Search results for: disease development

Authors: Dar-Bin Shieh, Gwo-Bin Lee, Chen-Ming Chang, Chen Sheng Yeh, Chih-Chia Huang, Tsung-Ju Li

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Mitochondrial defects have a significant impact in many human diseases and aging associated phenotypes. The pathogenic mitochondrial DNA (mtDNA) mutations are diverse and usually present as heteroplasmic. mtDNA 4977bps deletion is one of the common mtDNA defects, and the ratio of mutated versus normal copy is significantly associated with clinical symptoms thus their quantitative detection has become an important unmet needs for advanced disease diagnosis and therapeutic guidelines. This study revealed a Micro-electro-mechanical-system (MEMS) enabled automatic microfluidic chip that only required minimal sample. The system integrated multiple laboratory operation steps into a Lab-on-a-Chip for high-sensitive and prompt measurement. The entire process including magnetic nanoparticle based mtDNA extraction in chip, mutation selective photonic DNA cleavage, and nanoparticle accelerated photonic quantitative polymerase chain reaction (qPCR). All subsystems were packed inside a miniature three-dimensional micro structured system and operated in an automatic manner. Integration of magnetic beads with microfluidic transportation could promptly extract and enrich the specific mtDNA. The near infrared responsive magnetic nanoparticles enabled micro-PCR to be operated by pulse-width-modulation controlled laser pulsing to amplify the desired mtDNA while quantified by fluorescence intensity captured by a complementary metal oxide system array detector. The proportions of pathogenic mtDNA in total DNA were thus obtained. Micro capillary electrophoresis module was used to analyze the amplicone products. In conclusion, this study demonstrated a new magnetophotonic based qPCR MEMS system that successfully detects and quantify specific disease related DNA mutations thus provides a promising future for rapid diagnosis of mitochondria diseases.

Keywords: mitochondrial DNA, micro-electro-mechanical-system, magnetophotonics, PCR

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Authors: Osifeko Olalekan Remigious, Osifeko Christiana Osikorede, Folarin Bolanle Eunice, Olugbenga Adebola Shodiya

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In this period of economic problem, nations are looking for avenues to improve their economy, preserve their environment and socio-political environment, educational institutions are not left out as there is the need for them to increase their economy and preserve their socio political environment. Sports is one of the ways through which sustainable development can be achieved. The purpose of this study was to examine the barriers to sports participation. A total of 1025 students were purposively selected from all the five schools in the College. A questionnaire which has a reliability coefficient of 0.71 was used for data collection. Data collected were subjected to the descriptive survey research design. Findings showed that facilities, funds and lectures schedule were significant barriers to sports participation. It was recommended that sports facilities should be provided by the Lagos State government.

Keywords: MOCPED sports, sustainable development, sports participation, state government

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Authors: Usha Khatiwada

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Nepal’s overall energy baseline: It has been proposed that hydropower projects for domestic consumption can earn CDM revenue in Nepal if a new methodology is established that takes into account not only consumption in Nepal of grid electricity but also other fuels such as kerosene, diesel, and firewood, used by a vast majority of the population for their lighting and other needs. However, this would mean that we would be trying to combine grid electricity supply and consumers not supplied from the grid into one methodology. Such a sweeping baseline may have a very small chance of success with the CDM Executive Board.

Keywords: environment, clean development mechanism, hydropower, Nepal

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Authors: Lavdosh Lazemetaj

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The labor market in W.B. Countries presents problems and challenges, this is dictated by different risk factors. The levels of unemployment in the region are high and the rates of its reduction are a challenge. This paper presents these challenges and problems that the countries face. of the BP region. The region as a whole and the countries in their particularity are analyzed, according to the specifics, the development trends related to the labor market are looked at. Conclusions are also given that emerge from the analysis of the labor markets prior to the monitoring done by the EU and the World Bank.

Keywords: Economic Development, European Union, Economic Growth, Labor Market

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Authors: Mi Ok Kang

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This study examined the influences of including LGBTQ-related content in a multicultural teacher education course on the development of prospective teachers’ social justice identities. Appling a content analysis to 53 reflection texts written by participating prospective teachers in response to the relevant course content, this study deduced the stages of social justice identity development (naïve, acceptance, resistance, redefinition, and internalization) that participants reached during the course. The analysis demonstrated that the participants reached various stages in the social identity development model and none of the participants remained at the naïve stage during/after class. The majority (53%) of the participants reached the internalization stage during the coursework and became conscious about the heterosexual privileges they have had and aware of possible impacts of such privilege on their future LGBTQ students. Also the participants had begun to develop pedagogic action plans and devised applicable teaching strategies for their future students based on the new understanding of heteronormativity. We expect this study will benefit teacher educators and educational administrators who want to address LGBTQ-related issues in their multicultural education programs and/or revisit the goals, directions, and implications of their approach.

Keywords: LGBTQ, heteronormativity, social justice identity, teacher education, multicultural education, content analysis

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Authors: Eny Syatriana, Ardiansyah

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The purpose of recent study was to develop a learning model on writing, based on the reading texts which will be read by the students using reflection strategy. The strategy would allow the students to read the text and then they would write back the main idea and to develop the text by using their own sentences. So, the writing practice was begun by reading an interesting text, then the students would develop the text which has been read into their writing. The problem questions are (1) what kind of learning model that can develop the students writing ability? (2) what is the achievement of the students of STKIP YPUP through reflection strategy? (3) is the using of the strategy effective to develop students competence In writing? (4) in what level are the students interest toward the using of a strategy In writing subject? This development research consisted of some steps, they are (1) need analysis (2) model design (3) implementation (4) model evaluation. The need analysis was applied through discussion among the writing lecturers to create a learning model for writing subject. To see the effectiveness of the model, an experiment would be delivered for one class. The instrument and learning material would be validated by the experts. In every steps of material development, there was a learning process, where would be validated by an expert. The research used development design. These Principles and procedures or research design and development .This study, researcher would do need analysis, creating prototype, content validation, and limited empiric experiment to the sample. In each steps, there should be an assessment and revision to the drafts before continue to the next steps. The second year, the prototype would be tested empirically to four classes in STKIP YPUP for English department. Implementing the test greatly was done through the action research and followed by evaluation and validation from the experts.

Keywords: learning model, reflection, strategy, reading, writing, development

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Authors: E. M. Mhlongo, E. Lutge

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In 2010, South Africa’s National Department of Health (NDoH) launched national primary health care (PHC) initiative to strengthen health promotion, disease prevention, and early disease detection. The strategy, called Re-engineering Primary Health Care (rPHC), aims to support a preventive and health-promoting community-based PHC model by using community-based outreach teams (known in South Africa as Ward-based Primary Health Care Outreach teams or WBPHCOTs). These teams provide health education, promote healthy behaviors, assess community health needs, manage minor health problems, and support linkages to health services and health facilities. Ward based primary health care outreach teams are supervised by a professional nurse who is the outreach team leader. In South Africa, the WBPHCOTs have been established, registered, and are reporting their activities in the District Health Information System (DHIS). This study explored and described the challenges faced by outreach team leaders in supporting and supervising the WBPHCOTs. Qualitative data were obtained through interviews conducted with the outreach team leaders at a sub-district level. Thematic analysis of data was done. Findings revealed some challenges faced by team leaders in day to day execution of their duties. Issues such as staff shortages, inadequate resources to carry out health promotion activities, and lack of co-operation from team members may undermine the capacity of team leaders to support and supervise the WBPHCOTs. Many community members are under the impression that the outreach team is responsible for bringing the clinic to the community while the outreach teams do not carry any medication/treatment with them when doing home visits. The study further highlights issues around the challenges of WBPHCOTs at a household level. In conclusion, the WBPHCOTs are an important component of National Health Insurance (NHI), and in order for NHI to be optimally implemented, the issues raised in this research should be addressed with some urgency.

Keywords: community health worker, national health insurance, primary health care, ward-based primary health care outreach teams

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Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

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Authors: Elena Bulmer

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The research for this study has found that the formation of alliances for the successful revitalization of the global partnership for sustainable development, as defined by UN Sustainable Development Goal 17, entails considerable difficulty. This study uses for its empirical work marine environmental conservation projects and analyses the potential involvement of nonhuman actors as primordial stakeholders in these types of projects. The idea is to extend the scope of SDG 17 for it to also consider nonhuman subjects in order for it to better achieve its goal. The results of this study may be extrapolated to the business and management fields, which depend on natural resources for the development of their products. In the same way, in these areas, natural resources as nonhuman actors are not present in the stakeholder maps of these projects. Environmental Conservation projects are thus especially interesting to study with regards to their stakeholder context and have been used as the experimental setting for the empirical work of this study. The primordial stakeholders of these projects are not social objects and therefore go beyond the present limits of present stakeholder theory. The study that has been used to analyse this concept is a marine conservation project based in Spain, and to shed light in potential extending the role of the 17th Sustainable Development Goal to include nonhuman beings to be able to better achieve the rest of the SDGs, in this case, SDG 14 whose aim is to promote the conservation and sustainability of the world´s oceans.

Keywords: SDG 17, sustainability, stakeholder management, environmental conservation projects

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Authors: Matthew J. Zagumny

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The QUEST is an assessment of scientific epistemic beliefs and was developed to measure students’ intellectual development in regards to beliefs about knowledge and knowing. The QUEST utilizes Q-sort methodology, which requires participants to rate the degree to which statements describe them personally. As a measure of personal theories of knowledge, the QUEST instrument is described with the Q-sort distribution and scoring explained. A preliminary demonstration of the QUEST assessment is described with two samples of undergraduate students (novice/lower division compared to advanced/upper division students) being assessed and their average QUEST scores compared. The usefulness of an assessment of epistemology is discussed in terms of the principle that assessment tends to drive educational practice and university mission. The critical need for university and academic programs to focus on development of students’ scientific epistemology is briefly discussed.

Keywords: scientific epistemology, critical thinking, Q-sort method, STEM undergraduates

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Authors: Olga V. Chervyakova, Elmira T. Tailakova, Vitaliy M. Strochkov, Kulyaisan T. Sultankulova, Nurlan T. Sandybayev, Lev G. Nemchinov, Rosemarie W. Hammond

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Sheep pox is a highly contagious infection that OIE regards to be one of the most dangerous animal diseases. It causes enormous economic losses because of death and slaughter of infected animals, lower productivity, cost of veterinary and sanitary as well as quarantine measures. To control spread of sheep pox infection the attenuated vaccines are widely used in the Republic of Kazakhstan and other Former Soviet Union countries. In spite of high efficiency of live vaccines, the possible presence of the residual virulence, potential genetic instability restricts their use in disease-free areas that leads to necessity to exploit new approaches in vaccine development involving recombinant DNA technology. Vaccines on the basis of recombinant proteins are the newest generation of prophylactic preparations. The main advantage of these vaccines is their low reactogenicity and this fact makes them widely used in medical and veterinary practice for vaccination of humans and farm animals. The objective of the study is to produce recombinant immunogenic proteins for development of the high-performance means for sheep pox prophylaxis. The SPV proteins were chosen for their homology with the known immunogenic vaccinia virus proteins. Assay of nucleotide and amino acid sequences of the target SPV protein genes. It has been shown that four proteins SPPV060 (ortholog L1), SPPV074 (ortholog H3), SPPV122 (ortholog A33) and SPPV141 (ortholog B5) possess transmembrane domains at N- or C-terminus while in amino acid sequences of SPPV095 (ortholog А 4) and SPPV117 (ortholog А 27) proteins these domains were absent. On the basis of these findings the primers were constructed. Target genes were amplified and subsequently cloned into the expression vector рЕТ26b(+) or рЕТ28b(+). Six constructions (pSPPV060ΔТМ, pSPPV074ΔТМ, pSPPV095, pSPPV117, pSPPV122ΔТМ and pSPPV141ΔТМ) were obtained for expression of the SPV genes under control of T7 promoter in Escherichia coli. To purify and detect recombinant proteins the amino acid sequences were modified by adding six histidine molecules at C-terminus. Induction of gene expression by IPTG was resulted in production of the proteins with molecular weights corresponding to the estimated values for SPPV060, SPPV074, SPPV095, SPPV117, SPPV122 and SPPV141, i.e. 22, 30, 20, 19, 17 and 22 kDa respectively. Optimal protocol of expression for each gene that ensures high yield of the recombinant protein was identified. Assay of cellular lysates by western blotting confirmed expression of the target proteins. Recombinant proteins bind specifically with antibodies to polyhistidine. Moreover all produced proteins are specifically recognized by the serum from experimentally SPV-infected sheep. The recombinant proteins SPPV060, SPPV074, SPPV117, SPPV122 and SPPV141 were also shown to induce formation of antibodies with virus-neutralizing activity. The results of the research will help to develop a new-generation high-performance means for specific sheep pox prophylaxis that is one of key moments in animal health protection. The research was conducted under the International project ISTC # K-1704 “Development of methods to construct recombinant prophylactic means for sheep pox with use of transgenic plants” and under the Grant Project RK MES G.2015/0115RK01983 "Recombinant vaccine for sheep pox prophylaxis".

Keywords: prophylactic preparation, recombinant protein, sheep pox virus, subunit vaccine

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Authors: Kunal Garg, Louise Theusen Hermansan, Kanoktip Puttaraska, Oliver Hendricks, Heidi Pirttinen, Leona Gilbert

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The Germ Theory (one infectious determinant is equal to one disease) has unarguably evolved our capability to diagnose and treat infectious diseases over the years. Nevertheless, the advent of technology, climate change, and volatile human behavior has brought about drastic changes in our environment, leading us to question the relevance of the Germ Theory in our day, i.e. will vector-borne disease (VBD) sufferers produce multiple immune responses when tested for multiple microbes? Vector diseased patients producing multiple immune responses to different microbes would evidently suggest human polymicrobial infections (HPI). Ongoing diagnostic tools are exceedingly unequipped with the current research findings that would aid in diagnosing patients for polymicrobial infections. This shortcoming has caused misdiagnosis at very high rates, consequently diminishing the patient’s quality of life due to inadequate treatment. Equipped with the state-of-art scientific knowledge, PolyScan intends to address the pitfalls in current VBD diagnostics. PolyScan is a multiplex and multifunctional enzyme linked Immunosorbent assay (ELISA) platform that can test for numerous VBD microbes and allow simultaneous screening for multiple types of antibodies. To validate PolyScan, Lyme Borreliosis (LB) and spondyloarthritis (SpA) patient groups (n = 54 each) were tested for Borrelia burgdorferi, Borrelia burgdorferi Round Body (RB), Borrelia afzelii, Borrelia garinii, and Ehrlichia chaffeensis against IgM and IgG antibodies. LB serum samples were obtained from Germany and SpA serum samples were obtained from Denmark under relevant ethical approvals. The SpA group represented chronic LB stage because reactive arthritis (SpA subtype) in the form of Lyme arthritis links to LB. It was hypothesized that patients from both the groups will produce multiple immune responses that as a consequence would evidently suggest HPI. It was also hypothesized that the multiple immune response proportion in SpA patient group would be significantly larger when compared to the LB patient group across both antibodies. It was observed that 26% LB patients and 57% SpA patients produced multiple immune responses in contrast to 33% LB patients and 30% SpA patients that produced solitary immune responses when tested against IgM. Similarly, 52% LB patients and an astounding 73% SpA patients produced multiple immune responses in contrast to 30% LB patients and 8% SpA patients that produced solitary immune responses when tested against IgG. Interestingly, IgM immune dysfunction in both the patient groups was also recorded. Atypically, 6% of the unresponsive 18% LB with IgG antibody was recorded producing multiple immune responses with the IgM antibody. Similarly, 12% of the unresponsive 19% SpA with IgG antibody was recorded producing multiple immune responses with the IgM antibody. Thus, results not only supported hypothesis but also suggested that IgM may atypically prevail longer than IgG. The PolyScan concept will aid clinicians to detect patients for early, persistent, late, polymicrobial, & immune dysfunction conditions linked to different VBD. PolyScan provides a paradigm shift for the VBD diagnostic industry to follow that will drastically shorten patient’s time to receive adequate treatment.

Keywords: diagnostics, immune dysfunction, polymicrobial, TICK-TAG

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Authors: Sabina Garayeva

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To determine the significant risk factors for intrauterine growth restriction (IUGR), we carried out a thorough study of the social status of the parents of children with IUGR. We observed 315 mothers who gave birth to children with (IUGR), of which 172 mothers with asymmetric type and 143 mothers with symmetric type of IUGR. Through a detailed survey was gathered detailed information about education of parents. The results show that the majority of mothers with IUGR had secondary education (44,8 ± 2,8%), and fathers - higher education (35,2 ± 2,7%). Whereas in the control group, the largest number of parents had higher education (mother 35,3 ± 4,4%, fathers 42,9 ± 4,5%). Number of mothers with secondary education with IUGR was significantly (p1 <0,01; χ2 = 22,67) differs from the number of mothers with physiological pregnancy with the same level of education. Meanwhile, in the group with a symmetrical embodiment of IUGR mothers with secondary formation of significantly greater 53,1 ± 4,2%, than the asymmetric embodiment IUGR 37,8 ± 3,7% (p2 <0,05; χ2 = 8 06). Among fathers with secondary education significant difference was noted in the symmetric version of IUGR 37,8 ± 4,1% more than in the control group (p1 <0,05), and among parents of children with asymmetric IUGR option prevailed fathers with higher education - 37 2 ± 3,7%. Thus, our results revealed a low educational level of the mother as a risk factor for IUGR, which further help to develop preventive and therapeutic measures to eliminate the severity of its consequences. As seen from the data presented, mothers of children with asymmetric IUGR had a school education and fathers - higher education, while in the symmetric type of both parents had secondary education. It is found that frequency of children, born with IUGR, of mothers - housewives and fathers, engage in physical labor, was high. Thus, the analysis conducted by the social status of the parents with IUGR revealed a low level of education and unemployed mothers as risk factors for this disease, which in the future will help to develop preventive and therapeutic measures to eliminate the severity of its.

Keywords: intrauterine growth restriction, education of mothers, education influence, IUGR

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Authors: Nony Rahadiva

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The development of housing in urban areas can not be separated from the high rate of population growth from both natural population growth and population growth due to migration. The development is bounded by urban land area so that construction of flats become a development priority. Quality of residential flats are influenced by the patterns of behavior of its inhabitants. The frequency of contact between the occupants become one of the effects of good social relations, but harmful activity can degrade the environment, especially in flats. One of the social relationships that can be seen on the flats development is the residents in Kutobedah flat built in Malang city. Problems that occur in that place is unfavorable flat management due to social activities such as daily activities and also the neighboring activities of apartment dwellers who tend not to pay attention to the environment. Based on these problems we can do a study on social interaction in Kutobedah flat and its influence on the management of flat facilities and infrastructures. This research was carried out by submitting a questionnaire to the residents of the apartment based social activities , operations and maintenance of the flats. By using a weighted analysis, we can find that social interaction tenants is high, but the level of infrastructure and facilities management of the tenants is low so it is needed to counsel the residents how to use and maintain the infrastructure properly.

Keywords: activities, flat, infrastructure management, social interaction

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Authors: Vichai Tienthavorn

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Background: Recently, the patients of non-communicable diseases (NCDs) are increasing in Thailand; especially hypertension and diabetes. Hypertension and Diabetes patients were found to be of 3.7 million in 2008. The varieties of human behaviors have been extensively changed in health. Hence, Thai Government has a policy to reduce NCDs. Generally, primary care plays an important role in treatment using medical process. However, NCDs patients have not been decreased. Objectives: This study not only reduce the patient and mortality rate but also increase the quality of life, could apply in different areas and propose to be the national policy, effectively for a long term operation. Methods: Here we report that primary health care (PHC), which is a primary process to screening, rapidly seek the person's risk. The screening tool of the study was Vichai's 7 color balls model, the medical education tool to transfer knowledge from student health team to community through health volunteers, creating community engagement in terms of social participation. It was found that people in community were realized in their health and they can evaluate the level of risk using this model. Results: Projects implementation (2015) in Nong Lom Health Center in Phayao (target group 15-65 years, 2529); screening hypertension coveraged 99.01%, risk group (light green) was decreased to normal group (white) from 1806 to 1893, significant severe patient (red) was decreased to moderate (orange) from 10 to 5. Health Program in behaving change with best practice of 3Es (Eating, Exercise, Emotion) and 3Rs (Reducing tobacco, alcohol, obesity) were applied in risk group; and encourage strictly medication, investigation in severe patient (red). Conclusion: This is the first demonstration of knowledge transfer to community engagement by student, which is the sustainable education in PHC.

Keywords: non-communicable disease, surveillance control and prevention systems, community engagement, primary health care

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Authors: Cecilia Sosa, Fernanda Figueroa, Leonardo Calzada

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Biosphere reserves (BR) are considered as the main strategy for biodiversity and ecosystems conservation. Mexican BR are mainly inhabited by rural communities who strongly depend on forests and their resources. Even though the dual objective of conservation and development has been sought in BR, land cover change is a common process in these areas, while most rural communities are highly marginalized, partly as a result of restrictions imposed by conservation to the access and use of resources. Achieving ecosystems conservation and social development face serious challenges. Factors such as financial support for development projects (public/private), environmental conditions, infrastructure and regional economic conditions might influence both land use change and wellbeing. Examining the temporal trends of conservation and development in BR is central for the evaluation of outcomes for these conservation strategies. In this study, we analyzed changes in primary vegetation cover (as a proxy for conservation) and the index of marginalization (as a proxy for development) in Mexican BR (2000-2015); we also explore the influence of various factors affecting these trends, such as conservation-development projects financial support (public or private), geographical distribution in ecoregions (as a proxy for shared environmental conditions) and in economic zones (as a proxy for regional economic conditions). We developed a spatial analysis at the municipal scale (2,458 municipalities nationwide) in ArcGIS, to obtain road densities, geographical distribution in ecoregions and economic zones, the financial support received, and the percent of municipality area under protection by protected areas and, particularly, by BR. Those municipalities with less than 25% of area under protection were regarded as part of the protected area. We obtained marginalization indexes for all municipalities and, using MODIS in Google Earth Engine, the number of pixels covered by primary vegetation. We used a linear mixed model in RStudio for the analysis. We found a positive correlation between the marginalization index and the percent of primary vegetation cover per year (r=0.49-0.5); i.e., municipalities with higher marginalization also show higher percent of primary vegetation cover. Also, those municipalities with higher area under protection have more development projects (r=0.46) and some environmental conditions were relevant for percent of vegetation cover. Time, economic zones and marginalization index were all important. Time was particularly, in 2005, when both marginalization and deforestation decreased. Road densities and financial support for conservation-development projects were irrelevant as factors in the general correlation. Marginalization is still being affected by the conservation strategies applied in BR, even though that this management category considers both conservation and development of local communities as its objectives. Our results suggest that roads densities and support for conservation-development projects have not been a factor of poverty alleviation. As better conservation is being attained in the most impoverished areas, we face the dilemma of how to improve wellbeing in rural communities under conservation, since current strategies have not been able to leave behind the conservation-development contraposition.

Keywords: deforestation, local development, marginalization, protected areas

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Authors: C. F. Popoola, P. Osho, S. B. Babarinde

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This study examined economic indicators as correlates of inward FDI. An exploratory research design was used to obtained annual published data on inflation rate, market size, exchange rate, political instability, human development, and infrastructure from Central Bank of Nigeria, National Bureau of Statistics, Nigerian Capital Market, Nigeria Institute of Social and Economic Research, and UNCTAD. Data generated were analyzed using Pearson correlation, analysis of variance and regression. The findings of the study revealed that market size (r = 0.852, p < 0.001), infrastructure (r = 0.264, p < 0.001), human development (r = 0.154, p < 0.01) and exchange rate ( r= 0.178, p < 0.05) correlate positively with inward FDI, while inflation rate (r = -0.88, p < 0.001), and political instability (r= -0.102, p < 0.05) correlate negatively with inward FDI. Findings also revealed that the economic indicators significantly predicted inward FDI (R2 = 0.913; F(1,19) = 29.40; p < 0.05) for Nigeria. It was concluded that exchange rate, market size, human development, and infrastructure positively related to inward FDI while the high level of inflation and political instability negatively related to inward FDI. Therefore, it was suggested that policy makers and government agencies should readdress steps and design policies that would encourage more FDI into the country.

Keywords: exchange rate, foreign direct investment, human development, inflation rate, infrastructure, market size, political instability

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Authors: Srividya Sheshadri, Christopher Coley, Roa. R. Bhavani

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India currently accounts for 60 percent of the open defecation that is practiced globally. While research in the domain of sanitation development makes it apparent that girls and women living in rural India are disproportionately affected, interventions to address this dilemma are lacking. An important but relatively unexplored connection with poor sanitation is that women living in rural India are not only the largest marginalized group without access to adequate sanitation facilities, they also represent a majority of India’s unskilled workers. By training women to build their own toilets, through an approach that has demonstrated success in empowering marginalized communities through technical and vocational education and training (TVET), a collaborative dynamic emerges that can engage entire communities in the movement towards total sanitation. Designed and implemented by Amrita University, this technology-enhanced, community-based approach to skill development, known as Amrita computerized Vocational Education and Training (or Amrita cVET), has begun to show promise in addressing the struggle to end open defecation, and raise sanitation awareness, as well as strengthen personal and community development among women living in rural India. While Amrita cVET project, known as Women Empowerment: Sanitation, is currently in implementation in seven states throughout India, this paper will discuss early stages of the intervention in rural villages within the Indian states of: Karnataka and Goa, where previous sanitation efforts have failed to take hold.

Keywords: community based development, empowerment studies, sanitation in India, computerized vocational training

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Authors: Farah Naja, Mohamad Alameddine

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Background: The difficulty of compliance to therapeutic and lifestyle management of type 2 diabetes mellitus (T2DM) encourages patients to use complementary and alternative medicine (CAM) therapies. Little is known about the prevalence and mode of CAM use among diabetics in the Eastern Mediterranean Region in general and Lebanon in particular. Objective: To assess the prevalence and modes of CAM use among patients with T2DM residing in Beirut, Lebanon. Methods: A cross-sectional survey of T2DM patients was conducted on patients recruited from two major referral centers - a public hospital and a private academic medical center in Beirut. In a face-to-face interview, participants completed a survey questionnaire comprised of three sections: socio-demographic, diabetes characteristics and types and modes of CAM use. Descriptive statistics, univariate and multivariate logistic regression analyses were utilized to assess the prevalence, mode and correlates of CAM use in the study population. The main outcome in this study (CAM use) was defined as using CAM at least once since diagnosis with T2DM. Results: A total of 333 T2DM patients completed the survey (response rate: 94.6%). Prevalence of CAM use in the study population was 38%, 95% CI (33.1-43.5). After adjustment, CAM use was significantly associated with a “married” status, a longer duration of T2DM, the presence of disease complications, and a positive family history of the disease. Folk foods and herbs were the most commonly used CAM followed by natural health products. One in five patients used CAM as an alternative to conventional treatment. Only 7 % of CAM users disclosed the CAM use to their treating physician. Health care practitioners were the least cited (7%) as influencing the choice of CAM among users. Conclusion: The use of CAM therapies among T2DM patients in Lebanon is prevalent. Decision makers and care providers must fully understand the potential risks and benefits of CAM therapies to appropriately advise their patients. Attention must be dedicated to educating T2DM patients on the importance of disclosing CAM use to their physicians especially patients with a family history of diabetes, and those using conventional therapy for a long time.

Keywords: nutritional supplements, type 2 diabetes mellitus, complementary and alternative medicine (CAM), conventional therapy

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Authors: Ibrahim Aliyu Isah, Mohd Mansor Ismail, Salim Hassan, Norsida Man, Oluwatoyin Olagunju

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Stingless beekeeping is not only a profitable activity for Malaysian beekeepers but also for the Malaysian economy. However, natural honey has faced some difficulties, which resulted in low production due to a lack of information on improved technology as well as the capacity and potential building of stingless beekeeping farmers, which depend mostly on information received from the extension agents. Hence, it is the responsibility of the extension agents to give useful information on the available technology and develop the capacity of the farmers to make the right decision that will improve their level of production. This study assessed how technology transfer and human resource development skills influence the work performance of the extension agents toward sustainable beekeeping production among beekeepers. The study sought to establish the role of relevant technology transfer and human resource development skills in effective performance. The research design was a descriptive and quantitative survey of stingless beekeepers on technology transfer and human resource development by the extension agent. Data was obtained from 54 beekeeping farmers and was analyzed using descriptive and inferential statistics. The results revealed that technology skill, technology dissemination skill, technology evaluation skill, Decision-making process skill, Leadership development skill and work performance were rated moderate by stingless beekeeping farmers, while Social skill was rated high. A significant and positive correlation (P<0.01) existed between all variables and performance. Regression results showed that leadership development skills, Decision-making process skills, and social skills are significant (P=.05), while technology skills, technology dissemination skills, and technology evaluation skills are not significant. The highest contributing factor is social skill (β=.446). Beekeeping is a profitable project in Malaysia and can be sustained if the extension services and programs are well carried out by competent extension agents and relevant agricultural government agencies.

Keywords: beekeeping, extension agents, human resource development, sustainable, technology transfer, work performance

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Authors: Adelia Desi Agnesita

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The advent of a new disease called covid-19 made many major changes in the world, one of which is the process of learning and teaching. Learning formerly offline but now is done online, which makes students need adaptation to the learning process. The covid-19 pandemic that occurs almost worldwide causes activities that involve many people to be avoided, one of which is learning to teach. In Indonesia, since March 2020, the process of college learning is turning into online/ long-distance learning. It's to prevent the spread of the covid-19. Student online learning presents some of the obstacles to poor signals, many of the tasks, lack of focus, difficulty sleeping, and resulting stress.

Keywords: learning, online, covid-19, pandemic

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Authors: Ambissah Asah Brigitte

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This research is guided by observations in the types of education offered at the secondary level in Cameroon. The secondary education system in Cameroon comprises two types of education, including General Education and Technical and Vocational Education. Although General Education and, Technical and Vocational Education are given equal importance by public authorities, General Education remains on the thriving trend, enjoying the greatest enrolment. In the meantime, Technical and Vocational Education is still to reach the adequate momentum expected to fostering the country’s full-fledged development, as specified in the National Development Strategy, which is the blue print of State policies in Cameroon for the 2020-2030 decade. Vocational Education is credited for its ability to foster a country’s development, since it teaches students the precise skills and knowledge needed to carry out a specific craft, technical skill or trade. Yet, formal training on Vocational Education for teachers offers a pale face in secondary education. This limits the ability of the educational system to nurture vocations and provide the country’s economy with the manpower necessary to achieving development goals. This article seeks to analyse how concretely does the institutional framework spur vocational skills in secondary school teachers. It overviews the instruments instituting Vocational Education at the secondary level in Cameroon, then assesses their effective implementation on the ground. Questionnaires addressed to both active teachers and vocational education policy-makers serve to collect data which are analysed using descriptive statistics. The final objective is to contribute in the debate urging to rethink the role of teachers in bolstering Vocational Education, which is the cornerstone of industrial development. This is true everywhere in the world. In Cameroon and in Africa in general, teachers must be empowered in this field with specific sets of competencies they will need to pass on to learners. They equally need to be given opportunities to acquire and adapt their knowledge and teaching skills accordingly.

Keywords: vocational education, cameroon, institutional framework, national development, competencies and skills

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Authors: Juliette Begin, Juliano Colapelle, Andrea Taratanu, Daniel Thirion, Amelie Marsot, Bryan A. Ross

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Chronic obstructive pulmonary disease (COPD), a leading cause of death globally, is characterized by chronic airflow obstruction and acute exacerbations (AECOPDs) that are often triggered by respiratory infections. Pseudomonas aeruginosa (P. aeruginosa), a potentially serious bacterial cause of AECOPDs, is treated with targeted anti-pseudomonal antibiotics. These select few antimicrobials are often used as first-line therapy in patients who are clinically unwell and/or in those suspected of P. aeruginosa-related infection prior to confirmation, potentially contributing to antimicrobial resistance. The present study evaluates prescribing practices in patients with a confirmed sputum history of P. aeruginosa admitted for AECOPD at the McGill University Health Centre (MUHC) and treated with anti-pseudomonal antibiotics. Serum antibiotic concentrations were measured from the same-day peak, trough, and mid-dose blood sampling intervals after reaching steady-state (on or after day 3) and were quantified using ultra-high-performance liquid chromatography (UHPLC). Demographic, clinical, and treatment outcomes were extracted from patient medical charts. Treatment failure was defined by respiratory-related death or mechanical ventilation after ≥3 days of antibiotics; antibiotic therapy extended beyond 2 weeks or a new antibiotic regimen started; or urgent care readmission within 30 days for AECOPD. To date, 9 of 30 planned participants have completed testing: seven received ciprofloxacin, one received meropenem, and one received piperacillin-tazobactam. Due to serum sample batching requirements, the serum ciprofloxacin concentration results for the first 2/8 participants are presented at the time of writing. The first participant had serum levels of 5.45mg/L (T₀), 4.74mg/L (T₅₀), and 4.49mg/L (T₁₀₀), while the second had serum levels of 5mg/L (T₀), 2.6mg/L (T₅₀), and 2.51mg/L (T₁₀₀). Pharmacokinetic parameters Cmax (5.18±0.43mg/L), T₁/₂ (23.56±18.94hours), and AUC (181.9±155.95mg*h/l) were higher than reported monograph values and met target AUC-to-MIC ratio of >125. The patients treated with meropenem and with piperacillin-tazobactam experienced treatment failure. Preliminary results suggest that standard ciprofloxacin dosing in patients experiencing an AECOPD and colonized with P. aeruginosa appears to achieve effective serum concentrations. Final cohort results will inform the pharmacokinetic appropriateness and clinical sufficiency of current AECOPD antimicrobial strategies in P. aeruginosa-colonized patients. This study will guide clinicians in determining the appropriate dosing for AECOPD treatment to achieve therapeutic levels, optimizing outcomes, and minimizing adverse effects. It could also highlight the value of routine antibiotic level monitoring in patients with treatment failure to ensure optimal serum concentrations.

Keywords: acute exacerbation, antimicrobial resistance, chronic obstructive pulmonary disease, pharmacokinetics/pharmacodynamics, Pseudomonas aeruginosa

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Authors: Monica Gonzalez Machorro

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Dementia is hard to diagnose because of the lack of early physical symptoms. Early dementia recognition is key to improving the living condition of patients. Speech technology is considered a valuable biomarker for this challenge. Recent works have utilized conventional acoustic features and machine learning methods to detect dementia in speech. BERT-like classifiers have reported the most promising performance. One constraint, nonetheless, is that these studies are either based on human transcripts or on transcripts produced by automatic speech recognition (ASR) systems. This research contribution is to explore a method that does not require transcriptions to detect early Alzheimer’s disease (AD) and mild cognitive impairment (MCI). This is achieved by fine-tuning a pre-trained ASR model for the downstream early AD and MCI tasks. To do so, a subset of the thoroughly studied Pitt Corpus is customized. The subset is balanced for class, age, and gender. Data processing also involves cropping the samples into 10-second segments. For comparison purposes, a baseline model is defined by training and testing a Random Forest with 20 extracted acoustic features using the librosa library implemented in Python. These are: zero-crossing rate, MFCCs, spectral bandwidth, spectral centroid, root mean square, and short-time Fourier transform. The baseline model achieved a 58% accuracy. To fine-tune HuBERT as a classifier, an average pooling strategy is employed to merge the 3D representations from audio into 2D representations, and a linear layer is added. The pre-trained model used is ‘hubert-large-ls960-ft’. Empirically, the number of epochs selected is 5, and the batch size defined is 1. Experiments show that our proposed method reaches a 69% balanced accuracy. This suggests that the linguistic and speech information encoded in the self-supervised ASR-based model is able to learn acoustic cues of AD and MCI.

Keywords: automatic speech recognition, early Alzheimer’s recognition, mild cognitive impairment, speech impairment

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Authors: Md, MCS, MPH Munyangi Wa Nkola Jerome

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The pandemic of COVID-19, a recently discovered contagious respiratory disease called SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus 2 Majority of people infected with SARS-CoV-2: Asymptomatic or mildly ill 14% of patients will develop severe illness requiring hospitalization and oxygen support, and 5% of these will be transferred to an intensive care unit, Urgent need for new treatments that can be used quickly to avoid transfer of patients to intensive care and death. Objective: To evaluate the clinical activity (efficacy) of ArtiCovid Hypothesis: Administration of 3 times a teaspoon per day by COVID patients (symptomatic, mild, or moderate forms) results in the disappearance of symptoms and improvement of biological parameters (including viral suppression). Clinical efficacy: the disappearance of clinical signs after seven days of treatment; reduction in the rate of patients transferred to intensive care units for mechanical ventilation and a decrease in mortality related to this infection Paraclinical efficacy: improvement of biological parameters (mainly d-dimer, CRP) Virological efficacy: suppression of the viral load after seven days of treatment (control test on the seventh day is negative) Pilot study using a standardized solution based on Artemisia annua (ARTICOVID) Obtaining authorization from the health authorities of the province of Central Kongo Recruitment of volunteer patients, mainly in the Kinkanda HospitalCarrying out tests before and after treatment as well as analyses before and after treatment. The protocol obtained the approval of the ethics committee 50 patients who completed the treatment were aged between 2 and 70 years, with an average age of 36 yearsMore half were male (56%). One in four patients was a health professional (25%) Of the 12 health professionals, 4 were physicians. For those who reported the date of onset of the disease, the average duration between the appearance of the first symptoms and the medical consultation was 5 days. The 50 patients put on ARTICOVID were discharged alive with CRP levels substantially normalizedAfter seven to eight days, the control test came back negative. This pilot study suggests that ARTICOVID may be effective against COVID-19 infection.

Keywords: artiCovid, DRC, Covid-19, SARS_COV_2

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Authors: Hsin-Hsin Chang, Jann-Tay Wang, Wang-Huei Sheng

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Background: Hospital-associated infections (HAIs) have significant medical and social resource consumption. In view of medical technology change rapidly and the prolonged average life expectancy, the patients' chances of receiving invasive medical devices have also increased. As well as the potential disease of the patients, the aging, and immune dysfunction makes the disease more serious, raising the risk of HAIs. In our adult intensive care units, catheter-associated urinary tract infections (CAUTIs) have an average of 4.6% in 2014, which is much higher than that of the National Healthcare Safety Network (NHSN). Therefore, we started the intervention of CAUTI bundle care. Methods: This 3-year intervention was conducted in adults’ intensive care units (ICUs) during January 2015 to December 2017. The implementation of CAUTI bundle care in order to reduce invasive catheter-associated infections were built on evidence-based infection control measures. Prospective surveillance was performed on all patients admitted to hospital. The four major directions are 'Leader Engagement', 'Educate Personnel', 'Executive Multidisciplinary Teamwork', 'Innovation and Improvement of Tools'. Results: During the intervention period, there were 167,024 patient-days with a total of 508 episodes of CAUTIs in the entire adult ICUs identified. The incidence of CAUTIs in adult ICU was significantly decreased in the intervention period (from 2015 to 2017), from 4.6 to 3.6 per 1000 catheter days (p=0.05). Conclusion: The necessity for the implementation of CAUTI bundle care in the health care system plays an important role in the quality and policy of infection control. Multidisciplinary teamwork, education, a comprehensive checklist and from time to time audit feedback to improve healthcare workers’ compliance are the keys to success.

Keywords: bundle care, hospital-associated infections, leader engagement, multidisciplinary team work

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Authors: Peter Smolianov, Steven Dion, Christopher Schoen, Jaclyn Norberg, Nicholas Stone, Soufiane Rafi

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This study assessed the micro-level elements of track and field development in the US against a model for integrating high-performance sport with mass participation. This investigation is important for the country’s international sport performance, which declined relative to other countries and wellbeing, which in its turn deteriorated as over half of the US population became overweight. A questionnaire was designed for the following elements of the model: talent identification and development as well as advanced athlete support. Survey questions were validated by 12 experts, including academics, executives from sport governing bodies, coaches, and administrators. To determine the areas for improvement, the questionnaires were completed by 102 US track and field coaches representing the country’s regions and coaching levels. Possible advancements were further identified through semi-structured discussions with 10 US track and field administrators. The study found that talent search and development is a critically important area for improvement: 49 percent of respondents had overall negative perceptions, and only 16 percent were positive regarding these US track and field practices. Both quantitative survey results and open responses revealed that the key reason for the inadequate athlete development was a shortage of well-educated and properly paid coaches: 77 percent of respondents indicated that coach expertise is never or rarely high across all participant ages and levels. More than 40 percent of the respondents were uncertain of or not familiar with world’s best talent identification and development practices, particularly methods of introducing children to track and field from outside the sport’s participation base. Millions more could be attracted to the sport by adopting best international practices. First, physical education should be offered a minimum three times a week in all school grades, and track and field together with other healthy sports, should be taught at school to all children. Second, multi-sport events, including track and field disciplines, should be organized for everyone within and among all schools, cities and regions. Three, Australian and Eastern European methods of talent search at schools should be utilized and tailored to the US conditions. Four, comprehensive long term athlete development guidelines should be used for the advancement of the American Development Model, particularly track and field tests and guidelines as part of both school education and high-performance athlete development for every age group from six to over 70 years old. These world’s best practices are to improve the country’s international performance while increasing national sport participation and positively influencing public health.

Keywords: high performance, mass participation, sport development, track and field, USA

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Authors: A. Berraf-Tebbal, Z. Bouznad, , A.J.L. Phillips

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Phaeomoniella is a fungus genus in the mitosporic ascomycota which includes Phaeomoniella chlamydospora specie associated with two declining diseases on grapevine (Vitis vinifera) namely Petri disease and esca. Recent studies have shown that several Phaeomoniella species also cause disease on many other woody crops, such as forest trees and woody ornamentals. Two new species, Phaeomoniella zymoides and Phaeomoniella pinifoliorum H.B. Lee, J.Y. Park, R.C. Summerbell et H.S. Jung, were isolated from the needle surface of Pinus densiflora Sieb. et Zucc. in Korea. The identification of species in Phaeomoniella genus can be a difficult task if based solely on morphological and cultural characters. In this respect, the application of molecular methods, particularly PCR-based techniques, may provide an important contribution. MSP-PCR (microsatellite primed-PCR) fingerprinting has proven useful in the molecular typing of fungal strains. The high discriminatory potential of this method is particularly useful when dealing with closely related or cryptic species. In the present study, the application of PCR fingerprinting was performed using the micro satellite primer M13 for the purpose of species identification and strain typing of 84 Phaeomoniella -like isolates collected from grapevines with typical symptoms of dieback. The bands produced by MSP-PCR profiles divided the strains into 3 clusters and 5 singletons with a reproducibility level of 80%. Representative isolates from each group and, when possible, isolates from Eutypa dieback and esca symptoms were selected for sequencing of the ITS region. The ITS sequences for the 16 isolates selected from the MSP-PCR profiles were combined and aligned with sequences of 18 isolates retrieved from GenBank, representing a selection of all known Phaeomoniella species. DNA sequences were compared with those available in GenBank using Neighbor-joining (NJ) and Maximum-parsimony (MP) analyses. The phylogenetic trees of the ITS region revealed that the Phaeomoniella isolates clustered with Phaeomoniella chlamydospora reference sequences with a bootstrap support of 100 %. The complexity of the pathosystems vine-trunk diseases shows clearly the need to identify unambiguously the fungal component in order to allow a better understanding of the etiology of these diseases and justify the establishment of control strategies against these fungal agents.

Keywords: Genotyping, MSP-PCR, ITS, phylogeny, trunk diseases

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Authors: Sibel Ecemiş Kılıç, Muhammed Aydoğan

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The rapid development of culture tourism has drawn attention to conserving cultural values especially by developing countries that would like to benefit from the economic contribution this type of tourism attracts. Tourism can have both positive and negative outcomes for historical settlements and their residents. The accommodation-purposed rehabilitation and revitalization project in “Sigacik Old City Zone” are to be discussed with spatial, economic, social and organizational dimensions. It is aimed to evaluate the relationship between the development of tourism and sustainable heritage conservation.

Keywords: Sığacık, urban conservation, sustainable tourism, Seferihisar

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

Procedia PDF Downloads 391