Search results for: patients outcomes
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 7899

Search results for: patients outcomes

279 A Proposed Framework for Better Managing Small Group Projects on an Undergraduate Foundation Programme at an International University Campus

Authors: Sweta Rout-Hoolash

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Each year, selected students from around 20 countries begin their degrees at Middlesex University with the International Foundation Program (IFP), developing the skills required for academic study at a UK university. The IFP runs for 30 learning/teaching weeks at Middlesex University Mauritius Branch Campus, which is an international campus of UK’s Middlesex University. Successful IFP students join their degree courses already settled into life at their chosen campus (London, Dubai, Mauritius or Malta) and confident that they understand what is required for degree study. Although part of the School of Science and Technology, in Mauritius it prepares students for undergraduate level across all Schools represented on campus – including disciplines such as Accounting, Business, Computing, Law, Media and Psychology. The researcher has critically reviewed the framework and resources in the curriculum for a particular six week period of IFP study (dedicated group work phase). Despite working together closely for 24 weeks, IFP students approach the final 6 week small group work project phase with mainly inhibitive feelings. It was observed that students did not engage effectively in the group work exercise. Additionally, groups who seemed to be working well did not necessarily produce results reflecting effective collaboration, nor individual members’ results which were better than prior efforts. The researcher identified scope for change and innovation in the IFP curriculum and how group work is introduced and facilitated. The study explores the challenges of groupwork in the context of the Mauritius campus, though it is clear that the implications of the project are not restricted to one campus only. The presentation offers a reflective review on the previous structure put in place for the management of small group assessed projects on the programme from both the student and tutor perspective. The focus of the research perspective is the student voice, by taking into consideration past and present IFP students’ experiences as written in their learning journals. Further, it proposes the introduction of a revised framework to help students take greater ownership of the group work process in order to engage more effectively with the learning outcomes of this crucial phase of the programme. The study has critically reviewed recent and seminal literature on how to achieve greater student ownership during this phase especially under an environment of assessed multicultural group work. The presentation proposes several new approaches for encouraging students to take more control of the collaboration process. Detailed consideration is given to how the proposed changes impact on the work of other stakeholders, or partners to student learning. Clear proposals are laid out for evaluation of the different approaches intended to be implemented during the upcoming academic year (student voice through their own submitted reflections, focus group interviews and through the assessment results). The proposals presented are all realistic and have the potential to transform students’ learning. Furthermore, the study has engaged with the UK Professional Standards Framework for teaching and supporting learning in higher education, and demonstrates practice at the level of ‘fellow’ of the Higher Education Academy (HEA).

Keywords: collaborative peer learning, enhancing learning experiences, group work assessment, learning communities, multicultural diverse classrooms, studying abroad

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278 Exploring Type V Hydrogen Storage Tanks: Shape Analysis and Material Evaluation for Enhanced Safety and Efficiency Focusing on Drop Test Performance

Authors: Mariam Jaber, Abdullah Yahya, Mohammad Alkhedher

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The shift toward sustainable energy solutions increasingly focuses on hydrogen, recognized for its potential as a clean energy carrier. Despite its benefits, hydrogen storage poses significant challenges, primarily due to its low energy density and high volatility. Among the various solutions, pressure vessels designed for hydrogen storage range from Type I to Type V, each tailored for specific needs and benefits. Notably, Type V vessels, with their all-composite, liner-less design, significantly reduce weight and costs while optimizing space and decreasing maintenance demands. This study focuses on optimizing Type V hydrogen storage tanks by examining how different shapes affect performance in drop tests—a crucial aspect of achieving ISO 15869 certification. This certification ensures that if a tank is dropped, it will fail in a controlled manner, ideally by leaking before bursting. While cylindrical vessels are predominant in mobile applications due to their manufacturability and efficient use of space, spherical vessels offer superior stress distribution and require significantly less material thickness for the same pressure tolerance, making them advantageous for high-pressure scenarios. However, spherical tanks are less efficient in terms of packing and more complex to manufacture. Additionally, this study introduces toroidal vessels to assess their performance relative to the more traditional shapes, noting that the toroidal shape offers a more space-efficient option. The research evaluates how different shapes—spherical, cylindrical, and toroidal—affect drop test outcomes when combined with various composite materials and layup configurations. The ultimate goal is to identify optimal vessel geometries that enhance the safety and efficiency of hydrogen storage systems. For our materials, we selected high-performance composites such as Carbon T-700/Epoxy, Kevlar/Epoxy, E-Glass Fiber/Epoxy, and Basalt/Epoxy, configured in various orientations like [0,90]s, [45,-45]s, and [54,-54]. Our tests involved dropping tanks from different angles—horizontal, vertical, and 45 degrees—with an internal pressure of 35 MPa to replicate real-world scenarios as closely as possible. We used finite element analysis and first-order shear deformation theory, conducting tests with the Abaqus Explicit Dynamics software, which is ideal for handling the quick, intense stresses of an impact. The results from these simulations will provide valuable insights into how different designs and materials can enhance the durability and safety of hydrogen storage tanks. Our findings aim to guide future designs, making them more effective at withstanding impacts and safer overall. Ultimately, this research will contribute to the broader field of lightweight composite materials and polymers, advancing more innovative and practical approaches to hydrogen storage. By refining how we design these tanks, we are moving toward more reliable and economically feasible hydrogen storage solutions, further emphasizing hydrogen's role in the landscape of sustainable energy carriers.

Keywords: hydrogen storage, drop test, composite materials, type V tanks, finite element analysis

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277 The Beneficial Effects of Inhibition of Hepatic Adaptor Protein Phosphotyrosine Interacting with PH Domain and Leucine Zipper 2 on Glucose and Cholesterol Homeostasis

Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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276 Investigating Links in Achievement and Deprivation (ILiAD): A Case Study Approach to Community Differences

Authors: Ruth Leitch, Joanne Hughes

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This paper presents the findings of a three-year government-funded study (ILiAD) that aimed to understand the reasons for differential educational achievement within and between socially and economically deprived areas in Northern Ireland. Previous international studies have concluded that there is a positive correlation between deprivation and underachievement. Our preliminary secondary data analysis suggested that the factors involved in educational achievement within multiple deprived areas may be more complex than this, with some areas of high multiple deprivation having high levels of student attainment, whereas other less deprived areas demonstrated much lower levels of student attainment, as measured by outcomes on high stakes national tests. The study proposed that no single explanation or disparate set of explanations could easily account for the linkage between levels of deprivation and patterns of educational achievement. Using a social capital perspective that centralizes the connections within and between individuals and social networks in a community as a valuable resource for educational achievement, the ILiAD study involved a multi-level case study analysis of seven community sites in Northern Ireland, selected on the basis of religious composition (housing areas are largely segregated by religious affiliation), measures of multiple deprivation and differentials in educational achievement. The case study approach involved three (interconnecting) levels of qualitative data collection and analysis - what we have termed Micro (or community/grassroots level) understandings, Meso (or school level) explanations and Macro (or policy/structural) factors. The analysis combines a statistical mapping of factors with qualitative, in-depth data interpretation which, together, allow for deeper understandings of the dynamics and contributory factors within and between the case study sites. Thematic analysis of the qualitative data reveals both cross-cutting factors (e.g. demographic shifts and loss of community, place of the school in the community, parental capacity) and analytic case studies of explanatory factors associated with each of the community sites also permit a comparative element. Issues arising from the qualitative analysis are classified either as drivers or inhibitors of educational achievement within and between communities. Key issues that are emerging as inhibitors/drivers to attainment include: the legacy of the community conflict in Northern Ireland, not least in terms of inter-generational stress, related with substance abuse and mental health issues; differing discourses on notions of ‘community’ and ‘achievement’ within/between community sites; inter-agency and intra-agency levels of collaboration and joined-up working; relationship between the home/school/community triad and; school leadership and school ethos. At this stage, the balance of these factors can be conceptualized in terms of bonding social capital (or lack of it) within families, within schools, within each community, within agencies and also bridging social capital between the home/school/community, between different communities and between key statutory and voluntary organisations. The presentation will outline the study rationale, its methodology, present some cross-cutting findings and use an illustrative case study of the findings from a community site to underscore the importance of attending to community differences when trying to engage in research to understand and improve educational attainment for all.

Keywords: educational achievement, multiple deprivation, community case studies, social capital

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275 Climate Safe House: A Community Housing Project Tackling Catastrophic Sea Level Rise in Coastal Communities

Authors: Chris Fersterer, Col Fay, Tobias Danielmeier, Kat Achterberg, Scott Willis

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New Zealand, an island nation, has an extensive coastline peppered with small communities of iconic buildings known as Bachs. Post WWII, these modest buildings were constructed by their owners as retreats and generally were small, low cost, often using recycled material and often they fell below current acceptable building standards. In the latter part of the 20th century, real estate prices in many of these communities remained low and these areas became permanent residences for people attracted to this affordable lifestyle choice. The Blueskin Resilient Communities Trust (BRCT) is an organisation that recognises the vulnerability of communities in low lying settlements as now being prone to increased flood threat brought about by climate change and sea level rise. Some of the inhabitants of Blueskin Bay, Otago, NZ have already found their properties to be un-insurable because of increased frequency of flood events and property values have slumped accordingly. Territorial authorities also acknowledge this increased risk and have created additional compliance measures for new buildings that are less than 2 m above tidal peaks. Community resilience becomes an additional concern where inhabitants are attracted to a lifestyle associated with a specific location and its people when this lifestyle is unable to be met in a suburban or city context. Traditional models of social housing fail to provide the sense of community connectedness and identity enjoyed by the current residents of Blueskin Bay. BRCT have partnered with the Otago Polytechnic Design School to design a new form of community housing that can react to this environmental change. It is a longitudinal project incorporating participatory approaches as a means of getting people ‘on board’, to understand complex systems and co-develop solutions. In the first period, they are seeking industry support and funding to develop a transportable and fully self-contained housing model that exploits current technologies. BRCT also hope that the building will become an educational tool to highlight climate change issues facing us today. This paper uses the Climate Safe House (CSH) as a case study for education in architectural sustainability through experiential learning offered as part of the Otago Polytechnics Bachelor of Design. Students engage with the project with research methodologies, including site surveys, resident interviews, data sourced from government agencies and physical modelling. The process involves collaboration across design disciplines including product and interior design but also includes connections with industry, both within the education institution and stakeholder industries introduced through BRCT. This project offers a rich learning environment where students become engaged through project based learning within a community of practice, including architecture, construction, energy and other related fields. The design outcomes are expressed in a series of public exhibitions and forums where community input is sought in a truly participatory process.

Keywords: community resilience, problem based learning, project based learning, case study

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274 Providing Health Promotion Information by Digital Animation to International Visitors in Japan: A Factorial Design View of Nurses

Authors: Mariko Nishikawa, Masaaki Yamanaka, Ayami Kondo

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Background: International visitors to Japan are at a risk of travel-related illnesses or injury that could result in hospitalization in a country where the language and customs are unique. Over twelve million international visitors came to Japan in 2015, and more are expected leading up to the Tokyo Olympics. One aspect of this is the potentially greater demand on healthcare services by foreign visitors. Nurses who take care of them have anxieties and concerns of their knowledge of the Japanese health system. Objectives: An effective distribution of travel-health information is vital for facilitating care for international visitors. Our research investigates whether a four-minute digital animation (Mari Info Japan), designed and developed by the authors and applied to a survey of 513 nurses who take care of foreigners daily, could clarify travel health procedures, reduce anxieties, while making it enjoyable to learn. Methodology: Respondents to a survey were divided into two groups. The intervention group watched Mari Info Japan. The control group read a standard guidebook. The participants were requested to fill a two-page questionnaire called Mari Meter-X, STAI-Y in English and mark a face scale, before and after the interventions. The questions dealt with knowledge of health promotion, the Japanese healthcare system, cultural concerns, anxieties, and attitudes in Japan. Data were collected from an intervention group (n=83) and control group (n=83) of nurses in a hospital, Japan for foreigners from February to March, 2016. We analyzed the data using Text Mining Studio for open-ended questions and JMP for statistical significance. Results: We found that the intervention group displayed more confidence and less anxiety to take care of foreign patients compared to the control group. The intervention group indicated a greater comfort after watching the animation. However, both groups were most likely to be concerned about language, the cost of medical expenses, informed consent, and choice of hospital. Conclusions: From the viewpoint of nurses, the provision of travel-health information by digital animation to international visitors to Japan was more effective than traditional methods as it helped them be better prepared to treat travel-related diseases and injury among international visitors. This study was registered number UMIN000020867. Funding: Grant–in-Aid for Challenging Exploratory Research 2010-2012 & 2014-16, Japanese Government.

Keywords: digital animation, health promotion, international visitor, Japan, nurse

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273 Using Lysosomal Immunogenic Cell Death to Target Breast Cancer via Xanthine Oxidase/Micro-Antibody Fusion Protein

Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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272 A Triple Win: Linking Students, Academics, and External Organisations to Provide Real-World Learning Experiences with Real-World Benefits

Authors: Anne E. Goodenough

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Students often learn best ‘on the job’ through holistic real-world projects. They need real-world experiences to make classroom learning applicable and to increase their employability. Academics typically value working on projects where new knowledge is created and have a genuine desire to help students engage with learning and develop new skills. They might also have institutional pressure to enhance student engagement, retention, and satisfaction. External organizations - especially non-governmental bodies, charities, and small enterprises - often have fundamental and pressing questions, but lack the manpower and academic expertise to answer them effectively. They might also be on the lookout for talented potential employees. This study examines ways in which these diverse requirements can be met simultaneously by creating three-way projects that provide excellent academic and real-world outcomes for all involved. It studied a range of innovative projects across natural sciences (biology, ecology, physical geography and social sciences (human geography, sociology, criminology, and community engagement) to establish how to best harness the potential of this powerful approach. Focal collaborations included: (1) development of practitioner-linked modules; (2) frameworks where students collected/analyzed data for link organizations in research methods modules; (3) placement-based internships and dissertations; and (4) immersive fieldwork projects in novel locations to allow students engage first-hand with contemporary issues as diverse as rhino poaching in South Africa, segregation in Ireland, and gun crime in Florida. Although there was no ‘magic formula’ for success, the approach was found to work best when small projects were developed that were achievable in a short time-frame, both to tie into modular curricula and meet the immediacy expectations of many link organizations. Bigger projects were found to work well in some cases, especially when they were essentially a series of linked smaller projects, either running concurrently or successively with each building on previous work. Opportunities were maximized when there were tangible benefits to the link organization as this generally increased organization investment in the project and motivated students too. The importance of finding the right approach for a given project was found to be key: it was vital to ensure that something that could work effectively as an independent research project for one student, for example, was not shoehorned into being a project for multiple students within a taught module. In general, students were very positive about collaboration projects. They identified benefits to confidence, time-keeping and communication, as well as conveying their enthusiasm when their work was of benefit to the wider community. Several students have gone on to do further work with the link organization in a voluntary capacity or as paid staff, or used the experiences to help them break into the ever-more competitive job market in other ways. Although this approach involves a substantial time investment, especially from academics, the benefits can be profound. The approach has strong potential to engage students, help retention, improve student satisfaction, and teach new skills; keep the knowledge of academics fresh and current; and provide valuable tangible benefits for link organizations: a real triple win.

Keywords: authentic learning, curriculum development, effective education, employability, higher education, innovative pedagogy, link organizations, student experience

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271 A Prospective Study of a Clinically Significant Anatomical Change in Head and Neck Intensity-Modulated Radiation Therapy Using Transit Electronic Portal Imaging Device Images

Authors: Wilai Masanga, Chirapha Tannanonta, Sangutid Thongsawad, Sasikarn Chamchod, Todsaporn Fuangrod

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The major factors of radiotherapy for head and neck (HN) cancers include patient’s anatomical changes and tumour shrinkage. These changes can significantly affect the planned dose distribution that causes the treatment plan deterioration. A measured transit EPID images compared to a predicted EPID images using gamma analysis has been clinically implemented to verify the dose accuracy as part of adaptive radiotherapy protocol. However, a global gamma analysis dose not sensitive to some critical organ changes as the entire treatment field is compared. The objective of this feasibility study is to evaluate the dosimetric response to patient anatomical changes during the treatment course in HN IMRT (Head and Neck Intensity-Modulated Radiation Therapy) using a novel comparison method; organ-of-interest gamma analysis. This method provides more sensitive to specific organ change detection. Random replanned 5 HN IMRT patients with causes of tumour shrinkage and patient weight loss that critically affect to the parotid size changes were selected and evaluated its transit dosimetry. A comprehensive physics-based model was used to generate a series of predicted transit EPID images for each gantry angle from original computed tomography (CT) and replan CT datasets. The patient structures; including left and right parotid, spinal cord, and planning target volume (PTV56) were projected to EPID level. The agreement between the transit images generated from original CT and replanned CT was quantified using gamma analysis with 3%, 3mm criteria. Moreover, only gamma pass-rate is calculated within each projected structure. The gamma pass-rate in right parotid and PTV56 between predicted transit of original CT and replan CT were 42.8%( ± 17.2%) and 54.7%( ± 21.5%). The gamma pass-rate for other projected organs were greater than 80%. Additionally, the results of organ-of-interest gamma analysis were compared with 3-dimensional cone-beam computed tomography (3D-CBCT) and the rational of replan by radiation oncologists. It showed that using only registration of 3D-CBCT to original CT does not provide the dosimetric impact of anatomical changes. Using transit EPID images with organ-of-interest gamma analysis can provide additional information for treatment plan suitability assessment.

Keywords: re-plan, anatomical change, transit electronic portal imaging device, EPID, head, and neck

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270 Anti-Phospholipid Antibody Syndrome Presenting with Seizure, Stroke and Atrial Mass: A Case Report

Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

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Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

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269 Monitoring of Serological Test of Blood Serum in Indicator Groups of the Population of Central Kazakhstan

Authors: Praskovya Britskaya, Fatima Shaizadina, Alua Omarova, Nessipkul Alysheva

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Planned preventive vaccination, which is carried out in the Republic of Kazakhstan, promoted permanent decrease in the incidence of measles and viral hepatitis B. In the structure of VHB patients prevail people of young, working age. Monitoring of infectious incidence, monitoring of coverage of immunization of the population, random serological control over the immunity enable well-timed identification of distribution of the activator, effectiveness of the taken measures and forecasting. The serological blood analysis was conducted in indicator groups of the population of Central Kazakhstan for the purpose of identification of antibody titre for vaccine preventable infections (measles, viral hepatitis B). Measles antibodies were defined by method of enzyme-linked assay (ELA) with test-systems "VektoKor" – Ig G ('Vektor-Best' JSC). Antibodies for HBs-antigen of hepatitis B virus in blood serum was identified by method of enzyme-linked assay (ELA) with VektoHBsAg test systems – antibodies ('Vektor-Best' JSC). The result of the analysis is positive, the concentration of IgG to measles virus in the studied sample is equal to 0.18 IU/ml or more. Protective level of concentration of anti-HBsAg makes 10 mIU/ml. The results of the study of postvaccinal measles immunity showed that the share of seropositive people made 87.7% of total number of surveyed. The level of postvaccinal immunity to measles in age groups differs. So, among people older than 56 the percentage of seropositive made 95.2%. Among people aged 15-25 were registered 87.0% seropositive, at the age of 36-45 – 86.6%. In age groups of 25-35 and 36-45 the share of seropositive people was approximately at the same level – 88.5% and 88.8% respectively. The share of people seronegative to a measles virus made 12.3%. The biggest share of seronegative people was found among people aged 36-45 – 13.4% and 15-25 – 13.0%. The analysis of results of the examined people for the existence of postvaccinal immunity to viral hepatitis B showed that from all surveyed only 33.5% have the protective level of concentration of anti-HBsAg of 10 mIU/ml and more. The biggest share of people protected from VHB virus is observed in the age group of 36-45 and makes 60%. In the indicator group – above 56 – seropositive people made 4.8%. The high percentage of seronegative people has been observed in all studied age groups from 40.0% to 95.2%. The group of people which is least protected from getting VHB is people above 56 (95.2%). The probability to get VHB is also high among young people aged 25-35, the percentage of seronegative people made 80%. Thus, the results of the conducted research testify to the need for carrying out serological monitoring of postvaccinal immunity for the purpose of operational assessment of the epidemiological situation, early identification of its changes and prediction of the approaching danger.

Keywords: antibodies, blood serum, immunity, immunoglobulin

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268 Exploring Participatory Research Approaches in Agricultural Settings: Analyzing Pathways to Enhance Innovation in Production

Authors: Michele Paleologo, Marta Acampora, Serena Barello, Guendalina Graffigna

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Introduction: In the face of increasing demands for higher agricultural productivity with minimal environmental impact, participatory research approaches emerge as promising means to promote innovation. However, the complexities and ambiguities surrounding these approaches in both theory and practice present challenges. This Scoping Review seeks to bridge these gaps by mapping participatory approaches in agricultural contexts, analyzing their characteristics, and identifying indicators of success. Methods: Following PRISMA guidelines, we conducted a systematic Scoping Review, searching Scopus and Web of Science databases. Our review encompassed 34 projects from diverse geographical regions and farming contexts. Thematic analysis was employed to explore the types of innovation promoted and the categories of participants involved. Results: The identified innovation types encompass technological advancements, sustainable farming practices, and market integration, forming 5 main themes: climate change, cultivar, irrigation, pest and herbicide, and technical improvement. These themes represent critical areas where participatory research drives innovation to address pressing agricultural challenges. Participants were categorized as citizens, experts, NGOs, private companies, and public bodies. Understanding their roles is vital for designing effective participatory initiatives that embrace diverse stakeholders. The review also highlighted 27 theoretical frameworks underpinning participatory projects. Clearer guidelines and reporting standards are crucial for facilitating the comparison and synthesis of findings across studies, thereby enhancing the robustness of future participatory endeavors. Furthermore, we identified three main categories of barriers and facilitators: pragmatic/behavioral, emotional/relational, and cognitive. These insights underscore the significance of participant engagement and collaborative decision-making for project success beyond theoretical considerations. Regarding participation, projects were classified as contributory (5 cases), where stakeholders contributed insights; collaborative (10 cases), with active co-designing of solutions; and co-created (19 cases), featuring deep stakeholder involvement from ideation to implementation, resulting in joint ownership of outcomes. Such diverse participation modes highlight the adaptability of participatory approaches to varying agricultural contexts. Discussion: In conclusion, this Scoping Review demonstrates the potential of participatory research in driving transformative changes in farmers' practices, fostering sustainability and innovation in agriculture. Understanding the diverse landscape of participatory approaches, theoretical frameworks, and participant engagement strategies is essential for designing effective and context-specific interventions. Collaborative efforts among researchers, practitioners, and stakeholders are pivotal in harnessing the full potential of participatory approaches and driving positive change in agricultural settings worldwide. The identified themes of innovation and participation modes provide valuable insights for future research and targeted interventions in agricultural innovation.

Keywords: participatory research, co-creation, agricultural innovation, stakeholders' engagement

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267 Reducing Falls in Memory Care through Implementation of the Stopping Elderly Accidents, Deaths, and Injuries Program

Authors: Cory B. Lord

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Falls among the elderly population has become an area of concern in healthcare today. The negative impacts of falls lead to increased morbidity, mortality, and financial burdens for both patients and healthcare systems. Falls in the United States is reported at an annual rate of 36 million in those aged 65 and older. Each year, one out of four people in this age group will suffer a fall, with 20% of these falls causing injury. The setting for this Doctor of Nursing Practice (DNP) project was a memory care unit in an assisted living community, as these facilities house cognitively impaired older adults. These communities lack fall prevention programs; therefore, the need exists to add to the body of knowledge to positively impact this population. The objective of this project was to reduce fall rates through the implementation of the Center for Disease Control and Prevention (CDC) STEADI (stopping elderly accidents, deaths, and injuries) program. The DNP project performed was a quality improvement pilot study with a pre and post-test design. This program was implemented in the memory care setting over 12 weeks. The project included an educational session for staff and a fall risk assessment with appropriate resident referrals. The three aims of the DNP project were to reduce fall rates among the elderly aged 65 and older who reside in the memory care unit, increase staff knowledge of STEADI fall prevention measures after an educational session, and assess the willingness of memory care unit staff to adopt an evidence-based a fall prevention program. The Donabedian model was used as a guiding conceptual framework for this quality improvement pilot study. The fall rate data for 12 months before the intervention was evaluated and compared to post-intervention fall rates. The educational session comprised of a pre and post-test to assess staff knowledge of the fall prevention program and the willingness of staff to adopt the fall prevention program. The overarching goal was to reduce falls in the elderly population who live in memory care units. The results of the study showed, on average that the fall rate during the implementation period of STEADI (μ=6.79) was significantly lower when compared to the prior 12 months (μ= 9.50) (p=0.02, α = 0.05). The mean staff knowledge scores improved from pretest (μ=77.74%) to post-test (μ=87.42%) (p=0.00, α= 0.05) after the education session. The results of the willingness to adopt a fall prevention program were scored at 100%. In summation, implementing the STEADI fall prevention program can assist in reducing fall rates for residents aged 65 and older who reside in a memory care setting.

Keywords: dementia, elderly, falls, STEADI

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266 Anti-Apoptotic Effect of Pueraria tuberosa in Rats with Streptozotocin Induced Diabetic Nephropathy

Authors: Rashmi Shukla, Yamini Bhusan Tripathi

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Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

Procedia PDF Downloads 191
265 Industrial Production of the Saudi Future Dwelling: A Saudi Volumetric Solution for Single Family Homes, Leveraging Industry 4.0 with Scalable Automation, Hybrid Structural Insulated Panels Technology and Local Materials

Authors: Bandar Alkahlan

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The King Abdulaziz City for Science and Technology (KACST) created the Saudi Future Dwelling (SFD) initiative to identify, localize and commercialize a scalable home manufacturing technology suited to deployment across the Kingdom of Saudi Arabia (KSA). This paper outlines the journey, the creation of the international project delivery team, the product design, the selection of the process technologies, and the outcomes. A target was set to remove 85% of the construction and finishing processes from the building site as these activities could be more efficiently completed in a factory environment. Therefore, integral to the SFD initiative is the successful industrialization of the home building process using appropriate technologies, automation, robotics, and manufacturing logistics. The technologies proposed for the SFD housing system are designed to be energy efficient, economical, fit for purpose from a Saudi cultural perspective, and will minimize the use of concrete, relying mainly on locally available Saudi natural materials derived from the local resource industries. To this end, the building structure is comprised of a hybrid system of structural insulated panels (SIP), combined with a light gauge steel framework manufactured in a large format panel system. The paper traces the investigative process and steps completed by the project team during the selection process. As part of the SFD Project, a pathway was mapped out to include a proof-of-concept prototype housing module and the set-up and commissioning of a lab-factory complete with all production machinery and equipment necessary to simulate a full-scale production environment. The prototype housing module was used to validate and inform current and future product design as well as manufacturing process decisions. A description of the prototype design and manufacture is outlined along with valuable learning derived from the build and how these results were used to enhance the SFD project. The industrial engineering concepts and lab-factory detailed design and layout are described in the paper, along with the shop floor I.T. management strategy. Special attention was paid to showcase all technologies within the lab-factory as part of the engagement strategy with private investors to leverage the SFD project with large scale factories throughout the Kingdom. A detailed analysis is included in the process surrounding the design, specification, and procurement of the manufacturing machinery, equipment, and logistical manipulators required to produce the SFD housing modules. The manufacturing machinery was comprised of a combination of standardized and bespoke equipment from a wide range of international suppliers. The paper describes the selection process, pre-ordering trials and studies, and, in some cases, the requirement for additional research and development by the equipment suppliers in order to achieve the SFD objectives. A set of conclusions is drawn describing the results achieved thus far, along with a list of recommended ongoing operational tests, enhancements, research, and development aimed at achieving full-scale engagement with private sector investment and roll-out of the SFD project across the Kingdom.

Keywords: automation, dwelling, manufacturing, product design

Procedia PDF Downloads 98
264 Self-Care and Emotional Wellbeing of Nurses Using Playback Theatre and Expressive Arts

Authors: Radhika Jain

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The nursing community in India face unique challenges ranging from lack of adequate career progression, low social status attached to the profession, poor nurse-to-patient ratio leading to heavy workload resulting in stress and burnout, lack of general recognition and the responsibility of often having to deal with the ire of the patients and their families. This study explores how a combination of Playback Theatre and Expressive Arts could be used as a very powerful tool to understand the concerns, and consequently as a self-care tool to bring about the sense of well-being and emotional awareness for the nurses. For the purpose of this study, Playback Theatre was used as an entry tool to understand the thoughts, feelings and concerns. Playback theatre is a unique improvisational form of theatre developed by Jonathan Fox and Jo Salas in 1975, in which audience share their own stories from their lives and the performers play them back through a range of improv techniques such as metaphor, poetry, music and movement. Playback Theatre helped in first warming them up to the idea of sharing and then gave them the confidence of a safe space to collectively go deeper into their emotional experiences. As the next step, structured sessions of Expressive Arts were conducted with the same set of nurses, for them to work on the issues and concerns they have (and which they shared during the Playback performance). These sessions were to enable longer engagements as many of the concerns expressed were related to perceptions and beliefs that have been ingrained over a period of time and hence it needs a longer engagement to be worked on in detail. The Expressive Art sessions helped in this regard. Expressive arts therapy combines psychology and the creative process to promote emotional growth and healing. The study was conducted at two places: one a geriatric centre and the other, a palliative care centre. The study revealed that concerns and challenges would not be identical across the nursing community or across similar types of health care organizations but would be specific to each organization or centre as the circumstances and set-up at each place would be different. At the geriatric centre, stress and burnout emerged as the main concerns while at the palliative care centre, the main concern that came up was around the difficulty the nurses faced in expressing emotions and in communicating their feelings. The objective analysis of the results of the study indicated how longer-term engagements using Expressive Arts as the modality helped the nurses have better awareness of their emotions and helped them develop tools of self-care tools while also tapping into their emotions to express and experience. The process of eliciting the main concerns from the nurses using a Playback Theatre performance and then following that with subsequent sessions of expressive arts helped the nurses in the way nurses approached their job and the reduced level of overwhelm that they felt.

Keywords: palliative care, nurses, self-care, expressive arts, playback theatre

Procedia PDF Downloads 93
263 Elimination of Mother to Child Transmission of HIV/AIDS: A Study of the Knowledge, Attitudes and Perceptions of Healthcare Workers in Abuja Nigeria

Authors: Ezinne K. Okoro, Takahiko Katoh, Yoko Kawamura, Stanley C. Meribe

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HIV infection in children is largely as a result of vertical transmission (mother to child transmission [MTCT]). Thus, elimination of mother to child transmission of HIV/AIDS is critical in eliminating HIV infection in children. In Nigeria, drawbacks such as; limited pediatric screening, limited human capital, insufficient advocacy and poor understanding of ART guidelines, have impacted efforts at combating the disease, even as treatment services are free. Prevention of Mother to Child Transmission (PMTCT) program relies on health workers who not only counsel pregnant women on first contact but can competently provide HIV-positive pregnant women with accurate information about the PMTCT program such as feeding techniques and drug adherence. In developing regions like Nigeria where health care delivery faces a lot of drawbacks, it becomes paramount to address these issues of poor PMTCT coverage by conducting a baseline assessment of the knowledge, practices and perceptions related to HIV prevention amongst healthcare workers in Nigeria. A descriptive cross-sectional study was conducted amongst 250 health workers currently employed in health facilities in Abuja, Nigeria where PMTCT services were offered with the capacity to carry out early infant diagnosis testing (EID). Data was collected using a self-administered, pretested, structured questionnaire. This study showed that the knowledge of PMTCT of HIV was poor (30%) among healthcare workers who offer this service day-to-day to pregnant women. When PMTCT practices were analyzed in keeping with National PMTCT guidelines, over 61% of the respondents reported observing standard practices and the majority (58%) had good attitudes towards caring for patients with HIV/AIDS. Although 61% of the respondents reported being satisfied with the quality of service being rendered, 63% reported not being satisfied with their level of knowledge. Predictors of good knowledge were job designation and level of educational attainment. Health workers who were more satisfied with their working conditions and those who had worked for a longer time in the PMTCT service were more likely to observe standard PMTCT practices. With over 62% of the healthcare workers suggesting that more training would improve the quality of service being rendered, this is a strong pointer to stakeholders to consider a ‘healthcare worker-oriented approach’ when planning and conducting PMTCT training for healthcare workers. This in turn will increase pediatric ARV coverage, the knowledge and effectiveness of the healthcare workers in carrying out appropriate PMTCT interventions and culminating in the reduction/elimination of HIV transmission to newborns.

Keywords: attitudes, HIV/AIDS, healthcare workers, knowledge, mother to child transmission, Nigeria, perceptions

Procedia PDF Downloads 177
262 Exploring Managerial Approaches towards Green Manufacturing: A Thematic Analysis

Authors: Hakimeh Masoudigavgani

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Since manufacturing firms deplete non-renewable resources and pollute air, soil, and water in greatly unsustainable manner, industrial activities or production of products are considered to be a key contributor to adverse environmental impacts. Hence, management strategies and approaches that involve an effective supply chain decision process in a manufacturing sector could be extremely significant to the application of environmental initiatives. Green manufacturing (GM) is one of these strategies which minimises negative effects on the environment through reducing greenhouse gas emissions, waste, and the consumption of energy and natural resources. This paper aims to explore what greening methods and mechanisms could be applied in the manufacturing supply chain and what are the outcomes of adopting these methods in terms of abating environmental burdens? The study is an interpretive research with an exploratory approach, using thematic analysis by coding text, breaking down and grouping the content of collected literature into various themes and categories. It is found that green supply chain could be attained through execution of some pre-production strategies including green building, eco-design, and green procurement as well as a number of in-production and post-production strategies involving green manufacturing and green logistics. To achieve an effective GM, the pre-production strategies are suggested to be employed. This paper defines GM as (1) the analysis of the ecological impacts generated by practices, products, production processes, and operational functions, and (2) the implementation of greening methods to reduce damaging influences of them on the natural environment. Analysis means assessing, monitoring, and auditing of practices in order to measure and pinpoint their harmful impacts. Moreover, greening methods involved within GM (arranged in order from the least to the most level of environmental compliance and techniques) consist of: •product stewardship (e.g. less use of toxic, non-renewable, and hazardous materials in the manufacture of the product; and stewardship of the environmental problems with regard to the product in all production, use, and end-of-life stages); •process stewardship (e.g. controlling carbon emission, energy and resources usage, transportation method, and disposal; reengineering polluting processes; recycling waste materials generated in production); •lean and clean production practices (e.g. elimination of waste, materials replacement, materials reduction, resource-efficient consumption, energy-efficient usage, emission reduction, managerial assessment, waste re-use); •use of eco-industrial parks (e.g. a shared warehouse, shared logistics management system, energy co-generation plant, effluent treatment). However, the focus of this paper is only on methods related to the in-production phase and needs further research on both pre-production and post-production environmental innovations. The outlined methods in this investigation may possibly be taken into account by policy/decision makers. Additionally, the proposed future research direction and identified gaps can be filled by scholars and researchers. The paper compares and contrasts a variety of viewpoints and enhances the body of knowledge by building a definition for GM through synthesising literature and categorising the strategic concept of greening methods, drivers, barriers, and successful implementing tactics.

Keywords: green manufacturing (GM), product stewardship, process stewardship, clean production, eco-industrial parks (EIPs)

Procedia PDF Downloads 560
261 Improving the Utility of Social Media in Pharmacovigilance: A Mixed Methods Study

Authors: Amber Dhoot, Tarush Gupta, Andrea Gurr, William Jenkins, Sandro Pietrunti, Alexis Tang

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Background: The COVID-19 pandemic has driven pharmacovigilance towards a new paradigm. Nowadays, more people than ever before are recognising and reporting adverse reactions from medications, treatments, and vaccines. In the modern era, with over 3.8 billion users, social media has become the most accessible medium for people to voice their opinions and so provides an opportunity to engage with more patient-centric and accessible pharmacovigilance. However, the pharmaceutical industry has been slow to incorporate social media into its modern pharmacovigilance strategy. This project aims to make social media a more effective tool in pharmacovigilance, and so reduce drug costs, improve drug safety and improve patient outcomes. This will be achieved by firstly uncovering and categorising the barriers facing the widespread adoption of social media in pharmacovigilance. Following this, the potential opportunities of social media will be explored. We will then propose realistic, practical recommendations to make social media a more effective tool for pharmacovigilance. Methodology: A comprehensive systematic literature review was conducted to produce a categorised summary of these barriers. This was followed by conducting 11 semi-structured interviews with pharmacovigilance experts to confirm the literature review findings whilst also exploring the unpublished and real-life challenges faced by those in the pharmaceutical industry. Finally, a survey of the general public (n = 112) ascertained public knowledge, perception, and opinion regarding the use of their social media data for pharmacovigilance purposes. This project stands out by offering perspectives from the public and pharmaceutical industry that fill the research gaps identified in the literature review. Results: Our results gave rise to several key analysis points. Firstly, inadequacies of current Natural Language Processing algorithms hinder effective pharmacovigilance data extraction from social media, and where data extraction is possible, there are significant questions over its quality. Social media also contains a variety of biases towards common drugs, mild adverse drug reactions, and the younger generation. Additionally, outdated regulations for social media pharmacovigilance do not align with new, modern General Data Protection Regulations (GDPR), creating ethical ambiguity about data privacy and level of access. This leads to an underlying mindset of avoidance within the pharmaceutical industry, as firms are disincentivised by the legal, financial, and reputational risks associated with breaking ambiguous regulations. Conclusion: Our project uncovered several barriers that prevent effective pharmacovigilance on social media. As such, social media should be used to complement traditional sources of pharmacovigilance rather than as a sole source of pharmacovigilance data. However, this project adds further value by proposing five practical recommendations that improve the effectiveness of social media pharmacovigilance. These include: prioritising health-orientated social media; improving technical capabilities through investment and strategic partnerships; setting clear regulatory guidelines using multi-stakeholder processes; creating an adverse drug reaction reporting interface inbuilt into social media platforms; and, finally, developing educational campaigns to raise awareness of the use of social media in pharmacovigilance. Implementation of these recommendations would speed up the efficient, ethical, and systematic adoption of social media in pharmacovigilance.

Keywords: adverse drug reaction, drug safety, pharmacovigilance, social media

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260 Oncolytic H-1 Parvovirus Entry in Cancer Cells through Clathrin-Mediated Endocytosis

Authors: T. Ferreira, A. Kulkarni, C. Bretscher, K. Richter, M. Ehrlich, A. Marchini

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H-1 protoparvovirus (H-1PV) is a virus with inherent oncolytic and oncosuppressive activities while remaining non-pathogenic in humans. H-1PV was the first oncolytic parvovirus to undergo clinical testing. Results from trials in patients with glioblastoma or pancreatic carcinoma showed an excellent safety profile and first signs of efficacy. H-1PV infection is vastly dependent on cellular factors, from cell attachment and entry to viral replication and egress. Hence, we believe that the characterisation of the parvovirus life cycle would ultimately help further improve H-1PV clinical outcome. In the present study, we explored the entry pathway of H-1PV in cervical HeLa and glioma NCH125 cancer cell lines. Electron and confocal microscopy showed viral particles associated with clathrin-coated pits and vesicles, providing the first evidence that H-1PV cell entry occurs through clathrin-mediated endocytosis. Accordingly, we observed that by blocking clathrin-mediated endocytosis with hypertonic sucrose, chlorpromazine, or pitstop 2, H-1PV transduction was markedly decreased. Accordingly, siRNA-mediated knockdown of AP2M1, which retains a crucial role in clathrin-mediated endocytosis, verified the reliance of H-1PV on this route to enter HeLa and NCH125 cancer cells. By contrast, we found no evidence of viral entry through caveolae-mediated endocytosis. Indeed, pre-treatment of cells with nystatin or methyl-β-cyclodextrin, both inhibitors of caveolae-mediated endocytosis, did not affect viral transduction levels. Unexpectedly, siRNA-mediated knockdown of caveolin-1, the main driver of caveolae-mediated endocytosis, increased H-1PV transduction, suggesting caveolin-1 is a negative modulator of H-1PV infection. We also show that H-1PV entry is dependent on dynamin, a protein responsible for mediating the scission of vesicle neck and promoting further internalisation. Furthermore, since dynamin inhibition almost completely abolished H-1PV infection, makes it unlikely that H-1PV uses macropinocytosis as an alternative pathway to enter cells. After viral internalisation, H-1PV passes through early to late endosomes as observed by confocal microscopy. Inside these endocytic compartments, the acidic environment proved to be crucial for a productive infection. Inhibition of acidification of pH dramatically reduced H-1PV transduction. Besides, a fraction of H-1PV particles was observed inside LAMP1-positive lysosomes, most likely following a non-infectious route. To the author's best knowledge, this is the first study to characterise the cell entry pathways of H-1PV. Along these lines, this work will further contribute to understand H-1PV oncolytic properties as well as to improve its clinical potential in cancer virotherapy.

Keywords: clathrin-mediated endocytosis, H-1 parvovirus, oncolytic virus, virus entry

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259 Neuroprotection against N-Methyl-D-Aspartate-Induced Optic Nerve and Retinal Degeneration Changes by Philanthotoxin-343 to Alleviate Visual Impairments Involve Reduced Nitrosative Stress

Authors: Izuddin Fahmy Abu, Mohamad Haiqal Nizar Mohamad, Muhammad Fattah Fazel, Renu Agarwal, Igor Iezhitsa, Nor Salmah Bakar, Henrik Franzyk, Ian Mellor

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Glaucoma is the global leading cause of irreversible blindness. Currently, the available treatment strategy only involves lowering intraocular pressure (IOP); however, the condition often progresses despite lowered or normal IOP in some patients. N-methyl-D-aspartate receptor (NMDAR) excitotoxicity often occurs in neurodegeneration-related glaucoma; thus it is a relevant target to develop a therapy based on neuroprotection approach. This study investigated the effects of Philanthotoxin-343 (PhTX-343), an NMDAR antagonist, on the neuroprotection of NMDA-induced glaucoma to alleviate visual impairments. Male Sprague-Dawley rats were equally divided: Groups 1 (control) and 2 (glaucoma) were intravitreally injected with phosphate buffer saline (PBS) and NMDA (160nM), respectively, while group 3 was pre-treated with PhTX-343 (160nM) 24 hours prior to NMDA injection. Seven days post-treatments, rats were subjected to visual behavior assessments and subsequently euthanized to harvest their retina and optic nerve tissues for histological analysis and determination of nitrosative stress level using 3-nitrotyrosine ELISA. Visual behavior assessments via open field, object, and color recognition tests demonstrated poor visual performance in glaucoma rats indicated by high exploratory behavior. PhTX-343 pre-treatment appeared to preserve visual abilities as all test results were significantly improved (p < 0.05). H&E staining of the retina showed a marked reduction of ganglion cell layer thickness in the glaucoma group; in contrast, PhTX-343 significantly increased the number by 1.28-folds (p < 0.05). PhTX-343 also increased the number of cell nuclei/100μm2 within inner retina by 1.82-folds compared to the glaucoma group (p < 0.05). Toluidine blue staining of optic nerve tissues showed that PhTX-343 reduced the degeneration changes compared to the glaucoma group which exhibited vacuolation overall sections. PhTX-343 also decreased retinal 3- nitrotyrosine concentration by 1.74-folds compared to the glaucoma group (p < 0.05). All results in PhTX-343 group were comparable to control (p > 0.05). We conclude that PhTX-343 protects against NMDA-induced changes and visual impairments in the rat model by reducing nitrosative stress levels.

Keywords: excitotoxicity, glaucoma, nitrosative stress , NMDA receptor , N-methyl-D-aspartate , philanthotoxin, visual behaviour

Procedia PDF Downloads 105
258 Perception of Health Care Providers: A Need to Introduce Screening of Maternal Mental Health at Primary Health Care in Nepal

Authors: Manisha Singh, Padam Simkhada

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Background: Although mental health policy has been adapted in Nepal since 1997, the implementation of the policy framework is yet to happen. The fact that mental health services are largely concentrated in urban areas more specific to treatment only provides a clear picture of the scarcity of mental health services in the country. The shreds of evidence from around the world, along with WHO’s (World Health Organization) Mental Health Gap Action Program (mhGAP) suggest that effective mental health services can be provided from Primary Health Care (PHC) centers through community-based programs without having to place a specialized health worker. However, the country is still facing the same challenges to date with very few psychiatrists and psychologists, but they are largely based in cities. Objectives: The main objectives of this study are; (a) to understand the perception of health workers at PHC on maternal mental health, and (b) to assess the availability of the mental health services at PHC to address maternal mental health. Methods: This study used a qualitative approach where an in-depth interview was conducted with the health workers at the primary level. “Mayadevi” rural municipality in Rupendehi District that comprised of 13 small villages, was chosen as the study site. A total 8 health institutions which covered all 13 sites were included where either the health post in- charge or health worker working in maternal and child health care was interviewed for the study. All the health posts in the study area were included in the study. The interviews were conducted in Nepali; later, they were translated in English, transcribed, and triangulated. NViVO was used for the analysis. Results: The findings show that most of the health workers understood what maternal mental health was and deemed it as a public health issue. They could explain the symptoms and knew what medication to prescribe if need be. However, the majority of them failed to name the screening tools in place for maternal mental health. Moreover, they hadn’t even seen one. None of the health care centers had any provision for screening mental health status. However, one of the centers prescribed medication when the patients displayed symptoms of depression. But they believed there were a significant number of hidden cases in the community due to the stigma around mental health and being a woman with mental health problem makes the situation even difficult. Nonetheless, the health workers understood the importance of having screening tools and acknowledged the need of training and support in order to provide the services from PHC. Conclusion: Community health workers can identify cases with mental health problems and prevent them from deteriorating further. But there is a need for robust training and support to build the capacity of the health workers. The screening tools on mental health needs to be encouraged to be used in the PHC levels. Furthermore, community-based culture-sensitive programs need to be initiated and implemented to mitigate the stigma related issues around mental health.

Keywords: maternal mental health, health care providers, screening, Nepal

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257 Management Problems in a Patient With Long-term Undiagnosed Permanent Hypoparathyroidism

Authors: Babarina Maria, Andropova Margarita

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Introduction: Hypoparathyroidism (HypoPT) is a rare endocrine disorder with an estimated prevalence of 0.25 per 1000 individuals. The most common cause of HypoPT is the loss of active parathyroid tissue following thyroid or parathyroid surgery. Sometimes permanent postoperative HypoPT occures, manifested by hypocalcemia in combination with low levels of PTH during 6 months or more after surgery. Cognitive impairments in patients with hypocalcemia due to chronic HypoPT are observed, and this can lead to problems and challenges in everyday living: memory loss and impaired concentration, that may be the cause of poor compliance. Clinical case: Patient K., 66 years old, underwent thyroidectomy in 2013 (at the age of 55) because of papillary thyroid cancer T1NxMx, histopathology findings confirmed the diagnosis. 5 years after the surgery, she was followed up on an outpatient basis, TSH levelsonly were monitored, and the dose of levothyroxine was adjusted. In 2018 due to, increasing complaints include tingling and cramps in the arms and legs, memory loss, sleep disorder, fatigue, anxiety, hair loss, muscle pain, tachycardia, positive Chvostek, and Trousseau signs were diagnosed during examination, also in blood analyses: total Ca 1.86 mmol/l (2.15-2.55), Ca++ 0.96 mmol/l (1.12-1.3), P 1.55 mmol/l (0.74-1.52), Mg 0.79 mmol/l (0.66-1.07) - chronic postoperative HypoPT was diagnosed. Therapy was initiated: alfacalcidol 0.5 mcg per day, calcium carbonate 2000 mg per day, cholecalciferol 1000 IU per day, magnesium orotate 3000 mg per day. During the case follow-up, hypocalcemia, hyperphosphatemia persisted, hypercalciuria15.7 mmol/day (2.5-6.5) was diagnosed. Dietary recommendations were given because of the high content of phosphorus rich foods, and therapy was adjusted: the dose of alfacalcidol was increased to 2.5 mcg per day, and the dose of calcium carbonate was reduced to 1500 mg per day. As part of the screening for complications of hypoPT, data for cataracts, Fahr syndrome, nephrocalcinosis, and kidney stone disease were not obtained. However, HypoPT compensation was not achieved, and therefore hydrochlorothiazide 25 mg was initiated, the dose of alfacalcidol was increased to 3 mcg per day, calcium carbonate to 3000 mg per day, magnesium orotate and cholecalciferol were continued at the same doses. Therapeutic goals were achieved: calcium phosphate product <4.4 mmol2/l2, there were no episodes of hypercalcemia, twenty-four-hour urinary calcium excretion was significantly reduced. Conclusion: Timely prescription, careful explanation of drugs usage rules, and monitoring and maintaining blood and urine parameters within the target contribute to the prevention of HypoPT complications development and life-threatening events.

Keywords: hypoparathyroidism, hypocalcemia, hyperphosphatemia, hypercalciuria

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256 The Medical Student Perspective on the Role of Doubt in Medical Education

Authors: Madhavi-Priya Singh, Liam Lowe, Farouk Arnaout, Ludmilla Pillay, Giordan Perez, Luke Mischker, Steve Costa

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Introduction: An Emergency Department consultant identified the failure of medical students to complete the task of clerking a patient in its entirety. As six medical students on our first clinical placement, we recognised our own failure and endeavored to examine why this failure was consistent among all medical students that had been given this task, despite our best motivations as adult learners. Aim: Our aim is to understand and investigate the elements which impeded our ability to learn and perform as medical students in the clinical environment, with reference to the prescribed task. We also aim to generate a discussion around the delivery of medical education with potential solutions to these barriers. Methods: Six medical students gathered together to have a comprehensive reflective discussion to identify possible factors leading to the failure of the task. First, we thoroughly analysed the delivery of the instructions with reference to the literature to identify potential flaws. We then examined personal, social, ethical, and cultural factors which may have impacted our ability to complete the task in its entirety. Results: Through collation of our shared experiences, with support from discussion in the field of medical education and ethics, we identified two major areas that impacted our ability to complete the set task. First, we experienced an ethical conflict where we believed the inconvenience and potential harm inflicted on patients did not justify the positive impact the patient interaction would have on our medical learning. Second, we identified a lack of confidence stemming from multiple factors, including the conflict between preclinical and clinical learning, perceptions of perfectionism in the culture of medicine, and the influence of upward social comparison. Discussion: After discussions, we found that the various factors we identified exacerbated the fears and doubts we already had about our own abilities and that of the medical education system. This doubt led us to avoid completing certain aspects of the tasks that were prescribed and further reinforced our vulnerability and perceived incompetence. Exploration of philosophical theories identified the importance of the role of doubt in education. We propose the need for further discussion around incorporating both pedagogic and andragogic teaching styles in clinical medical education and the acceptance of doubt as a driver of our learning. Conclusion: Doubt will continue to permeate our thoughts and actions no matter what. The moral or psychological distress that arises from this is the key motivating factor for our avoidance of tasks. If we accept this doubt and education embraces this doubt, it will no longer linger in the shadows as a negative and restrictive emotion but fuel a brighter dialogue and positive learning experience, ultimately assisting us in achieving our full potential.

Keywords: ethics, medical student, doubt, medical education, faith

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255 Emotion-Convolutional Neural Network for Perceiving Stress from Audio Signals: A Brain Chemistry Approach

Authors: Anup Anand Deshmukh, Catherine Soladie, Renaud Seguier

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Emotion plays a key role in many applications like healthcare, to gather patients’ emotional behavior. Unlike typical ASR (Automated Speech Recognition) problems which focus on 'what was said', it is equally important to understand 'how it was said.' There are certain emotions which are given more importance due to their effectiveness in understanding human feelings. In this paper, we propose an approach that models human stress from audio signals. The research challenge in speech emotion detection is finding the appropriate set of acoustic features corresponding to an emotion. Another difficulty lies in defining the very meaning of emotion and being able to categorize it in a precise manner. Supervised Machine Learning models, including state of the art Deep Learning classification methods, rely on the availability of clean and labelled data. One of the problems in affective computation is the limited amount of annotated data. The existing labelled emotions datasets are highly subjective to the perception of the annotator. We address the first issue of feature selection by exploiting the use of traditional MFCC (Mel-Frequency Cepstral Coefficients) features in Convolutional Neural Network. Our proposed Emo-CNN (Emotion-CNN) architecture treats speech representations in a manner similar to how CNN’s treat images in a vision problem. Our experiments show that Emo-CNN consistently and significantly outperforms the popular existing methods over multiple datasets. It achieves 90.2% categorical accuracy on the Emo-DB dataset. We claim that Emo-CNN is robust to speaker variations and environmental distortions. The proposed approach achieves 85.5% speaker-dependant categorical accuracy for SAVEE (Surrey Audio-Visual Expressed Emotion) dataset, beating the existing CNN based approach by 10.2%. To tackle the second problem of subjectivity in stress labels, we use Lovheim’s cube, which is a 3-dimensional projection of emotions. Monoamine neurotransmitters are a type of chemical messengers in the brain that transmits signals on perceiving emotions. The cube aims at explaining the relationship between these neurotransmitters and the positions of emotions in 3D space. The learnt emotion representations from the Emo-CNN are mapped to the cube using three component PCA (Principal Component Analysis) which is then used to model human stress. This proposed approach not only circumvents the need for labelled stress data but also complies with the psychological theory of emotions given by Lovheim’s cube. We believe that this work is the first step towards creating a connection between Artificial Intelligence and the chemistry of human emotions.

Keywords: deep learning, brain chemistry, emotion perception, Lovheim's cube

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254 Comparison of the Effectiveness of Tree Algorithms in Classification of Spongy Tissue Texture

Authors: Roza Dzierzak, Waldemar Wojcik, Piotr Kacejko

Abstract:

Analysis of the texture of medical images consists of determining the parameters and characteristics of the examined tissue. The main goal is to assign the analyzed area to one of two basic groups: as a healthy tissue or a tissue with pathological changes. The CT images of the thoracic lumbar spine from 15 healthy patients and 15 with confirmed osteoporosis were used for the analysis. As a result, 120 samples with dimensions of 50x50 pixels were obtained. The set of features has been obtained based on the histogram, gradient, run-length matrix, co-occurrence matrix, autoregressive model, and Haar wavelet. As a result of the image analysis, 290 descriptors of textural features were obtained. The dimension of the space of features was reduced by the use of three selection methods: Fisher coefficient (FC), mutual information (MI), minimization of the classification error probability and average correlation coefficients between the chosen features minimization of classification error probability (POE) and average correlation coefficients (ACC). Each of them returned ten features occupying the initial place in the ranking devised according to its own coefficient. As a result of the Fisher coefficient and mutual information selections, the same features arranged in a different order were obtained. In both rankings, the 50% percentile (Perc.50%) was found in the first place. The next selected features come from the co-occurrence matrix. The sets of features selected in the selection process were evaluated using six classification tree methods. These were: decision stump (DS), Hoeffding tree (HT), logistic model trees (LMT), random forest (RF), random tree (RT) and reduced error pruning tree (REPT). In order to assess the accuracy of classifiers, the following parameters were used: overall classification accuracy (ACC), true positive rate (TPR, classification sensitivity), true negative rate (TNR, classification specificity), positive predictive value (PPV) and negative predictive value (NPV). Taking into account the classification results, it should be stated that the best results were obtained for the Hoeffding tree and logistic model trees classifiers, using the set of features selected by the POE + ACC method. In the case of the Hoeffding tree classifier, the highest values of three parameters were obtained: ACC = 90%, TPR = 93.3% and PPV = 93.3%. Additionally, the values of the other two parameters, i.e., TNR = 86.7% and NPV = 86.6% were close to the maximum values obtained for the LMT classifier. In the case of logistic model trees classifier, the same ACC value was obtained ACC=90% and the highest values for TNR=88.3% and NPV= 88.3%. The values of the other two parameters remained at a level close to the highest TPR = 91.7% and PPV = 91.6%. The results obtained in the experiment show that the use of classification trees is an effective method of classification of texture features. This allows identifying the conditions of the spongy tissue for healthy cases and those with the porosis.

Keywords: classification, feature selection, texture analysis, tree algorithms

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253 A Systematic Review of Chronic Neurologic Complications of COVID-19; A Potential Risk Factor for Narcolepsy, Parkinson's Disease, and Multiple Sclerosis.

Authors: Sulemana Saibu, Moses Ikpeme

Abstract:

Background: The severity of the COVID-19 pandemic, brought on by the SARS-CoV-2 coronavirus, has been unprecedented since the 1918 influenza pandemic. SARS-CoV-2 cases of CNS and peripheral nervous system disease, including neurodegenerative disorders and chronic immune-mediated diseases, may be anticipated based on knowledge of past coronaviruses, particularly those that caused the severe acute respiratory syndrome and Middle East respiratory syndrome outbreaks. Although respiratory symptoms are the most common clinical presentation, neurological symptoms are becoming increasingly recognized, raising concerns about their potential role in causing Parkinson's disease, Multiple sclerosis, and Narcolepsy. This systematic review aims to summarize the current evidence by exploring the association between COVID-19 infection and how it may overlap with etiological mechanisms resulting in Narcolepsy, Parkinson's disease, and Multiple sclerosis. Methods: A systematic search was conducted using electronic databases ((PubMed/MedLine, Embase, PsycINFO, ScieLO, Web of Science, ProQuest (Biotechnology, Virology, and AIDS), Scopus, and CINAHL)) to identify studies published between January 2020 and December 2022 that investigated the association between COVID-19 and Parkinson's disease, multiple sclerosis, and Narcolepsy. Per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, the review was performed and reported. Study quality was assessed using the Critical Appraisal Skills Programme Checklist and the Joanna Briggs Institute Critical appraisal tools. Results: A total of 21 studies out of 1025 met the inclusion criteria, including 8 studies reporting Parkinson's disease, 11 on multiple sclerosis, and 2 on Narcolepsy. In COVID-19 individuals compared to the general population, Narcolepsy, Parkinson's disease, and multiple sclerosis were shown to have a higher incidence. The findings imply that COVID-19 may worsen the signs or induce multiple sclerosis and Parkinson's disease and may raise the risk of developing Narcolepsy. Further research is required to confirm these connections because the available data is insufficient. Conclusion: According to the existing data, COVID-19 may raise the risk of Narcolepsy and have a causative relationship with Parkinson's disease, multiple sclerosis, and other diseases. More study is required to confirm these correlations and pinpoint probable mechanisms behind these interactions. Clinicians should be aware of how COVID-19 may affect various neurological illnesses and should treat patients who are affected accordingly.

Keywords: COVID-19, parkinson’s disease, multiple sclerosis, narcolepsy, neurological disorders, sars-cov-2, neurodegenerative disorders, chronic immune-mediated diseases

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252 The Dynamic Nexus of Public Health and Journalism in Informed Societies

Authors: Ali Raza

Abstract:

The dynamic landscape of communication has brought about significant advancements that intersect with the realms of public health and journalism. This abstract explores the evolving synergy between these fields, highlighting how their intersection has contributed to informed societies and improved public health outcomes. In the digital age, communication plays a pivotal role in shaping public perception, policy formulation, and collective action. Public health, concerned with safeguarding and improving community well-being, relies on effective communication to disseminate information, encourage healthy behaviors, and mitigate health risks. Simultaneously, journalism, with its commitment to accurate and timely reporting, serves as the conduit through which health information reaches the masses. Advancements in communication technologies have revolutionized the ways in which public health information is both generated and shared. The advent of social media platforms, mobile applications, and online forums has democratized the dissemination of health-related news and insights. This democratization, however, brings challenges, such as the rapid spread of misinformation and the need for nuanced strategies to engage diverse audiences. Effective collaboration between public health professionals and journalists is pivotal in countering these challenges, ensuring that accurate information prevails. The synergy between public health and journalism is most evident during public health crises. The COVID-19 pandemic underscored the pivotal role of journalism in providing accurate and up-to-date information to the public. However, it also highlighted the importance of responsible reporting, as sensationalism and misinformation could exacerbate the crisis. Collaborative efforts between public health experts and journalists led to the amplification of preventive measures, the debunking of myths, and the promotion of evidence-based interventions. Moreover, the accessibility of information in the digital era necessitates a strategic approach to health communication. Behavioral economics and data analytics offer insights into human decision-making and allow tailored health messages to resonate more effectively with specific audiences. This approach, when integrated into journalism, enables the crafting of narratives that not only inform but also influence positive health behaviors. Ethical considerations emerge prominently in this alliance. The responsibility to balance the public's right to know with the potential consequences of sensational reporting underscores the significance of ethical journalism. Health journalists must meticulously source information from reputable experts and institutions to maintain credibility, thus fortifying the bridge between public health and the public. As both public health and journalism undergo transformative shifts, fostering collaboration between these domains becomes essential. Training programs that familiarize journalists with public health concepts and practices can enhance their capacity to report accurately and comprehensively on health issues. Likewise, public health professionals can gain insights into effective communication strategies from seasoned journalists, ensuring that health information reaches a wider audience. In conclusion, the convergence of public health and journalism, facilitated by communication advancements, is a cornerstone of informed societies. Effective communication strategies, driven by collaboration, ensure the accurate dissemination of health information and foster positive behavior change. As the world navigates complex health challenges, the continued evolution of this synergy holds the promise of healthier communities and a more engaged and educated public.

Keywords: public awareness, journalism ethics, health promotion, media influence, health literacy

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251 Traditional Medicine in Children: A Significant Cause of Morbidity and Mortality

Authors: Atitallah Sofien, Bouyahia Olfa, Romdhani Meriam, Missaoui Nada, Ben Rabeh Rania, Yahyaoui Salem, Mazigh Sonia, Boukthir Samir

Abstract:

Introduction: Traditional medicine refers to a diverse range of therapeutic practices and knowledge systems that have been employed by different cultures over an extended period to uphold and rejuvenate health. These practices can involve herbal remedies, acupuncture, massage, and alternative healing methods that deviate from conventional medical approaches. In Tunisia, we often use unidentified utensils to scratch the oral cavity internally in infants in order to widen the oral cavity for better breathing and swallowing. However, these practices can be risky and may jeopardize the patients' prognosis or even their lives. Aim: This is the case of a nine-month-old infant, admitted to the pediatric department and subsequently to the intensive care unit due to a peritonsillar abscess following the utilization of an unidentifiable tool to scrape the interior of the oral cavity. Case Report: This is a 9-month-old infant with no particular medical history, admitted for high respiratory distress and a fever persisting for 4 days. On clinical examination, he had a respiratory rate of 70 cycles per minute with an oxygen saturation of 97% and subcostal retractions, along with a heart rate of 175 beats per minute. His white blood cell count was 40,960/mm³, and his C-reactive protein was 250 mg/L. Given the severity of the clinical presentation, the infant was transferred to the intensive care unit, intubated, and mechanically ventilated. A cervical-thoracic CT scan was performed, revealing a ruptured 18 mm left peritonsillar abscess in the oropharynx associated with cellulitis of the retropharyngeal space. The oto-rhino-laryngoscopic examination revealed an asymmetry involving the left lateral wall of the oropharynx with the presence of a fistula behind the posterior pillar. Dissection of the collection cavity was performed, allowing the drainage of 2 ml of pus. The culture was negative. The patient received cefotaxime in combination with metronidazole and gentamicin for a duration of 10 days, followed by a switch to amoxicillin-clavulanic acid for 7 days. The patient was extubated after 4 days of treatment, and the clinical and radiological progress was favorable. Conclusions: Traditional medicine remains risky due to the lack of scientific evidence and the potential for injuries and transmission of infectious diseases, especially in children, who constitute a vulnerable population. Therefore, parents should consult healthcare professionals and rely on evidence-based care.

Keywords: children, peritonsillar abscess, traditional medicine, respiratory distress

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250 Novel EGFR Ectodomain Mutations and Resistance to Anti-EGFR and Radiation Therapy in H&N Cancer

Authors: Markus Bredel, Sindhu Nair, Hoa Q. Trummell, Rajani Rajbhandari, Christopher D. Willey, Lewis Z. Shi, Zhuo Zhang, William J. Placzek, James A. Bonner

Abstract:

Purpose: EGFR-targeted monoclonal antibodies (mAbs) provide clinical benefit in some patients with H&N squamous cell carcinoma (HNSCC), but others progress with minimal response. Missense mutations in the EGFR ectodomain (ECD) can be acquired under mAb therapy by mimicking the effect of large deletions on receptor untethering and activation. Little is known about the contribution of EGFR ECD mutations to EGFR activation and anti-EGFR response in HNSCC. Methods: We selected patient-derived HNSCC cells (UM-SCC-1) for resistance to mAb Cetuximab (CTX) by repeated, stepwise exposure to mimic what may occur clinically and identified two concurrent EGFR ECD mutations (UM-SCC-1R). We examined the competence of the mutants to bind EGF ligand or CTX. We assessed the potential impact of the mutations through visual analysis of space-filling models of the native sidechains in the original structures vs. their respective side-chain mutations. We performed CRISPR in combination with site-directed mutagenesis to test for the effect of the mutants on ligand-independent EGFR activation and sorting. We determined the effects on receptor internalization, endocytosis, downstream signaling, and radiation sensitivity. Results: UM-SCC-1R cells carried two non-synonymous missense mutations (G33S and N56K) mapping to domain I in or near the EGF binding pocket of the EGFR ECD. Structural modeling predicted that these mutants restrict the adoption of a tethered, inactive EGFR conformation while not permitting association of EGFR with the EGF ligand or CTX. Binding studies confirmed that the mutant, untethered receptor displayed a reduced affinity for both EGF and CTX but demonstrated sustained activation and presence at the cell surface with diminished internalization and sorting for endosomal degradation. Single and double-mutant models demonstrated that the G33S mutant is dominant over the N56K mutant in its effect on EGFR activation and EGF binding. CTX-resistant UM-SCC-1R cells demonstrated cross-resistance to mAb Panitumuab but, paradoxically, remained sensitive to the reversible receptor tyrosine kinase inhibitor Erlotinib. Conclusions: HNSCC cells can select for EGFR ECD mutations under EGFR mAb exposure that converge to trap the receptor in an open, constitutively activated state. These mutants impede the receptor’s competence to bind mAbs and EGF ligand and alter its endosomal trafficking, possibly explaining certain cases of clinical mAb and radiation resistance.

Keywords: head and neck cancer, EGFR mutation, resistance, cetuximab

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