Search results for: injectable designs for new drugs
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2162

Search results for: injectable designs for new drugs

362 The Untreated Burden of Parkinson’s Disease: A Patient Perspective

Authors: John Acord, Ankita Batla, Kiran Khepar, Maude Schmidt, Charlotte Allen, Russ Bradford

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Objectives: Despite the availability oftreatment options, Parkinson’s disease (PD) continues to impact heavily on a patient’s quality of life (QoL), as many symptoms that bother the patient remain unexplored and untreated in clinical settings. The aims of this research were to understand the burden of PDsymptoms from a patient perspective, particularly those which are the most persistent and debilitating, and to determine if current treatments and treatment algorithms adequately focus on their resolution. Methods: A13-question, online, patient-reported survey was created based on the MDS-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS)and symptoms listed on Parkinson’s Disease Patient Advocacy Groups websites, and then validated by 10 Parkinson’s patients. In the survey, patients were asked to choose both their most common and their most bothersome symptoms, whether they had received treatment for those and, if so, had it been effective in resolving those symptoms. Results: The most bothersome symptoms reported by the 111 participants who completed the survey were sleep problems (61%), feeling tired (56%), slowness of movements (54%), and pain in some parts of the body (49%). However, while 86% of patients reported receiving dopamine or dopamine like drugs to treat their PD, far fewer reported receiving targeted therapies for additional symptoms. For example, of the patients who reported having sleep problems, only 33% received some form of treatment for this symptom. This was also true for feeling tired (30% received treatment for this symptom), slowness of movements (62% received treatment for this symptom), and pain in some parts of the body (61% received treatment for this symptom). Additionally, 65% of patients reported that the symptoms they experienced were not adequately controlled by the treatments they received, and 9% reported that their current treatments had no effect on their symptoms whatsoever. Conclusion: The survey outcomes highlight that the majority of patients involved in the study received treatment focused on their disease, however, symptom-based treatments were less well represented. Consequently, patient-reported symptoms such as sleep problems and feeling tired tended to receive more fragmented intervention than ‘classical’ PD symptoms, such as slowness of movement, even though they were reported as being amongst the most bothersome symptoms for patients. This research highlights the need to explore symptom burden from the patient’s perspective and offer Customised treatment/support for both motor and non-motor symptoms maximize patients’ quality of life.

Keywords: survey, patient reported symptom burden, unmet needs, parkinson's disease

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361 Use of Thrombolytics for Acute Myocardial Infarctions in Resource-Limited Settings, Globally: A Systematic Literature Review

Authors: Sara Zelman, Courtney Meyer, Hiren Patel, Lisa Philpotts, Sue Lahey, Thomas Burke

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Background: As the global burden of disease shifts from infectious diseases to noncommunicable diseases, there is growing urgency to provide treatment for time-sensitive illnesses, such as ST-Elevation Myocardial Infarctions (STEMIs). The standard of care for STEMIs in developed countries is Percutaneous Coronary Intervention (PCI). However, this is inaccessible in resource-limited settings. Before the discovery of PCI, Streptokinase (STK) and other thrombolytic drugs were first-line treatments for STEMIs. STK has been recognized as a cost-effective and safe treatment for STEMIs; however, in settings which lack access to PCI, it has not become the established second-line therapy. A systematic literature review was conducted to geographically map the use of STK for STEMIs in resource-limited settings. Methods: Our literature review group searched the databases Cinhal, Embase, Ovid, Pubmed, Web of Science, and WHO’s Index Medicus. The search terms included ‘thrombolytics’ AND ‘myocardial infarction’ AND ‘resource-limited’ and were restricted to human studies and papers written in English. A considerable number of studies came from Latin America; however, these studies were not written in English and were excluded. The initial search yielded 3,487 articles, which was reduced to 3,196 papers after titles were screened. Three medical professionals then screened abstracts, from which 291 articles were selected for full-text review and 94 papers were chosen for final inclusion. These articles were then analyzed and mapped geographically. Results: This systematic literature review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with 18 of 94 studies taking place in India. Furthermore, 13 studies occurred in Pakistan, followed by Iran (6), Sri Lanka (5), Brazil (4), China (4), and South Africa (4). Conclusion: Our systematic review revealed that STK has been used for the treatment of STEMIs in 33 resource-limited countries, with the highest utilization occurring in India. This demonstrates that even though STK has high utility for STEMI treatment in resource-limited settings, it still has not become the standard of care. Future research should investigate the barriers preventing the establishment of STK use as second-line treatment after PCI.

Keywords: cardiovascular disease, global health, resource-limited setting, ST-Elevation Myocardial Infarction, Streptokinase

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360 Assessment of Selected Marine Organisms from Malaysian Coastal Areas for Inhibitory Activity against the Chikungunya Virus

Authors: Yik Sin Chan, Nam Weng Sit, Fook Yee Chye, van Ofwegen Leen, de Voogd Nicole, Kong Soo Khoo

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Chikungunya fever is an arboviral disease transmitted by the Aedes mosquitoes. It has resulted in epidemics of the disease in tropical countries in the Indian Ocean and South East Asian regions. The recent spread of this disease to the temperate countries such as France and Italy, coupled with the absence of vaccines and effective antiviral drugs make chikungunya fever a worldwide health threat. This study aims to investigate the anti-chikungunya virus activity of selected marine organism samples collected from Malaysian coastal areas, including seaweeds (Caulerpa racemosa, Caulerpa sertularioides and Kappaphycus alvarezii), a soft coral (Lobophytum microlobulatum) and a sponge (Spheciospongia vagabunda). Following lyophilization (oven drying at 40C for K. alvarezii) and grinding to powder form, each sample was subjected to sequential solvent extraction using hexane, chloroform, ethyl acetate, ethanol, methanol and distilled water in order to extract bioactive compounds. The antiviral activity was evaluated using monkey kidney epithelial (Vero) cells infected with the virus (multiplicity of infection=1). The cell viability was determined by Neutral Red uptake assay. 70% of the 30 extracts showed weak inhibitory activity with cell viability ≤30%. Seven of the extracts exhibited moderate inhibitory activity (cell viability: 31%-69%). These were the chloroform, ethyl acetate, ethanol and methanol extracts of C. racemosa; chloroform and ethyl acetate extracts of L. microlobulatum; and the chloroform extract of C. sertularioides. Only the hexane and ethanol extracts of L. microlobulatum showed strong inhibitory activity against the virus, resulting in cell viabilities (mean±SD; n=3) of 73.3±2.6% and 79.2±0.9%, respectively. The corresponding mean 50% effective concentrations (EC50) for the extracts were 14.2±0.2 and 115.3±1.2 µg/mL, respectively. The ethanol extract of the soft coral L. microlobulatum appears to hold the most promise for further characterization of active principles as it possessed greater selectivity index (SI>5.6) compared to the hexane extract (SI=2.1).

Keywords: antiviral, seaweed, sponge, soft coral, vero cell

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359 How Childhood Trauma Changes the Recovery Models

Authors: John Michael Weber

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The following research results spanned six months and 175 people addicted to some form of substance, from alcohol to heroin. One question was asked, and the answers were amazing and consistent. The following work is the detailed results of this writer’s answer to his own question and the 175 that followed. A constant pattern took shape throughout the bio-psycho-social assessments, these addicts had “first memories,” the memories were vivid and took place between the ages of three to six years old, to a person those first memories were traumatic. This writer’s personal search into his childhood was not to find an excuse for the way he became, but to explain the reason for becoming an addict. To treat addiction, these memories that have caused Post Traumatic Stress Disorder (PTSD), must be recognized as the catalyst that sparked a predisposition. Cognitive Behavioral Therapy (CBT), integrated with treatment specifically focused on PTSD, gives the addict a better chance at recovery sans relapse. This paper seeks to give the findings of first memories of the addicts assessed and provide the best treatment plan for such an addict, considering, the childhood trauma in congruence with treatment of the Substance Use Disorder (SUD). The question posed was concerning what their first life memory wa It is the hope of this author to take the knowledge that trauma is one of the main catalysts for addiction, will allow therapists to provide better treatment and reduce relapse from abstinence from drugs and alcohol. This research led this author to believe that if treatment of childhood trauma is not a priority, the twelve steps of Alcoholics Anonymous, specifically steps 4 and 5, will not be thoroughly addressed and odds for relapse increase. With this knowledge, parents can be educated on childhood trauma and the effect it has on their children. Parents could be mindful of the fact that the things they perceive as traumatic, do not match what a child, in the developmental years, absorbs as traumatic. It is this author’s belief that what has become the status quo in treatment facilities has not been working for a long time. It is for that reason this author believes things need to change. Relapse has been woven into the fabric of standard operating procedure and that, in this authors view, is not necessary. Childhood Trauma is not being addressed early in recovery and that creates an environment of inevitable relapse. This paper will explore how to break away from the status -quo and rethink the current “evidencebased treatments.” To begin breaking away from status-quo, this ends the Abstract, with hopes an interest has been peaked to read on.

Keywords: childood, trauma, treatment, addiction, change

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358 The Impact of Entrepreneurship Education on the Entrepreneurial Tendencies of Students: A Quasi-Experimental Design

Authors: Lamia Emam

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The attractiveness of entrepreneurship education stems from its perceived value as a venue through which students can develop an entrepreneurial mindset, skill set, and practice, which may not necessarily lead to them starting a new business, but could, more importantly, be manifested as a life skill that could be applied to all types of organizations and career endeavors. This, in turn, raises important questions about what happens in our classrooms; our role as educators, the role of students, center of learning, and the instructional approach; all of which eventually contribute to achieving the desired EE outcomes. With application to an undergraduate entrepreneurship course -Entrepreneurship as Practice- the current paper aims to explore the effect of entrepreneurship education on the development of students’ general entrepreneurial tendencies. Towards that purpose, the researcher herein uses a pre-test and post-test quasi-experimental research design where the Durham University General Enterprising Tendency Test (GET2) is administered to the same group of students before and after course delivery. As designed and delivered, the Entrepreneurship as Practice module is a highly applied and experiential course where students are required to develop an idea for a start-up while practicing the entrepreneurship-related knowledge, mindset, and skills that are taught in class, both individually and in groups. The course is delivered using a combination of short lectures, readings, group discussions, case analysis, guest speakers, and, more importantly, actively engaging in a series of activities that are inspired by diverse methods for developing successful and innovative business ideas, including design thinking, lean-start up and business feasibility analysis. The instructional approach of the course particularly aims at developing the students' critical thinking, reflective, analytical, and creativity-based problem-solving skills that are needed to launch one’s own start-up. The analysis and interpretation of the experiment’s outcomes shall simultaneously incorporate the views of both the educator and students. As presented, the study responds to the rising call for the application of experimental designs in entrepreneurship in general and EE in particular. While doing so, the paper presents an educator’s perspective of EE to complement the dominant stream of research which is constrained to the students’ point of view. Finally, the study sheds light on EE in the MENA region, where the study is applied.

Keywords: entrepreneurship education, andragogy and heutagogy, scholarship of teaching and learning, experiment

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357 Use of Bamboo Piles in Ground Improvement Design: Case Study

Authors: Thayalan Nall, Andreas Putra

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A major offshore reclamation work is currently underway in Southeast Asia for a container terminal. The total extent of the reclamation extent is 2600m x 800m and the seabed level is around -5mRL below mean sea level. Subsoil profile below seabed comprises soft marine clays of thickness varying from 8m to 15m. To contain the dredging spoil within the reclamation area, perimeter bunds have been constructed to +2.5mRL. They include breakwaters of trapezoidal geometry, made of boulder size rock along the northern, eastern and western perimeters, with a sand bund along the southern perimeter. Breakwaters were constructed on a composite bamboo pile and raft foundation system. Bamboo clusters 8m long, with 7 individual Bamboos bundled together as one, have been installed within the footprint of the breakwater below seabed in soft marine clay. To facilitate drainage two prefabricated vertical drains (PVD) have been attached to each cluster. Once the cluster piles were installed, a bamboo raft was placed as a load transfer platform. Rafts were made up of 5 layers of bamboo mattress, and in each layer bamboos were spaced at 200mm centres. The rafts wouldn’t sink under their own weight, and hence, they were sunk by loading quarry run rock onto them. Bamboo is a building material available in abundance in Indonesia and obtained at a relatively low cost. They are commonly used as semi-rigid inclusions to improve compressibility and stability of soft soils. Although bamboo is widely used in soft soil engineering design, no local design guides are available and the designs are carried out based on local experience. In June 2015, when the 1st load of sand was pumped by a dredging vessel next to the breakwater, a 150m long section of the breakwater underwent failure and displaced the breakwater between 1.2m to 4.0m. The cause of the failure was investigated to implement remedial measures to reduce the risk of further failures. Analyses using both limit equilibrium approach and finite element modelling revealed two plausible modes of breakwater failure. This paper outlines: 1) Developed Geology and the ground model, 2) The techniques used for the installation of bamboo piles, 3) Details of the analyses including modes and mechanism of failure and 4) Design changes incorporated to reduce the risk of failure.

Keywords: bamboo piles, ground improvement, reclamation, breakwater failure

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356 Silver-Curcumin Nanoparticle Eradicate Enterococcus faecalis in Human ex vivo Dentine Model

Authors: M. Gowri, E. K. Girija, V. Ganesh

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Background and Significance: Among the dental infections, inflammation and infection of the root canal are common among all age groups. Currently, the management of root canal infections involves cleaning the canal with powerful irrigants followed by intracanal medicament application. Though these treatments have been in vogue for a long time, root canal failures do occur. Treatment for root canal infections is limited due to the anatomical complexity in terms of small micrometer volumes and poor penetration of drugs. Thus, infections of the root canal seem to be a challenge that demands development of new agents that can eradicate E. faecalis. Methodology: In the present study, we synthesized and screened silver-curcumin nanoparticle against E. faecalis. Morphological cell damage and antibiofilm activity of silver-curcumin nanoparticle on E. faecalis was studied using scanning electron microscopy (SEM). Biochemical evidence for membrane damage was studied using flow cytometry. Further, the antifungal activity of silver-curcumin nanoparticle was evaluated in an ex vivo dentinal tubule infection model. Results: Screening data showed that silver-curcumin nanoparticle was active against E. faecalis. silver-curcumin nanoparticle exerted time kill effect. Further, SEM images of E. faecalis showed that silver-curcumin nanoparticle caused membrane damage and inhibited biofilm formation. Biochemical evidence for membrane damage was confirmed by increased propidium iodide (PI) uptake in flow cytometry. Further, the antifungal activity of silver-curcumin nanoparticle was evaluated in an ex vivo dentinal tubule infection model, which mimics human tooth root canal infection. Confocal laser scanning microscopy studies showed eradication of E. faecalis and reduction in colony forming unit (CFU) after 24 h treatment in the infected tooth samples in this model. Further, silver-curcumin nanoparticle was found to be hemocompatible, not cytotoxic to normal mammalian NIH 3T3 cells and non-mutagenic. Conclusion: The results of this study can pave the way for developing new antibacterial agents with well deciphered mechanisms of action and can be a promising antibacterial agent or medicament against root canal infection.

Keywords: ex vivo dentine model, inhibition of biofilm formation, root canal infection, silver-curcumin nanoparticle

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355 Finite Element Modelling of Mechanical Connector in Steel Helical Piles

Authors: Ramon Omar Rosales-Espinoza

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Pile-to-pile mechanical connections are used if the depth of the soil layers with sufficient bearing strength exceeds the original (“leading”) pile length, with the additional pile segment being termed “extension” pile. Mechanical connectors permit a safe transmission of forces from leading to extension pile while meeting strength and serviceability requirements. Common types of connectors consist of an assembly of sleeve-type external couplers, bolts, pins, and other mechanical interlock devices that ensure the transmission of compressive, tensile, torsional and bending stresses between leading and extension pile segments. While welded connections allow for a relatively simple structural design, mechanical connections are advantageous over welded connections because they lead to shorter installation times and significant cost reductions since specialized workmanship and inspection activities are not required. However, common practices followed to design mechanical connectors neglect important aspects of the assembly response, such as stress concentration around pin/bolt holes, torsional stresses from the installation process, and interaction between the forces at the installation (torsion), service (compression/tension-bending), and removal stages (torsion). This translates into potentially unsatisfactory designs in terms of the ultimate and service limit states, exhibiting either reduced strength or excessive deformations. In this study, the experimental response under compressive forces of a type of mechanical connector is presented, in terms of strength, deformation and failure modes. The tests revealed that the type of connector used can safely transmit forces from pile to pile. Using the results from the compressive tests, an analysis model was developed using the finite element (FE) method to study the interaction of forces under installation and service stages of a typical mechanical connector. The response of the analysis model is used to identify potential areas for design optimization, including size, gap between leading and extension piles, number of pin/bolts, hole sizes, and material properties. The results show the design of mechanical connectors should take into account the interaction of forces present at every stage of their life cycle, and that the torsional stresses occurring during installation are critical for the safety of the assembly.

Keywords: piles, FEA, steel, mechanical connector

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354 A Framework of Virtualized Software Controller for Smart Manufacturing

Authors: Pin Xiu Chen, Shang Liang Chen

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A virtualized software controller is developed in this research to replace traditional hardware control units. This virtualized software controller transfers motion interpolation calculations from the motion control units of end devices to edge computing platforms, thereby reducing the end devices' computational load and hardware requirements and making maintenance and updates easier. The study also applies the concept of microservices, dividing the control system into several small functional modules and then deploy into a cloud data server. This reduces the interdependency among modules and enhances the overall system's flexibility and scalability. Finally, with containerization technology, the system can be deployed and started in a matter of seconds, which is more efficient than traditional virtual machine deployment methods. Furthermore, this virtualized software controller communicates with end control devices via wireless networks, making the placement of production equipment or the redesign of processes more flexible and no longer limited by physical wiring. To handle the large data flow and maintain low-latency transmission, this study integrates 5G technology, fully utilizing its high speed, wide bandwidth, and low latency features to achieve rapid and stable remote machine control. An experimental setup is designed to verify the feasibility and test the performance of this framework. This study designs a smart manufacturing site with a 5G communication architecture, serving as a field for experimental data collection and performance testing. The smart manufacturing site includes one robotic arm, three Computer Numerical Control machine tools, several Input/Output ports, and an edge computing architecture. All machinery information is uploaded to edge computing servers and cloud servers via 5G communication and the Internet of Things framework. After analysis and computation, this information is converted into motion control commands, which are transmitted back to the relevant machinery for motion control through 5G communication. The communication time intervals at each stage are calculated using the C++ chrono library to measure the time difference for each command transmission. The relevant test results will be organized and displayed in the full-text.

Keywords: 5G, MEC, microservices, virtualized software controller, smart manufacturing

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353 Prevalence of Adverse Events in Children and Adolescents on Antiretroviral Therapy: Examining the Pediatric Cohort in the Eastern Cape

Authors: Shannon Glaspy, Gerald Boon, Jack Lambert

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Studies on AE of highly active antiretroviral therapy (HAART) in children and adolescents are rare. The aim of this study is to observe the frequency of treatment limiting adverse drug reactions against years on ARVs and specific ARV regimen. Methods: A retrospective cohort study was conducted in East London, South Africa. All patient files in the pediatric (0 – 18 years) ARV cohort were examined, selecting only those patients started on HAART. ARV regimen changes explicitly due to AE, age on ARV treatment onset, age of AE onset, and gender were extrapolated. Eligible subjects were obtained from patient folders, anonymized and cross-referenced with data obtained from electronic records. A total of 1120 patients [592 male (52.9%) and 528 female (47.1%)] were charted by incidence and year. Additional information was extrapolated in cases where the patient experienced lipodystrophy and lipoatrophy to include the number of years on ARVs prior to the onset of the AE. Results: Of the 1120 HIV infected children of the hospital cohort, a total of 105 (9.37%) AE (53.3% male) observed were deemed eligible for the study due to completeness of medical history and agreement between electronic records and paper files. The AE cited were as follows: lipoatrophy 62 (5.53% of all subjects), lipodystrophy 27 (2.41%), neuropathy 9 (0.8%), anemia 2 (0.17%), Steven Johnsons Syndrome 1 (0.08%), elevated LFTs 1 (0.8%), breast hypertrophy (0.08%), gastritis 1 (0.08%) and rash 1 (0.08%). The most prevalence ARV regimens associated with the onset of the AE are: D4T/3TC/EFV 72 cases (64.86% of all AE), D4T/3TC/LOPr 24 cases (21.62%). Lipoatrophy and lipodystrophy combined represent 84.76% (89 cases) of all adverse events documented in this cohort. Within the 60 cases of lipoatrophy, the average number of years on ARVs associated with an AE is 3.54, with 14 cases experiencing an AE between 0-2 years of HAART. Within the 29 cases of lipodystrophy, the average number of years on ARVs associated with an AE is 3.89, with 4 cases experiencing an AE between 0-2 years on HAART. The regimen D4T/3TC/EFV is associated with 43 cases (71.66%) of lipoatrophy and 21 cases (72.41%) of lipodystrophy. D4T/3TC/LOPr is associated with 15 cases (25%) of lipoatrophy and 7 cases (24.14%) of lipodystrophy. The frequency of AE associated with ARV regimens could be misrepresented due to prevalence of different 1st line regimens which were not captured in this study, particularly with the systematic change of 1st line drugs from D4T to ABC in 2010. Conclusion: In this descriptive study we found a 9.37% prevalence of AE were significant enough to be treatment limiting among our cohort. Lipoatrophy accounted for 59.04% of all documented AE. Overall, D4T/3TC/EFV was associated with 64.86% of all AE, 71.66% of lipoatrophy cases and 72.41% of lipodystrophy cases.

Keywords: ARV, adverse events, HAART, pediatric

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352 A Program of Data Analysis on the Possible State of the Antibiotic Resistance in Bangladesh Environment in 2019

Authors: S. D. Kadir

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Background: Antibiotics have always been at the centrum of the revolution of modern microbiology. Micro-organisms and its pathogenicity, resistant organisms, inappropriate or over usage of various types of antibiotic agents are fuelled multidrug-resistant pathogenic organisms. Our present time review report mainly focuses on the therapeutic condition of antibiotic resistance and the possible roots behind the development of antibiotic resistance in Bangladesh in 2019. Methodology: The systemic review has progressed through a series of research analyses on various manuscripts published on Google Scholar, PubMed, Research Gate, and collected relevant information from established popular healthcare and diagnostic center and its subdivisions all over Bangladesh. Our research analysis on the possible assurance of antibiotic resistance been ensured by the selective medical reports and on random assay on the extent of individual antibiotic in 2019. Results: 5 research articles, 50 medical report summary, and around 5 patients have been interviewed while going through the estimation process. We have prioritized research articles where the research analysis been performed by the appropriate use of the Kirby-Bauer method. Kirby-Bauer technique is preferred as it provides greater efficiency, ensures lower performance expenditure, and supplies greater convenience and simplification in the application. In most of the reviews, clinical and laboratory standards institute guidelines were strictly followed. Most of our reports indicate significant resistance shown by the Beta-lactam drugs. Specifically by the derivatives of Penicillin's, Cephalosporin's (rare use of the first generation Cephalosporin and overuse of the second and third generation of Cephalosporin and misuse of the fourth generation of Cephalosporin), which are responsible for almost 67 percent of the bacterial resistance. Moreover, approximately 20 percent of the resistance was due to the fact of drug pumping from the bacterial cell by tetracycline and sulphonamides and their derivatives. Conclusion: 90 percent of the approximate antibiotic resistance is due to the usage of relative and true broad-spectrum antibiotics. The environment has been created by the following circumstances where; the excessive usage of broad-spectrum antibiotics had led to a condition where the disruption of native bacteria and a series of anti-microbial resistance causing a disturbance of the surrounding environments in medium, leading to a state of super-infection.

Keywords: antibiotics, antibiotic resistance, Kirby Bauer method, microbiology

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351 Prevailing Clinical Evidence on Medicinal Hemp (Cannabis Sativa L.)

Authors: Siti Hajar Muhamad Rosli, Xin Yi Lim, Terence Yew Chin Tan, Muhammad nor Farhan Sa’At, Syazwani Sirdar Ali, Ami Fazlin Syed Mohamed

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A growing interest on therapeutic benefits of hemp (Cannabis sativa subsp. sativa) is evident in the pharmaceutical market, attributed to its lower levels of psychoactive constituent delta-9-tetrahydronannabidiol (THC). Deemed as a legal and safer alternative to its counterpart marijuana, the use of medicinal hemp is highly debatable as current scientific evidence on the efficacy for clinical use is yet to be established This study was aimed to provide an overview of the current landscape of hemp research, through recent clinical findings specific to the pharmacological properties of the hemp plant and its derived compounds. A systematic search was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analysis-ScR (PRISMA) checklist on electronic databases (MEDLINE, OVID, Cochrane Library Central, and Clinicaltrials.gov) for articles published from 2009 to 2019. With predetermined inclusion criteria, all human trials with hemp intervention were included. A total of 18 human trials were identified, investigating therapeutic effects on the neuronal, gastrointestinal, musculoskeletal and immune system, with sample sizes ranging from one to 194 subjects. Three randomised controlled trials showed hempseed pills (in Traditional Chinese Medicine formulation MaZiRenWan) consumption significantly improved spontaneous bowel movement in functional constipation. The use of commercial cannabidiol (CBD) sourced from hemp suggested benefits in cannabis dependence, epilepsy, and anxiety disorders. However, there was insufficient evidence to suggest analgesic or anxiolytics effects of hemp being equivalent to marijuana. All clinical trials reviewed varied in terms of test item formulation and standardisation, which made it challenging to confirm overall efficacy for a specific disease or condition. Published efficacy data on hemp are still at a preliminary level, with limited high quality clinical evidence for any specific therapeutic indication. With multiple variants of this plant having different phytochemical and bioactive compounds, future empirical research should focus on uniformity in experimental designs to further strengthen the notion of using medicinal hemp.

Keywords: cannabis, complementary medicine, hemp, herbal medicine.

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350 An Integrated Power Generation System Design Developed between Solar Energy-Assisted Dual Absorption Cycles

Authors: Asli Tiktas, Huseyin Gunerhan, Arif Hepbasli

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Solar energy, with its abundant and clean features, is one of the prominent renewable energy sources in multigeneration energy systems where various outputs, especially power generation, are produced together. In the literature, concentrated solar energy systems, which are an expensive technology, are mostly used in solar power plants where medium-high capacity production outputs are achieved. In addition, although different methods have been developed and proposed for solar energy-supported integrated power generation systems by different investigators, absorption technology, which is one of the key points of the present study, has been used extensively in cooling systems in these studies. Unlike these common uses mentioned in the literature, this study designs a system in which a flat plate solar collector (FPSC), Rankine cycle, absorption heat transformer (AHT), and cooling systems (ACS) are integrated. The system proposed within the scope of this study aims to produce medium-high-capacity electricity, heating, and cooling outputs using a technique different from the literature, with lower production costs than existing systems. With the proposed integrated system design, the average production costs based on electricity, heating, and cooling load production for similar scale systems are 5-10% of the average production costs of 0.685 USD/kWh, 0.247 USD/kWh, and 0.342 USD/kWh. In the proposed integrated system design, this will be achieved by increasing the outlet temperature of the AHT and FPSC system first, expanding the high-temperature steam coming out of the absorber of the AHT system in the turbine up to the condenser temperature of the ACS system, and next directly integrating it into the evaporator of this system and then completing the AHT cycle. Through this proposed system, heating and cooling will be carried out by completing the AHT and ACS cycles, respectively, while power generation will be provided because of the expansion of the turbine. Using only a single generator in the production of these three outputs together, the costs of additional boilers and the need for a heat source are also saved. In order to demonstrate that the system proposed in this study offers a more optimum solution, the techno-economic parameters obtained based on energy, exergy, economic, and environmental analysis were compared with the parameters of similar scale systems in the literature. The design parameters of the proposed system were determined through a parametric optimization study to exceed the maximum efficiency and effectiveness and reduce the production cost rate values of the compared systems.

Keywords: solar energy, absorption technology, Rankine cycle, multigeneration energy system

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349 Utility of Thromboelastography Derived Maximum Amplitude and R-Time (MA-R) Ratio as a Predictor of Mortality in Trauma Patients

Authors: Arulselvi Subramanian, Albert Venencia, Sanjeev Bhoi

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Coagulopathy of trauma is an early endogenous coagulation abnormality that occurs shortly resulting in high mortality. In emergency trauma situations, viscoelastic tests may be better in identifying the various phenotypes of coagulopathy and demonstrate the contribution of platelet function to coagulation. We aimed to determine thrombin generation and clot strength, by estimating a ratio of Maximum amplitude and R-time (MA-R ratio) for identifying trauma coagulopathy and predicting subsequent mortality. Methods: We conducted a prospective cohort analysis of acutely injured trauma patients of the adult age groups (18- 50 years), admitted within 24hrs of injury, for one year at a Level I trauma center and followed up on 3rd day and 5th day of injury. Patients with h/o coagulation abnormalities, liver disease, renal impairment, with h/o intake of drugs were excluded. Thromboelastography was done and a ratio was calculated by dividing the MA by the R-time (MA-R). Patients were further stratified into sub groups based on the calculated MA-R quartiles. First sampling was done within 24 hours of injury; follow up on 3rd and 5thday of injury. Mortality was the primary outcome. Results: 100 acutely injured patients [average, 36.6±14.3 years; 94% male; injury severity score 12.2(9-32)] were included in the study. Median (min-max) on admission MA-R ratio was 15.01(0.4-88.4) which declined 11.7(2.2-61.8) on day three and slightly rose on day 5 13.1(0.06-68). There were no significant differences between sub groups in regard to age, or gender. In the lowest MA-R ratios subgroup; MA-R1 (<8.90; n = 27), injury severity score was significantly elevated. MA-R2 (8.91-15.0; n = 23), MA-R3 (15.01-19.30; n = 24) and MA-R4 (>19.3; n = 26) had no difference between their admission laboratory investigations, however slight decline was observed in hemoglobin, red blood cell count and platelet counts compared to the other subgroups. Also significantly prolonged R time, shortened alpha angle and MA were seen in MA-R1. Elevated incidence of mortality also significantly correlated with on admission low MA-R ratios (p 0.003). Temporal changes in the MA-R ratio did not correlated with mortality. Conclusion: The MA-R ratio provides a snapshot of early clot function, focusing specifically on thrombin burst and clot strength. In our observation, patients with the lowest MA-R time ratio (MA-R1) had significantly increased mortality compared with all other groups (45.5% MA-R1 compared with <25% in MA-R2 to MA-R3, and 9.1% in MA-R4; p < 0.003). Maximum amplitude and R-time may prove highly useful to predict at-risk patients early, when other physiologic indicators are absent.

Keywords: coagulopathy, trauma, thromboelastography, mortality

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348 Non-Canonical Beclin-1-Independent Autophagy and Apoptosis in Cell Death Induced by Rhus coriaria in Human Colon HT-29 Cancer Cells

Authors: Rabah Iratni, Husain El Hasasna, Khawlah Athamneh, Halima Al Sameri, Nehla Benhalilou, Asma Al Rashedi

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Background: Cancer therapies have witnessed great advances in the recent past, however, cancer continues to be a leading cause of death, with colorectal cancer being the fourth cause of cancer-related deaths. Colorectal cancer affects both sexes equally with poor survival rate once it metastasizes. Phytochemicals, which are plant derived compounds, have been on a steady rise as anti-cancer drugs due to the accumulation of evidences that support their potential. Here, we investigated the anticancer effect of Rhus coriaria on colon cancer cells. Material and Method: Human colon cancer HT-29 cell line was used. Protein expression and protein phosphorylation were examined using Western blotting. Transcription activity was measure using Quantitative RT-PCR. Human tumoral clonogenic assay was used to assess cell survival. Senescence was assessed by the senescence-associated beta-galactosidase assay. Results: Rhus coriaria extract (RCE) was found to significantly inhibit the viability and colony growth of human HT-29 colon cancer cells. RCE induced senescence and cell cycle arrest at G1 phase. These changes were concomitant with upregulation of p21, p16, downregulation of cyclin D1, p27, c-myc and expression of Senescence-associated-β-Galactosidase activity. Moreover, RCE induced non-canonical beclin-1independent autophagy and subsequent apoptotic cell death through activation of activation caspase 8 and caspase 7. The blocking of autophagy by 3-methyladenine (3-MA) or chloroquine (CQ) reduced RCE-induced cell death. Further, RCE induced DNA damage, reduced mutant p53 protein level and downregulated phospho-AKT and phospho-mTOR, events that preceded autophagy. Mechanistically, we found that RCE inhibited the AKT and mTOR pathway, a regulator of autophagy, by promoting the proteasome-dependent degradation of both AKT and mTOR proteins. Conclusion: Our findings provide strong evidence that Rhus coriaria possesses strong anti-colon cancer activity through induction of senescence and autophagic cell death, making it a promising alternative or adjunct therapeutic candidate against colon cancer.

Keywords: autophagy, proteasome degradation, senescence, mTOR, apoptosis, Beclin-1

Procedia PDF Downloads 253
347 Comparison of Traditional and Green Building Designs in Egypt: Energy Saving

Authors: Hala M. Abdel Mageed, Ahmed I. Omar, Shady H. E. Abdel Aleem

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This paper describes in details a commercial green building that has been designed and constructed in Marsa Matrouh, Egypt. The balance between homebuilding and the sustainable environment has been taken into consideration in the design and construction of this building. The building consists of one floor with 3 m height and 2810 m2 area while the envelope area is 1400 m2. The building construction fulfills the natural ventilation requirements. The glass curtain walls are about 50% of the building and the windows area is 300 m2. 6 mm greenish gray tinted temper glass as outer board lite, 6 mm safety glass as inner board lite and 16 mm thick dehydrated air spaces are used in the building. Visible light with 50% transmission, 0.26 solar factor, 0.67 shading coefficient and 1.3 W/m2.K thermal insulation U-value are implemented to realize the performance requirements. Optimum electrical distribution for lighting system, air conditions and other electrical loads has been carried out. Power and quantity of each type of the lighting system lamps and the energy consumption of the lighting system are investigated. The design of the air conditions system is based on summer and winter outdoor conditions. Ventilated, air conditioned spaces and fresh air rates are determined. Variable Refrigerant Flow (VRF) is the air conditioning system used in this building. The VRF outdoor units are located on the roof of the building and connected to indoor units through refrigerant piping. Indoor units are distributed in all building zones through ducts and air outlets to ensure efficient air distribution. The green building energy consumption is evaluated monthly all over one year and compared with the consumed energy in the non-green conditions using the Hourly Analysis Program (HAP) model. The comparison results show that the total energy consumed per year in the green building is about 1,103,221 kWh while the non-green energy consumption is about 1,692,057 kWh. In other words, the green building total annual energy cost is reduced from 136,581 $ to 89,051 $. This means that, the energy saving and consequently the money-saving of this green construction is about 35%. In addition, 13 points are awarded by applying one of the most popular worldwide green energy certification programs (Leadership in Energy and Environmental Design “LEED”) as a rating system for the green construction. It is concluded that this green building ensures sustainability, saves energy and offers an optimum energy performance with minimum cost.

Keywords: energy consumption, energy saving, green building, leadership in energy and environmental design, sustainability

Procedia PDF Downloads 296
346 Effects of Forest Therapy on Depression among Healthy Adults 

Authors: Insook Lee, Heeseung Choi, Kyung-Sook Bang, Sungjae Kim, Minkyung Song, Buhyun Lee

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Backgrounds: A clearer and comprehensive understanding of the effects of forest therapy on depression is needed for further refinements of forest therapy programs. The purpose of this study was to review the literature on forest therapy programs designed to decrease the level of depression among adults to evaluate current forest therapy programs. Methods: This literature review was conducted using various databases including PubMed, EMBASE, CINAHL, PsycArticle, KISS, RISS, and DBpia to identify relevant studies published up to January 2016. The two authors independently screened the full text articles using the following criteria: 1) intervention studies assessing the effects of forest therapy on depression among healthy adults ages 18 and over; 2) including at least one control group or condition; 3) being peer-reviewed; and 4) being published either in English. The Scottish Intercollegiate Guideline Network (SIGN) measurement tool was used to assess the risk of bias in each trial. Results: After screening current literature, a total of 14 articles (English: 6, Korean: 8) were included in the present review. None of the studies used randomized controlled (RCT) study design and the sample size ranged from 11 to 300. Walking in the forest and experiencing the forest using the five senses was the key component of the forest therapy that was included in all studies. The majority of studies used one-time intervention that usually lasted a few hours or half-day. The most widely used measure for depression was Profile of Mood States (POMS). Most studies used self-reported, paper-and-pencil tests, and only 5 studies used both paper-and-pencil tests and physiological measures. Regarding the quality assessment based on the SIGN criteria, only 3 articles were rated ‘acceptable’ and the rest of the 14 articles were rated ‘low quality.’ Regardless of the diversity in format and contents of forest therapies, most studies showed a significant effect of forest therapy in curing depression. Discussions: This systematic review showed that forest therapy is one of the emerging and effective intervention approaches for decreasing the level of depression among adults. Limitations of the current programs identified from the review were as follows; 1) small sample size; 2) a lack of objective and comprehensive measures for depression; and 3) inadequate information about research process. Futures studies assessing the long-term effect of forest therapy on depression using rigorous study designs are needed.

Keywords: forest therapy, systematic review, depression, adult

Procedia PDF Downloads 288
345 Isolation, Identification and Measurement of Cottonseed Oil Gossypol in the Treatment of Drug-Resistant Cutaneous Leishmaniasis

Authors: Sara Taghdisi, Mehrosadat Mirmohammadi, Mostafa Mokhtarian, Mohammad Hossein Pazandeh

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Leishmaniasis is one of the 10 most important diseases of the World Health Organization with health problems in more than 90 countries. Over one billion people are at risk of these diseases on almost every continent. The present human study was performed to evaluate the therapeutic effect of cotton plant on cutaneous leishmaniasis leision. firstly, the cotton seeds were cleaned and grinded to smaller particles. In the second step, the seeds were oiled by cold press method. In order to separate bioactive compound, after saponification of the oil, its gossypol was hydrolyzed and crystalized. finally, the therapeutic effect of Cottonseed Oil on cutaneous leishmaniasis was investigated. In the current project, Gossypol was extracted with a liquid-liquid extraction method in 120 minutes in the presence of Phosphoric acid from the cotton seed oil of Golestan beach varieties, then got crystallized in darkness using Acetic acid and isolated as Gossypol Acetic acid. The efficiency of the extracted crystal was obtained at 1.28±0.12. the cotton plant could be efficient in the treatment of Cutaneous leishmaniasis. This double-blind randomized controlled clinical trial was performed on 88 cases of leishmaniasis wounds. Patients were randomly divided into two groups of 44 cases. two groups received conventional treatment. In addition to the usual treatment (glucantime), the first group received cottonseed oil and the control group received placebo. The results of the present study showed that the surface of lesion before the intervention and in the first to fourth weeks after the intervention was not significantly different between the two groups (P-value> 0.05). But the surface of lesion in the Intervention group in the eighth and twelfth weeks was lower than the control group (P-value <0.05). This study showed that the improvement of leishmaniasis lesion using topical cotton plant mark in the eighth and twelfth weeks after the intervention was significantly more than the control group. Considering the most common chemical drugs for Cutaneous leishmaniasis treatment are sodium stibogluconate, and meglumine antimonate, which not only have relatively many side effects, but also some species of the Leishmania genus have become resistant to them. Therefore, a plant base bioactive compound such as cottonseed oil can be useful whit fewer side effects.

Keywords: cottonseed oil, crystallization, gossypol, leishmaniasis

Procedia PDF Downloads 54
344 Creativity and Innovation in Postgraduate Supervision

Authors: Rajendra Chetty

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The paper aims to address two aspects of postgraduate studies: interdisciplinary research and creative models of supervision. Interdisciplinary research can be viewed as a key imperative to solve complex problems. While excellent research requires a context of disciplinary strength, the cutting edge is often found at the intersection between disciplines. Interdisciplinary research foregrounds a team approach and information, methodologies, designs, and theories from different disciplines are integrated to advance fundamental understanding or to solve problems whose solutions are beyond the scope of a single discipline. Our aim should also be to generate research that transcends the original disciplines i.e. transdisciplinary research. Complexity is characteristic of the knowledge economy, hence, postgraduate research and engaged scholarship should be viewed by universities as primary vehicles through which knowledge can be generated to have a meaningful impact on society. There are far too many ‘ordinary’ studies that fall into the realm of credentialism and certification as opposed to significant studies that generate new knowledge and provide a trajectory for further academic discourse. Secondly, the paper will look at models of supervision that are different to the dominant ‘apprentice’ or individual approach. A reflective practitioner approach would be used to discuss a range of supervision models that resonate well with the principles of interdisciplinarity, growth in the postgraduate sector and a commitment to engaged scholarship. The global demand for postgraduate education has resulted in increased intake and new demands to limited supervision capacity at institutions. Team supervision lodged within large-scale research projects, working with a cohort of students within a research theme, the journal article route of doctoral studies and the professional PhD are some of the models that provide an alternative to the traditional approach. International cooperation should be encouraged in the production of high-impact research and institutions should be committed to stimulating international linkages which would result in co-supervision and mobility of postgraduate students and global significance of postgraduate research. International linkages are also valuable in increasing the capacity for supervision at new and developing universities. Innovative co-supervision and joint-degree options with global partners should be explored within strategic planning for innovative postgraduate programmes. Co-supervision of PhD students is probably the strongest driver (besides funding) for collaborative research as it provides the glue of shared interest, advantage and commitment between supervisors. The students’ field serves and informs the co-supervisors own research agendas and helps to shape over-arching research themes through shared research findings.

Keywords: interdisciplinarity, internationalisation, postgraduate, supervision

Procedia PDF Downloads 235
343 Teicoplanin Derivatives with Antiviral Activity: Synthesis and Biological Evaluation

Authors: Zsolt Szucs, Viktor Kelemen, Son Le Thai, Magdolna Csavas, Erzsebet Roth, Gyula Batta, Annelies Stevaert, Evelien Vanderlinden, Aniko Borbas, Lieve Naesens, Pal Herczegh

Abstract:

The approval of modern glycopeptide antibiotics such as dalbavancin and oritavancin which have excellent activity against Gram-positive bacteria, encouraged our research group to prepare semisynthetic compounds from several members of glycopeptides by various chemical methods. Derivatives from the aglycone of ristocetin, eremomycin, vancomycin and a pseudoaglycon of teicoplanin have been synthesized in a systematic manner. Interestingly, some of the aglycoristocetin derivatives displayed noteworthy anti-influenza activity. More recently our group has been focusing on the modifications of one of the pseudoaglycons of teicoplanin. The reaction of N-ethoxycarbonyl maleimide derivatives with the primary amino function, the copper-catalysed azide-alkyne click reaction and the sulfonylation of the N-terminus were utilized to obtain systematic series of compounds. All substituents provide a more lipophilic character to the new molecules compared to the parent antibiotics, which is known to be favourable for activity against resistant bacteria. Lipoglycopeptides are also known to have antiviral properties, which has been predominantly studied on HIV by others. The structure-activity relationship study of our compounds revealed the influence of a few structural elements on biological activity. In many cases, minimal changes in lipophilicity and structure produced great differences in efficacy and cytotoxicity. In vitro experiments showed that these compounds are not only active against glycopeptide resistant Gram-positive bacteria but in several cases they prevent the infection of cell cultures by different strains of influenza viruses. This is probably related to the inhibition of the viral entry into the host cell nucleus, of which the exact mechanism is unknown. In some instances, reasonably low concentrations were sufficient to observe this effect. Several derivatives were highly cytotoxic at the same time, but some of them displayed a good selectivity index. The antiviral properties of the compounds are not restricted to influenza viruses e.g., some of them showed good activity against Human Coronavirus 229E. This work could potentially lead to the development of antiviral drugs which possess the crucial structural motifs that are needed for antiviral activity, while missing those which contribute to the antibacterial effect.

Keywords: antiviral, glycopeptide, semisynthetic, teicoplanin

Procedia PDF Downloads 155
342 Investigating the Indoor Air Quality of the Respiratory Care Wards

Authors: Yu-Wen Lin, Chin-Sheng Tang, Wan-Yi Chen

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Various biological specimens, drugs, and chemicals exist in the hospital. The medical staffs and hypersensitive inpatients expose might expose to multiple hazards while they work or stay in the hospital. Therefore, the indoor air quality (IAQ) of the hospital should be paid more attention. Respiratory care wards (RCW) are responsible for caring the patients who cannot spontaneously breathe without the ventilators. The patients in RCW are easy to be infected. Compared to the bacteria concentrations of other hospital units, RCW came with higher values in other studies. This research monitored the IAQ of the RCW and checked the compliances of the indoor air quality standards of Taiwan Indoor Air Quality Act. Meanwhile, the influential factors of IAQ and the impacts of ventilator modules, with humidifier or with filter, were investigated. The IAQ of two five-bed wards and one nurse station of a RCW in a regional hospital were monitored. The monitoring was proceeded for 16 hours or 24 hours during the sampling days with a sampling frequency of 20 minutes per hour. The monitoring was performed for two days in a row and the AIQ of the RCW were measured for eight days in total. The concentrations of carbon dioxide (CO₂), carbon monoxide (CO), particulate matter (PM), nitrogen oxide (NOₓ), total volatile organic compounds (TVOCs), relative humidity (RH) and temperature were measured by direct reading instruments. The bioaerosol samples were taken hourly. The hourly air change rate (ACH) was calculated by measuring the air ventilation volume. Human activities were recorded during the sampling period. The linear mixed model (LMM) was applied to illustrate the impact factors of IAQ. The concentrations of CO, CO₂, PM, bacterial and fungi exceeded the Taiwan IAQ standards. The major factors affecting the concentrations of CO, PM₁ and PM₂.₅ were location and the number of inpatients. The significant factors to alter the CO₂ and TVOC concentrations were location and the numbers of in-and-out staff and inpatients. The number of in-and-out staff and the level of activity affected the PM₁₀ concentrations statistically. The level of activity and the numbers of in-and-out staff and inpatients are the significant factors in changing the bacteria and fungi concentrations. Different models of the patients’ ventilators did not affect the IAQ significantly. The results of LMM can be utilized to predict the pollutant concentrations under various environmental conditions. The results of this study would be a valuable reference for air quality management of RCW.

Keywords: respiratory care ward, indoor air quality, linear mixed model, bioaerosol

Procedia PDF Downloads 105
341 Anti-Inflammatory Effect of Carvedilol 1% Ointment in Topical Application to the Animal Model

Authors: Berina Pilipović, Saša Pilipović, Maja Pašić-Kulenović

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Inflammation is the body's response to impaired homeostasis caused by infection, injury or trauma resulting in systemic and local effects. Inflammation causes the body's response to injury and is characterized by a series of events including inflammatory response, response to pain receptors and the recovery process. Inflammation can be acute and chronic. The inflammatory response is described in three different phases. Free radical is an atom or molecule that has the unpaired electron and is therefore generally very reactive chemical species. Biologically important example of reaction with free radicals is called Lipid peroxidation (LP). Lipid peroxidation reactions occur in biological membranes, and if at the outset is not stopped with the action of antioxidants, it will bring damage to the membrane, which results in partial or complete loss of their physiological functions. Calcium antagonists and beta-adrenergic receptor antagonists are known drugs, and for many years and widely used in the treatment of cardiovascular diseases. Some of these compounds also show antioxidant activity. The mechanism of antioxidant activities of calcium antagonists and beta-blockers is unknown, since their structure varies widely. This research investigated the possible local anti-inflammatory activity of ointments containing 1% carvedilol in the white petrolatum USP. Ear inflammation was induced by 3% croton oil acetone solution, in quantity of 10 µl on both mouse ears. Albino Swiss mouse (n = 8) are treated with 2.5 mg/ear ointment, and control group was treated on the same way as previous with hydrocortisone 1% ointment (2.5 mg/ear). The other ear of the same animal was used as control one. Ointments were administered once per day, on the left ear. After treatment, ears were observed for three days. After three days, we measured mass (mg) of 6 mm ear punch of treated and controlled ears. The results of testing anti-inflammatory effects of ointments with carvedilol in the mouse ear model show stronger observed effect than ointment with 1% hydrocortisone in the same basis. Identical results were confirmed by the difference between the mass of 6 mm ears punch. The results were also confirmed by histological examination. Ointments with carvedilol showed significant reduction of the inflammation process caused by croton oil on the mouse inflammation model.

Keywords: antioxidant, carvedilol, inflammation, mouse ear

Procedia PDF Downloads 229
340 The Impact of Artificial Intelligence on Medicine Production

Authors: Yasser Ahmed Mahmoud Ali Helal

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The use of CAD (Computer Aided Design) technology is ubiquitous in the architecture, engineering and construction (AEC) industry. This has led to its inclusion in the curriculum of architecture schools in Nigeria as an important part of the training module. This article examines the ethical issues involved in implementing CAD (Computer Aided Design) content into the architectural education curriculum. Using existing literature, this study begins with the benefits of integrating CAD into architectural education and the responsibilities of different stakeholders in the implementation process. It also examines issues related to the negative use of information technology and the perceived negative impact of CAD use on design creativity. Using a survey method, data from the architecture department of University was collected to serve as a case study on how the issues raised were being addressed. The article draws conclusions on what ensures successful ethical implementation. Millions of people around the world suffer from hepatitis C, one of the world's deadliest diseases. Interferon (IFN) is treatment options for patients with hepatitis C, but these treatments have their side effects. Our research focused on developing an oral small molecule drug that targets hepatitis C virus (HCV) proteins and has fewer side effects. Our current study aims to develop a drug based on a small molecule antiviral drug specific for the hepatitis C virus (HCV). Drug development using laboratory experiments is not only expensive, but also time-consuming to conduct these experiments. Instead, in this in silicon study, we used computational techniques to propose a specific antiviral drug for the protein domains of found in the hepatitis C virus. This study used homology modeling and abs initio modeling to generate the 3D structure of the proteins, then identifying pockets in the proteins. Acceptable lagans for pocket drugs have been developed using the de novo drug design method. Pocket geometry is taken into account when designing ligands. Among the various lagans generated, a new specific for each of the HCV protein domains has been proposed.

Keywords: drug design, anti-viral drug, in-silicon drug design, hepatitis C virus (HCV) CAD (Computer Aided Design), CAD education, education improvement, small-size contractor automatic pharmacy, PLC, control system, management system, communication

Procedia PDF Downloads 73
339 Performance Assessment of the Gold Coast Desalination Plant Offshore Multiport Brine Diffuser during ‘Hot Standby’ Operation

Authors: M. J. Baum, B. Gibbes, A. Grinham, S. Albert, D. Gale, P. Fisher

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Alongside the rapid expansion of Seawater Reverse Osmosis technologies there is a concurrent increase in the production of hypersaline brine by-products. To minimize environmental impact, these by-products are commonly disposed into open-coastal environments via submerged diffuser systems as inclined dense jet outfalls. Despite the widespread implementation of this process, diffuser designs are typically based on small-scale laboratory experiments under idealistic quiescent conditions. Studies concerning diffuser performance in the field are limited. A set of experiments were conducted to assess the near field characteristics of brine disposal at the Gold Coast Desalination Plant offshore multiport diffuser. The aim of the field experiments was to determine the trajectory and dilution characteristics of the plume under various discharge configurations with production ranging 66 – 100% of plant operative capacity. The field monitoring system employed an unprecedented static array of temperature and electrical conductivity sensors in a three-dimensional grid surrounding a single diffuser port. Complimenting these measurements, Acoustic Doppler Current Profilers were also deployed to record current variability over the depth of the water column and wave characteristics. Recorded data suggested the open-coastal environment was highly active over the experimental duration with ambient velocities ranging 0.0 – 0.5 m∙s-1, with considerable variability over the depth of the water column observed. Variations in background electrical conductivity corresponding to salinity fluctuations of ± 1.7 g∙kg-1 were also observed. Increases in salinity were detected during plant operation and appeared to be most pronounced 10 – 30 m from the diffuser, consistent with trajectory predictions described by existing literature. Plume trajectories and respective dilutions extrapolated from salinity data are compared with empirical scaling arguments. Discharge properties were found to adequately correlate with modelling projections. Temporal and spatial variation of background processes and their subsequent influence upon discharge outcomes are discussed with a view to incorporating the influence of waves and ambient currents in the design of brine outfalls into the future.

Keywords: brine disposal, desalination, field study, negatively buoyant discharge

Procedia PDF Downloads 237
338 Prednisone and Its Active Metabolite Prednisolone Attenuate Lipid Accumulation in Macrophages

Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

Procedia PDF Downloads 142
337 Obtainment of Systems with Efavirenz and Lamellar Double Hydroxide as an Alternative for Solubility Improvement of the Drug

Authors: Danilo A. F. Fontes, Magaly A. M.Lyra, Maria L. C. Moura, Leslie R. M. Ferraz, Salvana P. M. Costa, Amanda C. Q. M. Vieira, Larissa A. Rolim, Giovanna C. R. M. Schver, Ping I. Lee, Severino Alves-Júnior, José L. Soares-Sobrinho, Pedro J. Rolim-Neto

Abstract:

Efavirenz (EFV) is a first-choice drug in antiretroviral therapy with high efficacy in the treatment of infection by Human Immunodeficiency Virus, which causes Acquired Immune Deficiency Syndrome (AIDS). EFV has low solubility in water resulting in a decrease in the dissolution rate and, consequently, in its bioavailability. Among the technological alternatives to increase solubility, the Lamellar Double Hydroxides (LDH) have been applied in the development of systems with poorly water-soluble drugs. The use of analytical techniques such as X-Ray Diffraction (XRD), Infrared Spectroscopy (IR) and Differential Scanning Calorimetry (DSC) allowed the elucidation of drug interaction with the lamellar compounds. The objective of this work was to characterize and develop the binary systems with EFV and LDH in order to increase the solubility of the drug. The LDH-CaAl was synthesized by the method of co-precipitation from salt solutions of calcium nitrate and aluminum nitrate in basic medium. The systems EFV-LDH and their physical mixtures (PM) were obtained at different concentrations (5-60% of EFV) using the solvent technique described by Takahashi & Yamaguchi (1991). The characterization of the systems and the PM’s was performed by XRD techniques, IR, DSC and dissolution test under non-sink conditions. The results showed improvements in the solubility of EFV when associated with LDH, due to a possible change in its crystal structure and formation of an amorphous material. From the DSC results, one could see that the endothermic peak at 173°C, temperature that correspond to the melting process of EFZ in the crystal form, was present in the PM results. For the EFZ-LDH systems (with 5, 10 and 30% of drug loading), this peak was not observed. XRD profiles of the PM showed well-defined peaks for EFV. Analyzing the XRD patterns of the systems, it was found that the XRD profiles of all the systems showed complete attenuation of the characteristic peaks of the crystalline form of EFZ. The IR technique showed that, in the results of the PM, there was the appearance of one band and overlap of other bands, while the IR results of the systems with 5, 10 and 30% drug loading showed the disappearance of bands and a few others with reduced intensity. The dissolution test under non-sink conditions showed that systems with 5, 10 and 30% drug loading promoted a great increase in the solubility of EFV, but the system with 10% of drug loading was the only one that could keep substantial amount of drug in solution at different pHs.

Keywords: Efavirenz, Lamellar Double Hydroxides, Pharmaceutical Techonology, Solubility

Procedia PDF Downloads 577
336 New Suspension Mechanism for a Formula Car using Camber Thrust

Authors: Shinji Kajiwara

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The basic ability of a vehicle is the ability to “run”, “turn” and “stop”. The safeness and comfort during a drive on various road surfaces and speed depends on the performance of these basic abilities of the vehicle. Stability and maneuverability of a vehicle is vital in automotive engineering. Stability of a vehicle is the ability of the vehicle to revert back to a stable state during a drive when faced with crosswind and irregular road conditions. Maneuverability of a vehicle is the ability of the vehicle to change direction during a drive swiftly based on the steering of the driver. The stability and maneuverability of a vehicle can also be defined as the driving stability of the vehicle. Since fossil fueled vehicle is the main type of transportation today, the environmental factor in automotive engineering is also vital. By improving the fuel efficiency of the vehicle, the overall carbon emission will be reduced thus reducing the effect of global warming and greenhouse gas on the Earth. Another main focus of the automotive engineering is the safety performance of the vehicle especially with the worrying increase of vehicle collision every day. With better safety performance on a vehicle, every driver will be more confidence driving every day. Next, let us focus on the “turn” ability of a vehicle. By improving this particular ability of the vehicle, the cornering limit of the vehicle can be improved thus increasing the stability and maneuverability factor. In order to improve the cornering limit of the vehicle, a study to find the balance between the steering systems, the stability of the vehicle, higher lateral acceleration and the cornering limit detection must be conducted. The aim of this research is to study and develop a new suspension system that that will boost the lateral acceleration of the vehicle and ultimately improving the cornering limit of the vehicle. This research will also study environmental factor and the stability factor of the new suspension system. The double wishbone suspension system is widely used in four-wheel vehicle especially for high cornering performance sports car and racing car. The double wishbone designs allow the engineer to carefully control the motion of the wheel by controlling such parameters as camber angle, caster angle, toe pattern, roll center height, scrub radius, scuff and more. The development of the new suspension system will focus on the ability of the new suspension system to optimize the camber control and to improve the camber limit during a cornering motion. The research will be carried out using the CAE analysis tool. Using this analysis tool we will develop a JSAE Formula Machine equipped with the double wishbone system and also the new suspension system and conduct simulation and conduct studies on performance of both suspension systems.

Keywords: automobile, camber thrust, cornering force, suspension

Procedia PDF Downloads 318
335 Efficacy of Yoga and Meditation Based Lifestyle Intervention on Inflammatory Markers in Patients with Rheumatoid Arthritis

Authors: Surabhi Gautam, Uma Kumar, Rima Dada

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A sustained acute-phase response in Rheumatoid Arthritis (RA) is associated with increased joint damage and inflammation leading to progressive disability. It is induced continuously by consecutive stimuli of proinflammatory cytokines, following a wide range of pathophysiological reactions, leading to increased synthesis of acute phase proteins like C - reactive protein (CRP) and dysregulation in levels of immunomodulatory soluble Human Leukocyte Antigen-G (HLA-G) molecule. This study was designed to explore the effect of yoga and meditation based lifestyle intervention (YMLI) on inflammatory markers in RA patients. Blood samples of 50 patients were collected at baseline (day 0) and after 30 days of YMLI. Patients underwent a pretested YMLI under the supervision of a certified yoga instructor for 30 days including different Asanas (physical postures), Pranayama (breathing exercises), and Dhayna (meditation). Levels of CRP, IL-6, IL-17A, soluble HLA-G and erythrocyte sedimentation rate (ESR) were measured at day 0 and 30 interval. Parameters of disease activity, disability quotient, pain acuity and quality of life were also assessed by disease activity score (DAS28), health assessment questionnaire (HAQ), visual analogue scale (VAS), and World Health Organization Quality of Life (WHOQOL-BREF) respectively. There was reduction in mean levels of CRP (p < 0.05), IL-6 (interleukin-6) (p < 0.05), IL-17A (interleukin-17A) (p < 0.05) and ESR (p < 0.05) and elevation in soluble HLA-G (p < 0.05) at 30 days compared to baseline level (day 0). There was reduction seen in DAS28-ESR (p < 0.05), VAS (p < 0.05) and HAQ (p < 0.05) after 30 days with respect to the base line levels (day 0) and significant increase in WHOQOL-BREF scale (p < 0.05) in all 4 domains of physical health, psychological health, social relationships, and environmental health. The present study has demonstrated that yoga practices are associated with regression of inflammatory processes by reducing inflammatory parameters and regulating the levels of soluble HLA-G significantly in active RA patients. Short term YMLI has significantly improved pain perception, disability quotient, disease activity and quality of life. Thus this simple life style intervention can reduce disease severity and dose of drugs used in the treatment of RA.

Keywords: inflammation, quality of life, rheumatoid arthritis, yoga and meditation

Procedia PDF Downloads 162
334 Formulation and Evaluation of Glimepiride (GMP)-Solid Nanodispersion and Nanodispersed Tablets

Authors: Ahmed. Abdel Bary, Omneya. Khowessah, Mojahed. al-jamrah

Abstract:

Introduction: The major challenge with the design of oral dosage forms lies with their poor bioavailability. The most frequent causes of low oral bioavailability are attributed to poor solubility and low permeability. The aim of this study was to develop solid nanodispersed tablet formulation of Glimepiride for the enhancement of the solubility and bioavailability. Methodology: Solid nanodispersions of Glimepiride (GMP) were prepared using two different ratios of 2 different carriers, namely; PEG6000, pluronic F127, and by adopting two different techniques, namely; solvent evaporation technique and fusion technique. A full factorial design of 2 3 was adopted to investigate the influence of formulation variables on the prepared nanodispersion properties. The best chosen formula of nanodispersed powder was formulated into tablets by direct compression. The Differential Scanning Calorimetry (DSC) analysis and Fourier Transform Infra-Red (FTIR) analysis were conducted for the thermal behavior and surface structure characterization, respectively. The zeta potential and particle size analysis of the prepared glimepiride nanodispersions was determined. The prepared solid nanodispersions and solid nanodispersed tablets of GMP were evaluated in terms of pre-compression and post-compression parameters, respectively. Results: The DSC and FTIR studies revealed that there was no interaction between GMP and all the excipients used. Based on the resulted values of different pre-compression parameters, the prepared solid nanodispersions powder blends showed poor to excellent flow properties. The resulted values of the other evaluated pre-compression parameters of the prepared solid nanodispersion were within the limits of pharmacopoeia. The drug content of the prepared nanodispersions ranged from 89.6 ± 0.3 % to 99.9± 0.5% with particle size ranged from 111.5 nm to 492.3 nm and the resulted zeta potential (ζ ) values of the prepared GMP-solid nanodispersion formulae (F1-F8) ranged from -8.28±3.62 mV to -78±11.4 mV. The in-vitro dissolution studies of the prepared solid nanodispersed tablets of GMP concluded that GMP- pluronic F127 combinations (F8), exhibited the best extent of drug release, compared to other formulations, and to the marketed product. One way ANOVA for the percent of drug released from the prepared GMP-nanodispersion formulae (F1- F8) after 20 and 60 minutes showed significant differences between the percent of drug released from different GMP-nanodispersed tablet formulae (F1- F8), (P<0.05). Conclusion: Preparation of glimepiride as nanodispersed particles proven to be a promising tool for enhancing the poor solubility of glimepiride.

Keywords: glimepiride, solid Nanodispersion, nanodispersed tablets, poorly water soluble drugs

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333 Effects of Concomitant Use of Metformin and Powdered Moringa Oleifera Leaves on Glucose Tolerance in Sprague-Dawley Rats

Authors: Emielex M. Aguilar, Kristen Angela G. Cruz, Czarina Joie L. Rivera, Francis Dave C. Tan, Gavino Ivan N. Tanodra, Dianne Katrina G. Usana, Mary Grace T. Valentin, Nico Albert S. Vasquez, Edwin Monico C. Wee

Abstract:

The risk of diabetes mellitus is increasing in the Philippines, with Metformin and Insulin as drugs commonly used for its management. The use of herbal medicines has grown increasingly, especially among the elderly population. Moringa oleifera or malunggay is one of the most common plants in the country, and several studies have shown the plant to exhibit a hypoglycemic property with its flavonoid content. This study aims to investigate the possible effects of concomitant use of Metformin and powdered M. oleifera leaves (PMOL) on blood glucose levels. Twenty male Sprague-Dawley rats were equally distributed into four groups. Fasting blood glucose levels of the rats were measured prior to experimentation. The following treatments were administered to the four groups, respectively: glucose only 2 g/kg; glucose 2 g/kg + Metformin 100 mg/kg; glucose 2 g/kg + PMOL 200 mg/kg; and glucose 2 g/kg + PMOL 200 mg/kg and Metformin 100 mg/kg. Blood glucose levels were determined on the 1st, 2nd, 3rd, and 4th hour post-treatment and compared between groups. Statistical analysis showed that the type of intervention did not show significance in the reduction of blood glucose levels when compared with the other groups (p=0.378), while the effect of time exhibited significance (p=0.000). The interaction between the type of intervention and time of blood glucose measurement was shown to be significant (p=0.024). Within each group, the control and PMOL-treated groups showed significant reduction in blood glucose levels over time with p-values of 0.000 and 0.000, respectively, while the Metformin-treated and the combination groups had p-values of 0.062 and 0.093, respectively, which are not significant. The descriptive data also showed that the mean total reduction of blood glucose levels of the Metformin and PMOL combination treatment group was lower than the PMOL-treated group alone, while the mean total reduction of blood glucose levels of the combination group was higher than the Metformin-treated group alone. Based on the results obtained, the combination of Metformin and PMOL did not significantly lower the blood glucose levels of the rats as compared to the other groups. However, the concomitant use of Metformin and PMOL may affect each other’s blood glucose lowering activity. Additionally, prolonged time of exposure and delay in the first blood glucose measurement after treatment could exhibit a significant effect in the blood glucose levels. Further studies are recommended regarding the effects of the concomitant use of the two agents on blood glucose levels.

Keywords: blood glucose levels, concomitant use, metformin, Moringa oleifera

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