Search results for: quarantine treatment
Commenced in January 2007
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Paper Count: 8275

Search results for: quarantine treatment

535 Harnessing Clinical Trial Capacity to Mitigate Zoonotic Diseases: The Role of Expert Scientists in Ethiopia

Authors: Senait Belay Adugna, Mirutse Giday, Tsegahun Manyazewal

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Background: The emergence and resurgence of zoonotic diseases have continued to be a major threat to global health and the economy. Developing countries are particularly vulnerable due to agricultural expansions and the domestication of animals by humans. Scientifically sound clinical trials are important to find better ways to prevent, diagnose, and treat zoonotic diseases, while there is a lack of evidence to inform the clinical trials’ capacity and practice in countries highly affected by the diseases. This study aimed to investigate researchers’ perceptions and experiences in conducting clinical trials on zoonotic diseases in Ethiopia. Methods: This study employed a descriptive, qualitative study design. It included major academic and research institutions in Ethiopia that had active engagements in veterinary and public health research. It included the National Veterinary Institute, the National Animal Health Diagnostic and Investigation Center, the College of Veterinary Medicine at Addis Ababa University, the Ethiopian Public Health Institute, the Armauer Hansen Research Institute, and the College of Health Sciences at Addis Ababa University. In-depth interviews were conducted with 14 senior researcher investigators in the institutions who hold a proven exhibit primarily leading research activities or research units. Data were collected from October 2019 to April 2020. Data analysis was undertaken using open code 4.03 for qualitative data analysis. Results: Five major themes, with 18 sub-themes, emerged from the in-depth interview in connection. These were: challenges in the prevention, control, and treatment of zoonotic diseases; One Health approach to mitigate zoonotic diseases; personal and institutional experiences in conducting clinical trials on zoonotic diseases; barriers in conducting clinical trials towards zoonotic diseases; and strategies that promote conducting clinical trials on zoonotic diseases. Conducting clinical trials on zoonotic diseases in Ethiopia is hampered by a lack of clearly articulated ethics and regulatory frameworks, trial experts, financial resources, and good governance. Conclusions: In Ethiopia, conducting clinical trials on zoonotic diseases deserves due attention. Strengthening institutional and human resources capacity is a precondition to harnessing effective implementation of clinical trials on zoonotic diseases in the country. In Ethiopia, where skilled human resource is scarce, the One Health approach has the potential to form multidisciplinary teams to systematically improve clinical trials capacity and outcomes in the country.

Keywords: Ethiopia, clinical triak, zoonoses, disease

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534 Legal Considerations in Fashion Modeling: Protecting Models' Rights and Ensuring Ethical Practices

Authors: Fatemeh Noori

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The fashion industry is a dynamic and ever-evolving realm that continuously shapes societal perceptions of beauty and style. Within this industry, fashion modeling plays a crucial role, acting as the visual representation of brands and designers. However, behind the glamorous façade lies a complex web of legal considerations that govern the rights, responsibilities, and ethical practices within the field. This paper aims to explore the legal landscape surrounding fashion modeling, shedding light on key issues such as contract law, intellectual property, labor rights, and the increasing importance of ethical considerations in the industry. Fashion modeling involves the collaboration of various stakeholders, including models, designers, agencies, and photographers. To ensure a fair and transparent working environment, it is imperative to establish a comprehensive legal framework that addresses the rights and obligations of each party involved. One of the primary legal considerations in fashion modeling is the contractual relationship between models and agencies. Contracts define the terms of engagement, including payment, working conditions, and the scope of services. This section will delve into the essential elements of modeling contracts, the negotiation process, and the importance of clarity to avoid disputes. Models are not just individuals showcasing clothing; they are integral to the creation and dissemination of artistic and commercial content. Intellectual property rights, including image rights and the use of a model's likeness, are critical aspects of the legal landscape. This section will explore the protection of models' image rights, the use of their likeness in advertising, and the potential for unauthorized use. Models, like any other professionals, are entitled to fair and ethical treatment. This section will address issues such as working conditions, hours, and the responsibility of agencies and designers to prioritize the well-being of models. Additionally, it will explore the global movement toward inclusivity, diversity, and the promotion of positive body image within the industry. The fashion industry has faced scrutiny for perpetuating harmful standards of beauty and fostering a culture of exploitation. This section will discuss the ethical responsibilities of all stakeholders, including the promotion of diversity, the prevention of exploitation, and the role of models as influencers for positive change. In conclusion, the legal considerations in fashion modeling are multifaceted, requiring a comprehensive approach to protect the rights of models and ensure ethical practices within the industry. By understanding and addressing these legal aspects, the fashion industry can create a more transparent, fair, and inclusive environment for all stakeholders involved in the art of modeling.

Keywords: fashion modeling contracts, image rights in modeling, labor rights for models, ethical practices in fashion, diversity and inclusivity in modeling

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533 Atypical Retinoid ST1926 Nanoparticle Formulation Development and Therapeutic Potential in Colorectal Cancer

Authors: Sara Assi, Berthe Hayar, Claudio Pisano, Nadine Darwiche, Walid Saad

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Nanomedicine, the application of nanotechnology to medicine, is an emerging discipline that has gained significant attention in recent years. Current breakthroughs in nanomedicine have paved the way to develop effective drug delivery systems that can be used to target cancer. The use of nanotechnology provides effective drug delivery, enhanced stability, bioavailability, and permeability, thereby minimizing drug dosage and toxicity. As such, the use of nanoparticle (NP) formulations in drug delivery has been applied in various cancer models and have shown to improve the ability of drugs to reach specific targeted sites in a controlled manner. Cancer is one of the major causes of death worldwide; in particular, colorectal cancer (CRC) is the third most common type of cancer diagnosed amongst men and women and the second leading cause of cancer related deaths, highlighting the need for novel therapies. Retinoids, consisting of natural and synthetic derivatives, are a class of chemical compounds that have shown promise in preclinical and clinical cancer settings. However, retinoids are limited by their toxicity and resistance to treatment. To overcome this resistance, various synthetic retinoids have been developed, including the adamantyl retinoid ST1926, which is a potent anti-cancer agent. However, due to its limited bioavailability, the development of ST1926 has been restricted in phase I clinical trials. We have previously investigated the preclinical efficacy of ST1926 in CRC models. ST1926 displayed potent inhibitory and apoptotic effects in CRC cell lines by inducing early DNA damage and apoptosis. ST1926 significantly reduced the tumor doubling time and tumor burden in a xenograft CRC model. Therefore, we developed ST1926-NPs and assessed their efficacy in CRC models. ST1926-NPs were produced using Flash NanoPrecipitation with the amphiphilic diblock copolymer polystyrene-b-ethylene oxide and cholesterol as a co-stabilizer. ST1926 was formulated into NPs with a drug to polymer mass ratio of 1:2, providing a stable formulation for one week. The contin ST1926-NP diameter was 100 nm, with a polydispersity index of 0.245. Using the MTT cell viability assay, ST1926-NP exhibited potent anti-growth activities as naked ST1926 in HCT116 cells, at pharmacologically achievable concentrations. Future studies will be performed to study the anti-tumor activities and mechanism of action of ST1926-NPs in a xenograft mouse model and to detect the compound and its glucuroconjugated form in the plasma of mice. Ultimately, our studies will support the use of ST1926-NP formulations in enhancing the stability and bioavailability of ST1926 in CRC.

Keywords: nanoparticles, drug delivery, colorectal cancer, retinoids

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532 Correlation between Visual Perception and Social Function in Patients with Schizophrenia

Authors: Candy Chieh Lee

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Objective: The purpose of this study is to investigate the relationship between visual perception and social function in patients with schizophrenia. The specific aims are: 1) To explore performances in visual perception and social function in patients with schizophrenia 2) to examine the correlation between visual perceptual skills and social function in patients with schizophrenia The long-term goal is to be able to provide the most adequate intervention program for promoting patients’ visual perceptual skills and social function, as well as compensatory techniques. Background: Perceptual deficits in schizophrenia have been well documented in the visual system. Clinically, a considerable portion (up to 60%) of schizophrenia patients report distorted visual experiences such as visual perception of motion, color, size, and facial expression. Visual perception is required for the successful performance of most activities of daily living, such as dressing, making a cup of tea, driving a car and reading. On the other hand, patients with schizophrenia usually exhibit psychotic symptoms such as auditory hallucination and delusions which tend to alter their perception of reality and affect their quality of interpersonal relationship and limit their participation in various social situations. Social function plays an important role in the prognosis of patients with schizophrenia; lower social functioning skills can lead to poorer prognosis. Investigations on the relationship between social functioning and perceptual ability in patients with schizophrenia are relatively new but important as the results could provide information for effective intervention on visual perception and social functioning in patients with schizophrenia. Methods: We recruited 50 participants with schizophrenia in the mental health hospital (Taipei City Hospital, Songde branch, Taipei, Taiwan) acute ward. Participants who have signed consent forms, diagnosis of schizophrenia and having no organic vision deficits were included. Participants were administered the test of visual-perceptual skills (non-motor), third edition (TVPS-3) and the personal and social performance scale (PSP) for assessing visual perceptual skill and social function. The assessments will take about 70-90 minutes to complete. Data Analysis: The IBM SPSS 21.0 will be used to perform the statistical analysis. First, descriptive statistics will be performed to describe the characteristics and performance of the participants. Lastly, Pearson correlation will be computed to examine the correlation between PSP and TVPS-3 scores. Results: Significant differences were found between the means of participants’ TVPS-3 raw scores of each subtest with the age equivalent raw score provided by the TVPS-3 manual. Significant correlations were found between all 7 subtests of TVPS-3 and PSP total score. Conclusions: The results showed that patients with schizophrenia do exhibit visual perceptual deficits and is correlated social functions. Understanding these facts of patients with schizophrenia can assist health care professionals in designing and implementing adequate rehabilitative treatment according to patients’ needs.

Keywords: occupational therapy, social function, schizophrenia, visual perception

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531 The Pioneering Model in Teaching Arabic as a Mother Tongue through Modern Innovative Strategies

Authors: Rima Abu Jaber Bransi, Rawya Jarjoura Burbara

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This study deals with two pioneering approaches in teaching Arabic as a mother tongue: first, computerization of literary and functional texts in the mother tongue; second, the pioneering model in teaching writing skills by computerization. The significance of the study lies in its treatment of a serious problem that is faced in the era of technology, which is the widening gap between the pupils and their mother tongue. The innovation in the study is that it introduces modern methods and tools and a pioneering instructional model that turns the process of mother tongue teaching into an effective, meaningful, interesting and motivating experience. In view of the Arabic language diglossia, standard Arabic and spoken Arabic, which constitutes a serious problem to the pupil in understanding unused words, and in order to bridge the gap between the pupils and their mother tongue, we resorted to computerized techniques; we took texts from the pre-Islamic period (Jahiliyya), starting with the Mu'allaqa of Imru' al-Qais and other selected functional texts and computerized them for teaching in an interesting way that saves time and effort, develops high thinking strategies, expands the literary good taste among the pupils, and gives the text added values that neither the book, the blackboard, the teacher nor the worksheets provide. On the other hand, we have developed a pioneering computerized model that aims to develop the pupil's ability to think, to provide his imagination with the elements of growth, invention and connection, and motivate him to be creative, and raise level of his scores and scholastic achievements. The model consists of four basic stages in teaching according to the following order: 1. The Preparatory stage, 2. The reading comprehension stage, 3. The writing stage, 4. The evaluation stage. Our lecture will introduce a detailed description of the model with illustrations and samples from the units that we built through highlighting some aspects of the uniqueness and innovation that are specific to this model and the different integrated tools and techniques that we developed. One of the most significant conclusions of this research is that teaching languages through the employment of new computerized strategies is very likely to get the Arabic speaking pupils out of the circle of passive reception into active and serious action and interaction. The study also emphasizes the argument that the computerized model of teaching can change the role of the pupil's mind from being a store of knowledge for a short time into a partner in producing knowledge and storing it in a coherent way that prevents its forgetfulness and keeping it in memory for a long period of time. Consequently, the learners also turn into partners in evaluation by expressing their views, giving their notes and observations, and application of the method of peer-teaching and learning.

Keywords: classical poetry, computerization, diglossia, writing skill

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530 Efficacy of Mitomycin C in Reducing Recurrence of Anterior Urethral Stricture after Internal Optical Urethrotomy

Authors: Liaqat Ali, Ehsan, Muhammad Shahzad, Nasir Orakzai

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Introduction: Internal optical urethrotomy is the main stay treatment modality in management of urethral stricture. Being minimal invasive with less morbidity, it is commonly performed and favored procedure by urologists across the globe. Although short-term success rate of optical urethrotomy is promising but long-term efficacy of IOU is questionable with high recurrence rate in different studies. Numerous techniques had been adopted to reduce the recurrence after IOU like prolong catheterization and self-clean intermittent catheterization with varying success. Mitomycin C has anti-fibroblast and anti-collagen properties and has been used in trabeculectomy, myringotomy and after keloid scar excision in contemporary surgical practice. Present study according to the best of our knowledge is a pioneer pilot study in Pakistan to determine the efficacy of Mitomycin C in preventing recurrence of urethral stricture after internal optical urethrotomy. Objective: To determine the efficacy of Mitomycin C in reducing the recurrence of anterior urethral stricture after internal optical urethrotomy. Methods: It is a randomized control trial conducted in department of urology, Institute of Kidney Diseases Hayatabad Medical Complex Peshawar from March 2011 till December 2013. After approval of hospital ethical committee, we included maximum of 2 cm anterior urethral stricture irrespective of etiology. Total of 140 patients were equally divided into two groups by lottery method. Group A (Case) comprising of 70 patients in whom Mitomycin C 0.1% was injected sub mucosal in stricture area at 1,11,6 and 12 O clock position using straight working channel paediatric cystoscope after conventional optical urethrotomy. Group B (Control) 70 patients in whom only optical urethrotomy was performed. SCIC was not offered in both the groups. All the patients were regularly followed on a monthly basis for 3 months then three monthly for remaining 9 months. Recurrence was diagnosed by using diagnostic tools of retrograde urethrogram and flexible urethroscopy in selected cased. Data was collected on structured Proforma and was analyzed on SPSS. Result: The mean age in Group A was 33 ±1.5 years and Group B was 35 years. External trauma was leading cause of urethral stricture in both groups 46 (65%) Group A and 50 (71.4%) Group B. In Group A. Iatrogenic urethral trauma was 2nd etiological factor in both groups. 18(25%) Group A while 15( 21.4%) in Group B. At the end of 1 year, At the end of one year, recurrence of urethral stricture was recorded in 11 (15.71%) patient in Mitomycin C Group A and it was recorded in 27 (38.5 %) patients in group B. Significant difference p=0.001 was found in favour of group A Mitomycin group. Conclusion: Recurrence of urethral stricture is high after optical urethrotomy. Mitomycin C is found highly effective in preventing recurrence of urethral stricture after IOU.

Keywords: urethral stricture, mitomycine, internal optical urethrotomy, medical and health sciences

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529 (Re)Processing of ND-Fe-B Permanent Magnets Using Electrochemical and Physical Approaches

Authors: Kristina Zuzek, Xuan Xu, Awais Ikram, Richard Sheridan, Allan Walton, Saso Sturm

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Recycling of end-of-life REEs based Nd-Fe-B magnets is an important strategy for reducing the environmental dangers associated with rare-earth mining and overcoming the well-documented supply risks related to the REEs. However, challenges on their reprocessing still remain. We report on the possibility of direct electrochemical recycling and reprocessing of Nd-Fe(B)-based magnets. In this investigation, we were able first to electrochemically leach the end-of-life NdFeB magnet and to electrodeposit Nd–Fe using a 1-ethyl-3-methyl imidazolium dicyanamide ([EMIM][DCA]) ionic liquid-based electrolyte. We observed that Nd(III) could not be reduced independently. However, it can be co-deposited on a substrate with the addition of Fe(II). Using advanced TEM techniques of electron-energy-loss spectroscopy (EELS) it was shown that Nd(III) is reduced to Nd(0) during the electrodeposition process. This gave a new insight into determining the Nd oxidation state, as X-ray photoelectron spectroscopy (XPS) has certain limitations. This is because the binding energies of metallic Nd (Nd0) and neodymium oxide (Nd₂O₃) are very close, i. e., 980.5-981.5 eV and 981.7-982.3 eV, respectively, making it almost impossible to differentiate between the two states. These new insights into the electrodeposition process represent an important step closer to efficient recycling of rare piles of earth in metallic form at mild temperatures, thus providing an alternative to high-temperature molten-salt electrolysis and a step closer to deposit Nd-Fe-based magnetic materials. Further, we propose a new concept of recycling the sintered Nd-Fe-B magnets by direct recovering the 2:14:1 matrix phase. Via an electrochemical etching method, we are able to recover pure individual 2:14:1 grains that can be re-used for new types of magnet production. In the frame of physical reprocessing, we have successfully synthesized new magnets out of hydrogen (HDDR)-recycled stocks with a contemporary technique of pulsed electric current sintering (PECS). The optimal PECS conditions yielded fully dense Nd-Fe-B magnets with the coercivity Hc = 1060 kA/m, which was boosted to 1160 kA/m after the post-PECS thermal treatment. The Br and Hc were tackled further and increased applied pressures of 100 – 150 MPa resulted in Br = 1.01 T. We showed that with a fine tune of the PECS and post-annealing it is possible to revitalize the Nd-Fe-B end-of-life magnets. By applying advanced TEM, i.e. atomic-scale Z-contrast STEM combined with EDXS and EELS, the resulting magnetic properties were critically assessed against various types of structural and compositional discontinuities down to atomic-scale, which we believe control the microstructure evolution during the PECS processing route.

Keywords: electrochemistry, Nd-Fe-B, pulsed electric current sintering, recycling, reprocessing

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528 Controllable Modification of Glass-Crystal Composites with Ion-Exchange Technique

Authors: Andrey A. Lipovskii, Alexey V. Redkov, Vyacheslav V. Rusan, Dmitry K. Tagantsev, Valentina V. Zhurikhina

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The presented research is related to the development of recently proposed technique of the formation of composite materials, like optical glass-ceramics, with predetermined structure and properties of the crystalline component. The technique is based on the control of the size and concentration of the crystalline grains using the phenomenon of glass-ceramics decrystallization (vitrification) induced by ion-exchange. This phenomenon was discovered and explained in the beginning of the 2000s, while related theoretical description was given in 2016 only. In general, the developed theory enables one to model the process and optimize the conditions of ion-exchange processing of glass-ceramics, which provide given properties of crystalline component, in particular, profile of the average size of the crystalline grains. The optimization is possible if one knows two dimensionless parameters of the theoretical model. One of them (β) is the value which is directly related to the solubility of crystalline component of the glass-ceramics in the glass matrix, and another (γ) is equal to the ratio of characteristic times of ion-exchange diffusion and crystalline grain dissolution. The presented study is dedicated to the development of experimental technique and simulation which allow determining these parameters. It is shown that these parameters can be deduced from the data on the space distributions of diffusant concentrations and average size of crystalline grains in the glass-ceramics samples subjected to ion-exchange treatment. Measurements at least at two temperatures and two processing times at each temperature are necessary. The composite material used was a silica-based glass-ceramics with crystalline grains of Li2OSiO2. Cubical samples of the glass-ceramics (6x6x6 mm3) underwent the ion exchange process in NaNO3 salt melt at 520 oC (for 16 and 48 h), 540 oC (for 8 and 24 h), 560 oC (for 4 and 12 h), and 580 oC (for 2 and 8 h). The ion exchange processing resulted in the glass-ceramics vitrification in the subsurface layers where ion-exchange diffusion took place. Slabs about 1 mm thick were cut from the central part of the samples and their big facets were polished. These slabs were used to find profiles of diffusant concentrations and average size of the crystalline grains. The concentration profiles were determined from refractive index profiles measured with Max-Zender interferometer, and profiles of the average size of the crystalline grains were determined with micro-Raman spectroscopy. Numerical simulation were based on the developed theoretical model of the glass-ceramics decrystallization induced by ion exchange. The simulation of the processes was carried out for different values of β and γ parameters under all above-mentioned ion exchange conditions. As a result, the temperature dependences of the parameters, which provided a reliable coincidence of the simulation and experimental data, were found. This ensured the adequate modeling of the process of the glass-ceramics decrystallization in 520-580 oC temperature interval. Developed approach provides a powerful tool for fine tuning of the glass-ceramics structure, namely, concentration and average size of crystalline grains.

Keywords: diffusion, glass-ceramics, ion exchange, vitrification

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527 Prediction of Outcome after Endovascular Thrombectomy for Anterior and Posterior Ischemic Stroke: ASPECTS on CT

Authors: Angela T. H. Kwan, Wenjun Liang, Jack Wellington, Mohammad Mofatteh, Thanh N. Nguyen, Pingzhong Fu, Juanmei Chen, Zile Yan, Weijuan Wu, Yongting Zhou, Shuiquan Yang, Sijie Zhou, Yimin Chen

Abstract:

Background: Endovascular Therapy (EVT)—in the form of mechanical thrombectomy—following intravenous thrombolysis is the standard gold treatment for patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). It is well established that an ASPECTS ≥ 7 is associated with an increased likelihood of positive post-EVT outcomes, as compared to an ASPECTS < 7. There is also prognostic utility in coupling posterior circulation ASPECTS (pc-ASPECTS) with magnetic resonance imaging for evaluating the post-EVT functional outcome. However, the value of pc-ASPECTS applied to CT must be explored further to determine its usefulness in predicting functional outcomes following EVT. Objective: In this study, we aimed to determine whether pc-ASPECTS on CT can predict post-EVT functional outcomes among patients with AIS due to LVO. Methods: A total of 247 consecutive patients aged 18 and over receiving EVT for LVO-related AIS were recruited into a prospective database. The data were retrospectively analyzed between March 2019 to February 2022 from two comprehensive tertiary care stroke centers: Foshan Sanshui District People’s Hospital and First People's Hospital of Foshan in China. Patient parameters included EVT within 24hrs of symptom onset, premorbid modified Rankin Scale (mRS) ≤ 2, presence of distal and terminal cerebral blood vessel occlusion, and subsequent 24–72-hour post-stroke onset CT scan. Univariate comparisons were performed using the Fisher exact test or χ2 test for categorical variables and the Mann–Whitney U test for continuous variables. A p-value of ≤ 0.05 was statistically significant. Results: A total of 247 patients met the inclusion criteria; however, 3 were excluded due to the absence of post-CTs and 8 for pre-EVT ASPECTS < 7. Overall, 236 individuals were examined: 196 anterior circulation ischemic strokes and 40 posterior strokes of basilar artery occlusion. We found that both baseline post- and pc-ASPECTS ≥ 7 serve as strong positive markers of favorable outcomes at 90 days post-EVT. Moreover, lower rates of inpatient mortality/hospice discharge, 90-day mortality, and 90-day poor outcome were observed. Moreover, patients in the post-ASPECTS ≥ 7 anterior circulation group had shorter door-to-recanalization time (DRT), puncture-to-recanalization time (PRT), and last known normal-to-puncture-time (LKNPT). Conclusion: Patients of anterior and posterior circulation ischemic strokes with baseline post- and pc-ASPECTS ≥ 7 may benefit from EVT.

Keywords: endovascular therapy, thrombectomy, large vessel occlusion, cerebral ischemic stroke, ASPECTS

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526 The Relationship between Osteoporosis-Related Knowledge and Physical Activity among Women Age over 50 Years

Authors: P. Tardi, B. Szilagyi, A. Makai, P. Acs, M. Hock, M. Jaromi

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Osteoporosis is becoming a major public health problem, particularly in postmenopausal women, as the incidence of this disease is getting higher. Nowadays, one of the most common chronic musculoskeletal diseases is osteoporosis. Osteoporosis-related knowledge is an important contributor to prevent or to treat osteoporosis. The most important strategies to prevent or treat the disease are increasing the level of physical activity at all ages, cessation of smoking, reduction of alcohol consumption, adequate dietary calcium, and vitamin D intake. The aim of the study was to measure the osteoporosis-related knowledge and physical activity among women age over 50 years. For the measurements, we used the osteoporosis questionnaire (OPQ) to examine the disease-specific knowledge and the global physical activity questionnaire (GPAQ) to measure the quantity and quality of the physical activity. The OPQ is a self-administered 20-item questionnaire with five categories: general information, risk factors, investigations, consequences, and treatment. There are four choices per question (one of them is the 'I do not know'). The filler gets +1 for a good answer, -1 point for a bad answer, and 0 for 'I do not know' answer. We contacted with 326 women (63.08 ± 9.36 year) to fill out the questionnaires. Descriptive analysis was carried out, and we calculated Spearman's correlation coefficient to examine the relationship between the variables. Data were entered into Microsoft Excel, and all statistical analyses were performed using SPSS (Version 24). The participants of the study (n=326) reached 8.76 ± 6.94 points on OPQ. Significant (p < 0.001) differences were found in the results of OPQ according to the highest level of education. It was observed that the score of the participants with osteoporosis (10.07 ± 6.82 points) was significantly (p=0.003) higher than participants without osteoporosis (9.38 ± 6.66 points) and the score of those women (6.49 ± 6.97 points) who did not know that osteoporosis exists in their case. The GPAQ results showed the sample physical activity in the dimensions of vigorous work (479.86 ± 684.02 min/week); moderate work (678.16 ± 804.5 min/week); travel (262.83 ± 380.27 min/week); vigorous recreation (77.71 ± 123.46 min/week); moderate recreation (115.15 ± 154.82 min/week) and total weekly physical activity (1645.99 ± 1432.88 min/week). Significant correlations were found between the osteoporosis-related knowledge and the physical activity in travel (R=0.21; p < 0.001), vigorous recreation (R=0.35; p < 0.001), moderate recreation (R=0.35; p < 0.001), total vigorous minutes/week (R=0.15; p=0.001) and total moderate minutes/week (R=0.13; p=0.04) dimensions. According to the results that were achieved, the highest level of education significantly determines osteoporosis-related knowledge. Physical activity is an important contributor to prevent or to treat osteoporosis, and it showed a significant correlation with osteoporosis-related knowledge. Based on the results, the development of osteoporosis-related knowledge may help to improve the level of physical activity, especially recreation. Acknowledgment: Supported by the ÚNKP-20-1 New National Excellence Program of The Ministry for Innovation and Technology from the Source of the National Research, Development and Innovation Fund.

Keywords: osteoporosis, osteoporosis-related knowledge, physical activity, prevention

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525 Decision Support System for Hospital Selection in Emergency Medical Services: A Discrete Event Simulation Approach

Authors: D. Tedesco, G. Feletti, P. Trucco

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The present study aims to develop a Decision Support System (DSS) to support the operational decision of the Emergency Medical Service (EMS) regarding the assignment of medical emergency requests to Emergency Departments (ED). In the literature, this problem is also known as “hospital selection” and concerns the definition of policies for the selection of the ED to which patients who require further treatment are transported by ambulance. The employed research methodology consists of the first phase of revision of the technical-scientific literature concerning DSSs to support the EMS management and, in particular, the hospital selection decision. From the literature analysis, it emerged that current studies are mainly focused on the EMS phases related to the ambulance service and consider a process that ends when the ambulance is available after completing a request. Therefore, all the ED-related issues are excluded and considered as part of a separate process. Indeed, the most studied hospital selection policy turned out to be proximity, thus allowing to minimize the transport time and release the ambulance in the shortest possible time. The purpose of the present study consists in developing an optimization model for assigning medical emergency requests to the EDs, considering information relating to the subsequent phases of the process, such as the case-mix, the expected service throughput times, and the operational capacity of different EDs in hospitals. To this end, a Discrete Event Simulation (DES) model was created to evaluate different hospital selection policies. Therefore, the next steps of the research consisted of the development of a general simulation architecture, its implementation in the AnyLogic software and its validation on a realistic dataset. The hospital selection policy that produced the best results was the minimization of the Time To Provider (TTP), considered as the time from the beginning of the ambulance journey to the ED at the beginning of the clinical evaluation by the doctor. Finally, two approaches were further compared: a static approach, which is based on a retrospective estimate of the TTP, and a dynamic approach, which is based on a predictive estimate of the TTP determined with a constantly updated Winters model. Findings reveal that considering the minimization of TTP as a hospital selection policy raises several benefits. It allows to significantly reduce service throughput times in the ED with a minimum increase in travel time. Furthermore, an immediate view of the saturation state of the ED is produced and the case-mix present in the ED structures (i.e., the different triage codes) is considered, as different severity codes correspond to different service throughput times. Besides, the use of a predictive approach is certainly more reliable in terms of TTP estimation than a retrospective approach but entails a more difficult application. These considerations can support decision-makers in introducing different hospital selection policies to enhance EMSs performance.

Keywords: discrete event simulation, emergency medical services, forecast model, hospital selection

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524 Cardiac Biosignal and Adaptation in Confined Nuclear Submarine Patrol

Authors: B. Lefranc, C. Aufauvre-Poupon, C. Martin-Krumm, M. Trousselard

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Isolated and confined environments (ICE) present several challenges which may adversely affect human’s psychology and physiology. Submariners in Sub-Surface Ballistic Nuclear (SSBN) mission exposed to these environmental constraints must be able to perform complex tasks as part of their normal duties, as well as during crisis periods when emergency actions are required or imminent. The operational and environmental constraints they face contribute to challenge human adaptability. The impact of such a constrained environment has yet to be explored. Establishing a knowledge framework is a determining factor, particularly in view of the next long space travels. Ensuring that the crews are maintained in optimal operational conditions is a real challenge because the success of the mission depends on them. This study focused on the evaluation of the impact of stress on mental health and sensory degradation of submariners during a mission on SSBN using cardiac biosignal (heart rate variability, HRV) clustering. This is a pragmatic exploratory study of a prospective cohort included 19 submariner volunteers. HRV was recorded at baseline to classify by clustering the submariners according to their stress level based on parasympathetic (Pa) activity. Impacts of high Pa (HPa) versus low Pa (LPa) level at baseline were assessed on emotional state and sensory perception (interoception and exteroception) as a cardiac biosignal during the patrol and at a recovery time one month after. Whatever the time, no significant difference was found in mental health between groups. There are significant differences in the interoceptive, exteroceptive and physiological functioning during the patrol and at recovery time. To sum up, compared to the LPa group, the HPa maintains a higher level in psychosensory functioning during the patrol and at recovery but exhibits a decrease in Pa level. The HPa group has less adaptable HRV characteristics, less unpredictability and flexibility of cardiac biosignals while the LPa group increases them during the patrol and at recovery time. This dissociation between psychosensory and physiological adaptation suggests two treatment modalities for ICE environments. To our best knowledge, our results are the first to highlight the impact of physiological differences in the HRV profile on the adaptability of submariners. Further studies are needed to evaluate the negative emotional and cognitive effects of ICEs based on the cardiac profile. Artificial intelligence offers a promising future for maintaining high level of operational conditions. These future perspectives will not only allow submariners to be better prepared, but also to design feasible countermeasures that will help support analog environments that bring us closer to a trip to Mars.

Keywords: adaptation, exteroception, HRV, ICE, interoception, SSBN

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523 Participatory Approach: A Tool for Improving Food Security and Empowering a Local Community in Chitima, Mozambique

Authors: Matias Hargreaves, Martin Del Valle, Diego Rodriguez, Riveros Jose Luis

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Trough years, all kind of social development projects have tried to solve social problems such as hunger, poverty, malnutrition, food insecurity, among others, with poor success. Both private and state initiatives have invested resources in several countries and communities. Nevertheless, most of these initiatives are scientific or external developers-centered, with a lack of local participation. This compromises the sustainability of any intervention and also leads to a poor empowerment of local community. The participatory approach aims to rescue and enhance the local knowledge since it recognizes that this kind of problems are better known by native actors. The objective of the study was to describe the role played by the community empowerment on food security improvement in the NGO “O Viveiro” (15°43'37.77"S; 32°46'27.53"E) and Barrio Broma village (15°43'58.78"S; 32°46'7.27"E) in Chitima, Mozambique. A center for training in goat livestock and orchard was build. A community orchard was co-constructed between foreign technicians and local actors. The prototype was installed in February, 2016 by the technician team and local community with 16 m2 as a nursery garden. Two orchard workshops were conducted in order to design a sustainable productive model which mixes both local and technological approaches. Two goat meat workshops were conducted in order to describe local methods and train the community to conduce their own techniques with high sanitary and productive standards. Technician team stayed in Mozambique until May, 2016. The quorum for the orchard workshops was 20 and 14 persons respectively, which represents 100% and 70%of the total requested quorum (20). For the goat meat workshops were 4 and 5 persons, which representa80% and 100% of the total requested quorum (5). Until August, 2016, the orchard is 3.219 m2 and it grows several vegetables as beans, chili pepper, garlic, onion, tomatoes, lettuce, sweet potato, yuca potato, cabbage, eggplant, papaya trees, mango, and cassava. The process of increasing in size and diversification of vegetables grown was led entirely by the local community. In connection with this, the local community started to harvest and began to sell the vegetable products at the local market. At the meat goat workshops, local participants rescued a local knowledge by describing and practicing a traditional way to process goat meat by drying it outdoors and then doing a smoked treatment. This information might contribute to describe the level of empowerment of this community, and thus give evidence of acceptance of foreign intervention for improving their own proceedings and traditions.

Keywords: children malnutrition, food security, Local community, participatory approach

Procedia PDF Downloads 276
522 Insecticidal Activity of Bacillus Thuringiensis Strain AH-2 Against Hemiptera Insects Pests: Aphis. Gossypii, and Lepidoptera Insect Pests: Plutella Xylostella and Hyphantria Cunea

Authors: Ajuna B. Henry

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In recent decades, climate change has demanded biological pesticides; more Bt strains are being discovered worldwide, some containing novel insecticidal genes while others have been modified through molecular approaches for increased yield, toxicity, and wider host target. In this study, B. thuringiensis strain AH-2 (Bt-2) was isolated from the soil and tested for insecticidal activity against Aphis gossypii (Hemiptera: Aphididae) and Lepidoptera insect pests: fall webworm (Hyphantria cunea) and diamondback moth (Plutella xylostella). A commercial strain B. thuringiensis subsp. kurstaki (Btk), and a chemical pesticide, imidacloprid (for Hemiptera) and chlorantraniliprole (for Lepidoptera), were used as positive control and the same media (without bacterial inoculum) as a negative control. For aphidicidal activity, Bt-2 caused a mortality rate of 70.2%, 78.1% or 88.4% in third instar nymphs of A. gossypii (3N) at 10%, 25% or 50% culture concentrations, respectively. Moreover, Bt-2 was effectively produced in cost-effective (PB) supplemented with either glucose (PBG) or sucrose (PBS) and maintained high aphicidal efficacy with 3N mortality rates of 85.9%, 82.9% or 82.2% in TSB, PBG or PBS media, respectively at 50% culture concentration. Bt-2 also suppressed adult fecundity by 98.3% compared to only 65.8% suppression by Btk at similar concentrations but was slightly lower than chemical treatment, which caused 100% suppression. Partial purification of 60 – 80% (NH4)2SO4 fraction of Bt-2 aphicidal proteins purified on anion exchange (DEAE-FF) column revealed a 105 kDa aphicidal protein with LC50 = 55.0 ng/µℓ. For Lepidoptera pests, chemical pesticide, Bt-2, and Btk cultures, mortality of 86.7%, 60%, and 60% in 3rd instar larvae of P. xylostella, and 96.7%, 80.0%, and 93.3% in 6th instar larvae of H. cunea, after 72h of exposure. When the entomopathogenic strains were cultured in a cost-effective PBG or PBS, the insecticidal activity in all strains was not significantly different compared to the use of a commercial medium (TSB). Bt-2 caused a mortality rate of 60.0%, 63.3%, and 50.0% against P. xylostella larvae and 76.7%, 83.3%, and 73.3% against H. cunea when grown in TSB, PBG, and PBS media, respectively. Bt-2 (grown in cost-effective PBG medium) caused a dose-dependent toxicity of 26.7%, 40.0%, and 63.3% against P. xylostella and 46.7%, 53.3%, and 76.7% against H. cunea at 10%, 25% and 50% culture concentration, respectively. The partially purified Bt-2 insecticidal proteins fractions F1, F2, F3, and F4 (extracted at different ratios of organic solvent) caused low toxicity (50.0%, 40.0%, 36.7%, and 30.0%) against P. xylostella and relatively high toxicity (56.7%, 76.7%, 66.7%, and 63.3%) against H. cunea at 100 µg/g of artificial diets. SDS-PAGE analysis revealed that a128kDa protein is associated with toxicity of Bt-2. Our result demonstrates a medium and strong larvicidal activity of Bt-2 against P. xylostella and H. cunea, respectively. Moreover, Bt-2 could be potentially produced using a cost-effective PBG medium which makes it an effective alternative biocontrol strategy to reduce chemical pesticide application.

Keywords: biocontrol, insect pests, larvae/nymph mortality, cost-effective media, aphis gossypii, plutella xylostella, hyphantria cunea, bacillus thuringiensi

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521 Nanostructured Pt/MnO2 Catalysts and Their Performance for Oxygen Reduction Reaction in Air Cathode Microbial Fuel Cell

Authors: Maksudur Rahman Khan, Kar Min Chan, Huei Ruey Ong, Chin Kui Cheng, Wasikur Rahman

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Microbial fuel cells (MFCs) represent a promising technology for simultaneous bioelectricity generation and wastewater treatment. Catalysts are significant portions of the cost of microbial fuel cell cathodes. Many materials have been tested as aqueous cathodes, but air-cathodes are needed to avoid energy demands for water aeration. The sluggish oxygen reduction reaction (ORR) rate at air cathode necessitates efficient electrocatalyst such as carbon supported platinum catalyst (Pt/C) which is very costly. Manganese oxide (MnO2) was a representative metal oxide which has been studied as a promising alternative electrocatalyst for ORR and has been tested in air-cathode MFCs. However, the single MnO2 has poor electric conductivity and low stability. In the present work, the MnO2 catalyst has been modified by doping Pt nanoparticle. The goal of the work was to improve the performance of the MFC with minimum Pt loading. MnO2 and Pt nanoparticles were prepared by hydrothermal and sol-gel methods, respectively. Wet impregnation method was used to synthesize Pt/MnO2 catalyst. The catalysts were further used as cathode catalysts in air-cathode cubic MFCs, in which anaerobic sludge was inoculated as biocatalysts and palm oil mill effluent (POME) was used as the substrate in the anode chamber. The as-prepared Pt/MnO2 was characterized comprehensively through field emission scanning electron microscope (FESEM), X-Ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and cyclic voltammetry (CV) where its surface morphology, crystallinity, oxidation state and electrochemical activity were examined, respectively. XPS revealed Mn (IV) oxidation state and Pt (0) nanoparticle metal, indicating the presence of MnO2 and Pt. Morphology of Pt/MnO2 observed from FESEM shows that the doping of Pt did not cause change in needle-like shape of MnO2 which provides large contacting surface area. The electrochemical active area of the Pt/MnO2 catalysts has been increased from 276 to 617 m2/g with the increase in Pt loading from 0.2 to 0.8 wt%. The CV results in O2 saturated neutral Na2SO4 solution showed that MnO2 and Pt/MnO2 catalysts could catalyze ORR with different catalytic activities. MFC with Pt/MnO2 (0.4 wt% Pt) as air cathode catalyst generates a maximum power density of 165 mW/m3, which is higher than that of MFC with MnO2 catalyst (95 mW/m3). The open circuit voltage (OCV) of the MFC operated with MnO2 cathode gradually decreased during 14 days of operation, whereas the MFC with Pt/MnO2 cathode remained almost constant throughout the operation suggesting the higher stability of the Pt/MnO2 catalyst. Therefore, Pt/MnO2 with 0.4 wt% Pt successfully demonstrated as an efficient and low cost electrocatalyst for ORR in air cathode MFC with higher electrochemical activity, stability and hence enhanced performance.

Keywords: microbial fuel cell, oxygen reduction reaction, Pt/MnO2, palm oil mill effluent, polarization curve

Procedia PDF Downloads 557
520 A Comparative Approach for Modeling the Toxicity of Metal Mixtures in Two Ecologically Related Three-Spined (Gasterosteus aculeatus L.) And Nine-Spined (Pungitius pungitius L.) Sticklebacks

Authors: Tomas Makaras

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Sticklebacks (Gasterosteiformes) are increasingly used in ecological and evolutionary research and become well-established role as model species for biologists. However, ecotoxicology studies concerning behavioural effects in sticklebacks regarding stress responses, mainly induced by chemical mixtures, have hardly been addressed. Moreover, although many authors in their studies emphasised the similarity between three-spined and nine-spined stickleback in morphological, neuroanatomical and behavioural adaptations to environmental changes, several comparative studies have revealed considerable differences between these species in and their susceptibility and resistance to variousstressors in laboratory experiments. The hypothesis of this study was that three-spined and nine-spined stickleback species will demonstrate apparent differences in response patterns and sensitivity to metal-based chemicals stimuli. For this purpose, we investigated the swimming behaviour (including mortality rate based on 96-h LC50 values) of two ecologically similar three-spined (Gasterosteusaculeatus) and nine-spined sticklebacks (Pungitiuspungitius) to short-term (up to 24 h) metal mixture (MIX) exposure. We evaluated the relevance and efficacy of behavioural responses of test species in the early toxicity assessment of chemical mixtures. Fish exposed to six (Zn, Pb, Cd, Cu, Ni and Cr) metals in the mixture were either singled out by the Water Framework Directive as priority or as relevant substances in surface water, which was prepared according to the environmental quality standards (EQSs) of these metals set for inland waters in the European Union (EU) (Directive 2013/39/EU). Based on acute toxicity results, G. aculeatus found to be slightly (1.4-fold) more tolerant of MIX impact than those of P. pungitius specimens. The performed behavioural analysis showed the main effect on the interaction between time, species and treatment variables. Although both species exposed to MIX revealed a decreasing tendency in swimming activity, these species’ responsiveness to MIX was somewhat different. Substantial changes in the activity of G. aculeatus were established after 3-h exposure to MIX solutions, which was 1.43-fold lower, while in the case of P. pungitius, 1.96-fold higher than established 96-h LC50 values for each species. This study demonstrated species-specific differences in response sensitivity to metal-based water pollution, indicating behavioural insensitivity of P. pungitiuscompared to G. aculeatus. While many studies highlight the usefulness and suitability of nine-spined sticklebacks for evolutionary and ecological research, attested by their increasing popularity in these fields, great caution must be exercised when using them as model species in ecotoxicological research to probe metal contamination. Meanwhile, G. aculeatus showed to be a promising bioindicator species in the environmental ecotoxicology field.

Keywords: acute toxicity, comparative behaviour, metal mixture, swimming activity

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519 Development of the Family Capacity of Management of Patients with Autism Spectrum Disorder Diagnosis

Authors: Marcio Emilio Dos Santos, Kelly C. F. Dos Santos

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Caregivers of patients diagnosed with ASD are subjected to high stress situations due to the complexity and multiple levels of daily activities that require the organization of events, behaviors and socioemotional situations, such as immediate decision making and in public spaces. The cognitive and emotional requirement needed to fulfill this caregiving role exceeds the regular cultural process that adults receive in their process of preparation for conjugal and parental life. Therefore, in many cases, caregivers present a high level of overload, poor capacity to organize and mediate the development process of the child or patient about their care. Aims: Improvement in the cognitive and emotional capacities related to the caregiver function, allowing the reduction of the overload, the feeling of incompetence and the characteristic level of stress, developing a more organized conduct and decision making more oriented towards the objectives and procedural gains necessary for the integral development of the patient with diagnosis of ASD. Method: The study was performed with 20 relatives, randomly selected from a total of 140 patients attended. The family members were submitted to the Wechsler Adult Intelligence Scale III intelligence test and the Family assessment Management Measure (FaMM) questionnaire as a previous evaluation. Therapeutic activity in a small group of family members or caregivers, with weekly frequency, with a minimum workload of two hours, using the Feuerstein Instrumental Enrichment Cognitive Development Program - Feuerstein Instrumental Enrichment for ten months. Reapplication of the previous tests to verify the gains obtained. Results and Discussion: There is a change in the level of caregiver overload, improvement in the results of the Family assessment Management Measure and highlight to the increase of performance in the cognitive aspects related to problem solving, planned behavior and management of behavioral crises. These results lead to the discussion of the need to invest in the integrated care of patients and their caregivers, mainly by enabling cognitively to deal with the complexity of Autism. This goes beyond the simple therapeutic orientation about adjustments in family and school routines. The study showed that when the caregiver improves his/her capacity of management, the results of the treatment are potentiated and there is a reduction of the level of the caregiver's overload. Importantly, the study was performed for only ten months and the number of family members attended in the study (n = 20) needs to be expanded to have statistical strength.

Keywords: caregiver overload, cognitive development program ASD caregivers, feuerstein instrumental enrichment, family assessment management measure

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518 The Structuring of Economic of Brazilian Innovation and the Institutional Proposal to the Legal Management for Global Conformity to Treat the Technological Risks

Authors: Daniela Pellin, Wilson Engelmann

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Brazil has sought to accelerate your development through technology and innovation as a response to the global influences, which has received in internal management practices. For this, it had edited the Brazilian Law of Innovation 13.243/2016. However observing the Law overestimated economic aspects the respective application will not consider the stakeholders and the technological risks because there is no legal treatment. The economic exploitation and the technological risks must be controlled by limits of democratic system to find better social development to contribute with the economics agents for making decision to conform with global directions. The research understands this is a problem to face given the social particularities of the country because there has been the literal import of the North American Triple Helix Theory consolidated in developed countries and the negative consequences when applied in developing countries. Because of this symptomatic scenario, it is necessary to create adjustment to conduct the management of the law besides social democratic interests to increase the country development. For this, therefore, the Government will have to adopt some conducts promoting side by side with universities, civil society and companies, informational transparency, catch of partnerships, create a Confort Letter document for preparation to ensure the operation, joint elaboration of a Manual of Good Practices, make accountability and data dissemination. Also the Universities must promote informational transparency, drawing up partnership contracts and generating revenue, development of information. In addition, the civil society must do data analysis about proposals received for discussing to give opinion related. At the end, companies have to give public and transparent information about investments and economic benefits, risks and innovation manufactured. The research intends as a general objective to demonstrate that the efficiency of the propeller deployment will be possible if the innovative decision-making process goes through the institutional logic. As specific objectives, the American influence must undergo some modifications to better suit the economic-legal incentives to potentiate the development of the social system. The hypothesis points to institutional model for application to the legal system can be elaborated based on emerging characteristics of the country, in such a way that technological risks can be foreseen and there will be global conformity with attention to the full development of society as proposed by the researchers.The method of approach will be the systemic-constructivist with bibliographical review, data collection and analysis with the construction of the institutional and democratic model for the management of the Law.

Keywords: development, governance of law, institutionalization, triple helix

Procedia PDF Downloads 140
517 From Preoccupied Attachment Pattern to Depression: Serial Mediation Model on the Female Sample

Authors: Tatjana Stefanovic Stanojevic, Milica Tosic Radev, Aleksandra Bogdanovic

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Depression is considered to be a leading cause of death and disability in the female population, and that is the reason why understanding the dynamics of the onset of depressive symptomatology is important. A review of the literature indicates the relationship between depressive symptoms and insecure attachment patterns, but very few studies have examined the mechanism underlying this relation. The aim of the study was to examine the pathway from the preoccupied attachment pattern to depressive symptomatology, as well as to test the mediation effect of mentalization, social anxiety and rumination in this relationship using a serial mediation model. The research was carried out on a geographical cluster sample from the general population of Serbia included within the project ‘Indicators and models of family and work roles harmonization’ funded by the Ministry of Education, Science and Technological Development of the Republic of Serbia. This research was carried out on a subsample of 791 working-age female adults from 37 urban and rural locations distributed through 20 administrative districts of Serbia. The respondents filled in a battery of instruments, including Relationship Questionnaire - Clinical Version (RQ - CV), The Mentalization Scale (MentS), Scale of Social Anxiety (SA), Patient Ruminative Thought Style Questionnaire (RTSQ), Health Questionnaire (PHQ-9). The results confirm our assumption that the total indirect effect of the preoccupied attachment pattern to depressive symptoms is significant across all mediators separately. More importantly, this effect is still present in a model with a sequential mediator relationship, where social anxiety, rumination, and mentalization were perceived as serial mediators of a relationship between preoccupied attachment and depressive symptoms (estimated indirect effect=0.004, boot-strapped 95% CI=0.002 to 0.007). Our findings suggest that there is a significant specific indirect effect of the preoccupied attachment pattern to depressive symptoms, occurring through mentalization, social anxiety and rumination, indicating that preoccupied attachment cause decrease of a self related mentalization, which in turn causes increasing of social anxiety and rumination, concluding in depressive symptoms as a final consequence. The finding that the path from the preoccupied attachment pattern to depressive symptoms is typical in women is understandable from the perspective of both evolutionary and culturally conditioned gender differences. The practical implications of the study are reflected in the recommendations for the prevention and forehand psychotherapy response among preoccupied women with depressive symptomatology. Treatment of this specific group of depressed patients should be focused on strengthening mentalization, learning to accept and to understand herself better, reducing anxiety in situations where mistakes are visible to others, and replacing the rumination strategy with more constructive coping strategies.

Keywords: preoccupied attachment, depression, serial mediation model, mentalization, rumination

Procedia PDF Downloads 142
516 Perception of Nurses and Caregivers on Fall Preventive Management for Hospitalized Children Based on Ecological Model

Authors: Mirim Kim, Won-Oak Oh

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Purpose: The purpose of this study was to identify hospitalized children's fall risk factors, fall prevention status and fall prevention strategies recognized by nurses and caregivers of hospitalized children and present an ecological model for fall preventive management in hospitalized children. Method: The participants of this study were 14 nurses working in medical institutions and having more than one year of child care experience and 14 adult caregivers of children under 6 years of age receiving inpatient treatment at a medical institution. One to one interview was attempted to identify their perception of fall preventive management. Transcribed data were analyzed through latent content analysis method. Results: Fall risk factors in hospitalized children were 'unpredictable behavior', 'instability', 'lack of awareness about danger', 'lack of awareness about falls', 'lack of child control ability', 'lack of awareness about the importance of fall prevention', 'lack of sensitivity to children', 'untidy environment around children', 'lack of personalized facilities for children', 'unsafe facility', 'lack of partnership between healthcare provider and caregiver', 'lack of human resources', 'inadequate fall prevention policy', 'lack of promotion about fall prevention', 'a performanceism oriented culture'. Fall preventive management status of hospitalized children were 'absence of fall prevention capability', 'efforts not to fall', 'blocking fall risk situation', 'limit the scope of children's activity when there is no caregiver', 'encourage caregivers' fall prevention activities', 'creating a safe environment surrounding hospitalized children', 'special management for fall high risk children', 'mutual cooperation between healthcare providers and caregivers', 'implementation of fall prevention policy', 'providing guide signs about fall risk'. Fall preventive management strategies of hospitalized children were 'restrain dangerous behavior', 'inspiring awareness about fall', 'providing fall preventive education considering the child's eye level', 'efforts to become an active subject of fall prevention activities', 'providing customed fall prevention education', 'open communication between healthcare providers and caregivers', 'infrastructure and personnel management to create safe hospital environment', 'expansion fall prevention campaign', 'development and application of a valid fall assessment instrument', 'conversion of awareness about safety'. Conclusion: In this study, the ecological model of fall preventive management for hospitalized children reflects various factors that directly or indirectly affect the fall prevention of hospitalized children. Therefore, these results can be considered as useful baseline data for developing systematic fall prevention programs and hospital policies to prevent fall accident in hospitalized children. Funding: This study was funded by the National Research Foundation of South Korea (grant number NRF-2016R1A2B1015455).

Keywords: fall down, safety culture, hospitalized children, risk factors

Procedia PDF Downloads 164
515 Comparison Between Bispectral Index Guided Anesthesia and Standard Anesthesia Care in Middle Age Adult Patients Undergoing Modified Radical Mastectomy

Authors: Itee Chowdhury, Shikha Modi

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Introduction: Cancer is beginning to outpace cardiovascular disease as a cause of death affecting every major organ system with profound implications for perioperative management. Breast cancer is the most common cancer in women in India, accounting for 27% of all cancers. The small changes in analgesic management of cancer patients can greatly improve prognosis and reduce the risk of postsurgical cancer recurrence as opioid-based analgesia has a deleterious effect on cancer outcomes. Shortened postsurgical recovery time facilitates earlier return to intended oncological therapy maximising the chance of successful treatment. Literature reveals that the role of BIS since FDA approval has been assessed in various types of surgeries, but clinical data on its use in oncosurgical patients are scanty. Our study focuses on the role of BIS-guided anaesthesia for breast cancer surgery patients. Methods: A prospective randomized controlled study in patients aged 36-55years scheduled for modified radical mastectomy was conducted in 51 patients in each group who met the inclusion and exclusion criteria, and randomization was done by sealed envelope technique. In BIS guided anaesthesia group (B), sevoflurane was titrated to keep the BIS value 45-60, and thereafter if the patient showed hypertension/tachycardia, an opioid was given. In standard anaesthesia care (group C), sevoflurane was titrated to keep MAC in the range of 0.8-1, and fentanyl was given if the patient showed hypertension/tachycardia. Intraoperative opioid consumption was calculated. Postsurgery recovery characteristics, including Aldrete score, were assessed. Patients were questioned for pain, PONV, and recall of the intraoperative event. A comparison of age, BMI, ASA, recovery characteristics, opioid, and VAS score was made using the non-parametric Mann-Whitney U test. Categorical data like intraoperative awareness of surgery and PONV was studied using the Chi-square test. A comparison of heart rate and MAP was made by an independent sample t-test. #ggplot2 package was used to show the trend of the BIS index for all intraoperative time points for each patient. For a statistical test of significance, the cut-off p-value was set as <0.05. Conclusions: BIS monitoring led to reduced opioid consumption and early recovery from anaesthesia in breast cancer patients undergoing MRM resulting in less postoperative nausea and vomiting and less pain intensity in the immediate postoperative period without any recall of the intraoperative event. Thus, the use of a Bispectral index monitor allows for tailoring of anaesthesia administration with a good outcome.

Keywords: bispectral index, depth of anaesthesia, recovery, opioid consumption

Procedia PDF Downloads 127
514 Optimization of Operational Water Quality Parameters in a Drinking Water Distribution System Using Response Surface Methodology

Authors: Sina Moradi, Christopher W. K. Chow, John Van Leeuwen, David Cook, Mary Drikas, Patrick Hayde, Rose Amal

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Chloramine is commonly used as a disinfectant in drinking water distribution systems (DWDSs), particularly in Australia and the USA. Maintaining a chloramine residual throughout the DWDS is important in ensuring microbiologically safe water is supplied at the customer’s tap. In order to simulate how chloramine behaves when it moves through the distribution system, a water quality network model (WQNM) can be applied. In this work, the WQNM was based on mono-chloramine decomposition reactions, which enabled prediction of mono-chloramine residual at different locations through a DWDS in Australia, using the Bentley commercial hydraulic package (Water GEMS). The accuracy of WQNM predictions is influenced by a number of water quality parameters. Optimization of these parameters in order to obtain the closest results in comparison with actual measured data in a real DWDS would result in both cost reduction as well as reduction in consumption of valuable resources such as energy and materials. In this work, the optimum operating conditions of water quality parameters (i.e. temperature, pH, and initial mono-chloramine concentration) to maximize the accuracy of mono-chloramine residual predictions for two water supply scenarios in an entire network were determined using response surface methodology (RSM). To obtain feasible and economical water quality parameters for highest model predictability, Design Expert 8.0 software (Stat-Ease, Inc.) was applied to conduct the optimization of three independent water quality parameters. High and low levels of the water quality parameters were considered, inevitably, as explicit constraints, in order to avoid extrapolation. The independent variables were pH, temperature and initial mono-chloramine concentration. The lower and upper limits of each variable for two water supply scenarios were defined and the experimental levels for each variable were selected based on the actual conditions in studied DWDS. It was found that at pH of 7.75, temperature of 34.16 ºC, and initial mono-chloramine concentration of 3.89 (mg/L) during peak water supply patterns, root mean square error (RMSE) of WQNM for the whole network would be minimized to 0.189, and the optimum conditions for averaged water supply occurred at pH of 7.71, temperature of 18.12 ºC, and initial mono-chloramine concentration of 4.60 (mg/L). The proposed methodology to predict mono-chloramine residual can have a great potential for water treatment plant operators in accurately estimating the mono-chloramine residual through a water distribution network. Additional studies from other water distribution systems are warranted to confirm the applicability of the proposed methodology for other water samples.

Keywords: chloramine decay, modelling, response surface methodology, water quality parameters

Procedia PDF Downloads 224
513 The Effects of Alpha-Lipoic Acid Supplementation on Post-Stroke Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Authors: Hamid Abbasi, Neda Jourabchi, Ranasadat Abedi, Kiarash Tajernarenj, Mehdi Farhoudi, Sarvin Sanaie

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Background: Alpha lipoic acid (ALA), fat- and water-soluble, coenzyme with sulfuret content, has received considerable attention for its potential therapeutic role in diabetes, cardiovascular diseases, cancers, and central nervous disease. This investigation aims to evaluate the probable protective effects of ALA in stroke patients. Methods: Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, This meta-analysis was performed. The PICO criteria for this meta-analysis were as follows: Population/Patients (P: stroke patients); Intervention (I: ALA); Comparison (C: control); Outcome (O: blood glucose, lipid profile, oxidative stress, inflammatory factors).In addition, Studies that were excluded from the analysis consisted of in vitro, in vivo, and ex vivo studies, case reports, quasi-experimental studies. Scopus, PubMed, Web of Science, EMBASE databases were searched until August 2023. Results: Of 496 records that were screened in the title/abstract stage, 9 studies were included in this meta-analysis. The sample sizes in the included studies vary between 28 and 90. The result of risk of bias was performed via risk of bias (RoB) in randomized-controlled trials (RCTs) based on the second version of the Cochrane RoB assessment tool. 8 studies had a definitely high risk of bias. Discussion: To the best of our knowledge, The present meta-analysis is the first study addressing the effectiveness of ALA supplementation in enhancing post-stroke metabolic markers, including lipid profile, oxidative stress, and inflammatory indices. It is imperative to acknowledge certain potential limitations inherent in this study. First of all, type of treatment (oral or intravenous infusion) could alter the bioavailability of ALA. Our study had restricted evidence regarding the impact of ALA supplementation on included outcomes. Therefore, further research is warranted to develop into the effects of ALA specifically on inflammation and oxidative stress. Funding: The research protocol was approved and supported by the Student Research Committee, Tabriz University of Medical Sciences (grant number: 72825). Registration: This study was registered in the International prospective register of systematic reviews (PROSPERO ID: CR42023461612).

Keywords: alpha-lipoic acid, lipid profile, blood glucose, inflammatory factors, oxidative stress, meta-analysis, post-stroke

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512 Isosorbide Bis-Methyl Carbonate: Opportunities for an Industrial Model Based on Biomass

Authors: Olga Gomez De Miranda, Jose R. Ochoa-Gomez, Stefaan De Wildeman, Luciano Monsegue, Soraya Prieto, Leire Lorenzo, Cristina Dineiro

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The chemical industry is facing a new revolution. As long as processes based on the exploitation of fossil resources emerged with force in the XIX century, Society currently demands a new radical change that will lead to the complete and irreversible implementation of a circular sustainable economic model. The implementation of biorefineries will be essential for this. There, renewable raw materials as sugars and other biomass resources are exploited for the development of new materials that will partially replace their petroleum-derived homologs in a safer, and environmentally more benign approach. Isosorbide, (1,4:3,6-dianhydro-d-glucidol) is a primary bio-based derivative obtained from the plant (poly) saccharides and a very interesting example of a useful chemical produced in biorefineries. It can, in turn, be converted to other secondary monomers as isosorbide bis-methyl carbonate (IBMC), whose main field of application can be as a key biodegradable intermediary substitute of bisphenol-A in the manufacture of polycarbonates, or as an alternative to the toxic isocyanates in the synthesis of new polyurethanes (non-isocyanate polyurethanes) both with a huge application market. New products will present advantageous mechanical or optical properties, as well as improved behavior in non-toxicity and biodegradability aspects in comparison to their petro-derived alternatives. A robust production process of IBMC, a biomass-derived chemical, is here presented. It can be used with different raw material qualities using dimethyl carbonate (DMC) as both co-reactant and solvent. It consists of the transesterification of isosorbide with DMC under soft operational conditions, using different basic catalysts, always active with the isosorbide characteristics and purity. Appropriate isolation processes have been also developed to obtain crude IBMC yields higher than 90%, with oligomers production lower than 10%, independently of the quality of the isosorbide considered. All of them are suitable to be used in polycondensation reactions for polymers obtaining. If higher qualities of IBMC are needed, a purification treatment based on nanofiltration membranes has been also developed. The IBMC reaction-isolation conditions established in the laboratory have been successfully modeled using appropriate software programs and moved to a pilot-scale (production of 100 kg of IBMC). It has been demonstrated that a highly efficient IBMC production process able to be up-scaled under suitable market conditions has been obtained. Operational conditions involved the production of IBMC involve soft temperature and energy needs, no additional solvents, and high operational efficiency. All of them are according to green manufacturing rules.

Keywords: biomass, catalyst, isosorbide bis-methyl carbonate, polycarbonate, polyurethane, transesterification

Procedia PDF Downloads 132
511 Use of Curcumin in Radiochemotherapy Induced Oral Mucositis Patients: A Control Trial Study

Authors: Shivayogi Charantimath

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Radiotherapy and chemotherapy are effective for treating malignancies but are associated with side effects like oral mucositis. Chlorhexidine gluconate is one of the most commonly used mouthwash in prevention of signs and symptoms of mucositis. Evidence shows that chlorhexidine gluconate has side effects in terms of colonization of bacteria, bad breadth and less healing properties. Thus, it is essential to find a suitable alternative therapy which is more effective with minimal side effects. Curcumin, an extract of turmeric is gradually being studied for its wide-ranging therapeutic properties such as antioxidant, analgesic, anti-inflammatory, antitumor, antimicrobial, antiseptic, chemo sensitizing and radio sensitizing properties. The present study was conducted to evaluate the efficacy and safety of topical curcumin gel on radio-chemotherapy induced oral mucositis in cancer patients. The aim of the study is to evaluate the efficacy and safety of curcumin gel in the management of oral mucositis in cancer patients undergoing radio chemotherapy and compare with chlorhexidine. The study was conducted in K.L.E. Society’s Belgaum cancer hospital. 40 oral cancer patients undergoing the radiochemotheraphy with oral mucositis was selected and randomly divided into two groups of 20 each. The study group A [20 patients] was advised Cure next gel for 2 weeks. The control group B [20 patients] was advised chlorhexidine gel for 2 weeks. The NRS, Oral Mucositis Assessment scale and WHO mucositis scale were used to determine the grading. The results obtained were calculated by using SPSS 20 software. The comparison of grading was done by applying Mann-Whitney U test and intergroup comparison was calculated by Wilcoxon matched pairs test. The NRS scores observed from baseline to 1st and 2nd week follow up in both the group showed significant difference. The percentage of change in erythema in respect to group A was 63.3% for first week and for second week, changes were 100.0% with p = 0.0003. The changes in Group A in respect to erythema was 34.6% for 1st week and 57.7% in second week. The intergroup comparison was significant with p value of 0.0048 and 0.0006 in relation to group A and group B respectively. The size of the ulcer score was measured which showed 35.5% [P=0.0010] of change in Group A for 1st and 2nd week showed totally reduction i.e. 103.4% [P=0.0001]. Group B showed 24.7% change from baseline to 1st week and 53.6% for 2nd week follow up. The intergroup comparison with Wilcoxon matched pair test was significant with p=0.0001 in group A. The result obtained by WHO mucositis score in respect to group A shows 29.6% [p=0.0004] change in first week and 75.0% [p=0.0180] change in second week which is highly significant in comparison to group B. Group B showed minimum changes i.e. 20.1% in 1st week and 33.3% in 2nd week. The p value with Wilcoxon was significant with 0.0025 in Group A for 1st week follow up and 0.000 for 2nd week follow up. Curcumin gel appears to an effective and safer alternative to chlorhexidine gel in treatment of oral mucositis.

Keywords: curcumin, chemotheraphy, mucositis, radiotheraphy

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510 Assessing Sydney Tar Ponds Remediation and Natural Sediment Recovery in Nova Scotia, Canada

Authors: Tony R. Walker, N. Devin MacAskill, Andrew Thalhiemer

Abstract:

Sydney Harbour, Nova Scotia has long been subject to effluent and atmospheric inputs of metals, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs) from a large coking operation and steel plant that operated in Sydney for nearly a century until closure in 1988. Contaminated effluents from the industrial site resulted in the creation of the Sydney Tar Ponds, one of Canada’s largest contaminated sites. Since its closure, there have been several attempts to remediate this former industrial site and finally, in 2004, the governments of Canada and Nova Scotia committed to remediate the site to reduce potential ecological and human health risks to the environment. The Sydney Tar Ponds and Coke Ovens cleanup project has become the most prominent remediation project in Canada today. As an integral part of remediation of the site (i.e., which consisted of solidification/stabilization and associated capping of the Tar Ponds), an extensive multiple media environmental effects program was implemented to assess what effects remediation had on the surrounding environment, and, in particular, harbour sediments. Additionally, longer-term natural sediment recovery rates of select contaminants predicted for the harbour sediments were compared to current conditions. During remediation, potential contributions to sediment quality, in addition to remedial efforts, were evaluated which included a significant harbour dredging project, propeller wash from harbour traffic, storm events, adjacent loading/unloading of coal and municipal wastewater treatment discharges. Two sediment sampling methodologies, sediment grab and gravity corer, were also compared to evaluate the detection of subtle changes in sediment quality. Results indicated that overall spatial distribution pattern of historical contaminants remains unchanged, although at much lower concentrations than previously reported, due to natural recovery. Measurements of sediment indicator parameter concentrations confirmed that natural recovery rates of Sydney Harbour sediments were in broad agreement with predicted concentrations, in spite of ongoing remediation activities. Overall, most measured parameters in sediments showed little temporal variability even when using different sampling methodologies, during three years of remediation compared to baseline, except for the detection of significant increases in total PAH concentrations noted during one year of remediation monitoring. The data confirmed the effectiveness of mitigation measures implemented during construction relative to harbour sediment quality, despite other anthropogenic activities and the dynamic nature of the harbour.

Keywords: contaminated sediment, monitoring, recovery, remediation

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509 Online Allocation and Routing for Blood Delivery in Conditions of Variable and Insufficient Supply: A Case Study in Thailand

Authors: Pornpimol Chaiwuttisak, Honora Smith, Yue Wu

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Blood is a perishable product which suffers from physical deterioration with specific fixed shelf life. Although its value during the shelf life is constant, fresh blood is preferred for treatment. However, transportation costs are a major factor to be considered by administrators of Regional Blood Centres (RBCs) which act as blood collection and distribution centres. A trade-off must therefore be reached between transportation costs and short-term holding costs. In this paper we propose a number of algorithms for online allocation and routing of blood supplies, for use in conditions of variable and insufficient blood supply. A case study in northern Thailand provides an application of the allocation and routing policies tested. The plan proposed for daily allocation and distribution of blood supplies consists of two components: firstly, fixed routes are determined for the supply of hospitals which are far from an RBC. Over the planning period of one week, each hospital on the fixed routes is visited once. A robust allocation of blood is made to hospitals on the fixed routes that can be guaranteed on a suitably high percentage of days, despite variable supplies. Secondly, a variable daily route is employed for close-by hospitals, for which more than one visit per week may be needed to fulfil targets. The variable routing takes into account the amount of blood available for each day’s deliveries, which is only known on the morning of delivery. For hospitals on the variables routes, the day and amounts of deliveries cannot be guaranteed but are designed to attain targets over the six-day planning horizon. In the conditions of blood shortage encountered in Thailand, and commonly in other developing countries, it is often the case that hospitals request more blood than is needed, in the knowledge that only a proportion of all requests will be met. Our proposal is for blood supplies to be allocated and distributed to each hospital according to equitable targets based on historical demand data, calculated with regard to expected daily blood supplies. We suggest several policies that could be chosen by the decision makes for the daily distribution of blood. The different policies provide different trade-offs between transportation and holding costs. Variations in the costs of transportation, such as the price of petrol, could make different policies the most beneficial at different times. We present an application of the policies applied to a realistic case study in the RBC at Chiang Mai province which is located in Northern region of Thailand. The analysis includes a total of more than 110 hospitals, with 29 hospitals considered in the variable route. The study is expected to be a pilot for other regions of Thailand. Computational experiments are presented. Concluding remarks include the benefits gained by the online methods and future recommendations.

Keywords: online algorithm, blood distribution, developing country, insufficient blood supply

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508 The Effect of Positional Release Technique versus Kinesio Tape on Iliocostalis lumborum in Back Myofascial Pain Syndrome

Authors: Shams Khaled Abdelrahman Abdallah Elbaz, Alaa Aldeen Abd Al Hakeem Balbaa

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Purpose: The purpose of this study was to compare the effects of Positional Release Technique versus Kinesio Tape on pain level, pressure pain threshold level and functional disability in patients with back myofascial pain syndrome at iliocostalis lumborum. Backgrounds/significance: Myofascial Pain Syndrome is a common muscular pain syndrome that arises from trigger points which are hyperirritable, painful and tender points within a taut band of skeletal muscle. In more recent literature, about 75% of patients with musculoskeletal pain presenting to a community medical centres suffer from myofascial pain syndrome.Iliocostalis lumborum are most likely to develop active trigger points. Subjects: Thirty patients diagnosed as back myofascial pain syndrome with active trigger points in iliocostalis lumborum muscle bilaterally had participated in this study. Methods and materials: Patients were randomly distributed into two groups. The first group consisted of 15 patients (8 males and 7 females) with mean age 30.6 (±3.08) years, they received positional release technique which was applied 3 times per session, 3/week every other day for 2 weeks. The second group consisted of 15 patients(5 males, 10 females) with a mean age 30.4 (±3.35) years, they received kinesio tape which was applied and changed every 3 days with one day off for a total 3 times in 2 weeks. Both techniques were applied over trigger points of the iliocostalis lumborum bilaterally. Patients were evaluated pretreatment and posttreatment program for Pain intensity (Visual analogue scale), pressure pain threshold (digital pressure algometry), and functional disability (The Oswestry Disability Index). Analyses: Repeated measures MANOVA was used to detect differences within and between groups pre and post treatment. Then the univariate ANOVA test was conducted for the analysis of each dependant variable within and between groups. All statistical analyses were done using SPSS. with significance level set at p<0.05 throughout all analyses. Results: The results revealed that there was no significant difference between positional release technique and kinesio tape technique on pain level, pressure pain threshold and functional activities (p > 0.05). Both groups of patients showed significant improvement in all the measured variables (p < 0.05) evident by significant reduction of both pain intensity and functional disability as well as significant increase of pressure pain threshold Conclusions : Both positional release technique and kinesio taping technique are effective in reducing pain level, improving pressure pain threshold and improving function in treating patients who suffering from back myofascial pain syndrome at iliocostalis lumborum. As there was no statistically significant difference was proven between both of them.

Keywords: positional release technique, kinesio tape, myofascial pain syndrome, Iliocostalis lumborum

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507 Use of Locomotor Activity of Rainbow Trout Juveniles in Identifying Sublethal Concentrations of Landfill Leachate

Authors: Tomas Makaras, Gintaras Svecevičius

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Landfill waste is a common problem as it has an economic and environmental impact even if it is closed. Landfill waste contains a high density of various persistent compounds such as heavy metals, organic and inorganic materials. As persistent compounds are slowly-degradable or even non-degradable in the environment, they often produce sublethal or even lethal effects on aquatic organisms. The aims of the present study were to estimate sublethal effects of the Kairiai landfill (WGS: 55°55‘46.74“, 23°23‘28.4“) leachate on the locomotor activity of rainbow trout Oncorhynchus mykiss juveniles using the original system package developed in our laboratory for automated monitoring, recording and analysis of aquatic organisms’ activity, and to determine patterns of fish behavioral response to sublethal effects of leachate. Four different concentrations of leachate were chosen: 0.125; 0.25; 0.5 and 1.0 mL/L (0.0025; 0.005; 0.01 and 0.002 as part of 96-hour LC50, respectively). Locomotor activity was measured after 5, 10 and 30 minutes of exposure during 1-minute test-periods of each fish (7 fish per treatment). The threshold-effect-concentration amounted to 0.18 mL/L (0.0036 parts of 96-hour LC50). This concentration was found to be even 2.8-fold lower than the concentration generally assumed to be “safe” for fish. At higher concentrations, the landfill leachate solution elicited behavioral response of test fish to sublethal levels of pollutants. The ability of the rainbow trout to detect and avoid contaminants occurred after 5 minutes of exposure. The intensity of locomotor activity reached a peak within 10 minutes, evidently decreasing after 30 minutes. This could be explained by the physiological and biochemical adaptation of fish to altered environmental conditions. It has been established that the locomotor activity of juvenile trout depends on leachate concentration and exposure duration. Modeling of these parameters showed that the activity of juveniles increased at higher leachate concentrations, but slightly decreased with the increasing exposure duration. Experiment results confirm that the behavior of rainbow trout juveniles is a sensitive and rapid biomarker that can be used in combination with the system for fish behavior monitoring, registration and analysis to determine sublethal concentrations of pollutants in ambient water. Further research should be focused on software improvement aimed to include more parameters of aquatic organisms’ behavior and to investigate the most rapid and appropriate behavioral responses in different species. In practice, this study could be the basis for the development and creation of biological early-warning systems (BEWS).

Keywords: fish behavior biomarker, landfill leachate, locomotor activity, rainbow trout juveniles, sublethal effects

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506 Modulation of Receptor-Activation Due to Hydrogen Bond Formation

Authors: Sourav Ray, Christoph Stein, Marcus Weber

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A new class of drug candidates, initially derived from mathematical modeling of ligand-receptor interactions, activate the μ-opioid receptor (MOR) preferentially at acidic extracellular pH-levels, as present in injured tissues. This is of commercial interest because it may preclude the adverse effects of conventional MOR agonists like fentanyl, which include but are not limited to addiction, constipation, sedation, and apnea. Animal studies indicate the importance of taking the pH value of the chemical environment of MOR into account when designing new drugs. Hydrogen bonds (HBs) play a crucial role in stabilizing protein secondary structure and molecular interaction, such as ligand-protein interaction. These bonds may depend on the pH value of the chemical environment. For the MOR, antagonist naloxone and agonist [D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin (DAMGO) form HBs with ionizable residue HIS 297 at physiological pH to modulate signaling. However, such interactions were markedly reduced at acidic pH. Although fentanyl-induced signaling is also diminished at acidic pH, HBs with HIS 297 residue are not observed at either acidic or physiological pH for this strong agonist of the MOR. Molecular dynamics (MD) simulations can provide greater insight into the interaction between the ligand of interest and the HIS 297 residue. Amino acid protonation states are adjusted to the model difference in system acidity. Unbiased and unrestrained MD simulations were performed, with the ligand in the proximity of the HIS 297 residue. Ligand-receptor complexes were embedded in 1-palmitoyl-2-oleoyl-sn glycero-3-phosphatidylcholine (POPC) bilayer to mimic the membrane environment. The occurrence of HBs between the different ligands and the HIS 297 residue of MOR at acidic and physiological pH values were tracked across the various simulation trajectories. No HB formation was observed between fentanyl and HIS 297 residue at either acidic or physiological pH. Naloxone formed some HBs with HIS 297 at pH 5, but no such HBs were noted at pH 7. Interestingly, DAMGO displayed an opposite yet more pronounced HB formation trend compared to naloxone. Whereas a marginal number of HBs could be observed at even pH 5, HBs with HIS 297 were more stable and widely present at pH 7. The HB formation plays no and marginal role in the interaction of fentanyl and naloxone, respectively, with the HIS 297 residue of MOR. However, HBs play a significant role in the DAMGO and HIS 297 interaction. Post DAMGO administration, these HBs might be crucial for the remediation of opioid tolerance and restoration of opioid sensitivity. Although experimental studies concur with our observations regarding the influence of HB formation on the fentanyl and DAMGO interaction with HIS 297, the same could not be conclusively stated for naloxone. Therefore, some other supplementary interactions might be responsible for the modulation of the MOR activity by naloxone binding at pH 7 but not at pH 5. Further elucidation of the mechanism of naloxone action on the MOR could assist in the formulation of cost-effective naloxone-based treatment of opioid overdose or opioid-induced side effects.

Keywords: effect of system acidity, hydrogen bond formation, opioid action, receptor activation

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