, and targeted delivery to lung cancer cells. CUR exhibits a diverse array of effects on cancer cells. It induces apoptosis by upregulating pro-apoptotic proteins, such as Bax and Bak, and downregulating anti-apoptotic proteins, such as Bcl-2. Additionally, CUR inhibits cell proliferation by modulating key signaling pathways involved in cancer progression. It suppresses the PI3K/Akt pathway, crucial for cell survival and growth, and attenuates the mTOR pathway, which regulates protein synthesis and cell proliferation. CUR also interferes with the MAPK pathway, which controls cell proliferation and survival, and modulates the Wnt/β-catenin pathway, which plays a role in cell proliferation and tumor development. Moreover, CUR exhibits potent antioxidant activity, reducing oxidative stress and protecting cells from DNA damage. Utilizing CUR as a standalone treatment is limited by poor bioavailability, lack of targeting, and degradation susceptibility. Nanoparticle-based delivery systems can overcome these challenges. They enhance CUR’s bioavailability, protect it from degradation, and improve absorption. Further, Nanoparticles enable targeted delivery to lung cancer cells through surface modifications or ligand-based targeting, ensuring sustained release of CUR to prolong therapeutic effects, reduce administration frequency, and facilitate penetration through the tumor microenvironment, thereby enhancing CUR’s access to cancer cells. Thus, nanoparticle-based CUR delivery systems promise to improve lung cancer treatment outcomes. This article provides an overview of lung cancer, explores CUR nanoparticles as a treatment approach, discusses the benefits and challenges of nanoparticle-based drug delivery, and highlights prospects for CUR nanoparticles in lung cancer treatment. Future research aims to optimize these delivery systems for improved efficacy and patient prognosis in lung cancer.Keywords: lung cancer, curcumin, nanomedicine, nanoparticle-based drug delivery
Procedia PDF Downloads 727174 Principal Components Analysis of the Causes of High Blood Pressure at Komfo Anokye Teaching Hospital, Ghana
Authors: Joseph K. A. Johnson
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Hypertension affects 20 percent of the people within the ages 55 upward in Ghana. Of these, almost one-third are unaware of their condition. Also at the age of 55, more men turned to have hypertension than women. After that age, the condition becomes more prevalent with women. Hypertension is significantly more common in African Americans of both sexes than the racial or ethnic groups. This study was conducted to determine the causes of high blood pressure in Ashanti Region, Ghana. The study employed One Hundred and Seventy (170) respondents. The sample population for the study was all the available respondents at the time of the data collection. The research was conducted using primary data where convenience sampling was used to locate the respondents. A set of questionnaire were used to gather the data for the study. The gathered data was analysed using principal component analysis. The study revealed that, personal description, lifestyle behavior and risk awareness as some of the causes of high blood pressure in Ashanti Region. The study therefore recommend that people must be advice to see to their personal characteristics that may contribute to high blood pressure such as controlling of their temper and how to react perfectly to stressful situations. They must be educated on the factors that may increase the level of their blood pressure such as the essence of seeing a medical doctor before taking in any drug. People must also be made known by the public health officers to those lifestyles behaviour such as smoking and drinking of alcohol which are major contributors of high blood pressure.Keywords: high blood pressure, principal component analysis, hypertension, public health
Procedia PDF Downloads 4857173 Embodied Spiritualities and Emerging Search for Social Transformation: An Embodied Ethnographic Study of Yoga Practices in Medellin, Colombia
Authors: Lina M. Vidal
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This paper discusses yoga practices involvement in both self-transformation and social transformations by means of an embodied ethnographic approach to different initiatives for social change in Medellín. In the context of gradual popularization of embodied spiritualities, yoga practices have opened their way in calls for social change in a performative perspective which involves collective experiences, reflections and production of embodied knowledge. Through the reflection on bodily dimension and corporal experience, this ethnographic approach acknowledges inter-corporality and somatic modes of attention during observations and personal experiences. In social change initiatives that include yoga practices were identified transformations of common understanding on social issues such as it is produced by institutionalized education, health system and other fields of knowledge. This is clearly visible in yoga projects for children in vulnerable conditions, homeless people, prisoners, and young people recovering from drug addiction. These projects are often promoted by organizations and networks, which incorporate individual life stories into collective experiences. Dissemination of yoga is heading to a broad institutional and cultural legitimation of yoga and of spirituality that impact different fields of social work and everyday life in general. This way, yoga is becoming an embodied activist way of life and a legitimate field for social work.Keywords: embodied ethnography, Medellin, social transformation, embodied spiritualities, yoga practices
Procedia PDF Downloads 1887172 LGBTQ+ Visibility: An Analysis of the Mechanisms for Safeguarding Sexual Minorities within the Common European Asylum System
Authors: Alessandra Tosi, Teia M. Rogers
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The Common European Asylum System (CEAS) is the framework that standardises the treatment of applicants for international protection and harmonises asylum systems throughout the European Union. This paper interrogates the rules applied within the CEAS, specifically Directive 2013/33/EU of the European Parliament and of the Council of 26 June 2013, which puts forth the standards for the reception of vulnerable people applying for asylum. Absent from the definition of ‘vulnerable people’ are sexual minorities who routinely experience discrimination in reception centres and emergency accommodations. This paper undertakes an analysis of policies and legalisation of reception centres within the European Union. In confronting the flaws inherent to the system of processing asylum applications, this paper argues for the reform of the CEAS with emphasis on the inclusion of LBGTQ+ asylum seekers as vulnerable people following standards set by international human rights law.Keywords: accommodation, asylum seekers, CEAS, Common European Asylum System, European Union, LGBTQ+, reception conditions, vulnerable people
Procedia PDF Downloads 1417171 Evaluation of Medication Administration Process in a Paediatric Ward
Authors: Zayed Alsulami, Asma Aldosseri, Ahmed Ezziden, Abdulrahman Alonazi
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Children are more susceptible to medication errors than adults. Medication administration process is the last stage in the medication treatment process and most of the errors detected in this stage. Little research has been undertaken about medication errors in children in the Middle East countries. This study was aimed to evaluate how the paediatric nurses adhere to the medication administration policy and also to identify any medication preparation and administration errors or any risk factors. An observational, prospective study of medication administration process from when the nurses preparing patient medication until administration stage (May to August 2014) was conducted in Saudi Arabia. Twelve paediatric nurses serving 90 paediatric patients were observed. 456 drug administered doses were evaluated. Adherence rate was variable in 7 steps out of 16 steps. Patient allergy information, dose calculation, drug expiry date were the steps in medication administration with lowest adherence rates. 63 medication preparation and administration errors were identified with error rate 13.8% of medication administrations. No potentially life-threating errors were witnessed. Few logistic and administrative factors were reported. The results showed that the medication administration policy and procedure need an urgent revision to be more sensible for nurses in practice. Nurses’ knowledge and skills regarding the medication administration process should be improved.Keywords: medication sasfety, paediatric, medication errors, paediatric ward
Procedia PDF Downloads 3967170 Comparative in vitro Anticancer Activity of Two Siddha Formulations: Neeradi Muthu Vallathymezugu and Thamira Kattu Chendooram
Authors: Vasudha Devi, Arul Amuthan, K. Narayanan, Praveen KS, Venkata Rao J
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Background: Siddha Medicine is one of the Indian traditional medical systems, in which the cancer disease is mentioned as 'putrunoi' which literally means the disease of growth like termite mound. There are number of formulations available for the treatment of cancer disease. Neeradi muthu vallathymezugu (NMV) and thamira kattu chendooram (TKC) are two drugs commonly prescribed by Siddha physicians. These drugs have been clinically reported to be safe and effective when given orally. Though these formulations are in practice for centuries, no efforts have been made to standardize them and explore their anti-cancer potential systematically. Objective: To compare the cytotoxic activity of NMV and TKC with doxorubicin using cancer cell lines. Materials and methods: For this study, ethanol extract of NMV was taken, whereas TKC was used as such. In vitro cytotoxic activity was evaluated by sulphorhodamine (SRB) assay against human hepatic cancer cells (HepG2), human breast cancer cells (MCF-7) and human cervical cancer cells [KeLa]. Doxorubicin was used as the standard. The SRB assay is based on the ability of cellular proteins to bind with sulphorhodamine-B. The number of live cells in drug treated cell lines directly affects the color formation in the assay, which is estimated calorimetrically by measuring the absorbance at 540 nm to calculate the cytotoxicity (inhibitory concentration - IC50 value) of the drug. Results: The IC50values of NMV, TKC and doxorubicin against HepG2 were 3.08 µg/ml, 20.21 µg/ml and 1.21µg/ml respectively. In MCF-7, it was 11.75 µg/ml, 17.67 µg/ml and 2.8µg/ml. In HeLa, the values were 24.76 µg/ml, 73.35 µg/ml and 1.12µg/ml. Conclusions: The study proves the possible anti-cancer potential of these two formulations. Compared to TKC, NMV showed good cytotoxic effect even at low dose. Human hepatic cancer cells responded well even at very low dose, when compared to other cancer cells. Though, cytotoxic potential of these compounds was found to be less compared to doxorubicin, the isolated lead compound may have the potential to be used as an anticancer drug clinically.Keywords: Neeradi muthu vallathymezugu (Hydnocarpus laurifolia), thamira kattu chendooram, cytotoxicity, in-vitro, Siddha Medicine
Procedia PDF Downloads 4737169 Effect of Anionic Lipid on Zeta Potential Values and Physical Stability of Liposomal Amikacin
Authors: Yulistiani, Muhammad Amin, Fasich
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A surface charge of the nanoparticle is a very important consideration in pulmonal drug delivery system. The zeta potential (ZP) is related to the surface charge which can predict stability of nanoparticles as nebules of liposomal amikacin. Anionic lipid such as 1,2-dipalmitoyl-sn-glycero-3-phosphatidylglycerol (DPPG) is expected to contribute to the physical stability of liposomal amikacin and the optimal ZP value. Suitable ZP can improve drug release profiles at specific sites in alveoli as well as their stability in dosage form. This study aimed to analyze the effect of DPPG on ZP values and physical stability of liposomal amikacin. Liposomes were prepared by using the reserved phase evaporation method. Liposomes consisting of DPPG, 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), cholesterol and amikacin were formulated in five different compositions 0/150/5/100, 10//150/5/100, 20/150/5/100, 30/150/5/100 and 40/150/5/100 (w/v) respectively. A chloroform/methanol mixture in the ratio of 1 : 1 (v/v) was used as solvent to dissolve lipids. These systems were adjusted in the phosphate buffer at pH 7.4. Nebules of liposomal amikacin were produced by using the vibrating nebulizer and then characterized by the X-ray diffraction, differential scanning calorimetry, particle size and zeta potential analyzer, and scanning electron microscope. Amikacin concentration from liposome leakage was determined by the immunoassay method. The study revealed that presence of DPPG could increase the ZP value. The addition of 10 mg DPPG in the composition resulted in increasing of ZP value to 3.70 mV (negatively charged). The optimum ZP value was reached at -28.780 ± 0.70 mV and particle size of nebules 461.70 ± 21.79 nm. Nebulizing process altered parameters such as particle size, conformation of lipid components and the amount of surface charges of nanoparticles which could influence the ZP value. These parameters might have profound effects on the application of nebules in the alveoli; however, negatively charge nanoparticles were unexpected to have a high ZP value in this system due to increased macrophage uptake and pulmonal clearance. Therefore, the ratio of liposome 20/150/5/100 (w/v) resulted in the most stable colloidal system and might be applicable to pulmonal drug delivery system.Keywords: anionic lipid, dipalmitoylphosphatidylglycerol, liposomal amikacin, stability, zeta potential
Procedia PDF Downloads 3397168 [Keynote Talk]: Existence of Random Fixed Point Theorem for Contractive Mappings
Authors: D. S. Palimkar
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Random fixed point theory has received much attention in recent years, and it is needed for the study of various classes of random equations. The study of random fixed point theorems was initiated by the Prague school of probabilistic in the 1950s. The existence and uniqueness of fixed points for the self-maps of a metric space by altering distances between the points with the use of a control function is an interesting aspect in the classical fixed point theory. In a new category of fixed point problems for a single self-map with the help of a control function that alters the distance between two points in a metric space which they called an altering distance function. In this paper, we prove the results of existence of random common fixed point and its uniqueness for a pair of random mappings under weakly contractive condition for generalizing alter distance function in polish spaces using Random Common Fixed Point Theorem for Generalized Weakly Contractions.Keywords: Polish space, random common fixed point theorem, weakly contractive mapping, altering function
Procedia PDF Downloads 2737167 Safety Profile of Anti-Retroviral Medicine in South Africa Based on Reported Adverse Drug Reactions
Authors: Sarah Gounden, Mukesh Dheda, Boikhutso Tlou, Elizabeth Ojewole, Frasia Oosthuizen
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Background: Antiretroviral therapy (ART) has been effective in the reduction of mortality and resulted in an improvement in the prognosis of HIV-infected patients. However, treatment with antiretrovirals (ARVs) has led to the development of many adverse drug reactions (ADRs). It is, therefore, necessary to determine the safety profile of these medicines in a South African population in order to ensure safe and optimal medicine use. Objectives: The aim of this study was to quantify ADRs experienced with the different ARVs currently used in South Africa, to determine the safety profile of ARV medicine in South Africa based on reported ADRs, and to determine the ARVs with the lowest risk profile based on specific patient populations. Methodology: This was a quantitative study. Individual case safety reports for the period January 2010 – December 2013 were obtained from the National Pharmacovigilance Center; these reports contained information on ADRs, ARV medicine, and patient demographics. Data was analysed to find associations that may exist between ADRs experienced, ARV medicines used and patient demographics. Results: A total of 1916 patient reports were received of which 1534 met the inclusion criteria for the study. The ARV with the lowest risk of ADRs were found to be lamivudine (0.51%, n=12), followed by lopinavir/ritonavir combination (0.8%, n=19) and abacavir (0.64%, n=15). A higher incidence of ADRs was observed in females compared to males. The age group 31–50 years and the weight group 61–80 kg had the highest incidence of ADRs reported. Conclusion: This study found that the safest ARVs to be used in a South African population are lamivudine, abacavir, and the lopinavir/ritonavir combination. Gender differences play a significant role in the occurrence of ADRs and both anatomical and physiological differences account for this. An increased BMI (body mass index) in both men and women showed an increase in the incidence of ADRs associated with ARV therapy.Keywords: adverse drug reaction, antiretrovirals, HIV/AIDS, pharmacovigilance, South Africa
Procedia PDF Downloads 3517166 Antimycobacterial Activity of Ethanolic Extract of Artemisia absinthium
Authors: T. Hojageldiyev, Y. Bolmammedov, S. Gurbanaliyev
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It is known that drugs used in the treatment of tuberculosis show toxic effect to organism especially to liver besides its therapeutic effect. Because of ineffectiveness of drugs used in the treatment regimen of tuberculosis against multidrug resistance (MDR) and extensively drug-resistance (XDR) tuberculosis requires the development of new treatment methods and new, novel drugs. Considering the usage of Artemisia absinthium in traditional medicine in treatment of wounds which suggests its antibacterial activity it seems that, also it may have significant antimycobacterial activity. The objective of present study was to evaluate antibacterial activity of ethanolic extract of A. absinthium against M. tuberculosis. In this study, the effect of ethanolic extract of A. absinthium was tested against tuberculosis and pharmaco-toxicological properties evaluated on laboratory animals. The 20%, 40%, 70% and 96% ethanolic extracts of A. absinthium prepared then its bacteriostatic and bactericidal activities were evaluated by validated methods. Data were analyzed by GraphPad Prism 7.0 at the level P < 0.05. Results showed that ethanolic extracts of A. absinthium show no toxicological properties with having high LD50. All concentrations of extract show high bacteriostatic activity on M. tuberculosis. 96% ethanolic extract has highest bactericidal effect among other concentrations. By conducting further studies, as a result of our study, antimycobacterial drug can be prepared from A. absinthium.Keywords: Artemisia absinthium, antimycobacterial, ethanolic extract, Mycobacteria tuberculosis
Procedia PDF Downloads 2927165 Copper Related Toxicity of 1-Hydroxy-2-Thiopyridines
Authors: Elena G. Salina, Vadim A. Makarov
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With the emergence of primary resistance to the current drugs and wide distribution of latent tuberculosis infection, a need for new compounds with a novel mode of action is growing steadily. Copper-mediated innate immunity and antibacterial toxicity propose novel strategies in TB drug discovery and development. Transcriptome of M. tuberculosis was obtained by RNA-seq, intracellular copper content was measured by ISP MS and complexes of 1-hydroxy-2-thiopyridines with copper were detected by HPLC.1-hydroxy-2-thiopyridine derivatives were found to be highly active in vitro against both actively growing and dormant non-culturable M. tuberculosis. Transcriptome response to 1-hydroxy-2-thiopyridines revealed signs of copper toxicity in M. tuberculosis bacilli. Indeed, Cu was found to accumulate inside cells treated with 1-hydroxy-2-thiopyridines. These compounds were found to form stable charged lipophylic complexes with Cu²⁺ ions which transport into mycobacterial cell. Subsequent metabolic destruction of the complex led to transformation of 1-hydroxy-2-thiopyridines into 2-methylmercapto-2-ethoxycarbonylpyridines, which did not possess antitubercular activity and releasing of free Cu²⁺ in the cytoplasm. 1-hydroxy-2-thiopyridines are a potent class of Cu-dependent inhibitors of M. tuberculosis which may control M. tuberculosis infection by impairment of copper homeostasis. Acknowledgment: This work was financially supported by the Ministry of Education and Science of the RussianFederation (Agreement No 14.616.21.0065; unique identifier RFMEFI61616X0065).Keywords: copper toxicity, drug discovery, M. tuberculosis inhibitors, 2-thiopyridines
Procedia PDF Downloads 1697164 Participatory Approach for Urban Sustainability through Ostrom’s Principles
Authors: Kuladeep Kumar Sadevi
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The shift towards raising global urban population has intense implications on the sustainability of the urban livelihoods. Rapid urbanization has made governments, companies and civil societies recognize that they are barely equipped to deal with growing urban demands, especially water, waste and energy management. Effective management of land, water, energy and waste at a community level should be addressed well to attain greener cities. In pursuit of Green livelihoods; various norms, codes, and green rating programmes have been followed by stakeholders at various levels. While the sustainability is being adapted at smaller scale developments, greening the urban environment at community/city level is still finding its path to reality. This is due to lack of the sense of ownership in the citizens for their immediate neighborhoods and city as a whole. This phenomenon can be well connected to the theory of 'tragedy of commons' with respect to the community engagement to manage the common pool resources. The common pool resource management has been well addressed by Elinor Ostrom, who shared the Nobel Prize in Economics in 2009 for her lifetime of scholarly work investigating how communities succeed or fail at managing common pool (finite) resources. This paper examines the applicability of Elinor Ostrom's 8 Principles for Managing a Commons, to meet urban sustainability. The key objective of this paper is to come up with a model for effective urban common pool resource management, which ultimately leads to sustainability as a whole. The paper brings out a methodology to understand various parameters involved in urban sustainability, examine the synergies of all such parameters, and application of Ostrom’s principles to correlate these parameters in order to attain effective urban resource management.Keywords: common pool resources, green cities, green communities, participatory management, sustainable development, urban resource management, urban sustainability
Procedia PDF Downloads 3567163 Production of Novel Antibiotics by Importing eryK and eryG Genes in Streptomyces fradiae
Authors: Neda Gegar Goshe, Hossein Rassi
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The antibacterial properties of macrolide antibiotics (such as erythromycin and tylosin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones. Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose). Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as erythromycin) have two sugar substituents. Streptomyces fradiae is an ideal host for development of generic polyketide-overproducing strains because it contains three of the most common precursors-malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA-used by modular PKS, and is a host that is amenable to genetic manipulation. As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses. Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the erythromycin producer Saccharopolyspora erythraea. The biotransformation of erythromycin-D into the desired major component erythromycin-A involves two final enzymatic reactions, EryK-catalyzed hydroxylation at the C-12 position of the aglycone and EryG-catalyzed O methylation at the C-3 position of macrose .This engineered S. fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.Keywords: Streptomyces fradiae, eryK and eryG genes, tylosin, antibiotics
Procedia PDF Downloads 3257162 Gender Division of Labor among Indigenous Peoples in the Municipality of Nabunturan, Compostela Valley Province, Philippines
Authors: Bonee Jaye Besana Bagaipo
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The goal of this study was to assess the status of gender division of labor among indigenous peoples in the Municipality of Nabunturan and coordinate the results to the Tribal Council for an appropriate blueprint in reaching Mansaka, Mandaya, and Aeta respectively. This is a qualitative type of research where the researcher utilized three methods of data gathering namely key informants’ interview, focus group discussions and survey questionnaire. Exceptional characteristics of each tribe like marriage practices, religious beliefs and sources of livelihood were presented as merely profiling. Results revealed that in productive role, respondents perceived that the statements presented are highly masculine task. In reproductive role, respondents perceived the statements presented are a common role task. In household and community services respondents perceived the statements presented are a common role task. In community management and political activities, respondents perceived the statements presented are a highly masculine and common role.Keywords: gender and development, indigenous people, public administration, policy making
Procedia PDF Downloads 4657161 Lumbar Punctures: Re-Audit of Procedure Documentation Following the Introduction of a Standardised Procedure Checklist
Authors: Hayley Lawrence, Nabi Shah, Sarah Dyer
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Aims: Lumbar punctures are a common bedside procedure performed in acute medicine. Published guidance exists on the standardised documentation of invasive procedures in order to reduce the risk of complications. The audit aim was to assess current standards of documentation in accordance with both the GMC and the National Standards for Invasive Procedures guidelines. A second cycle was conducted after introducing a standardised sticker created using current guidelines. This would assess whether the sticker improved documentation, aiming for 100% standard in each step of the procedure. Methods: An initial prospective audit of current practice was conducted over a 3-month period. Patients were identified by their presenting complaints and by colleagues assessing acute medical patients. Initial findings were presented locally, and a further prospective audit was conducted following the implementation of a standardised sticker. Results: 19 lumbar punctures were included in the first cycle and 13 procedures in the second. Pre-procedure documentation was collected for each cycle, whereby documentation of ‘Indication’ improved from 5.3% to 84.6%, ‘Consent’ from 84.2% to 100%, ‘Coagulopathy’ from 0% to 61.5%, ‘Drug Chart checked’ from 0% to 100%, ‘Position of patient’ from 26.3% to 100% and use of ‘Aseptic Technique’ from 83.3% to 100% from the first to the second cycle respectively. ‘Level of Doctor’ and ‘Supervision’ decreased from 53% to 31% and 53% to 46%, respectively, in the second cycle. Documentation of the procedure itself also demonstrated improvements, with ‘Level of Insertion’ 15.8% to 100%, ‘Name of Antiseptic Used’ 11.1% to 69.2%, ‘Local Anaesthetic Used’ 26.3% to 53.8%, ‘Needle Gauge’ 42.1% to 76.9%, ‘Number of Attempts’ 78.9% to 100% and ‘Traumatic/Atraumatic’ procedure 26.3% to 92.3%, respectively. A similar number of opening pressures were documented in each cycle at 57.9% and 53.8%, respectively, but its documentation was deemed ‘Not Applicable’ in a higher number of patients in the second cycle. Post-procedure documentation improved, with ‘Number of Samples obtained’ increasing from 52.6% to 92.3% and documentation of ‘Immediate Complications’ increasing from 78.9% to 100%. ‘Dressing Applied’ was poorly documented in the first cycle at 16.7%. This was not included on the standardised sticker, resulting in 0% documentation in the second cycle. Documentation of Clinicians’ Name and Bleep reduced from 63.2% to 15.4%, but when the name only was analysed, this increased to 84.6%. Conclusions: Standardised stickers for lumbar punctures do improve documentation and hence should result in improved patient safety. There is still room for improvement to reach 100% standard in each area, especially with respect to the clinician’s name and contact details being documented. Final adjustments will be made to the sticker before being included in a lumbar puncture kit, which will be made readily available in the acute medical wards. Future audits could be extended to include other common bedside procedures performed in acute medicine to ensure documentation of all these procedures reaches 100% standard.Keywords: invasive procedure, lumbar puncture, medical record keeping, procedure checklist, procedure documentation, standardised documentation
Procedia PDF Downloads 1037160 Production of Novel Antibiotics of Tylosin by Importing eryK and eryG Genes in Streptomyces fradiae
Authors: Neda Gegar Goshe, M. Moradi, Hossein Rassi
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The antibacterial properties of macrolide antibiotics (such as erythromycin and tylosin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones. Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose). Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as erythromycin) have two sugar substituents. Streptomyces fradiae is an ideal host for development of generic polyketide-overproducing strains because it contains three of the most common precursors-malonyl-CoA, methylmalonyl-CoA and ethylmalonyl-CoA-used by modular PKS, and is a host that is amenable to genetic manipulation. As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses. Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the erythromycin producer Saccharopolyspora erythraea. The bio transformation of erythromycin-D into the desired major component erythromycin-A involves two final enzymatic reactions, EryK-catalyzed hydroxylation at the C-12 position of the aglycone and EryG-catalyzed O methylation at the C-3 position of macrose. This engineered S. fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.Keywords: tylosin, eryK and eryG genes, streptomyces fradiae
Procedia PDF Downloads 352