Search results for: drug target

Authors: Elizabeth B. Katana, Brenda N. Simbwa, Josephine Namayanja, Bob O. Amodan, Edirisa J. Nsubuga, Eva A. O. Laker

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Background: Understanding stakeholders’ perceptions towards the implementation of a mass vaccination campaign is important to ensure the design of better strategies to address challenges. We explored stakeholders’ perceptions of the implementation of a nationwide door-to-door mass vaccination campaign for the oral polio vaccine (nOPV2) in Uganda for the two rounds that occurred in January and November 2022. Methods: A qualitative study was conducted among stakeholders who participated in the campaign implementation from 8 districts in Uganda using random sampling. We conducted 46 In-depth interviews lasting 30 – 40 minutes with 6 national/central supervisors, 12 district, 14 sub-county, and 14 parish-level supervisors. Stakeholders were asked about their experiences in the campaign implementation, including challenges faced and their opinions of the campaign impact and use of the door-to-door strategy. Data were analyzed thematically in line with the major campaign activities. Results: Most of the stakeholders were primarily concerned about poor planning, inadequate training of vaccination teams, community resistance including schools, challenges with recruitment and teaming of vaccinators, poor and delayed payments, lack of logistics and motivation for vaccination teams, the timing of the activities and implementing amidst COVID-19 and Ebola. The stakeholders believed that the first round was not well planned and implemented, while the second round was leveraged in their previous experiences. On the other hand, some positive experiences were noted with regard to communication, advocacy and mobilization, vaccine delivery and distribution, district readiness assessments, and cold chain management. Conclusion: This study identified many challenges that were faced in the implementation of the door-to-door mass campaign for nOPV2 in Uganda. This study identified that more needs to be done to improve door-to-door mass campaigns with a focus on motivating the implementers. These findings highlight the need for conducting performance reviews, improved planning, especially routine updates and verification of target populations and training in microplanning, and adequate mapping of community resistance to inform the implementation of future mass campaigns.

Keywords: mass polio vaccination campaigns, door-to-door strategy, stakeholders' perceptions, implementation challenges

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Authors: Abbas Sheikhtaheri, Nasim Hashemi

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Health information systems have great benefits for clinical and managerial processes of health care organizations. However, identifying and removing constraints and barriers of implementing and using health information systems before any implementation is essential. Physicians are one of the main users of health information systems, therefore, identifying the causes of their resistance and concerns about the barriers of the implementation of these systems is very important. So the purpose of this study was to determine the barriers of the development and implementation of health information systems in terms of the Iranian physicians’ perspectives. In this study conducted in 8 selected hospitals affiliated to Tehran and Iran Universities of Medical Sciences, Tehran, Iran in 2014, physicians (GPs, residents, interns, specialists) in these hospitals were surveyed. In order to collect data, a research made questionnaire was used (Cronbach’s α = 0.95). The instrument included 25 about organizational (9), personal (4), moral and legal (3) and technical barriers (9). Participants were asked to answer the questions using 5 point scale Likert (completely disagree=1 to completely agree=5). By using a simple random sampling method, 200 physicians (from 600) were invited to study that eventually 163 questionnaires were returned. We used mean score and t-test and ANOVA to analyze the data using SPSS software version 17. 52.1% of respondents were female. The mean age was 30.18 ± 7.29. The work experience years for most of them were between 1 to 5 years (80.4 percent). The most important barriers were organizational ones (3.4 ± 0.89), followed by ethical (3.18 ± 0.98), technical (3.06 ± 0.8) and personal (3.04 ± 1.2). Lack of easy access to a fast Internet (3.67±1.91) and the lack of exchanging information (3.61±1.2) were the most important technical barriers. Among organizational barriers, the lack of efficient planning for the development and implementation systems (3.56±1.32) and was the most important ones. Lack of awareness and knowledge of health care providers about the health information systems features (3.33±1.28) and the lack of physician participation in planning phase (3.27±1.2) as well as concerns regarding the security and confidentiality of health information (3.15 ± 1.31) were the most important personal and ethical barriers, respectively. Women (P = 0.02) and those with less experience (P = 0.002) were more concerned about personal barriers. GPs also were more concerned about technical barriers (P = 0.02). According to the study, technical and ethics barriers were considered as the most important barriers however, lack of awareness in target population is also considered as one of the main barriers. Ignoring issues such as personal and ethical barriers, even if the necessary infrastructure and technical requirements were provided, may result in failure. Therefore, along with the creating infrastructure and resolving organizational barriers, special attention to education and awareness of physicians and providing solution for ethics concerns are necessary.

Keywords: barriers, development health information systems, implementation, physicians

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Authors: George Hanna Abdelmelek Henien

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Quality and safety issues are common in Ethiopia's food processing industry, which can negatively impact consumers' health and livelihoods. The country is known for its various agricultural products that are important to the economy. However, food quality and safety policies and management practices in the food processing industry have led to many health problems, foodborne illnesses and economic losses. This article aims to show the causes and consequences of food safety and quality problems in the food processing industry in Ethiopia and discuss possible solutions to solve them. One of the main reasons for food quality and safety in Ethiopia's food processing industry is the lack of adequate regulation and enforcement mechanisms. Inadequate food safety and quality policies have led to inefficiencies in food production. Additionally, the failure to monitor and enforce existing regulations has created a good opportunity for unscrupulous companies to engage in harmful practices that endanger the lives of citizens. The impact on food quality and safety is significant due to loss of life, high medical costs, and loss of consumer confidence in the food processing industry. Foodborne diseases such as diarrhoea, typhoid and cholera are common in Ethiopia, and food quality and safety play an important role in . Additionally, food recalls due to contamination or contamination often cause significant economic losses in the food processing industry. To solve these problems, the Ethiopian government began taking measures to improve food quality and safety in the food processing industry. One of the most prominent initiatives is the Ethiopian Food and Drug Administration (EFDA), which was established in 2010 to monitor and control the quality and safety of food and beverage products in the country. EFDA has implemented many measures to improve food safety, such as carrying out routine inspections, monitoring the import of food products and implementing labeling requirements. Another solution that can improve food quality and safety in the food processing industry in Ethiopia is the implementation of food safety management system (FSMS). FSMS is a set of procedures and policies designed to identify, assess and control food safety risks during food processing. Implementing a FSMS can help companies in the food processing industry identify and address potential risks before they harm consumers. Additionally, implementing an FSMS can help companies comply with current safety and security regulations. Consequently, improving food safety policy and management system in Ethiopia's food processing industry is important to protect people's health and improve the country's economy. . Addressing the root causes of food quality and safety and implementing practical solutions that can help improve the overall food safety and quality in the country, such as establishing regulatory bodies and implementing food management systems.

Keywords: food quality, food safety, policy, management system, food processing industry food traceability, industry 4.0, internet of things, block chain, best worst method, marcos

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Authors: Olivera Lupescu, Taina Elena Avramescu, Mihail Nagea, Alexandru Dimitriu

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Acetabular fractures represent a real challenge due to their impact upon the long term function of the hip joint, and due to the risk of intra- and peri-operative complications especially that they affect young, active people. That is why treating these fractures require certain skills which must be exercised, regarding the pre-operative planning, as well as the execution of surgery.The authors retrospectively analyse 38 cases with acetabular fractures operated using the posterior approach in our hospital between 01.01.2013- 01.01.2015 for which complete medical records ensure a follow-up of 24 months, in order to establish the main causes of potential errors and to underline the methods for preventing them. This target is included in the Erasmus + project ‘Collaborative learning for enhancing practical skills for patient-focused interventions in gait rehabilitation after orthopedic surgery COR-skills’. This paper analyses the pitfalls revealed by these cases, as well as the measures necessary to enhance the practical skills of the surgeons who perform acetabular surgery. Pre-op planning matched the intra and post-operative outcome in 88% of the analyzed points, from 72% at the beginning to 94% in the last case, meaning that experience is very important in treating this injury. The main problems detected for the posterior approach were: nervous complications - 3 cases, 1 of them a complete paralysis of the sciatic nerve, which recovered 6 months after surgery, and in other 2 cases intra-articular position of the screws was demonstrated by post-operative CT scans, so secondary screw removal was necessary in these cases. We analysed this incident, too, due to lack of information about the relationship between the screws and the joint secondary to this approach. Septic complications appeared in 3 cases, 2 superficial and 1 profound (requiring implant removal). The most important problems were the reduction of the fractures and the positioning of the screws so as not to interfere with the the articular space. In posterior acetabular fractures, pre-op complex planning is important in order to achieve maximum treatment efficacy with minimum of risk; an optimal training of the surgeons insisting on the main points of potential mistakes ensure the success of the procedure, as well as a favorable outcome for the patient.

Keywords: acetabular fractures, articular congruency, surgical skills, vocational training

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Authors: Tracey Lion-Cachet

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Eating disorders typically manifest in adolescence and are notoriously difficult to treat. There are two notable reasons for this. Firstly, research consistently demonstrates that early intervention is a critical mediator of prognosis, with early intervention leading to a better prognosis. However, because eating disorders do not originate as full-syndrome diagnoses but rather as prodromal cases, they often go undetected; by the time symptoms meet diagnostic criteria, they have become recalcitrant. Another interrelated issue is motivation to change. Research demonstrates that in the early stages of an eating disorder, adolescents are highly resistant to change, and motivation increases only once symptoms have shifted from egosyntonic to egodystonic in nature. The purpose of this project was to design a prevention model based on the social psychology paradigm of Entertainment-Education, which embeds messages within the genre of film as a means of affecting change. The resulting project was a narrative screenplay targeting teenagers/young adults from diverse backgrounds. The goals of the project were to create a film script that, if ultimately made into a film, could serve to: 1) interrupt symptom progression and improve prognosis through early intervention; 2) incorporate techniques from third-wave cognitive behavioral treatment models, acceptance and commitment therapy (ACT) and rational recovery (RR), with a focus on the effects of mindfulness as a means of informing recovery; 3) target issues to do with motivation to change by shifting the perception of eating disorders from culturally specific psychiatric illnesses to habit-based brain wiring issues. Nine licensed clinicians were asked to evaluate two excerpts taken from the final script. They subsequently provided feedback on a Likert-scale, which assessed whether the script had achieved its goals. Overall, evaluators agreed that the project’s etiological and intervention models have the potential to inspire change and serve as an effective means of prevention and treatment of eating disorders. However, one-third of the evaluators did not find the content developmentally appropriate. This is a notable limitation to the study and will need to be addressed in the larger script before the final project can potentially be targeted to a teenage and young adult audience.

Keywords: adolescents, eating disorders, pediatrics, entertainment-education, mindfulness-based intervention, prevention

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Authors: Roya Vakili, Lekaa Elhajjmoussa, Barzin Omidi-Shal, Kim Blake

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Objective: The purpose of this case report is to highlight the successful treatment of a patient with Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness, (CHARGE syndrome) using a vagal nerve stimulator (VNS). Background: This is the first documented case report, to the authors' best knowledge, for a patient with CHARGE syndrome, epilepsy, autism, and postural orthostatic tachycardia syndrome (POTS) that was successfully treated with an implanted VNS therapeutic device. Methodology: The study is a case report. Results: This is the case of a 24-year-old female patient with CHARGE syndrome (non-random association of anomalies Coloboma, Heart defect, Atresia choanae, Retarded growth and development, Genital hypoplasia, Ear anomalies/deafness) and several other comorbidities including refractory epilepsy, Patent Ductus Arteriosus (PDA) and POTS who had significant improvement of her symptoms after VNS implantation. She was a VNS candidate given her longstanding history of drug-resistant epilepsy and current disposition secondary to CHARGE syndrome. Prior to VNS implantation, she experienced three generalized seizures a year and daily POTS-related symptoms. She was having frequent lightheadedness and syncope spells due to a rapid heart rate and low blood pressure. The VNS device was set to detect a rapid heart rate and send appropriate stimulation anytime the heart rate exceeded 20% of the patient’s normal baseline. The VNS device demonstrated frequent elevated heart rates and concurrent VNS release every 8 minutes in addition to the programmed events. Following VNS installation, the patient became more active, alert, and communicative and was able to verbally communicate with words she was unable to say prior. Her GI symptoms also improved, as she was able to tolerate food better orally in addition to her G and J tube, likely another result of the vagal nerve stimulation. Additionally, the patient’s seizures and POTS-related cardiac events appeared to be well controlled. She had prolonged electroencephalogram (EEG) testing, showing no significant change in epileptiform activity. Improvements in the patient’s disposition are believed to be secondary to parasympathetic stimulation, adequate heart rate control, and GI stimulation, in addition to behavioral changes and other benefits via her implanted VNS. Conclusion: VNS showed promising results in improving the patient's quality of life and managing her diverse symptoms, including dysautonomia, POTs, gastrointestinal mobility, cognitive functioning as well seizure control.

Keywords: autism, POTs, CHARGE, VNS

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Authors: Nadia Soledad Peralta

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Within the framework of socio-cognitive interaction, argumentation is understood as a psychological process that supports and induces reasoning and learning. Most authors emphasize the great potential of argumentation to negotiate with contradictions and complex decisions. So argumentation is a target for researchers who highlight the importance of social and cognitive processes in learning. In the context of social interaction among university students, different types of arguments are analyzed according to group size (dyads and triads) and the type of task (reading of frequency tables, causal explanation of physical phenomena, the decision regarding moral dilemma situations, and causal explanation of social phenomena). Eighty-nine first-year social sciences students of the National University of Rosario participated. Two groups were formed from the results of a pre-test that ensured the heterogeneity of points of view between participants. Group 1 consisted of 56 participants (performance in dyads, total: 28), and group 2 was formed of 33 participants (performance in triads, total: 11). A quasi-experimental design was performed in which effects of the two variables (group size and type of task) on the argumentation were analyzed. Three types of argumentation are described: authentic dialogical argumentative resolutions, individualistic argumentative resolutions, and non-argumentative resolutions. The results indicate that individualistic arguments prevail in dyads. That is, although people express their own arguments, there is no authentic argumentative interaction. Given that, there are few reciprocal evaluations and counter-arguments in dyads. By contrast, the authentically dialogical argument prevails in triads, showing constant feedback between participants’ points of view. It was observed that, in general, the type of task generates specific types of argumentative interactions. However, it is possible to emphasize that the authentically dialogic arguments predominate in the logical tasks, whereas the individualists or pseudo-dialogical are more frequent in opinion tasks. Nerveless, these relationships between task type and argumentative mode are best clarified in an interactive analysis based on group size. Finally, it is important to stress the value of dialogical argumentation in educational domains. Argumentative function not only allows a metacognitive reflection about their own point of view but also allows people to benefit from exchanging points of view in interactive contexts.

Keywords: sociocognitive interaction, argumentation, university students, size of the grup

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Authors: Christian Neunzig, Simon Fahle, Jürgen Schulz, Matthias Möller, Bernd Kuhlenkötter

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Digitalisation in production technology is a driver for the application of machine learning methods. Through the application of predictive quality, the great potential for saving necessary quality control can be exploited through the data-based prediction of product quality and states. However, the serial use of machine learning applications is often prevented by various problems. Fluctuations occur in real production data sets, which are reflected in trends and systematic shifts over time. To counteract these problems, data preprocessing includes rule-based data cleaning, the application of dimensionality reduction techniques, and the identification of comparable data subsets to extract stable features. Successful process control of the target variables aims to centre the measured values around a mean and minimise variance. Competitive leaders claim to have mastered their processes. As a result, much of the real data has a relatively low variance. For the training of prediction models, the highest possible generalisability is required, which is at least made more difficult by this data availability. The implementation of a machine learning application can be interpreted as a production process. The CRoss Industry Standard Process for Data Mining (CRISP-DM) is a process model with six phases that describes the life cycle of data science. As in any process, the costs to eliminate errors increase significantly with each advancing process phase. For the quality prediction of hydraulic test steps of directional control valves, the question arises in the initial phase whether a regression or a classification is more suitable. In the context of this work, the initial phase of the CRISP-DM, the business understanding, is critically compared for the use case at Bosch Rexroth with regard to regression and classification. The use of cross-process production data along the value chain of hydraulic valves is a promising approach to predict the quality characteristics of workpieces. Suitable methods for leakage volume flow regression and classification for inspection decision are applied. Impressively, classification is clearly superior to regression and achieves promising accuracies.

Keywords: classification, CRISP-DM, machine learning, predictive quality, regression

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Authors: Michael Lognoul

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In April 2021, the European Commission released its AI Act Proposal, which is the first policy proposal at the European Union level to target AI systems comprehensively, in a horizontal manner. This Proposal notably aims to achieve an ecosystem of trust in the European Union, based on the respect of fundamental rights, regarding AI. Among many other requirements, the AI Act Proposal aims to impose several generic transparency obligationson all AI systems to the benefit of natural persons facing those systems (e.g. information on the AI nature of systems, in case of an interaction with a human). The Proposal also provides for more stringent transparency obligations, specific to AI systems that qualify as high-risk, to the benefit of their users, notably on the characteristics, capabilities, and limitations of the AI systems they use. Against that background, this research firstly presents all such transparency requirements in turn, as well as related obligations, such asthe proposed obligations on record keeping. Secondly, it focuses on a legal analysis of their scope of application, of the content of the obligations, and on their practical implications. On the scope of transparency obligations tailored for high-risk AI systems, the research notably notes that it seems relatively narrow, given the proposed legal definition of the notion of users of AI systems. Hence, where end-users do not qualify as users, they may only receive very limited information. This element might potentially raise concern regarding the objective of the Proposal. On the content of the transparency obligations, the research highlights that the information that should benefit users of high-risk AI systems is both very broad and specific, from a technical perspective. Therefore, the information required under those obligations seems to create, prima facie, an adequate framework to ensure trust for users of high-risk AI systems. However, on the practical implications of these transparency obligations, the research notes that concern arises due to potential illiteracy of high-risk AI systems users. They might not benefit from sufficient technical expertise to fully understand the information provided to them, despite the wording of the Proposal, which requires that information should be comprehensible to its recipients (i.e. users).On this matter, the research points that there could be, more broadly, an important divergence between the level of detail of the information required by the Proposal and the level of expertise of users of high-risk AI systems. As a conclusion, the research provides policy recommendations to tackle (part of) the issues highlighted. It notably recommends to broaden the scope of transparency requirements for high-risk AI systems to encompass end-users. It also suggests that principles of explanation, as they were put forward in the Guidelines for Trustworthy AI of the High Level Expert Group, should be included in the Proposal in addition to transparency obligations.

Keywords: aI act proposal, explainability of aI, high-risk aI systems, transparency requirements

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Authors: Karthick Dharmalingam, Stalin Ramakrishnan, Haseena Banu Hedayathullah Khan, Sachidanandanam Thiruvaiyaru Panchanadham, Shanthi Palanivelu

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Background: Breast cancer is arising as the most dreadful cancer affecting women worldwide. Hence, there arises a need to search and test for new drugs. Herbal formulations used in Siddha preparations are proved to be effective against various types of cancer. They also offer advantage through synergistic amplification and diminish any possible adverse effects. Tridham (TD) is a herbal formulation prepared in our laboratory consisting of Terminalia chebula, Elaeocarpus ganitrus and Prosopis cineraria in a definite ratio and has been used for the treatment of mammary carcinoma. Objective: To study the restorative effect of Tridham and penta galloyl glucose (a component of TD) on DMBA induced mammary carcinoma in female Sprague Dawley rats. Materials and Methods: Rats were divided into seven groups of six animals each. Group I (Control) received corn oil. Group II– mammary carcinoma was induced by DMBA dissolved in corn oil single dose orally. Group III and Group IV were induced with DMBA and subsequently treated with Tridham and penta galloyl glucose, respectively for 48 days. Group V was treated with DMBA and subsequently with a standard drug, cyclophosphamide. Group VI and Group VII were given Tridham and penta galloyl glucose alone, respectively for 48 days. After the experimental period, the animals were sacrificed by cervical decapitation. The mammary gland tissue was excised and levels of antioxidants were determined by biochemical assay. p53 and PCNA expression were accessed using immunohistochemistry. Nrf-2, Cox-2 and caspase-3 protein expression were studied by Western Blotting analysis. p21, Bcl-2, Bax, Bad and caspase-8 gene expression were studied by RT-PCR. Results: Histopathological studies confirmed induction of mammary carcinoma in DMBA induced rats and treatment with TD and PGG resulted in regression of tumour. The levels of enzymic and non-enzymic antioxidants were decreased in DMBA induced rats when compared to control rats. The levels of cell cycle inhibitory markers and apoptotic markers were decreased in DMBA induced rats when compared to control rats. These parameters were restored to near normal levels on treatment with Tridham and PGG. Conclusion: The results of the present study indicate the antineoplastic effect of Tridham and PGG are exerted through the modulation of antioxidant status and expression of cell cycle regulatory markers as well as apoptotic markers. Acknowledgment: Financial assistance provided in the form of ICMR-SRF by Indian Council of Medical Research (ICMR), India is gratefully acknowledged here.

Keywords: antioxidants, Mammary carcinoma, pentaGalloyl glucose, Tridham

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Authors: Norbert W. Paul

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In 1988, parts of the scientific community still heralded findings to support that AIDS was likely to remain largely a ‘gay disease’. The value-ladden terminology of some of the articles suggested that rectum and fragile urethra are not sufficiently robust to provide a barrier against infectious fluids, especially body fluids contaminated with HIV while the female vagina, would provide natural protection against injuries and trauma facilitating HIV-infection. Anal sexual intercourse was constituted not only as dangerous but also as unnatural practice, while penile-vaginal intercourse would follow natural design and thus be relatively safe practice minimizing the risk of HIV. Statements like the latter were not uncommon in the early times of HIV/AIDS and contributed to captious certainties and an underestimation of heterosexual risks. Pseudo-scientific discourses on the origin of HIV were linked to local and global health politics in the 1980ies. The pathways of infection were related to normative concepts like deviant, subcultural behavior, cultural otherness, and guilt used to target, tag and separate specific groups at risk from the ‘normal’ population. Controlling populations at risk became the top item on the agenda rather than controlling modes of transmission and the virus. Hence, the Thai strategy to cope with HIV/AIDS by acknowledging social and sexual practices as they were – not as they were imagined – has become a role model for successful prevention in the highly scandalized realm of sexually transmitted disease. By accepting the globalized character of local HIV-risk and projecting the risk onto populations which are neither particularly vocal groups nor vested with the means to strive for health and justice Thailand managed to culturally implement knowledge-based tools of prevention. This paper argues, that pertinent cultural collisions regarding our strategies to cope with HIV/AIDS are deeply rooted in misconceptions, misreadings and scandalizations brought about in the early history of HIV in the 1980ties. The Thai strategy is used to demonstrate how local values can be balanced against globalized health risk and used to effectuated prevention by which knowledge and norms are translated into local practices. Issues of global health and injustice will be addressed in the final part of the paper dealing with the achievability of health as a human right.

Keywords: bioethics, HIV, global health, justice

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Authors: Maria Antonieta Erna Castillo Holly

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During the last decade, data analysis, strategic decision making, and the use of artificial intelligence (AI) tools in Latin American agriculture have been a challenge. In some countries, the availability, quality, and reliability of historical data, in addition to the current data recording methodology in the field, makes it difficult to use information systems, complete data analysis, and their support for making the right strategic decisions. This is something essential in Agriculture 4.0. where the increase in the global demand for fresh agricultural products of tropical origin, during all the seasons of the year requires a change in the production model and greater agility in the responses to the consumer market demands of quality, quantity, traceability, and sustainability –that means extensive data-. Having quality information available and updated in real-time on what, how much, how, when, where, at what cost, and the compliance with production quality standards represents the greatest challenge for sustainable and profitable agriculture in the region. The objective of this work is to present a methodological proposal for the collection of georeferenced data from the protected agriculture sector, specifically in production units (UP) with tall structures (Greenhouses), initially for Venezuela, taking the state of Mérida as the geographical framework, and horticultural products as target crops. The document presents some background information and explains the methodology and tools used in the 3 phases of the work: diagnosis, data collection, and analysis. As a result, an evaluation of the process is carried out, relevant data and dashboards are displayed, and the first satellite maps integrated with layers of information in a geographic information system are presented. Finally, some improvement proposals and tentatively recommended applications are added to the process, understanding that their objective is to provide better qualified and traceable georeferenced data for subsequent analysis of the information and more agile and accurate strategic decision making. One of the main points of this study is the lack of quality data treatment in the Latin America area and especially in the Caribbean basin, being one of the most important points how to manage the lack of complete official data. The methodology has been tested with horticultural products, but it can be extended to other tropical crops.

Keywords: greenhouses, protected agriculture, data analysis, geographic information systems, Venezuela

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Authors: Adebisi Adunola Demehin, Wanlaya Thamnarak, Jaruwan Chatwichien, Chatchakorn Eurtivong, Kiattawee Choowongkomon, Somsak Ruchirawat, Nopporn Thasana

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The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein involved in cellular signalling processes and, its aberrant activity is crucial in the development of many cancers such as lung cancer. Selaginellaceae are fern allies that have long been used in Chinese traditional medicine to treat various cancer types, especially lung cancer. Biflavonoids, the major secondary metabolites in Selaginellaceae, have numerous pharmacological activities, including anti-cancer and anti-inflammatory. For instance, amentoflavone induces a cytotoxic effect in the human NSCLC cell line via the inhibition of PARP-1. However, to the best of our knowledge, there are no studies on biflavonoids as EGFR inhibitors. Thus, this study aims to investigate the EGFR inhibitory activities of biflavonoids isolated from Selaginella siamensis and Selaginella bryopteris. Amentoflavone, tetrahydroamentoflavone, sciadopitysin, robustaflavone, robustaflavone-4-methylether, delicaflavone, and chrysocauloflavone were isolated from the ethyl-acetate extract of the whole plants. The structures were determined using NMR spectroscopy and mass spectrometry. In vitro study was conducted to evaluate their cytotoxicity against A549, HEPG2, and T47D human cancer cell lines using the MTT assay. In addition, a target-based assay was performed to investigate their EGFR inhibitory activity using the kinase inhibition assay. Finally, a molecular docking study was conducted to predict the binding modes of the compounds. Robustaflavone-4-methylether and delicaflavone showed the best cytotoxic activity on all the cell lines with IC50 (µM) values of 18.9 ± 2.1 and 22.7 ± 3.3 on A549, respectively. Of these biflavonoids, delicaflavone showed the most potent EGFR inhibitory activity with an 84% relative inhibition at 0.02 nM using erlotinib as a positive control. Robustaflavone-4-methylether showed a 78% inhibition at 0.15 nM. The docking scores obtained from the molecular docking study correlated with the kinase inhibition assay. Robustaflavone-4-methylether and delicaflavone had a docking score of 72.0 and 86.5, respectively. The inhibitory activity of delicaflavone seemed to be linked with the C2”=C3” and 3-O-4”’ linkage pattern. Thus, this study suggests that the structural features of these compounds could serve as a basis for developing new EGFR-TK inhibitors.

Keywords: anticancer, biflavonoids, EGFR, molecular docking, Selaginellaceae

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Authors: Ekta, G. K. Darbha

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Nanotechnology offers the potential of simultaneously increasing efficiency as compared to their bulk material as well as reducing harmful environmental impacts of pesticides in field of agriculture. The term nanopesticide covers different pesticides that are cumulative of several surfactants, polymers, metal ions, etc. of nanometer size ranges from 1-1000 nm and exhibit abnormal behavior (high efficacy and high specific surface area) of nanomaterials. Commercial formulations of pesticides used by farmers nowadays cannot be used effectively due to a number of problems associated with them. For example, more than 90% of applied formulations are either lost in the environment or unable to reach the target area required for effective pest control. Around 20−30% of pesticides are lost through emissions. A number of factors (application methods, physicochemical properties of the formulations, and environmental conditions) can influence the extent of loss during application. It is known that among various formulations, polymer-based formulations show the greatest potential due to their greater efficacy, slow release and protection against premature degradation of active ingredient as compared to other commercial formulations. However, the nanoformulations can have a significant effect on the fate of active ingredient as well as may release some new ingredients by reacting with existing soil contaminants. Environmental fate of these newly generated species is still not explored very well which is essential to field scale experiments and hence a lot to be explored in the field of environmental fate, nanotoxicology, transport properties and stability of such formulations. In our preliminary work, we have synthesized polymer based nanoformulation of commercially used weedicide atrazine. Atrazine belongs to triazine class of herbicide, which is used in the effective control of seed germinated dicot weeds and grasses. It functions by binding to the plastoquinone-binding protein in PS-II. Plant death results from starvation and oxidative damage caused by breakdown in electron transport system. The stability of the suspension of nanoformulation containing herbicide has been evaluated by considering different parameters like polydispersity index, particle diameter, zeta-potential under different environmental relevance condition such as pH range 4-10, temperature range from 25°C to 65°C and stability of encapsulation also have been studied for different amount of added polymer. Morphological characterization has been done by using SEM.

Keywords: atrazine, nanoformulation, nanopesticide, nanotoxicology

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Authors: C. C. Alamanjo, A. O. Adepoju, H. Martin, R. N. Baines

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Peri-urban agriculture in Jos Nigeria serves as a major means of livelihood for both urban and peri-urban poor, and constitutes huge commercial inclination with a target market that has spanned beyond Plateau State. Yet, the sustainability of this sector is threatened by intensive application of urban refuse ash contaminated with heavy metals, as a result of the highly heterogeneous materials used in ash production. Hence, this research aimed to understand the current fertilizer employed by farmers, their perception and acceptability in utilization of household sewage sludge for agricultural purposes and their capacity in mitigating risks associated with such practice. Mixed methods approach was adopted, and data collection tools used include survey questionnaire, focus group discussion with farmers, participants and field observation. The study identified that farmers maintain a complex mixture of organic and chemical fertilizers, with mixture composition that is dependent on fertilizer availability and affordability. Also, farmers have decreased the rate of utilization of urban refuse ash due to labor and increased logistic cost and are keen to utilize household sewage sludge for soil fertility improvement but are mainly constrained by accessibility of this waste product. Nevertheless, farmers near to sewage disposal points have commenced utilization of household sewage sludge for improving soil fertility. Farmers were knowledgeable on composting but find their strategic method of dewatering and sun drying more convenient. Irrigation farmers were not enthusiastic for treatment, as they desired both water and sludge. Secondly, household sewage sludge observed in the field is heterogeneous due to nearness between its disposal point and that of urban refuse, which raises concern for possible cross-contamination of pollutants and also portrays lack of extension guidance as regards to treatment and management of household sewage sludge for agricultural purposes. Hence, farmers concerns need to be addressed, particularly in providing extension advice and establishment of decentralized household sewage sludge collection centers, for continuous availability of liquid and concentrated sludge. Urgent need is also required for the Federal Government of Nigeria to increase commitment towards empowering her subsidiaries for efficient discharge of corporate responsibilities.

Keywords: ash, farmers, household, peri-urban, refuse, sewage, sludge, urban

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Authors: Bagnoud-Velásquez Mariluz, Damergi Eya, Grandjean Dominique, Frédéric Vogel, Ludwig Christian

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The sustainability of algae to biofuel processes is seriously affected by the energy intensive production of fertilizers. Large amounts of nitrogen and phosphorus are required for a large-scale production resulting in many cases in a negative impact of the limited mineral resources. In order to meet the algal bioenergy opportunity it appears crucial the promotion of processes applying a nutrient recovery and/or making use of renewable sources including waste. Hydrothermal (HT) conversion is a promising and suitable technology for microalgae to generate biofuels. Besides the fact that water is used as a “green” reactant and solvent and that no biomass drying is required, the technology offers a great potential for nutrient recycling. This study evaluated the possibility to treat the water HT effluent by the growth of microalgae while producing renewable algal biomass. As already demonstrated in previous works by the authors, the HT aqueous product besides having N, P and other important nutrients, presents a small fraction of organic compounds rarely studied. Therefore, extracted heteroaromatic compounds in the HT effluent were the target of the present research; they were profiled using GC-MS and LC-MS-MS. The results indicate the presence of cyclic amides, piperazinediones, amines and their derivatives. The most prominent nitrogenous organic compounds (NOC’s) in the extracts were carefully examined by their effect on microalgae, namely 2-pyrrolidinone and β-phenylethylamine (β-PEA). These two substances were prepared at three different concentrations (10, 50 and 150 ppm). This toxicity bioassay used three different microalgae strains: Phaeodactylum tricornutum, Chlorella sorokiniana and Scenedesmus vacuolatus. The confirmed IC50 was for all cases ca. 75ppm. Experimental conditions were set up for the growth of microalgae in the aqueous phase by adjusting the nitrogen concentration (the key nutrient for algae) to fit that one established for a known commercial medium. The values of specific NOC’s were lowered at concentrations of 8.5 mg/L 2-pyrrolidinone; 1mg/L δ-valerolactam and 0.5 mg/L β-PEA. The growth with the diluted HT solution was kept constant with no inhibition evidence. An additional ongoing test is addressing the possibility to apply an integrated water cleanup step making use of the existent hydrothermal catalytic facility.

Keywords: hydrothermal process, microalgae, nitrogenous organic compounds, nutrient recovery, renewable biomass

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Authors: Fatimah Abd Elghani, Raymonde Szargel, Vered Shani, Hazem Safory, Haya Hamza, Mor Savyon, Ruth Rott, Rina Bandopadhyay, Simone Engelender

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Background: PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. Down regulation of PINK1 results in abnormal mitochondrial morphology and altered membrane potential. Although PINK1 has a predicted mitochondrial import sequence, it’s cellular, and submitochondrial localization remains unclear, in part because it is rapidly degraded. In this work, we investigated the mechanisms involved in PINK1 degradation and how this may affect PINK1 stability and function, with implications for mitochondrial function in PD. In addition, pharmacological inhibition of proteasome activity was shown to lead to PINK1 accumulation, indicating that PINK1 degradation depends on the ubiquitin-proteasome system (UPS). Methods: Using co-immunoprecipitation assays, we identified E3 ubiquitin ligase SIAH1 as a PINK1-interacting protein in HEK293 cells as well as on rat brain tissues. In addition, we determined the effect of SIAH 1, SIAH2 and Parkin on PINK1 steady-state levels by Western blot analysis, and checked their possibility to ubiquitinate and mediate PINK1 degradation through the proteasome carried out in vivo ubiquitination experiments. Results: We have obtained results showing that SIAH-1 interacts with and ubiquitinates PINK1. The ubiquitination promoted by SIAH-1 leads to the proteasomal degradation of PINK1. We confirmed these findings by knocking down SIAH-1 and observing important accumulation of PINK1 in cells. Besides, we found that SIAH-1 decreases PINK1 steady-state levels but not the E3 ligase Parkin. We also investigated the interaction of SIAH-1 with PINK1 disease mutants and its ability to promote their ubiquitination and degradation. Although, no clear difference in the ability of SIAH-1 to promote the degradation of PINK1 disease mutants was observed. It is possible that dysfunction of proteasomal activity in the disease may lead to the accumulation and aggregation of ubiquitinated PINK1 in patients with PINK1 mutations, with possible implications to the pathogenesis of PD. Conclusions: Here, we demonstrated that SIAH-1 ubiquitinates and promotes the degradation of PINK1. In addition, SIAH-1 represents now a target that may help the improvement of mitophagy in PD. Further investigations needed to understand how mitophagy is regulated by PINK1-SIAH-1 axis to provide targets for future therapeutics.

Keywords: PD, Parkinson's disease, PINK1, PTEN-induced kinase1, SIAH, seven in absentia homolog, SN, substantia nigra

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Authors: Marina Aferiba Tandoh, Elsie Odei

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Peptic Ulcer Disease (PUD) is amongst the commonest gastrointestinal problems that require emergency treatment in order to preserve life. The prevalence of PUD is increasing within the Ghanaian population, deepening the need to identify factors that are associated with its occurrence. This cross-sectional study assessed the nutritional status, socioeconomic and lifestyle factors associated with PUD among patients attending the Out-Patient Department of the Tema General Hospital of Ghana. A food frequency questionnaire and a three-day, 24-hour recall were used to assess the dietary intakes of study participants. A standardized questionnaire was used to obtain information on the participants’ socio-demographic characteristics, lifestyle as well as medical history. The data was analyzed using SPSS version 22. The mean age of study participants was 32.8±15.41years. Females were significantly higher (61.4%) than males (38.6%) (p < 0.001). All participants had received some form of education, with tertiary education being the highest (52.6%). The majority of them managed their condition with medications only (86%), while 10.5% managed it with a combination of medications and diet. The rest were either by dietary counseling only (1.8%), or surgery only (1.8%). or herbal medicines (29.3%), which were made from home (7.2%) or bought from a medical store (10.8%). Most of the participants experienced a recurrence of the disease (42.1%). For those who had ever experienced recurrences of the disease, it happened when they ate acidic foods (1.8%), ate bigger portions (1.8%), starved themselves (1.8%), or were stressed (1.8%). Others also had triggers when they took certain medications (1.8%) or ate too much pepper (1.8%). About 49% of the participants were either overweight or obese with a recurrence of PUD (p>0.05). Obese patients had the highest rate of PUD recurrences (41%). Drinking alcohol was significantly associated with the recurrence of PUD (χ2= 5.243, p=0.026). Other lifestyles, such as weed smoking, fasting, and use of herbal medicine and NSAIDs did not have any significant association with the disease recurrence. There was no significant correlation between the various dietary patterns and anthropometric parameters except dietary pattern one (salty snacks, regular soft drinks, milk, sweetened yogurt, ice cream, and cooked vegetables), which had a positive correlation with weight (p=0.002) and BMI (p=0.038). PUD patients should target weight reduction actions and reduce alcohol intake as measures to control the recurrence of the disease. Nutrition Education among this population must be promoted to minimize the recurrence of PUD.

Keywords: Dietary patterns, lifestyle factors, nutritional status, peptic ulcer disease

Procedia PDF Downloads 61

Authors: Debjit Ray

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Horizontal gene transfer (HGT) and recombination leads to the emergence of bacterial antibiotic resistance and pathogenic traits. HGT events can be identified by comparing a large number of fully sequenced genomes across a species or genus, define the phylogenetic range of HGT, and find potential sources of new resistance genes. In-depth comparative phylogenomics can also identify subtle genome or plasmid structural changes or mutations associated with phenotypic changes. Comparative phylogenomics requires that accurately sequenced, complete and properly annotated genomes of the organism. Assembling closed genomes requires additional mate-pair reads or “long read” sequencing data to accompany short-read paired-end data. To bring down the cost and time required of producing assembled genomes and annotating genome features that inform drug resistance and pathogenicity, we are analyzing the performance for genome assembly of data from the Illumina NextSeq, which has faster throughput than the Illumina HiSeq (~1-2 days versus ~1 week), and shorter reads (150bp paired-end versus 300bp paired end) but higher capacity (150-400M reads per run versus ~5-15M) compared to the Illumina MiSeq. Bioinformatics improvements are also needed to make rapid, routine production of complete genomes a reality. Modern assemblers such as SPAdes 3.6.0 running on a standard Linux blade are capable in a few hours of converting mixes of reads from different library preps into high-quality assemblies with only a few gaps. Remaining breaks in scaffolds are generally due to repeats (e.g., rRNA genes) are addressed by our software for gap closure techniques, that avoid custom PCR or targeted sequencing. Our goal is to improve the understanding of emergence of pathogenesis using sequencing, comparative genomics, and machine learning analysis of ~1000 pathogen genomes. Machine learning algorithms will be used to digest the diverse features (change in virulence genes, recombination, horizontal gene transfer, patient diagnostics). Temporal data and evolutionary models can thus determine whether the origin of a particular isolate is likely to have been from the environment (could it have evolved from previous isolates). It can be useful for comparing differences in virulence along or across the tree. More intriguing, it can test whether there is a direction to virulence strength. This would open new avenues in the prediction of uncharacterized clinical bugs and multidrug resistance evolution and pathogen emergence.

Keywords: genomics, pathogens, genome assembly, superbugs

Procedia PDF Downloads 180

Authors: Qirat Naz, Abasiokpon Udoakah

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In developed countries, global migration is diversifying. The minority ethnic population, including refugees and asylum seekers who, fled their home countries due to war, terrorism, oppression, or natural disasters, and returning home is dangerous for them. They need sanctuary and peaceful environment in host countries. They begin the process of acculturation, in which a person adopts the social mores and behavioral patterns of the dominant culture, yet they still have unique multicultural needs that the dominant society fails to address. The aim of this research is to provide a holistic understanding of the living experiences of a minority population, particularly migrants, including asylum seekers and refugees, in the health and social care system of South Wales. The purpose of this study is to investigate three research objectives: the multicultural health care needs of minorities, as well as the barriers to seeking health and social care facilities. There are Welsh policies for promoting cultural competence in the health and social care sectors; this research will explore the implications and impact of these policies on the target population. This research study will be conducted using qualitative research methods, tools, and techniques. This research is an inductive approach to coming up with a grounded theory. The sample will be divided into two groups: migrants and professionals providing any kind of services to migrants; each group will contain 30 participants. Interpretive phenomenological analysis would be utilized during the process of coding and developing the main themes of this research. The positionality of the researcher would be minimized by unloaded and open-ended questions, researcher’s work experience in research, continuous evaluation of her positionality, daily base reflection of fieldwork and seeking the help of male and female gatekeepers. The research findings would be based on emic perspective, and by documenting the emic perspective of minorities, this research will contribute to the knowledge of appropriate channels, including organizations, academics, and policymakers, to discover possible solutions and coping mechanisms to deal with the challenges and meet the multicultural demands of minorities. This research will provide a more in-depth understanding of minorities and will help to promote the diversity of health and social care in South Wales.

Keywords: migration, migrants, cultural competence, cultural barriers, healthcare challenges

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Authors: Takaaki Nemoto

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Case presentation: A 69-year-old Japanese man presented with a low-grade fever and fatigue that had persisted for one month. The patient had an aortic dissection on the aortic arch 13 years prior, an abdominal aortic aneurysm seven years prior, and an aortic dissection on the distal aortic arch one year prior, which were all treated with artificial blood-vessel replacement surgery. Laboratory tests revealed an inflammatory response (CRP 7.61 mg/dl), high serum creatinine (Cr 1.4 mg/dL), and elevated transaminase (AST 47 IU/L, ALT 45 IU/L). The patient was admitted to our hospital on suspicion of prosthetic vascular graft infection. Following further workups on the inflammatory response, an enhanced chest computed tomography (CT) and a non-enhanced chest DWI (MRI) were performed. The patient was diagnosed with a pulmonary fistula and a prosthetic vascular graft infection on the distal aortic arch. After admission, the patient was administered Ceftriaxion and Vancomycine for 10 days, but his fever and inflammatory response did not improve. On day 13 of hospitalization, a lung fistula repair surgery and an omental filling operation were performed, and Meropenem and Vancomycine were administered. The fever and inflammatory response continued, and therefore we took repeated blood cultures. M. fortuitum was detected in a blood culture on day 16 of hospitalization. As a result, we changed the treatment regimen to Amikacin (400 mg/day), Meropenem (2 g/day), and Cefmetazole (4 g/day), and the fever and inflammatory response began to decrease gradually. We performed a test of sensitivity for Mycobacterium fortuitum, and found that the MIC was low for fluoroquinolone antibacterial agent. The clinical course was good, and the patient was discharged after a total of 8 weeks of intravenous drug administration. At discharge, we changed the treatment regimen to Levofloxacin (500 mg/day) and Clarithromycin (800 mg/day), and prescribed these two drugs as a long life suppressive therapy. Discussion: There are few cases of prosthetic vascular graft infection caused by mycobacteria, and a standard therapy remains to be established. For prosthetic vascular graft infections, it is ideal to provide surgical and medical treatment in parallel, but in this case, surgical treatment was difficult and, therefore, a conservative treatment was chosen. We attempted to increase the treatment success rate of this refractory disease by conducting a susceptibility test for mycobacteria and treating with different combinations of antimicrobial agents, which was ultimately effective. With our treatment approach, a good clinical course was obtained and continues at the present stage. Conclusion: Although prosthetic vascular graft infection resulting from mycobacteria is a refractory infectious disease, it may be curative to administer appropriate antibiotics based on the susceptibility test in addition to surgical treatment.

Keywords: prosthetic vascular graft infection, lung fistula, Mycobacterium fortuitum, conservative treatment

Procedia PDF Downloads 137

Authors: Chor Yi Ng, Christine Kong, Loretta Teo, Stephen Yau, FC Cheung, TL Poon, Francis Lee

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Purpose: Dynamic conformal arc (DCA) and intensity modulated radiotherapy (IMRT) are two treatment techniques commonly used for stereotactic radiosurgery/radiotherapy of cranial lesions. IMRT plans usually give better dose conformity while DCA plans have better dose fall off. Rapid dose fall off is preferred for radiotherapy of cranial lesions, but dose conformity is also important. For certain lesions, DCA plans have good conformity, while for some lesions, the conformity is just unacceptable with DCA plans, and IMRT has to be used. The choice between the two may not be apparent until each plan is prepared and dose indices compared. We described a deviation index (DI) which is a measurement of the deviation of the target shape from a sphere, and test its functionality to choose between the two techniques. Method and Materials: From May 2015 to May 2017, our institute has performed stereotactic radiotherapy for 105 patients treating a total of 115 lesions (64 DCA plans and 51 IMRT plans). Patients were treated with the Varian Clinac iX with HDMLC. Brainlab Exactrac system was used for patient setup. Treatment planning was done with Brainlab iPlan RT Dose (Version 4.5.4). DCA plans were found to give better dose fall off in terms of R50% (R50% (DCA) = 4.75 Vs R50% (IMRT) = 5.242) while IMRT plans have better conformity in terms of treatment volume ratio (TVR) (TVR(DCA) = 1.273 Vs TVR(IMRT) = 1.222). Deviation Index (DI) is proposed to better facilitate the choice between the two techniques. DI is the ratio of the volume of a 1 mm shell of the PTV and the volume of a 1 mm shell of a sphere of identical volume. DI will be close to 1 for a near spherical PTV while a large DI will imply a more irregular PTV. To study the functionality of DI, 23 cases were chosen with PTV volume ranged from 1.149 cc to 29.83 cc, and DI ranged from 1.059 to 3.202. For each case, we did a nine field IMRT plan with one pass optimization and a five arc DCA plan. Then the TVR and R50% of each case were compared and correlated with the DI. Results: For the 23 cases, TVRs and R50% of the DCA and IMRT plans were examined. The conformity for IMRT plans are better than DCA plans, with majority of the TVR(DCA)/TVR(IMRT) ratios > 1, values ranging from 0.877 to1.538. While the dose fall off is better for DCA plans, with majority of the R50%(DCA)/ R50%(IMRT) ratios < 1. Their correlations with DI were also studied. A strong positive correlation was found between the ratio of TVRs and DI (correlation coefficient = 0.839), while the correlation between the ratio of R50%s and DI was insignificant (correlation coefficient = -0.190). Conclusion: The results suggest DI can be used as a guide for choosing the planning technique. For DI greater than a certain value, we can expect the conformity for DCA plans to become unacceptably great, and IMRT will be the technique of choice.

Keywords: cranial lesions, dynamic conformal arc, IMRT, image guided radiotherapy, stereotactic radiotherapy

Procedia PDF Downloads 222

Authors: Sourav Ray, Christoph Stein, Marcus Weber

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

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

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Authors: Aswini M. S.

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Tomato (Solanum lycopersicum L.) is one of the most significant vegetable crops in terms of its economic benefits. Both fresh and processed tomatoes are consumed. Tomatoes have a limited genetic base, which makes breeding extremely challenging. Plant breeding has become much simpler and more effective with genome editing tools of CRISPR and CRISPR-associated 9 protein (CRISPR/Cas9), which address the problems with traditional breeding, chemical/physical mutagenesis, and transgenics. With the use of CRISPR/Cas9, a number of tomato traits have been functionally distinguished and edited. These traits include plant architecture as well as flower characters (leaf, flower, male sterility, and parthenocarpy), fruit ripening, quality and nutrition (lycopene, carotenoid, GABA, TSS, and shelf-life), disease resistance (late blight, TYLCV, and powdery mildew), tolerance to abiotic stress (heat, drought, and salinity) and resistance to herbicides. This study explores the potential of CRISPR/Cas9 genome editing for enhancing yield in tomato plants. The study utilized the CRISPR/Cas9 genome editing technology to functionally edit various traits in tomatoes. The de novo domestication of elite features from wild cousins to cultivated tomatoes and vice versa has been demonstrated by the introgression of CRISPR/Cas9. The CycB (Lycopene beta someri) gene-mediated Cas9 editing increased the lycopene content in tomato. Also, Cas9-mediated editing of the AGL6 (Agamous-like 6) gene resulted in parthenocarpic fruit development under heat-stress conditions. The advent of CRISPR/Cas has rendered it possible to use digital resources for single guide RNA design and multiplexing, cloning (such as Golden Gate cloning, GoldenBraid, etc.), creating robust CRISPR/Cas constructs, and implementing effective transformation protocols like the Agrobacterium and DNA free protoplast method for Cas9-gRNAs ribonucleoproteins (RNPs) complex. Additionally, homologous recombination (HR)-based gene knock-in (HKI) via geminivirus replicon and base/prime editing (Target-AID technology) remains possible. Hence, CRISPR/Cas facilitates fast and efficient breeding in the improvement of tomatoes.

Keywords: CRISPR-Cas, biotic and abiotic stress, flower and fruit traits, genome editing, polygenic trait, tomato and trait introgression

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Authors: Fabiola Xavier Leal, Lara Campanharo, Sueli Aparecida Rodrigues Lucas

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The phenomenon of judicialization in health policy brings with it a great deal of problematization, but in general, it means that some issues that were previously solved by traditional political bodies are being decided by the Judiciary bodies. It is, therefore, a controversial topic that has generated many reflections both in the academic and political fields, considering that not only a dispute of public funds is at stake, but also the debate on access to social rights provided for in the Brazilian Federal Constitution of 1988 and in the various public policies, such as healthcare. With regard to the phenomenon in the Mental Health Policy focusing on people who use drugs, the disputes that permeate this scenario are evident: moral, cultural, sanitary, economic, psychological aspects. There are also the individual and collective dimensions of suffering. And in this process, we all question: What is the role of the Brazilian State in this matter? In this context, another question that needs to be answered is the amount spent on this procedure in the state of Espírito Santo (ES), Brazil (in the last 04 years, around R$121,978,591.44 were paid only for compulsory hospitalization of individuals) in the field in question, which is the financing of the services of the Psychosocial Care Network (RAPS). Therefore, this article aims to problematize the phenomenon of judicialization in Mental Health Policy through the compulsory hospitalization of people who use drugs in Espírito Santo (ES). We proposed a study that sought to understand how this has been occurring and making an impact on the provision of RAPS services in the Espírito Santo scenario. Therefore, the general objective of this study is to analyze the expenses with compulsory hospitalizations for drug use carried out by the State Health Department (SESA) between 2014 and 2019, in which we will seek to identify its destination and the impact of these actions on public health policy. For the purposes of this article, we will present the preliminary data of this study, such as the amount spent by the state and the receiving institutions. For data collection, the following data sources were used: documents available publicly on the Transparency Portal (payments made per year, institutions that received, subjects hospitalized, period and the amount of the daily rates paid); as well as the processes generated by SESA through its own system - ONBASE. For qualitative analysis, content analysis was used; and for quantitative analysis, descriptive statistics was used. Thus, we seek to problematize the issue of judicialization for compulsory hospitalizations, considering the current situation in which this resource has been widely requested to legitimize the war on drugs. This scenario highlights the moral-legal discourse, pointing out strategies through the control of bodies and through faith as an alternative.

Keywords: compulsory hospitalization, drugs, judicialization, mental health

Procedia PDF Downloads 145

Authors: Omer Burak Iskender, Keck Voon Ling, Vincent Dubanchet, Luca Simonini

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This paper presents Guidance and Control (G&C) strategy to approach and synchronize with potentially rotating targets. The proposed strategy generates and tracks a safe trajectory for space servicing missions, including tasks like approaching, inspecting, and capturing. The main objective of this paper is to validate the G&C laws using a Hardware-In-the-Loop (HIL) setup with realistic rendezvous and docking equipment. Throughout this work, the assumption of full relative state feedback is relaxed by onboard sensors that bring realistic errors and delays and, while the proposed closed loop approach demonstrates the robustness to the above mentioned challenge. Moreover, G&C blocks are unified via the Model Predictive Control (MPC) paradigm, and the coupling between translational motion and rotational motion is addressed via dual quaternion based kinematic description. In this work, G&C is formulated as a convex optimization problem where constraints such as thruster limits and the output constraints are explicitly handled. Furthermore, the Monte-Carlo method is used to evaluate the robustness of the proposed method to the initial condition errors, the uncertainty of the target's motion and attitude, and actuator errors. A capture scenario is tested with the robotic test bench that has onboard sensors which estimate the position and orientation of a drifting satellite through camera imagery. Finally, the approach is compared with currently used robust H-infinity controllers and guidance profile provided by the industrial partner. The HIL experiments demonstrate that the proposed strategy is a potential candidate for future space servicing missions because 1) the algorithm is real-time implementable as convex programming offers deterministic convergence properties and guarantee finite time solution, 2) critical physical and output constraints are respected, 3) robustness to sensor errors and uncertainties in the system is proven, 4) couples translational motion with rotational motion.

Keywords: dual quaternion, model predictive control, real-time experimental test, rendezvous and docking, spacecraft autonomy, space servicing

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Authors: Reda Moussa Massoud Embark

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Tourism and hospitality graduate development is key to the future state of the tourism and hospitality industry. Meanwhile, Information and Communication Technology is increasingly becoming the engine for improving productivity and business opportunities in the travel and hospitality industry. Given the challenges and fierce global competition that have arisen in today's hospitality industry, it was important to shed light on strategic management. In addition, five-star hotels play a key role in supporting the tourism industry and investments in Egypt. Therefore, this study aims to examine the extent to which strategic management practices are implemented in five-star hotels in Egypt and to examine the differences between resort and inner-city hotels in terms of the implementation of strategic management processes. The influence of different hotel types on the implementation of the strategic management process is examined. A simple random sampling technique is used to select a sample of the target population, including hotels in the cities of Sharm el-Sheikh, Cairo and Hurghada. The data collection tool used in this study is an interviewer-administered questionnaire. Finally, combining the study results with the literature review allowed to present a set of recommendations to be addressed to hoteliers in the area of strategic management practices. Education and training in tourism and hospitality must take these changes into account in order to improve the ability of future managers to use a variety of tools and strategies to make their organizations more efficient and competitive. Therefore, this study aims to examine the types and effectiveness of training courses offered by tourism and hospitality departments in Egypt and to assess the importance of these training courses from the perspective of the graduate. The survey is aimed at graduates who have completed three different majors in the past decade: tourism and hospitality. Findings discussed the nature, level and effectiveness of the training provided at these faculties and the extent to which the training programs were valued by graduates working in different fields, and finally recommended specific practices to improve learning effectiveness increase and increase perceived employee benefits in the tourism and hospitality industry.

Keywords: marketing channels, crisis, hotel, international, tour, operators, online travel agencies, e-tourism, hotel websites, tourism, web-tourism, strategic-management, strategic tools, five-star hotels, resorts, downtown hotels, Egyptian Markets.

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Authors: Rebecca Pryce, Nijole Bernaitis, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Background: Warfarin is an oral anticoagulant widely used in the prevention of strokes in patients with atrial fibrillation (AF) and in the treatment and prevention of deep vein thrombosis (DVT). Regular monitoring of Internationalised Normalised Ratio (INR) is required to ensure therapeutic benefit with time in therapeutic range (TTR) used to measure warfarin control. A number of factors influence TTR including diet, concurrent illness, and drug interactions. Extensive literature exists regarding the effect of conventional medicines on warfarin control, but documented interactions relating to complementary medicines are limited. It has been postulated that fish oil and krill oil supplementation may affect warfarin due to their association with bleeding events. However, to date little is known as to whether fish and krill oil significantly alter the incidence of bleeding with warfarin or impact on warfarin control. Aim:To assess the influence of fish oil and krill oil supplementation on warfarin control in AF and DVT patients by determining the influence of these supplements on TTR and bleeding events. Methods:A retrospective cohort analysis was conducted utilising patient information from a large private pathology practice in Queensland. AF and DVT patients receiving warfarin management by the pathology practice were identified and their TTR calculated using the Rosendaal method. Concurrent medications were analysed and patients taking no other interacting medicines were identified and divided according to users of fish oil and krill oil supplements and those taking no supplements. Study variables included TTR and the incidence of bleeding with exclusion criteria being less than 30 days of treatment with warfarin. Subject characteristics were reported as the mean and standard deviation for continuous data and number and percentages for nominal or categorical data. Data was analysed using GraphPad InStat Version 3 with a p value of <0.05 considered to be statistically significant. Results:Of the 2081 patients assessed for inclusion into this study, a total of 573 warfarin users met the inclusion criteria. Of these, 416 (72.6%) patients were AF patients and 157 (27.4%) DVT patients and overall there were 316 (55.1%) male and 257 (44.9%) female patients. 145 patients were included in the fish oil/krill oil group (supplement) and 428 were included in the control group. The mean TTR of supplement users was 86.9% and for the control group 84.7% with no significant difference between these groups. Control patients experienced 1.6 times the number of minor bleeds per person compared to supplement patients and 1.2 times the number of major bleeds per person. However, this was not statistically significant nor was the comparison between thrombotic events. Conclusion: No significant difference was found between supplement and control patients in terms of mean TTR, the number of bleeds and thrombotic events. Fish oil and krill oil supplements when used concurrently with warfarin do not significantly affect warfarin control as measured by TTR and bleeding incidence.

Keywords: atrial fibrillation, deep vein thormbosis, fish oil, krill oil, warfarin

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Authors: Lea Boidin, Martha Baydoun, Bertrand Leroux, Olivier Morales, Samir Acherar, Celine Frochot, Nadira Delhem

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Ovarian cancer (OC) is one of the most defying diseases in gynecologic oncology. Even though surgery remains crucial in the therapy of patients with primary ovarian cancer, recurrent recidivism calls for the development of new therapy protocols to propose for patients dealing with this cancer. FRα is described as a tumor‐associated antigen in OC, where FRα expression is usually linked with more poorly differentiated, aggressive tumors. The Photodynamic treatment (PDT) available data have shown improvements in the uptake of small tumors and in the induction of a proper anti-tumoral immune response. In order to target specifically peritoneal metastatis, which overexpress FRα, a new-patented PS coupled with folic acid has been developed in our team. Herein we propose PDT using this new patented PS for PDT applied in an in vivo mice model. The efficacy of the treatment was evaluated in mice without and with PBMC reconstitution. Mice were divided into four groups: Non-Treated, PS, Light Only, and PDT Treated and subjected to illumination by laser set at 668nm with a duration of illumination of 45 minutes (or 1 min of illumination followed by 2 minutes of pause repeated 45 times). When mice were not reconstituted and after fractionized PDT protocol, a significant decrease in the tumor volume was noticed. An induction in the anti-tumoral cytokine IFNγ chaperoned this decrease while a subsequent inhibition in the cytokine TGFβ. Even more crucial, when mice were reconstituted and upon PDT, the fold of tumor decrease was even higher. An immune response was activated decoded with an increase in NK, CD3 +, LT helper and Cytotoxic T cells. Thereafter, an increase in the expression of the cytokines IFNγ and TNFα were noticed while an inhibition in TGFβ, IL8 and IL10 accompanied this immune response activation. Therefore, our work has shown for the first time that a fractionized PDT protocol using a folate-targeted PDT is effective for treatment of ovarian cancer. The interest in using PDT in this case, goes beyond the local induction of tumor apoptosis only, but can promote subsequent anti-tumor response. Most of the therapies currently used to treat ovarian cancer, have an uncooperative outcomes on the host immune response. The readiness of a tumor adjuvant treatment like PDT adequate in eliminating the tumor and in concert stimulating anti-tumor immunity would be weighty.

Keywords: folate receptor, ovarian cancer, photodynamic therapy, humanized mice model

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Authors: Lunthita M. Duthely, John T. Avella, John Ganapati Coleman

Abstract:

For as many as one in three adolescents living in the United States, the adolescent years is a period of low well-being and mental health challenges—from depressive symptoms to mild to moderate psychological diagnoses. Longitudinal population health studies demonstrated that these challenges persist in young adulthood, and beyond. The positive psychology (PS) approach is a more preventative approach to well-being, which contrasts the traditional, deficits approach to curing mental illness. The research among adult populations formed the basis for PS studies among adolescents. The empirical evidence for the effectiveness of PS interventions exists for both adult and youth populations. Positive Psychology interventions target individuals’ strengths, such as hope and optimism, and positive emotions, such as gratitude. Positive psychology interventions such as increasing gratitude, proved effective in many outcomes among youth, including psychological, social, and academically-related outcomes. Although gratitude-inducing studies have been conducted for the past decade in the United States, few studies have been conducted among samples of urban youth, particularly youth of diverse cultural backgrounds. For nearly two decades, the secular practice of meditation has been tested among adults and more recently among youth, focused mostly among clinical samples. The field of Contemplative Sciences explores practices such as Hatha Yoga, Tai Chi, and Meditation, as preventative practices among children and adolescents. A more recent initiative is to explore Contemplative Practices in the school environment. Contemplative Practices yield a variety of positive outcomes, including academic, social, psychological, physiological, and neurological changes among children and adolescents. Again, few studies were conducted among adolescents of diverse cultural backgrounds. The purpose of this doctoral dissertation research study was to test a gratitude-meditation intervention among middle school students attending a public charter school, located in an urban region of Metropolitan Miami. The objective of this presentation is to summarize the challenges and success of bringing a positive psychology and meditation intervention into an urban middle school. Also, the most recent findings on positive psychology and meditation interventions conducted in school environments will be presented as well.

Keywords: adolescents, contemplative intervention, gratitude, secular meditation, positive psychology, school engagement, Sri Chinmoy

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