Search results for: Selina Dangeleit
10 Defective Autophagy Disturbs Neural Migration and Network Activity in hiPSC-Derived Cockayne Syndrome B Disease Models
Authors: Julia Kapr, Andrea Rossi, Haribaskar Ramachandran, Marius Pollet, Ilka Egger, Selina Dangeleit, Katharina Koch, Jean Krutmann, Ellen Fritsche
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It is widely acknowledged that animal models do not always represent human disease. Especially human brain development is difficult to model in animals due to a variety of structural and functional species-specificities. This causes significant discrepancies between predicted and apparent drug efficacies in clinical trials and their subsequent failure. Emerging alternatives based on 3D in vitro approaches, such as human brain spheres or organoids, may in the future reduce and ultimately replace animal models. Here, we present a human induced pluripotent stem cell (hiPSC)-based 3D neural in a vitro disease model for the Cockayne Syndrome B (CSB). CSB is a rare hereditary disease and is accompanied by severe neurologic defects, such as microcephaly, ataxia and intellectual disability, with currently no treatment options. Therefore, the aim of this study is to investigate the molecular and cellular defects found in neural hiPSC-derived CSB models. Understanding the underlying pathology of CSB enables the development of treatment options. The two CSB models used in this study comprise a patient-derived hiPSC line and its isogenic control as well as a CSB-deficient cell line based on a healthy hiPSC line (IMR90-4) background thereby excluding genetic background-related effects. Neurally induced and differentiated brain sphere cultures were characterized via RNA Sequencing, western blot (WB), immunocytochemistry (ICC) and multielectrode arrays (MEAs). CSB-deficiency leads to an altered gene expression of markers for autophagy, focal adhesion and neural network formation. Cell migration was significantly reduced and electrical activity was significantly increased in the disease cell lines. These data hint that the cellular pathologies is possibly underlying CSB. By induction of autophagy, the migration phenotype could be partially rescued, suggesting a crucial role of disturbed autophagy in defective neural migration of the disease lines. Altered autophagy may also lead to inefficient mitophagy. Accordingly, disease cell lines were shown to have a lower mitochondrial base activity and a higher susceptibility to mitochondrial stress induced by rotenone. Since mitochondria play an important role in neurotransmitter cycling, we suggest that defective mitochondria may lead to altered electrical activity in the disease cell lines. Failure to clear the defective mitochondria by mitophagy and thus missing initiation cues for new mitochondrial production could potentiate this problem. With our data, we aim at establishing a disease adverse outcome pathway (AOP), thereby adding to the in-depth understanding of this multi-faced disorder and subsequently contributing to alternative drug development.Keywords: autophagy, disease modeling, in vitro, pluripotent stem cells
Procedia PDF Downloads 1209 Design Systems and the Need for a Usability Method: Assessing the Fitness of Components and Interaction Patterns in Design Systems Using Atmosphere Methodology
Authors: Patrik Johansson, Selina Mardh
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The present study proposes a usability test method, Atmosphere, to assess the fitness of components and interaction patterns of design systems. The method covers the user’s perception of the components of the system, the efficiency of the logic of the interaction patterns, perceived ease of use as well as the user’s understanding of the intended outcome of interactions. These aspects are assessed by combining measures of first impression, visual affordance and expectancy. The method was applied to a design system developed for the design of an electronic health record system. The study was conducted involving 15 healthcare personnel. It could be concluded that the Atmosphere method provides tangible data that enable human-computer interaction practitioners to analyze and categorize components and patterns based on perceived usability, success rate of identifying interactive components and success rate of understanding components and interaction patterns intended outcome.Keywords: atomic design, atmosphere methodology, design system, expectancy testing, first impression testing, usability testing, visual affordance testing
Procedia PDF Downloads 1798 Future Considerations for Wounded Service Members and Veterans of the Global War on Terror
Authors: Selina Doncevic, Lisa Perla, Angela Kindvall
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The Global War on Terror which began after September 11, 2011, increased survivability of severe injuries requiring varying trajectories of rehabilitation and recovery. The costs encompass physiologic, functional, social, emotional, psychological, vocational and scholastic domains of life. The purpose of this poster is to inform private sector health care practitioners and clinicians at various levels of the unique and long term dynamics of healthcare recovery for polytrauma, and traumatic brain injured service members and veterans in the United States of America. Challenges include care delivery between the private sector, the department of defense, and veterans affairs healthcare systems while simultaneously supporting the dynamics of acute as well as latent complications associated with severe injury and illness. Clinical relevance, subtleties of protracted recovery, and overwhelmed systems of care are discussed in the context of lessons learned and in reflection on previous wars. Additional concerns for consideration and discussion include: the cost of protracted healthcare, various U.S. healthcare payer systems, lingering community reintegration challenges, ongoing care giver support, the rise of veterans support groups and the development of private sector clinical partnerships.Keywords: brain injury, future, polytrauma, rehabilitation
Procedia PDF Downloads 1977 The European Pharmacy Market: The Density and its Influencing Factors
Authors: Selina Schwaabe
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Community pharmacies deliver high-quality health care and are responsible for medication safety. During the pandemic, accessibility to the nearest pharmacy became more essential to get vaccinated against Covid-19 and to get medical aid. The government's goal is to ensure nationwide, reachable, and affordable medical health care services by pharmacies. Therefore, the density of community pharmacies matters. Overall, the density of community pharmacies is fluctuating, with slightly decreasing tendencies in some countries. So far, the literature has shown that changes in the system affect prices and density. However, a European overview of the development of the density of community pharmacies and its triggers is still missing. This research is essential to counteract against decreasing density consulting in a lack of professional health care through pharmacies. The analysis focuses on liberal versus regulated market structures, mail-order prescription drug regulation, and third-party ownership consequences. In a panel analysis, the relative influence of the measures is examined across 27 European countries over the last 21 years. In addition, the paper examines seven selected countries in depth, selected for the substantial variance in their pharmacy system: Germany, Austria, Portugal, Denmark, Sweden, Finland and Poland. Overall, the results show that regulated pharmacy markets have over 10.75 pharmacies/100.000 inhabitants more than liberal markets. Further, mail-order prescription drugs decrease the density by -17.98 pharmacies/100.000 inhabitants. Countries allowing third-party ownership have 7.67 pharmacies/100.000 inhabitants more. The results are statistically significant at a 0.001 level. The output of this analysis recommends regulated pharmacy markets, with a ban on mail-order prescription drugs allowing third-party ownership to support nationwide medical health care through community pharmacies.Keywords: community pharmacy, market conditions, pharmacy, pharmacy market, pharmacy lobby, prescription, e-prescription, ownership structures
Procedia PDF Downloads 1306 Algae Biofertilizers Promote Sustainable Food Production and Nutrient Efficiency: An Integrated Empirical-Modeling Study
Authors: Zeenat Rupawalla, Nicole Robinson, Susanne Schmidt, Sijie Li, Selina Carruthers, Elodie Buisset, John Roles, Ben Hankamer, Juliane Wolf
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Agriculture has radically changed the global biogeochemical cycle of nitrogen (N). Fossil fuel-enabled synthetic N-fertiliser is a foundation of modern agriculture but applied to soil crops only use about half of it. To address N-pollution from cropping and the large carbon and energy footprint of N-fertiliser synthesis, new technologies delivering enhanced energy efficiency, decarbonisation, and a circular nutrient economy are needed. We characterised algae fertiliser (AF) as an alternative to synthetic N-fertiliser (SF) using empirical and modelling approaches. We cultivated microalgae in nutrient solution and modelled up-scaled production in nutrient-rich wastewater. Over four weeks, AF released 63.5% of N as ammonium and nitrate, and 25% of phosphorous (P) as phosphate to the growth substrate, while SF released 100% N and 20% P. To maximise crop N-use and minimise N-leaching, we explored AF and SF dose-response-curves with spinach in glasshouse conditions. AF-grown spinach produced 36% less biomass than SF-grown plants due to AF’s slower and linear N-release, while SF resulted in 5-times higher N-leaching loss than AF. Optimised blends of AF and SF boosted crop yield and minimised N-loss due to greater synchrony of N-release and crop uptake. Additional benefits of AF included greener leaves, lower leaf nitrate concentration, and higher microbial diversity and water holding capacity in the growth substrate. Life-cycle-analysis showed that replacing the most effective SF dosage with AF lowered the carbon footprint of fertiliser production from 2.02 g CO₂ (C-producing) to -4.62 g CO₂ (C-sequestering), with a further 12% reduction when AF is produced on wastewater. Embodied energy was lowest for AF-SF blends and could be reduced by 32% when cultivating algae on wastewater. We conclude that (i) microalgae offer a sustainable alternative to synthetic N-fertiliser in spinach production and potentially other crop systems, and (ii) microalgae biofertilisers support the circular nutrient economy and several sustainable development goals.Keywords: bioeconomy, decarbonisation, energy footprint, microalgae
Procedia PDF Downloads 1365 A Study of the Depression Status of Asian American Adolescents
Authors: Selina Lin, Justin M Fan, Vincent Zhang, Cindy Chen, Daniel Lam, Jason Yan, Ning Zhang
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Depression is one of the most common mental disorders in the United States, and past studies have shown a concerning increase in the rates of depression in youth populations over time. Furthermore, depression is an especially important issue for Asian Americans because of the anti-Asian violence taking place during the COVID-19 pandemic. While Asian American adolescents are reluctant to seek help for mental health issues, past research has found a prevalence of depressive symptoms in them that have yet to be fully investigated. There have been studies conducted to understand and observe the impacts of multifarious factors influencing the mental well-being of Asian American adolescents; however, they have been generally limited to qualitative investigation, and very few have attempted to quantitatively evaluate the relationship between depression levels and a comprehensive list of factors for those levels at the same time. To better quantify these relationships, this project investigated the prevalence of depression in Asian American teenagers mainly from the Greater Philadelphia Region, aged 12 to 19, and, with an anonymous survey, asked participants 48 multiple-choice questions pertaining to demographic information, daily behaviors, school life, family life, depression levels (quantified by the PHQ-9 assessment), school and family support against depression. Each multiple-choice question was assigned as a factor and variable for statistical and dominance analysis to determine the most influential factors on depression levels of Asian American adolescents. The results were validated via Bootstrap analysis and t-tests. While certain influential factors identified in this survey are consistent with the literature, such as parent-child relationship and peer pressure, several dominant factors were relatively overlooked in the past. These factors include the parents’ relationship with each other, the satisfaction with body image, sex identity, support from the family and support from the school. More than 25% of participants desired more support from their families and schools in handling depression issues. This study implied that it is beneficial for Asian American parents and adolescents to take programs on parents’ relationships with each other, parent-child communication, mental health, and sexual identity. A culturally inclusive school environment and more accessible mental health services would be helpful for Asian American adolescents to combat depression. This survey-based study paved the way for further investigation of effective approaches for helping Asian American adolescents against depression.Keywords: Asian American adolescents, depression, dominance analysis, t-test, bootstrap analysis
Procedia PDF Downloads 1374 Photovoice-Through Photographs to Feelings: Investigation of Experience Reporting in a Randomized Controlled Study
Authors: Selina Studer, Maria Kleinstäuber, Cornelia Weise
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Background: Finding words to report what you have been through may be challenging, especially when dealing with stressful or highly emotional experiences. Photovoice (PV) represents a possible way of facilitating experience reporting. In this approach, people take photos about a particular topic (in our study: worries about the future) and talk about the topic based on the photos. So far, the benefits of Photovoice have been quantitatively insufficiently tested. There is a lack of randomized controlled trials investigating PV in comparison to other methods. This study aimed to fill this research gap. Methods: 65 participants took part in the study and were randomly assigned to the PV group, the writing group (WG), or the control group (CG). The PV group received the task to take photos of worries regarding the future for one week and send max. 5 of them to the interviewer before the interview. The WG had to write down the worries about the future and send max. 5 of them to the interviewer before the interview. The control group did not receive a specific assignment. The semi-structured interview consisted of six open-ended questions and was applied to all future worries. The questions included the content of the future worries, the meaning, and how the worry expressed itself emotionally and physically. The interview was recorded and later transcribed. After the interview, online questionnaires were filled out. They covered a range of variables such as access to emotional content, ability to describe feelings, the extent of self-disclosure, and relationship quality. Results: Contrary to our hypotheses, one-way ANOVA revealed no differences between the three conditions concerning all variables (access to emotional content, ability to describe feelings, the extent of self-disclosure, and so on), all p's > 0.14, BF₀₁ = 1.78-7.66. In a subsequent step, the words in the transcribed interviews were analyzed. The LIWC program counted how many emotional words occurred in the text and assigned them to predefined categories. Planned contrasts revealed that the PV reported more negative emotional words compared to the two groups t(62) = 2.62, p = .011, and also compared to the WG only, t(62) = 2.36, p = .022, BF₀₁ = 0.62. Conclusions and implications: The applied self-report instruments did not reveal any differences between the groups. However, the PV group used more negative emotional words than the other two groups. The discrepancy between self-report and observation variables regarding emotionality is noticeable. It is suggested that the highly educated and above-average female sample may not have needed PV to access emotional content. It is possible that the approach would yield clearer results in a clinical sample. This and other approaches are currently being investigated in a follow-up study.Keywords: photovoice, controlled randomized study, online intervention, emotional awareness, self-disclosure, data triangulation, interviews
Procedia PDF Downloads 703 Analysis of Differentially Expressed Genes in Spontaneously Occurring Canine Melanoma
Authors: Simona Perga, Chiara Beltramo, Floriana Fruscione, Isabella Martini, Federica Cavallo, Federica Riccardo, Paolo Buracco, Selina Iussich, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari, Paola Modesto
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Introduction: Human and canine melanoma have common clinical, histologic characteristics making dogs a good model for comparative oncology. The identification of specific genes and a better understanding of the genetic landscape, signaling pathways, and tumor–microenvironmental interactions involved in the cancer onset and progression is essential for the development of therapeutic strategies against this tumor in both species. In the present study, the differential expression of genes in spontaneously occurring canine melanoma and in paired normal tissue was investigated by targeted RNAseq. Material and Methods: Total RNA was extracted from 17 canine malignant melanoma (CMM) samples and from five paired normal tissues stored in RNA-later. In order to capture the greater genetic variability, gene expression analysis was carried out using two panels (Qiagen): Human Immuno-Oncology (HIO) and Mouse-Immuno-Oncology (MIO) and the miSeq platform (Illumina). These kits allow the detection of the expression profile of 990 genes involved in the immune response against tumors in humans and mice. The data were analyzed through the CLCbio Genomics Workbench (Qiagen) software using the Canis lupus familiaris genome as a reference. Data analysis were carried out both comparing the biologic group (tumoral vs. healthy tissues) and comparing neoplastic tissue vs. paired healthy tissue; a Fold Change greater than two and a p-value less than 0.05 were set as the threshold to select interesting genes. Results and Discussion: Using HIO 63, down-regulated genes were detected; 13 of those were also down-regulated comparing neoplastic sample vs. paired healthy tissue. Eighteen genes were up-regulated, 14 of those were also down-regulated comparing neoplastic sample vs. paired healthy tissue. Using the MIO, 35 down regulated-genes were detected; only four of these were down-regulated, also comparing neoplastic sample vs. paired healthy tissue. Twelve genes were up-regulated in both types of analysis. Considering the two kits, the greatest variation in Fold Change was in up-regulated genes. Dogs displayed a greater genetic homology with humans than mice; moreover, the results have shown that the two kits are able to detect different genes. Most of these genes have specific cellular functions or belong to some enzymatic categories; some have already been described to be correlated to human melanoma and confirm the validity of the dog as a model for the study of molecular aspects of human melanoma.Keywords: animal model, canine melanoma, gene expression, spontaneous tumors, targeted RNAseq
Procedia PDF Downloads 1982 Management of Myofascial Temporomandibular Disorder in Secondary Care: A Quality Improvement Project
Authors: Rishana Bilimoria, Selina Tang, Sajni Shah, Marianne Henien, Christopher Sproat
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Temporomandibular disorders (TMD) may affect up to a third of the general population, and there is evidence demonstrating the majority of Myofascial TMD cases improve after education and conservative measures. In 2015 our department implemented a modified care pathway for myofascial TMD patients in an attempt to improve the patient journey. This involved the use of an interactive group therapy approach to deliver education, reinforce conservative measures and promote self-management. Patient reported experience measures from the new group clinic revealed 71% patient satisfaction. This service is efficient in improving aspects of health status while reducing health-care costs and redistributing clinical time. Since its’ establishment, 52 hours of clinical time, resources and funding have been redirected effectively. This Quality Improvement Project was initiated because it was felt that this new service was being underutilised by our surgical teams. The ‘Plan-Do-Study-Act cycle’ (PDSA) framework was employed to analyse utilisation of the service: The ‘plan’ stage involved outlining our aims: to raise awareness amongst clinicians of the unified care pathway and to increase referral to this clinic. The ‘do’ stage involved collecting data from a sample of 96 patients over 4 month period to ascertain the proportion of Myofascial TMD patients who were correctly referred to the designated clinic. ‘Suitable’ patients who weren’t referred were identified. The ‘Study’ phase involved analysis of results, which revealed that 77% of suitable patients weren’t referred to the designated clinic. They were reviewed on other clinics, which are often overbooked, or managed by junior staff members. This correlated with our original prediction. Barriers to referral included: lack of awareness of the clinic, individual consultant treatment preferences and patient, reluctance to be referred to a ‘group’ clinic. The ‘Act’ stage involved presenting our findings to the team at a clinical governance meeting. This included demonstration of the clinical effectiveness of the care-pathway and explaining the referral route and criteria. In light of the evaluation results, it was decided to keep the group clinic and maximize utilisation. The second cycle of data collection following these changes revealed that of 66 Myofascial TMD patients over a 4 month period, only 9% of suitable patients were not seen via the designated pathway; therefore this QIP was successful in meeting the set objectives. Overall, employing the PDSA cycle in this QIP resulted in appropriate utilisation of the modified care pathway for patients with myofascial TMD in Guy’s Oral Surgery Department. In turn, this leads to high patient satisfaction with the service and effectively redirected 52 hours of clinical time. It permitted adoption of a collaborative working style with oral surgery colleagues to investigate problems, identify solutions, and collectively raise standards of clinical care to ensure we adopt a unified care pathway in secondary care management of Myofascial TMD patients.Keywords: myofascial, quality Improvement, PDSA, TMD
Procedia PDF Downloads 1401 The Relationship between Motivation for Physical Activity and Level of Physical Activity over Time
Authors: Keyvan Molanorouzi, Selina Khoo, Tony Morris
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In recent years, there has been a decline in physical activity among adults. Motivation has been shown to be a crucial factor in maintaining physical activity. The purpose of this study was to whether PA motives measured by the Physical Activity and Leisure Motivation Scale PALMS predicted actual amount of PA at a later time to provide evidence for the construct validity of the PALMS. A quantitative, cross-sectional descriptive research design was employed. The Demographic Form, PALMS, and International Physical Activity Questionnaire Short form (IPAQ-S) questionnaires were used to assess motives and amount for physical activity in adults on two occasions. A sample of 640 (489 male, 151 female) undergraduate students aged 18 to 25 years (mean ±SD; 22.30±8.13 years) took part in the study. Male participants were divided into three types of activities, namely exercise, racquet sport, and team sports and female participants only took part in one type of activity, namely team sports. After 14 weeks, all 640 undergraduate students who had filled in the initial questionnaire (Occasion 1) received the questionnaire via email (Occasion 2). Of the 640 students, 493 (77%; 378 males, 115 females) emailed back the completed questionnaire. The results showed that not only were pertinent sub-scales of PALMS positively related to amount of physical activity, but separate regression analyses showed the positive predictive effect of PALMS motives for amount of physical activity for each type of physical activity among participants. This study supported the construct validity of the PALMS by showing that the motives measured by PALMS did predict amount of PA. This information can be obtained to match people with specific sport or activity which in turn could potentially promote longer adherence to the specific activity.Methods: A quantitative, cross-sectional descriptive research design was employed. The Demographic Form, PALMS, and International Physical Activity Questionnaire Short form (IPAQ-S) questionnaires were used to assess motives and amount for physical activity in adults on two occasions. A sample of 640 (489 male, 151 female) undergraduate students aged 18 to 25 years (mean ±SD; 22.30±8.13 years) took part in the study. Male participants were divided into three types of activities, namely exercise, racquet sport, and team sports and female participants only took part in one type of activity, namely team sports. After 14 weeks, all 640 undergraduate students who had filled in the initial questionnaire (Occasion 1) received the questionnaire via email (Occasion 2). Of the 640 students, 493 (77%; 378 males, 115 females) emailed back the completed questionnaire. Results: The results showed that not only were pertinent sub-scales of PALMS positively related to amount of physical activity, but separate regression analyses showed the positive predictive effect of PALMS motives for amount of physical activity for each type of physical activity among participants. This study supported the construct validity of the PALMS by showing that the motives measured by PALMS did predict amount of PA. Conclusion: This information can be obtained to match people with specific sport or activity which in turn could potentially promote longer adherence to the specific activity.Keywords: physical activity, motivation, level of physical activity, type of physical activity
Procedia PDF Downloads 469