Search results for: chimeric drug delivery vehicles

Authors: A. M. Malagon Escandon, J. A. Arenas Alatorre, C. P. Chaires Rosas, N. A. Vazquez Torres, B. Hernandez Tellez, G. Pinon Zarate, M. Herrera Enriquez, A. E. Castell Rodriguez

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The current approach to the treatment of bone defects involves the use of scaffolds that provide a biological and mechanically stable niche to favor tissue repair. Despite the significant progress in the field of bone tissue engineering, several main problems associated are attributed to giving a low biodegradation degree, does not promote osseointegration and regeneration, if the bone is not healing as well as expected or fails to heal, will not be given a proper ossification or new bone formation. The actual approaches of bone tissue regeneration are directed to the use of decellularized native extracellular matrices, which are able of retain their own architecture, mechanic properties, biodegradability and promote new bone formation because they are capable of conserving proteins and other factors that are founded in physiological concentrations. Therefore, we propose an extracellular matrix-based bioscaffolds derived from bovine cancellous bone, which is processed by decellularization, demineralization, and hydrolysis of the collagen protein, these protocols have been successfully carried out in other organs and tissues; the effectiveness of its biosafety has also been previously evaluated in vivo and Food and Drug Administration (FDA) approved. In the specific case of bone, a more complex treatment is needed in comparison with other organs and tissues because is necessary demineralization and collagen denaturalization. The present work was made in order to obtain a temporal scaffold that succeed in degradation in an inversely proportional way to the synthesis of extracellular matrix and the maturation of the bone by the cells of the host.

Keywords: bioactive, biodegradable, bone, extracellular matrix-based bioscaffolds, stem cells, tissue engineering

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Authors: Danielle Page

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Foregoing studies, statistics, and medical evaluations have established a relationship between Posttraumatic stress disorder (PTSD) and criminal justice involvement in Vietnam veterans. War is highly trauma inducing and can leave combat veterans with mental disorders ranging from psychopathic thoughts to suicidal ideation. The majority of those suffering are unaware that they have PTSD, and as a coping mechanism, they often turn to self isolation. Beyond isolation, many veterans with symptomatic PTSD turn to aggression and substance abuse to cope with their internal agony. The most common crimes committed by veterans with PTSD fall into the assault and drug/alcohol abuse categories. Thus, a relationship is established between veteran populations and the criminal justice system. This research aims to define the relationship between PTSD and criminal justice involvement in veterans, explore the mediating factors in this relationship, and analyze numerous court cases in this subject area. Further, it will examine the ways in which crime rates can be reduced for veterans with symptoms of PTSD. This ranges from the improvement of healthcare systems to the implementation of special courts to handle veteran cases. The contribution of this work to the field of forensic psychology will be significant, as it will analyze preexisting case studies and experimental data in an effort to improve the ways in which veteran cases are handled in the criminal justice system. Military personnel involved in the criminal justice system are a vulnerable population in need of healthcare and legislative attention, and this work will bring us one step closer to providing them with just that.

Keywords: forensic psychology, psychotraumatology, PTSD, veterans

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Authors: Ozlem Temiz Arpaci, Meryem Tasci, Hakan Goker

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Benzimidazole, a structural isostere of indol and purine nuclei that can interact with biopolymers, can be identified as master key. So that benzimidazole compounds are important fragments in medicinal chemistry because of their wide range of biological activities including antimicrobial activity. We planned to synthesize some benzimidazole compounds for developing new antimicrobial drug candidates. In this study, we put some heterocyclic rings on second position and an amidine group on the fifth position of benzimidazole ring and synthesized them using a multiple step procedure. For the synthesis of the compounds, as the first step, 4-chloro-3-nitrobenzonitrile was reacted with cyclohexylamine in dimethyl formamide. Imidate esters (compound 2) were then prepared with absolute ethanol saturated with dry HCl gas. These imidate esters which were not too stable were converted to compound 3 by passing ammonia gas through ethanol. At the Pd / C catalyst, the nitro group is reduced to the amine group (compound 4). Finally, various aldehyde derivatives were reacted with sodium metabisulfite addition products to give compound 5-20. Melting points were determined on a Buchi B-540 melting point apparatus in open capillary tubes and are uncorrected. Elemental analyses were done a Leco CHNS 932 elemental analyzer. 1H-NMR and 13C-NMR spectra were recorded on a Varian Mercury 400 MHz spectrometer using DMSO-d6. Mass spectra were acquired on a Waters Micromass ZQ using the ESI(+) method. The structures of them were supported by spectral data. The 1H-NMR, 13C NMR and mass spectra and elemental analysis results agree with those of the proposed structures. Antimicrobial activity studies of the synthesized compounds are under the investigation.

Keywords: benzimidazoles, synthesis, structure elucidation, antimicrobial

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Authors: Li-Te Lin, Chia-Jung Li, Kuan-Hao Tsui

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Cuproptosis, a newly identified cell death mechanism, has attracted attention for its association with various diseases. However, the genetic interplay between cuproptosis and ovarian aging remains largely unexplored. This study aims to address this gap by analyzing datasets related to ovarian aging and cuproptosis. Spatial transcriptome analyses were conducted in the ovaries of both young and aged female mice to elucidate the role of FDX1. Comprehensive bioinformatics analyses, facilitated by R software, identified FDX1 as a potential cuproptosis-related gene with implications for ovarian aging. Clinical infertility biopsies were examined to validate these findings, showing consistent results in elderly infertile patients. Furthermore, pharmacogenomic analyses of ovarian cell lines explored the intricate association between FDX1 expression levels and sensitivity to specific small molecule drugs. Spatial transcriptome analyses revealed a significant reduction in FDX1 expression in aging ovaries, supported by consistent findings in biopsies from elderly infertile patients. Pharmacogenomic investigations indicated that modulating FDX1 could influence drug responses in ovarian-related therapies. This study pioneers the identification of FDX1 as a cuproptosis-related gene linked to ovarian aging. These findings not only contribute to understanding the mechanisms of ovarian aging but also position FDX1 as a potential diagnostic biomarker and therapeutic target. Further research may establish FDX1's pivotal role in advancing precision medicine and therapies for ovarian-related conditions.

Keywords: cuproptosis, FDX1, ovarian aging, biomarker

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Authors: Lydie Audrey Amboua Schouame, Sylvie Kwedi Nolna, Antoine Socpa, Alexandre Benjamin Nkoum

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Background: Despite the struggle of the Cameroonian Ministry of Public Health against informal health centers (IHCs) because of their illegality, IHCs are booming in Cameroon and a large part of the population uses them. In 2017, more than 3.000 IHCs were counted across the country. Most of these IHCs have antenatal clinics and they screen pregnant women for HIV. However, there is no data on the Prevention of Mother-To-Child Transmission of HIV (PMTCT) in this informal health sector in Cameroon. This study aimed to investigate the initiation of Antiretroviral treatment (ART) in pregnant women screened HIV positive in IHCs and associated factors. Methods: From January 01, 2018, to June 30, 2020, we carried out a cohort study of pregnant women attending their first antenatal visit and screened HIV positive in informal health centers in the cities of Douala and Ebolowa in Cameroon. Consenting participants were interviewed at two points: at least one week after delivery of the HIV result and three months later. The collected data were entered into Kobo collected and analyzed in SPSS V23.0 software. Results: A total of 182 HIV-infected pregnant women were enrolled in the study. The median age at enrollment was 30 years (IQR, 24-34) and the median gestational age at first ANC was 25 weeks (IQR, 19-31). Overall 61% (111/182) had a secondary level of education, 65% (118/182) were married/in a common-law relationship and 69% (126/182) had no income activity. At their first ANC, 91% (166/182) were naïve to ARV treatment. Among them, only 45% (74/166) initiated ART. The median delay in initiating ARV treatment was 5 days (IQR, 0-25). Of those who have started ART, only 64% (48/74) remained on treatment 3 months later. Conclusion: In order to eliminate mother-to-child transmission of HIV, attention should be paid to IHCs.

Keywords: informal health centers, human immunodeficiency, antiretroviral treatment, pregnant women

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Authors: Shekher Kummari, V. Sunil Kumar, K. Vengatajalabathy Gobi

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A simple, cost-effective, reusable and reagent-free electrochemical biosensor is developed with functionalized multiwall carbon nanotube paste electrode (f-CNTPE) for the sensitive and selective determination of the important chemotherapeutic drug methotrexate (MTX), which is widely used for the treatment of various cancer and autoimmune diseases. The electrochemical response of the fabricated electrode towards the detection of MTX is examined by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV). CV studies have shown that f-CNTPE electrode system exhibited an excellent electrocatalytic activity towards the oxidation of MTX in phosphate buffer (0.2 M) compared with a conventional carbon paste electrode (CPE). The oxidation peak current is enhanced by nearly two times in magnitude. Applying the DPV method under optimized conditions, a linear calibration plot is achieved over a wide range of concentration from 4.0×10⁻⁷ M to 5.5×10⁻⁶ M with the detection limit 1.6×10⁻⁷ M. further, by applying the SWV method a parabolic calibration plot was achieved starting from a very low concentration of 1.0×10⁻⁸ M, and the sensor could detect as low as 2.9×10⁻⁹ M MTX in 10 s and 10 nM were detected in steady state current-time analysis. The f-CNTPE shows very good selectivity towards the specific recognition of MTX in the presence of important biological interference. The electrochemical biosensor detects MTX in-vitro directly from pharmaceutical sample, undiluted urine and human blood serum samples at a concentration range 5.0×10⁻⁷ M with good recovery limits.

Keywords: amperometry, electrochemical detection, human blood serum, methotrexate, MWCNT, SWV

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Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante

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Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.

Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane

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Authors: Mardi Falck, André Theron

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Traffic congestion on the Northern side of Table Bay is a major problem. In Gauteng, the implementation of the Gautrain between Pretoria and Johannesburg, solved their traffic congestion. In 2002 two entrepreneurs endeavoured to implement a hovercraft ferry service across the bay from Table View to the Port of Cape Town. However, the EIA process proved that disgruntled residents from the area did not agree with their location for a launch site. 17 years later the traffic problem has not gone away, but instead the congestion has increased. While property prices in the City Bowl of Cape Town are ever increasing, people tend to live more on the outskirts of the CBD and commute to work. This means more vehicles on the road every day and the public transport services cannot keep up with the demand. For this reason, the study area of the previous hovercraft plans is being extended further North. The study’s aim is thus to determine the feasibility of a launch site North of Bloubergstrand to launch and receive a public transport ferry across Table Bay. The feasibility is being established by researching ferry services across the world and on what makes them successful. Different types of ferries and their operational capacities in terms of weather and waves are researched and by establishing the offshore and nearshore wind and wave climate for the area, an appropriate protected launch site is determined. It was concluded that travel time could potentially be halved. A hovercraft proved to be the most feasible ferry type, because it does not require a conventional harbour. Other types of vessels require a protected launch site because of the wave climate. This means large breakwaters that influence the cost substantially. The Melkbos Cultural Centre proved to be the most viable option for the location of the launch site, because it already has buildings and infrastructure. It is recommended that, if a harbour is chosen for the proposed ferry service, it could be used for more services like fishing, eco-tourism and leisure. Further studies are recommended to optimise the feasibility of such a harbour.

Keywords: Cape Town, ferry, public, Table Bay

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Authors: Samir Kumar Pal

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Background: Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. Uncontrolled hyperbilirubinemia is a potential problem in developing countries, including India, because of the lack of reliable healthcare institutes for conventional phototherapy. In India, most of the rural subjects duel in the exchange limit during transport, leading to a risk of kernicterus when they arrive at the treatment centre. Thus, an alternative pharmaceutical agent is needed for the hours. Objective: Exploration of a distinct therapeutic strategy for the control of neonatal hyperbilirubinemia compared to conventional phototherapy in a clinical setting. Method: We synthesized, characterized and investigated a spinel-structured Manganese citrate nanocomplex (C-Mn₃O₄ NC, the nanodrug) along with conventional phototherapy in neonatal subjects. We have also observed BIND scores in order to assess neurological dysfunctions. Results: Our observational study clearly reveals that the rate of declination of bilirubin in neonatal subjects with nanodrug oral administration and phototherapy is faster compared to that in the case of phototherapy only. The associated neural dysfunctions were also found to be significantly lower in the case of combined therapy. Conclusion: This study demonstrates that combined therapy works better than conventional phototherapy only for the control of hyperbilirubinemia. We have observed that a significant portion of neonatal subjects requiring blood exchange has been prevented with the combined therapeutic strategy. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemo preventive approach to clinical settings.

Keywords: nanodrug, nanoparticle, Neonatal hyperbilirubinemia, alternative to phototherapy, redox modulation, redox medicine

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Authors: M. Sangeetha, D. Chamundeeswari, C. Saravanababu, C. Rose, V. Gopal

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Rheumatoid arthritis (RA) is a chronic, progressive, systemic inflammatory disorder affecting the synovial joints and typically producing symmetrical arthritis that leads to joint destruction, which is responsible for the deformity and disability. Despite improvements in the treatment of RA over the past decade, there still is a need for new therapeutic agents that are efficacious, less expensive, and free of severe adverse reactions. The present study aimed to investigate role of inflammatory markers in arthritic rats treated with ethanolic bark extract of Albizia procera. The protective effect of ethanolic bark extract of Albizia procera against complete Freund’s adjuvant (CFA) induced arthritis in rats. Arthritis was induced by an intradermal injection of 0.1 ml FCA in the foot pad of left hind limb of rats. ETBE (100 and 200 mg/kg b.wt./p.o) and the reference drug diclofenac (25 mg/kg b.wt./p.o) were administered to arthritic rats. Paw volume was measured for all the animals before inducing arthritis and thereafter once in seven days by using plethysmometer for 42 days. Gene expression of inflammatory markers such as IL-1β and IL-10 were investigated in paw tissues. Up regulation of IL-1β and Down regulation IL-10 were observed in CFA injected rats when compared to normal rats. ETBE attenuated these alterations dose dependently when compared to the vehicle treated rats. These results provide insights into the mechanism of anti-arthritic activity, and unravel potential therapeutic use of Albizia procera in arthritis.

Keywords: CFA-Complete Freund’s adjuvant, ETBE – ethanolic bark extract, IL- interleukins, RA-rheumatoid arthritis

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Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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Authors: Yamina Boukari, Nashiru Billa, Andrew Morris, Stephen Doughty, Kevin Shakesheff

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Poly (lactic-co-glycolic) acid (PLGA) is a synthetic polymer that can be used in bone tissue engineering with the aim of creating a scaffold in order to support the growth of cells. The formation of microspheres from this polymer is an attractive strategy that would allow for the development of an injectable system, hence avoiding invasive surgical procedures. The aim of this study was to develop a microsphere delivery system for use as an injectable scaffold in bone tissue engineering and evaluate various formulation parameters on its properties. Porous and lysozyme-containing PLGA microspheres were prepared using the double emulsion solvent evaporation method from various molecular weights (MW). Scaffolds were formed by sintering to contain 1 -3mg of lysozyme per gram of scaffold. The mechanical and physical properties of the scaffolds were assessed along with the release of lysozyme, which was used as a model protein. The MW of PLGA was found to have an influence on microsphere size during fabrication, with increased MW leading to an increased microsphere diameter. An inversely proportional relationship was displayed between PLGA MW and mechanical strength of formed scaffolds across loadings for low, intermediate and high MW respectively. Lysozyme release from both microspheres and formed scaffolds showed an initial burst release phase, with both microspheres and scaffolds fabricated using high MW PLGA showing the lowest protein release. Following the initial burst phase, the profiles for each MW followed a similar slow release over 30 days. Overall, the results of this study demonstrate that lysozyme can be successfully incorporated into porous PLGA scaffolds and released over 30 days in vitro, and that varying the MW of the PLGA can be used as a method of altering the physical properties of the resulting scaffolds.

Keywords: bone, microspheres, PLGA, tissue engineering

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Authors: G. Martino, F. Silva, E. Marchal

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The control over delivered iron ore blend characteristics is one of the most important aspects of the mining business. The iron ore price is a function of its composition, which is the outcome of the beneficiation process. So, end-to-end integrated planning of mine operations can reduce risks of penalties on the iron ore price. In a standard iron mining company, the production chain is composed of mining, ore beneficiation, and client supply. When mine planning and client supply decisions are made uncoordinated, the beneficiation plant struggles to deliver the best blend possible. Technological improvements in several fields allowed bridging the gap between departments and boosting integrated decision-making processes. Clusterization and classification algorithms over historical production data generate reasonable previsions for quality and volume of iron ore produced for each pile of run-of-mine (ROM) processed. Mathematical modeling can use those deterministic relations to propose iron ore blends that better-fit specifications within a delivery schedule. Additionally, a model capable of representing the whole production chain can clearly compare the overall impact of different decisions in the process. This study shows how flexibilization combined with a planning optimization model between the mine and the ore beneficiation processes can reduce risks of out of specification deliveries. The model capabilities are illustrated on a hypothetical iron ore mine with magnetic separation process. Finally, this study shows ways of cost reduction or profit increase by optimizing process indicators across the production chain and integrating the different plannings with the sales decisions.

Keywords: clusterization and classification algorithms, integrated planning, mathematical modeling, optimization, penalty minimization

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Authors: Benchouala Amira, Bojic Clement, Poupin Pascal, Cossu Leguille-carole

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The objective of this study is to evaluate in vitro the cytotoxic and androgenic potential of several antifungal molecules (amphotericin B, econazole, ketoconazole and miconazole) on MDA-Kb2 cell lines. This biological model is an effective tool for the detection of endocrine disruptors because it responds well to the main agonist of the androgen receptor (testosterone) and also to an antagonist: flutamide. The cytotoxicity of each chemical compound tested was measured using an MTT assay (tetrazolium salt, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) which measures the activity of the reductase function of mitochondrial succinate dehydrogenase enzymes of cultured cells. This complementary cytotoxicity test is essential to ensure that the effects of reduction in luminescence intensity observed during androgenic tests are only attributable to the anti-androgenic action of the compounds tested and not to their possible cytotoxic properties. Tests of the androgenic activity of antifungals show that these compounds do not have the capacity to induce transcription of the luciferase gene. These compounds do not exert an androgenic effect on MDA-Kb2 cells in culture for the environmental concentrations tested. The addition of flutamide for the same tested concentrations of antifungal molecules reduces the luminescence induced by amphotericin B, econazole and miconazole, which is explained by a strong interaction of these molecules with flutamide which may have a greater toxic effect than when tested alone. The cytotoxicity test shows that econazole and ketoconazole can cause cell death at certain concentrations tested. This cell mortality is perhaps induced by a direct or indirect action on deoxyribonucleic acid (DNA), ribonucleic acid (RNA) or proteins necessary for cell division.

Keywords: cytotoxicity, androgenic potential, antifungals, MDA-Kb2

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Authors: Minna K. Miller, Chantel. E. Canessa, Suzanna V. McRae, Susan Shumay, Alissa Collingridge

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Primary care provides the first point of contact and access to health care services. For the pediatric population, the goal is to help healthy children stay healthy and to help those that are sick get better. Primary care facilitates regular well baby/child visits; health promotion and disease prevention; investigation, diagnosis and management of acute and chronic illnesses; health education; both consultation and collaboration with, and referral to other health care professionals. There is a protective association between regular well-child visit care and preventable hospitalization. Further, low adherence to well-child care and poor continuity of care are independently associated with increased risk of hospitalization. With a declining number of family physicians caring for children, and only a portion of pediatricians providing primary care services, it is becoming increasingly difficult for children and their families to access primary care. Nurse practitioners are in a unique position to improve access to primary care and improve health outcomes for children. Limited literature is available on the nurse practitioner role in primary care pediatrics. The purpose of this paper is to describe the development, implementation and evaluation of a Nurse Practitioner-led pediatric primary care clinic in a tertiary care setting. Utilizing the participatory, evidence-based, patient-focused process for advanced practice nursing (PEPPA framework), this paper highlights the results of the initial needs assessment/gap analysis, the new service delivery model, populations served, and outcome measures.

Keywords: access, health outcomes, nurse practitioner, pediatric primary care, PEPPA framework

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Authors: Ibrahim Iddrisu, Joseph Ayariga, Junhuan Xu, Ayomide Adebanjo, Boakai K. Robertson, Michelle Samuel-Foo, Olufemi Ajayi

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The rise of antimicrobial resistance is a global public health crisis that threatens the effective control and prevention of infections. Due to the emergence of pan drug-resistant bacteria, most antibiotics have lost their efficacy. Bacteriophages or their components are known to target bacterial cell walls, cell membranes, and lipopolysaccharides (LPS) and hydrolyze them. Bacteriophages, being the natural predators of pathogenic bacteria, are inevitably categorized as ‘human friends’, thus fulfilling the adage that ‘the enemy of my enemy is my friend’. Leveraging on their lethal capabilities against pathogenic bacteria, researchers are searching for more ways to overcome the current antibiotic resistance challenge. In this study, we expressed and purified epsilon 34 phage tail spike protein (E34 TSP) from the E34 TSP gene, then assessed the ability of this bacteriophage protein in the killing of two CBD-resistant strains of Salmonella spp. We also assessed the ability of the tail spike protein to cause bacteria membrane disruption and dehydrogenase depletion. We observed that the combined treatment of CBD-resistant strains of Salmonella with CBD and E34 TSP showed poor killing ability, whereas the mono treatment with E34 TSP showed considerably higher killing efficiency. This study demonstrates that the inhibition of the bacteria by E34 TSP was due in part to membrane disruption and dehydrogenase inactivation by the protein. The results of this work provide an interesting background to highlight the crucial role phage proteins such as E34 TSP could play in pathogenic bacterial control.

Keywords: cannabidiol, resistance, Salmonella, antimicrobials, phages

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Authors: Hamed Nafar, Sajad Rezaei, Hamid Behbahani

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Safety analysis of the roads through the accident rates which is one of the widely used tools has been resulted from the direct exposure method which is based on the ratio of the vehicle-kilometers traveled and vehicle-travel time. However, due to some fundamental flaws in its theories and difficulties in gaining access to the data required such as traffic volume, distance and duration of the trip, and various problems in determining the exposure in a specific time, place, and individual categories, there is a need for an algorithm for prioritizing the road safety so that with a new exposure method, the problems of the previous approaches would be resolved. In this way, an efficient application may lead to have more realistic comparisons and the new method would be applicable to a wider range of time, place, and individual categories. Therefore, an algorithm was introduced to prioritize the safety of roads using the quasi-induced exposure method and utilizing the analytical hierarchy process. For this research, 11 provinces of Iran were chosen as case study locations. A rural accidents database was created for these provinces, the validity of quasi-induced exposure method for Iran’s accidents database was explored, and the involvement ratio for different characteristics of the drivers and the vehicles was measured. Results showed that the quasi-induced exposure method was valid in determining the real exposure in the provinces under study. Results also showed a significant difference in the prioritization based on the new and traditional approaches. This difference mostly would stem from the perspective of the quasi-induced exposure method in determining the exposure, opinion of experts, and the quantity of accidents data. Overall, the results for this research showed that prioritization based on the new approach is more comprehensive and reliable compared to the prioritization in the traditional approach which is dependent on various parameters including the driver-vehicle characteristics.

Keywords: road safety, prioritizing, Quasi-induced exposure, Analytical Hierarchy Process

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Authors: Sushil Kumar Singh, Ashok Kumar, Ankit Ganeshpurkar, Ravi Singh, Devendra Kumar

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In spectrum of neurodegenerative diseases, Alzheimer’s disease (AD) is characterized by the presence of amyloid β plaques and neurofibrillary tangles in the brain. It results in cognitive and memory impairment due to loss of cholinergic neurons, which is considered to be one of the contributing factors. Donepezil, an acetylcholinesterase (AChE) inhibitor which also inhibits butyrylcholinesterase (BuChE) and improves the memory and brain’s cognitive functions, is the most successful and prescribed drug to treat the symptoms of AD. The present work is based on designing of the selective BuChE inhibitors using computational techniques. In this work, machine learning models were trained using classification algorithms followed by screening of diverse chemical library of compounds. The various molecular modelling and simulation techniques were used to obtain the virtual hits. The amide derivatives of 4-(phenylsulfonamido) benzoic acid were synthesized and characterized using 1H & 13C NMR, FTIR and mass spectrometry. The enzyme inhibition assays were performed on equine plasma BuChE and electric eel’s AChE by method developed by Ellman et al. Compounds 31, 34, 37, 42, 49, 52 and 54 were found to be active against equine BuChE. N-(2-chlorophenyl)-4-(phenylsulfonamido)benzamide and N-(2-bromophenyl)-4-(phenylsulfonamido)benzamide (compounds 34 and 37) displayed IC50 of 61.32 ± 7.21 and 42.64 ± 2.17 nM against equine plasma BuChE. Ortho-substituted derivatives were more active against BuChE. Further, the ortho-halogen and ortho-alkyl substituted derivatives were found to be most active among all with minimal AChE inhibition. The compounds were selective toward BuChE.

Keywords: Alzheimer disease, butyrylcholinesterase, machine learning, sulfonamides

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Authors: H. Aldewachi, M. Hines, M. McCulloch, N. Woodroofe, P. Gardiner

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DPP-IV is an enzyme whose expression is affected in a variety of diseases, therefore, has been identified as possible diagnostic or prognostic marker for various tumours, immunological, inflammatory, neuroendocrine, and viral diseases. Recently, DPP-IV enzyme has been identified as a novel target for type II diabetes treatment where the enzyme is involved. There is, therefore, a need to develop sensitive and specific methods that can be easily deployed for the screening of the enzyme either as a tool for drug screening or disease marker in biological samples. A variety of assays have been introduced for the determination of DPP-IV enzyme activity using chromogenic and fluorogenic substrates, nevertheless these assays either lack the required sensitivity especially in inhibited enzyme samples or displays low water solubility implying difficulty for use in vivo samples in addition to labour and time-consuming sample preparation. In this study, novel strategies based on exploiting the high extinction coefficient of gold nanoparticles (GNPs) are investigated in order to develop fast, specific and reliable enzymatic assay by investigating synthetic peptide sequences containing a DPP IV cleavage site and coupling them to GNPs. The DPP IV could be detected by colorimetric response of peptide capped GNPs (P-GNPS) that could be monitored by a UV-visible spectrophotometer or even naked eyes, and the detection limit could reach 0.01 unit/ml. The P-GNPs, when subjected to DPP IV, showed excellent selectivity compared to other proteins (thrombin and human serum albumin) , which led to prominent colour change. This provided a simple and effective colorimetric sensor for on-site and real-time detection of DPP IV.

Keywords: gold nanoparticles, synthetic peptides, colorimetric detection, DPP-IV enzyme

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Authors: Kavian Khosravinia, Mohd Khair Hassan, Ribhan Zafira Abdul Rahman, Syed Abdul Rahman Al-Haddad

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The CAN (controller area network) bus is introduced as a multi-master, message broadcast system. The messages sent on the CAN are used to communicate state information, referred as a signal between different ECUs, which provides data consistency in every node of the system. OBD-II Dongles that are based on request and response method is the wide-spread solution for extracting sensor data from cars among researchers. Unfortunately, most of the past researches do not consider resolution and quantity of their input data extracted through OBD-II technology. The maximum feasible scan rate is only 9 queries per second which provide 8 data points per second with using ELM327 as well-known OBD-II dongle. This study aims to develop and design a programmable, and latency-sensitive vehicle data acquisition system that improves the modularity and flexibility to extract exact, trustworthy, and fresh car sensor data with higher frequency rates. Furthermore, the researcher must break apart, thoroughly inspect, and observe the internal network of the vehicle, which may cause severe damages to the expensive ECUs of the vehicle due to intrinsic vulnerabilities of the CAN bus during initial research. Desired sensors data were collected from various vehicles utilizing Raspberry Pi3 as computing and processing unit with using OBD (request-response) and direct CAN method at the same time. Two types of data were collected for this study. The first, CAN bus frame data that illustrates data collected for each line of hex data sent from an ECU and the second type is the OBD data that represents some limited data that is requested from ECU under standard condition. The proposed system is reconfigurable, human-readable and multi-task telematics device that can be fitted into any vehicle with minimum effort and minimum time lag in the data extraction process. The standard operational procedure experimental vehicle network test bench is developed and can be used for future vehicle network testing experiment.

Keywords: CAN bus, OBD-II, vehicle data acquisition, connected cars, telemetry, Raspberry Pi3

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Authors: N. Lakshmipathy, Ch. S. N. Murthy, M. Aruna

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The design of lighting systems for surface mines is not an easy task because of the unique environment and work procedures encountered in the mines. The primary objective of this paper is to identify the major problems encountered in mine lighting application and to provide guidance in the solution of these problems. In the surface mining reflectance of surrounding surfaces is one of the important factors, which improve the vision, in the night hours. But due to typical working nature in the mines it is very difficult to fulfill these requirements, and also the orientation of the light at work site is a challenging task. Due to this reason machine operator and other workers in a mine need to be able to orient themselves in a difficult visual environment. The haul roads always keep on changing to tune with the mining activity. Other critical area such as dumpyards, stackyards etc. also change their phase with time, and it is difficult to illuminate such areas. Mining is a hazardous occupation, with workers exposed to adverse conditions; apart from the need for hard physical labor, there is exposure to stress and environmental pollutants like dust, noise, heat, vibration, poor illumination, radiation, etc. Visibility is restricted when operating load haul dumper and Heavy Earth Moving Machinery (HEMM) vehicles resulting in a number of serious accidents. one of the leading causes of these accidents is the inability of the equipment operator to see clearly people, objects or hazards around the machine. Results indicate blind spots are caused primarily by posts, the back of the operator's cab, and by lights and light brackets. The careful designed and implemented, lighting systems provide mine workers improved visibility and contribute to improved safety, productivity and morale. Properly designed lighting systems can improve visibility and safety during working in the opencast mines.

Keywords: contrast, efficacy, illuminance, illumination, light, luminaire, luminance, reflectance, visibility

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Authors: Damilola Mofikoya

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Developed countries account for a large proportion of greenhouse gas emissions. In the last decade, countries including the United States and China have made a commitment to cut down carbon emissions by signing the Paris Climate Agreement. However, carbon neutrality is a challenging issue to tackle at the country level because of the scale of the problem. To overcome this challenge, cities are at the forefront of these efforts. Many cities in the United States are taking strategic actions and proposing programs and initiatives focused on renewable energy, green transportation, less use of fossil fuel vehicles, etc. There have been concerns about the implications of those strategies and a lack of community engagement. This paper is focused on community-based efforts that help actualize the reduction of carbon footprint through sustained and inclusive action. Existing zero-carbon assessment tools are examined to understand variables and indicators associated with the zero-carbon goals. Based on a broad, systematic review of literature on community strategies, and existing zero-carbon assessment tools, a dashboard was developed to help simplify and demystify carbon neutrality goals at a community level. The literature was able to shed light on the key contributing factors responsible for the success of community efforts in carbon neutrality. Stakeholder education is discussed as one of the strategies to help communities take action and generate momentum. The community-based efforts involving individuals and residents, such as reduction of food wastages, shopping preferences, transit mode choices, and healthy diets, play an important role in the context of zero-carbon initiatives. The proposed community-based dashboard will emphasize the importance of sustained, structured, and collective efforts at a communal scale. Finally, the present study discusses the relationship between life expectancy and quality of life and how it affects carbon neutrality in communities.

Keywords: carbon footprint, communities, life expectancy, quality of life

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Authors: Natasha Botha, Gary Corderely, Helen M. Inglis

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With the move to cleaner energy applications the transport industry is working towards on-board hydrogen, or compressed natural gas-fuelled vehicles. A popular method for storage is to use composite overwrapped pressure vessels (COPV) because of their high strength to weight ratios. The proper design of these COPVs are according to international standards; this study aims to provide a preliminary design for a 350 Bar Type IV COPV (i.e. a polymer liner with a composite overwrap). Netting analysis, a popular analytical approach, is used as a first step to generate an initial design concept for the composite winding. This design is further improved upon by following the American Society of Mechanical Engineers (ASME) Boiler and Pressure Vessel standards, Section X: Fibre-reinforced composite pressure vessels. A design program based on these two approaches is developed using Python. A numerical model of a burst test simulation is developed based on the two approaches and compared. The results indicate that the netting analysis provides a good preliminary design, while the ASME-based design is more robust and accurate as it includes a better approximation of the material behaviour. Netting analysis is an easy method to follow when considering an initial concept design for the composite winding when not all the material characteristics are known. Once these characteristics have been fully defined with experimental testing, an ASME-based design should always be followed to ensure that all designs conform to international standards and practices. Future work entails more detailed numerical testing of the design for improvement, this will include the boss design. Once finalised prototype manufacturing and experimental testing will be conducted, and the results used to improve on the COPV design.

Keywords: composite overwrapped pressure vessel, netting analysis, design, American Society of Mechanical Engineers section x, fiber-reinforced, hydrogen storage

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Authors: Johannes Dregger, Michael Schmidt, Christian Prasse, Michael ten Hompel

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Most of the today’s companies face increasing need to operate efficiently. Driven by global trends like shorter product cycles, mass customization and the rising speed of delivery, manufacturing value chains are becoming more and more distributed. Manufacturing processes are becoming highly integrated, e.g. 3D printing. All these changes are affecting companies´ organization. They are leading towards individual, small scale, and ad-hoc logistics processes and structures, and finally, towards a significant increase in the importance of logistics itself since traditional value chains transform into agile value networks. In the past logistics has been following manufacturing but in the future industry, this role allocation might change. With this increase in the logistics practice of companies and businesses, the relevance of logistics research as the methodological foundation of logistics networks and processes is gaining importance. Logistics research is evolving into a central and highly interdisciplinary science for the future industry. Using the example of Germany, this paper discusses ways to establish logistics as a central scientific discipline of the future industry. About three million people work in the logistics sector in Germany. Only automotive and retail industry have more employees. Even though there is a bunch of logistics degree programs at more than 100 institutions of higher education, a common understanding of logistics as a research discipline is missing. In this paper an innovative approach will be presented, including; identified perspectives on logistics, such as process orientation, IT orientation or employees orientation, relevant scientific disciplines for logistics science, a concept for interdisciplinary research approaches to unify the perspectives of the different scientific disciplines on logistics and the methodological base of logistics science.

Keywords: logistics, logistics science, logistics management, future challenges

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Authors: B. Chandar, M. K. Ramasamy, P. Madasamy

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The discovery and development of newer antibiotics are limited with the increase in resistance of such multi-drug resistant bacteria creating the need for alternative new therapeutic agents. The recently discovered New Delhi Metallo-betalactamase-1 (NDM-1), which confers antibiotic resistance to most of the currently available β-lactams, except colistin and tigecycline, is a global concern. Several antibacterial drugs approved are natural products or their semisynthetic derivatives, but plant extracts remain to be explored to find molecules that are effective against NDM-1 bacteria. Therefore, it is necessary to explore the possibility of finding new and effective antibacterial compounds against NDM-1 bacteria. In the present study, we have screened a diverse set South Indian plant species, and report most plant species as a potential source for antimicrobial compounds against NDM-1 bacteria. Ethanol extracts from the leaves of taxonomically diverse South Indian medicinal plants were screened for antibacterial activity against NDM-1 E. coli using streak plate method. Among the plant screened against NDM-1 E. coli, the ethanol extracts from many plant extracts showed minimum bactericidal concentration between 5 and 15 mg /ml and MIC between 2.54 and 5.12 mg/ml. These extracts also showed a potent synergistic effect when combined with antibiotics colistin and tetracycline. Combretum albidum that was effective was taken for further analysis. At 5mg/L concentration, these extracts inhibited the NDM-1 enzyme in vitro, and residual activity for Combretum albidum was 33.09%. Treatment of NDM-1 E. coli with the extracts disrupted the cell wall integrity and caused 89.7% cell death. The plant extract of Combretum albidum that was effective was subjected to fractionation and the fraction was further subjected to HPLC, LC-MS for identification of antibacterial compound.

Keywords: antibacterial activity, combretum albidum, Escherichia coli, NDM-1

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Authors: D. W. M. S. Samarathunga, Isuru Dharmarathne

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In aphasia, various levels of symbolic language processing (semantics) are affected. It is shown that Persons with Aphasia (PWA) often experience more problems comprehending some categories of words than others. The study aimed to determine lexical semantic deficits seen in Auditory Comprehension (AC) and to describe lexical-semantic deficits across six selected word categories. Thirteen (n =13) persons diagnosed with post-stroke aphasia (PSA) were recruited to perform an AC task. Foods, objects, clothes, vehicles, body parts and animals were selected as the six categories. As the test stimuli, black and white line drawings were adapted from a picture set developed for semantic studies by Snodgrass and Vanderwart. A pilot study was conducted with five (n=5) healthy nonbrain damaged Sinhala speaking adults to decide familiarity and applicability of the test material. In the main study, participants were scored based on the accuracy and number of errors shown. The results indicate similar trends of lexical semantic deficits identified in the literature confirming ‘animals’ to be the easiest category to comprehend. Mann-Whitney U test was performed to determine the association between the selected variables and the participants’ performance on AC task. No statistical significance was found between the errors and the type of aphasia reflecting similar patterns described in aphasia literature in other languages. The current study indicates the presence of selectivity of lexical semantic deficits in AC and a hierarchy was developed based on the complexity of the categories to comprehend by Sinhala speaking PWA, which might be clinically beneficial when improving language skills of Sinhala speaking persons with post-stroke aphasia. However, further studies on aphasia should be conducted with larger samples for a longer period to study deficits in Sinhala and other Sri Lankan languages (Tamil and Malay).

Keywords: aphasia, auditory comprehension, selective lexical-semantic deficits, semantic categories

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Authors: Rajnarayan Damor, Gayatri Swarnakar

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Fasciola gigantica are present in the biliary ducts of liver and gall bladder of domestic buffaloes. They are very harmful and causes significant lose to live stock owners, on account of poor growth and lower productivity of domestic buffaloes. Synthetic veterinary drugs have been used to eliminate parasites from cattle but these drugs are unaffordable and inaccessible for poor cattle farmers. The in vitro anthelmintic effect of Citrullus colocynthis fruit extract against Fasciola gigantica parasites were observed by light and scanning electron microscopy. Fruit extracts of C. colocynthis exhibit highest mortality 100% at 50 mg/ml in 15th hour of exposure. The oral and ventral sucker appeared to be slightly more swollen than control and synthetic drug albendazole. The tegument showed submerged spines by the swollen tegument around them. The tegument of the middle region showed deep furrows, folding and submerged spines which either lied very flat against the surface or had become submerged in the tegument by the swollen tegument around them leaving deep furrows. Posterior region showed with deep folding in the tegument, completely disappearance of spines and swelling of the tegument led to completely submerged spines leaving spine socket. The present study revealed that fruit extracts of Citrullus colocynthis found to be potential sources for novel anthelmintic and justify their ethno-veterinary use.

Keywords: anthelmintic, buffalo, Citrullus colocynthis, Fasciola gigantica, mortality, tegument

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Authors: Fisseha Shiferie (Bpharm, Mpharm)

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Diarrhea is a common gastrointestinal disorder characterized by an increase in stool frequency and a change in stool consistency. Inspite of the availability of many drugs as antidiarrheal agents, the search for a drug with affordable cost and better efficacy is essential to overcome diarrheal problems. The root extract of Echinops kebericho, is used by traditional practitioners for the treatment of diarrhea. However, the scientific basis for this usage has not been yet established. The purpose of the present study was to evaluate the antidiarrheal and spasmolytic activities of the aqueous extract of the roots of E. kebericho in rodents and isolated guinea-pig ileum preparations. In the castor oil induced intestinal transit test, E. kebericho produced a significant (p < 0.01) dose dependent decrease in propulsion with peristaltic index values of 45.05±3.3, 42.71±2.25 and 33.17±3.3%, respectively at doses of 100, 200 and 400 mg/kg compared with 63.43±7.3% for control. In the castor oil-induced diarrhea test, the mean defecation was reduced from 1.81±0.18 to 0.99 ± 0.21 compared with 2.59 ±0.81 for control. The extract (at doses stated above) significantly decreased the volume of intestinal fluid secretion induced by castor oil (2.31±0.1 to 2.01±0.2) in relation to 3.28±0.3 for control. When tested on a guinea-pig ileum, root extract of Echinops kebericho exhibited a dose dependent spasmolytic effect, 23.07 % being its highest inhibitory effect. The results obtained in this study give some scientific support to the use of Echinops kebericho as an antidiarrheal agent due to its inhibitory effects on the different diarrheal parameters used in this study.

Keywords: antidiarrheal activity, E. kebericho, traditional medicine, diarrhea, enteropooling, and intestinal transit

Procedia PDF Downloads 299

Authors: Nyasha Agnes Gurira, Patrick Ngulube

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Heritage as an asset can be used to achieve cultural and socio-economic development through its careful use as a tourist attraction. Cultural heritage sites, especially those listed as World Heritage sites generate a lot of revenue through their use as tourist attractions. According to article 5(a) of the World Heritage Convention, World Heritage Sites (WHS) must serve a function in the life of the communities. This is further stressed by the International Council on Monuments and Sites (ICOMOS) charter on cultural heritage tourism which recognizes the positive effects of tourism on cultural heritage and underlines that domestic and international tourism is among the foremost vehicles for cultural exchange, conservation should thus provide for responsible and well-managed opportunities for local communities. The inclusion of communities in the world heritage agenda identifies them as the owners of the heritage and partners in the management planning process. This reiterates the need to empower communities and enable them to participate in the decisions which relate to the use of their heritage divorcing from the ideals of viewing communities as beneficiaries from the heritage resource. It recognizes community ownership rights to cultural heritage an element enshrined in Zimbabwe’ national constitution. Through the use of contingency valuation approaches, by assessing the Willingness to pay for visitors at the site the research determined the tourism use value of Great Zimbabwe (WHS). It assessed the extent to which the communities at Great Zimbabwe (WHS) have been developed through the tourism use of the WHS. Findings show that the current management mechanism in place regards communities as stakeholders in the management of the WHS, their ownership and property rights are not fully recognized. They receive indirect benefits from the tourism use of the WHS. This paper calls for a shift in management approach where community ownership rights are fully recognized and more inclusive approaches are adopted to ensure that the goal of sustainable development is achieved. Pro-poor benefits of tourism are key to enhancing the livelihoods of communities and can only be achieved if their rights are recognized and respected.

Keywords: communities, cultural heritage tourism, development, property ownership rights, pro-poor benefits, sustainability, world heritage site

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Authors: Fatma Abdel Moneim Al Tawil

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This study was undertaken to evaluate an educational program regarding scientific writing and presentation skills among university students. This interventional study used a one-group, pretest/posttest design and was conducted in Al Jouf University among four colleges in Saudi Arabia. Baseline students’ assessment was conducted for developing educational program. Interventional, one group, pretest/posttest study was designed to evaluate the effectiveness of the educational program. Three parts evaluation sheet with total scores of 30 was used for 113 students for the development of the program and 52 students for test pretest phase. Wilcoxon signed ranks showed statistically significant improvement in the combined overall program skills score from a median of 56.7 pre to a median of 86.7 post, (z = 6.231, p < 0.001). When compared to preprogram intervention, post interventions 51.9 % of students achieve excellent performance. While pre intervention no students (0.0 %) achieve this score. Regarding to scientific writing skills, Wilcoxon signed ranks showed statistically significant improvement in the score from a median of 60 pre to a median of 90 post, (z = 6.122, p < 0.001). None of students had excellent performance changed to 73.1%. Regarding to oral presentation skills, Wilcoxon signed ranks showed statistically significant improvement in the score from a median of 50 pre to a median of 80 post, (z = 6.153, p < 0.001). None of students had excellent performance changed to 48.1%. Such educational program needs to be incorporated into classroom delivery of the students’ curriculum. Scientific writing skills book needed to be developed to be recommended as a basic educational strategy for all university faculties.

Keywords: scientific writing, presentation skills, university students, educational program

Procedia PDF Downloads 431