Search results for: chronic fatigue syndrome
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2529

Search results for: chronic fatigue syndrome

159 Design and Construction of a Home-Based, Patient-Led, Therapeutic, Post-Stroke Recovery System Using Iterative Learning Control

Authors: Marco Frieslaar, Bing Chu, Eric Rogers

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Stroke is a devastating illness that is the second biggest cause of death in the world (after heart disease). Where it does not kill, it leaves survivors with debilitating sensory and physical impairments that not only seriously harm their quality of life, but also cause a high incidence of severe depression. It is widely accepted that early intervention is essential for recovery, but current rehabilitation techniques largely favor hospital-based therapies which have restricted access, expensive and specialist equipment and tend to side-step the emotional challenges. In addition, there is insufficient funding available to provide the long-term assistance that is required. As a consequence, recovery rates are poor. The relatively unexplored solution is to develop therapies that can be harnessed in the home and are formulated from technologies that already exist in everyday life. This would empower individuals to take control of their own improvement and provide choice in terms of when and where they feel best able to undertake their own healing. This research seeks to identify how effective post-stroke, rehabilitation therapy can be applied to upper limb mobility, within the physical context of a home rather than a hospital. This is being achieved through the design and construction of an automation scheme, based on iterative learning control and the Riener muscle model, that has the ability to adapt to the user and react to their level of fatigue and provide tangible physical recovery. It utilizes a SMART Phone and laptop to construct an iterative learning control (ILC) system, that monitors upper arm movement in three dimensions, as a series of exercises are undertaken. The equipment generates functional electrical stimulation to assist in muscle activation and thus improve directional accuracy. In addition, it monitors speed, accuracy, areas of motion weakness and similar parameters to create a performance index that can be compared over time and extrapolated to establish an independent and objective assessment scheme, plus an approximate estimation of predicted final outcome. To further extend its assessment capabilities, nerve conduction velocity readings are taken by the software, between the shoulder and hand muscles. This is utilized to measure the speed of response of neuron signal transfer along the arm and over time, an online indication of regeneration levels can be obtained. This will prove whether or not sufficient training intensity is being achieved even before perceivable movement dexterity is observed. The device also provides the option to connect to other users, via the internet, so that the patient can avoid feelings of isolation and can undertake movement exercises together with others in a similar position. This should create benefits not only for the encouragement of rehabilitation participation, but also an emotional support network potential. It is intended that this approach will extend the availability of stroke recovery options, enable ease of access at a low cost, reduce susceptibility to depression and through these endeavors, enhance the overall recovery success rate.

Keywords: home-based therapy, iterative learning control, Riener muscle model, SMART phone, stroke rehabilitation

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158 Exploring Communities of Practice through Public Health Walks for Nurse Education

Authors: Jacqueline P. Davies

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Introduction: Student nurses must develop skills in observation, communication and reflection as well as public health knowledge from their first year of training. This paper will explain a method developed for students to collect their own findings about public health in urban areas. These areas are both rich in the history of old public health that informs the content of many traditional public health walks, but are also locations where new public health concerns about chronic disease are concentrated. The learning method explained in this paper enables students to collect their own data and write original work as first year students. Examples of their findings will be given. Methodology: In small groups, health care students are instructed to walk in neighbourhoods near to the hospitals they will soon attend as apprentice nurses. On their walks, they wander slowly, engage in conversations, and enter places open to the public. As they drift, they observe with all five senses in the real three dimensional world to collect data for their reflective accounts of old and new public health. They are encouraged to stop for refreshments and taste, as well as look, hear, smell, and touch while on their walk. They reflect as a group and later develop an individual reflective account in which they write up their deep reflections about what they observed on their walk. In preparation for their walk, they are encouraged to look at studies of quality of Life and other neighbourhood statistics as well as undertaking a risk assessment for their walk. Findings: Reflecting on their walks, students apply theoretical concepts around social determinants of health and health inequalities to develop their understanding of communities in the neighbourhoods visited. They write about the treasured historical architecture made of stone, bronze and marble which have outlived those who built them; but also how the streets are used now. The students develop their observations into thematic analyses such as: what we drink as illustrated by the empty coke can tossed into a now disused drinking fountain; the shift in home-life balance illustrated by streets where families once lived over the shop which are now walked by commuters weaving around each other as they talk on their mobile phones; and security on the street, with CCTV cameras placed at regular intervals, signs warning trespasses and barbed wire; but little evidence of local people watching the street. Conclusion: In evaluations of their first year, students have reported the health walk as one of their best experiences. The innovative approach was commended by the UK governing body of nurse education and it received a quality award from the nurse education funding body. This approach to education allows students to develop skills in the real world and write original work.

Keywords: education, innovation, nursing, urban

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157 Erectile Dysfunction in A Middle Aged Man 6 Years After Bariatric Surgery: A Case Report

Authors: Thaminda Liyanage, Chamila Shamika Kurukulasuriya

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Introduction: Morbid obesity has been successfully treated with bariatric surgery for over 60 years. Although operative procedures have improved and associated complications have reduced substantially, surgery still carries the risk of post-operative malabsorption, malnutrition and a range of gastrointestinal disorders. Overweight by itself can impair libido in both sexes and cause erectile dysfunction in males by inducing a state of hypogonadotropic hypogonadism, proportional to the degree of obesity. Impact of weight reduction on libido and sexual activity remains controversial, however it is broadly accepted that weight loss improves sexual drive. Zinc deficiency, subsequent to malabsorption, may lead to impaired testosterone synthesis in men while excessive and/or rapid weight loss in females may result in reversible amenorrhoea leading to sub-fertility. Methods: We describe a 37 year old male, 6 years post Roux-en-Y gastric bypass surgery, who presented with erectile dysfunction, loss of libido, worsening fatigue and generalized weakness for 4 months. He also complained of constipation and frequent muscle cramps but denied having headache, vomiting or visual disturbances. Patient had lost 38 kg of body weight post gastric bypass surgery over four years {135kg (BMI 42.6 kg/m2) to 97 kg (BMI 30.6 kg/m2)} and the weight had been stable for past two years. He had no recognised co-morbidities at the time of the surgery and noted marked improvement in general wellbeing, physical fitness and psychological confident post surgery, up until four months before presentation. Clinical examination revealed dry pale skin with normal body hair distribution, no thyroid nodules or goitre, normal size testicles and normal neurological examination with no visual field defects or diplopia. He had low serum testosterone, follicular stimulating hormone (FSH), luteinizing hormone (LH), T3, T4, thyroid stimulating hormone (TSH), insulin like growth factor 1 (IGF-1) and 24-hour urine cortisol levels. Serum cortisol demonstrated an appropriate rise to ACTH stimulation test but growth hormone (GH) failed increase on insulin tolerance test. Other biochemical and haematological studies were normal, except for low zinc and folate with minimally raised liver enzymes. MRI scan of the head confirmed a solid pituitary mass with no mass effect on optic chiasm. Results: In this patient clinical, biochemical and radiological findings were consistent with anterior pituitary dysfunction. However, there were no features of raised intracranial pressure or neurological compromise. He was commenced on appropriate home replacement therapy and referred for neurosurgical evaluation. Patient reported marked improvement in his symptoms, specially libido and erectile dysfunction, on subsequent follow up visits. Conclusion: Sexual dysfunction coupled with non specific constitutional symptoms has multiple aetiologies. Clinical symptoms out of proportion to nutritional deficiencies post bariatric surgery should be thoroughly investigated. Close long term follow up is crucial for overall success.

Keywords: obesity, bariatric surgery, erectile dysfunction, loss of libido

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156 In-Process Integration of Resistance-Based, Fiber Sensors during the Braiding Process for Strain Monitoring of Carbon Fiber Reinforced Composite Materials

Authors: Oscar Bareiro, Johannes Sackmann, Thomas Gries

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Carbon fiber reinforced polymer composites (CFRP) are used in a wide variety of applications due to its advantageous properties and design versatility. The braiding process enables the manufacture of components with good toughness and fatigue strength. However, failure mechanisms of CFRPs are complex and still present challenges associated with their maintenance and repair. Within the broad scope of structural health monitoring (SHM), strain monitoring can be applied to composite materials to improve reliability, reduce maintenance costs and safely exhaust service life. Traditional SHM systems employ e.g. fiber optics, piezoelectrics as sensors, which are often expensive, time consuming and complicated to implement. A cost-efficient alternative can be the exploitation of the conductive properties of fiber-based sensors such as carbon, copper, or constantan - a copper-nickel alloy – that can be utilized as sensors within composite structures to achieve strain monitoring. This allows the structure to provide feedback via electrical signals to a user which are essential for evaluating the structural condition of the structure. This work presents a strategy for the in-process integration of resistance-based sensors (Elektrisola Feindraht AG, CuNi23Mn, Ø = 0.05 mm) into textile preforms during its manufacture via the braiding process (Herzog RF-64/120) to achieve strain monitoring of braided composites. For this, flat samples of instrumented composite laminates of carbon fibers (Toho Tenax HTS40 F13 24K, 1600 tex) and epoxy resin (Epikote RIMR 426) were manufactured via vacuum-assisted resin infusion. These flat samples were later cut out into test specimens and the integrated sensors were wired to the measurement equipment (National Instruments, VB-8012) for data acquisition during the execution of mechanical tests. Quasi-static tests were performed (tensile, 3-point bending tests) following standard protocols (DIN EN ISO 527-1 & 4, DIN EN ISO 14132); additionally, dynamic tensile tests were executed. These tests were executed to assess the sensor response under different loading conditions and to evaluate the influence of the sensor presence on the mechanical properties of the material. Several orientations of the sensor with regards to the applied loading and sensor placements inside the laminate were tested. Strain measurements from the integrated sensors were made by programming a data acquisition code (LabView) written for the measurement equipment. Strain measurements from the integrated sensors were then correlated to the strain/stress state for the tested samples. From the assessment of the sensor integration approach it can be concluded that it allows for a seamless sensor integration into the textile preform. No damage to the sensor or negative effect on its electrical properties was detected during inspection after integration. From the assessment of the mechanical tests of instrumented samples it can be concluded that the presence of the sensors does not alter significantly the mechanical properties of the material. It was found that there is a good correlation between resistance measurements from the integrated sensors and the applied strain. It can be concluded that the correlation is of sufficient accuracy to determinate the strain state of a composite laminate based solely on the resistance measurements from the integrated sensors.

Keywords: braiding process, in-process sensor integration, instrumented composite material, resistance-based sensor, strain monitoring

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155 Development and Characterization of Topical 5-Fluorouracil Solid Lipid Nanoparticles for the Effective Treatment of Non-Melanoma Skin Cancer

Authors: Sudhir Kumar, V. R. Sinha

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Background: The topical and systemic toxicity associated with present nonmelanoma skin cancer (NMSC) treatment therapy using 5-Fluorouracil (5-FU) make it necessary to develop a novel delivery system having lesser toxicity and better control over drug release. Solid lipid nanoparticles offer many advantages like: controlled and localized release of entrapped actives, nontoxicity, and better tolerance. Aim:-To investigate safety and efficacy of 5-FU loaded solid lipid nanoparticles as a topical delivery system for the treatment of nonmelanoma skin cancer. Method: Topical solid lipid nanoparticles of 5-FU were prepared using Compritol 888 ATO (Glyceryl behenate) as lipid component and pluronic F68 (Poloxamer 188), Tween 80 (Polysorbate 80), Tyloxapol (4-(1,1,3,3-Tetramethylbutyl) phenol polymer with formaldehyde and oxirane) as surfactants. The SLNs were prepared with emulsification method. Different formulation parameters viz. type and ratio of surfactant, ratio of lipid and ratio of surfactant:lipid were investigated on particle size and drug entrapment efficiency. Results: Characterization of SLNs like–Transmission Electron Microscopy (TEM), Differential Scannig calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), Particle size determination, Polydispersity index, Entrapment efficiency, Drug loading, ex vivo skin permeation and skin retention studies, skin irritation and histopathology studies were performed. TEM results showed that shape of SLNs was spherical with size range 200-500nm. Higher encapsulation efficiency was obtained for batches having higher concentration of surfactant and lipid. It was found maximum 64.3% for SLN-6 batch with size of 400.1±9.22 nm and PDI 0.221±0.031. Optimized SLN batches and marketed 5-FU cream were compared for flux across rat skin and skin drug retention. The lesser flux and higher skin retention was obtained for SLN formulation in comparison to topical 5-FU cream, which ensures less systemic toxicity and better control of drug release across skin. Chronic skin irritation studies lacks serious erythema or inflammation and histopathology studies showed no significant change in physiology of epidermal layers of rat skin. So, these studies suggest that the optimized SLN formulation is efficient then marketed cream and safer for long term NMSC treatment regimens. Conclusion: Topical and systemic toxicity associated with long-term use of 5-FU, in the treatment of NMSC, can be minimized with its controlled release with significant drug retention with minimal flux across skin. The study may provide a better alternate for effective NMSC treatment.

Keywords: 5-FU, topical formulation, solid lipid nanoparticles, non melanoma skin cancer

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154 Physical Activity Rates and Motivational Profiles of Adolescents While Keeping a Daily Leisure-Time Physical Activity Record

Authors: Matt Fullmer, Carol Wilkinson, Keven Prusak, Dennis Eggett, Todd Pennington

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Obesity and chronic health issues are linked to physical inactivity. Physical education (PE) programs in school can play a major role in combating these health-related issues. This study focused on supporting competence through keeping a leisure-time physical activity (LTPA) record as part of PE. Keeping a daily LTPA record may be an effective intervention helping students feel more competent toward exercise, and thus, self-determined (within the context of self-determination theory) to exercise. Little is known about the relationship between daily LTPA records and perceived competence, motivational profiles, and LTPA levels of students enrolled in PE. This study examined the relationship between keeping a daily, online LTPA record and adolescent (a) motivational profiles toward LTPA, (b) perceived competence toward LTPA, and (c) LTPA behaviors. Secondary students (N = 124) in physical education classes completed a baseline questionnaire which consisted of the Behavioural Regulation in Exercise Questionnaire–2, the Perceived Competence Scale, and the Godin Leisure-Time Exercise Questionnaire. For three weeks, the students were assigned to keep the Presidential Active Lifestyle Award Challenge (PALAC) as their online LTPA record. They completed the questionnaire after each week. A 2 (gender) x 4 (trials) repeated measures ANCOVA examined the relationships between recording compliance and motivation, perceived competence, and physical activity. Results showed that recording compliance was not a significant predictor of perceived competence to participate in LTPA. Examining motivational factors, a significant interaction between recording compliance and introjected regulation was found. The more students recorded the less motivated they were by guilt or obligation to exercise in their leisure-time. Also, a significant interaction was found between recording compliance and intrinsic regulation, indicating that the more students recorded the more intrinsically motivated they were to exercise in their leisure-time. Lastly, there was a significant interaction between recording compliance and LTPA. As students kept the LTPA record, girls’ LTPA levels significantly decreased and boys’ LTPA levels significantly increased. The key findings are that, as implemented in this study: a) the lack of PALAC compliance suggests that daily LTPA records may NOT be the most effective intervention for this population, b) keeping a daily LTPA record did NOT help students feel more competent to exercise in their leisure-time, c) a daily LTPA record may help students move towards being more self-determined in their feelings towards LTPA, and d) the outcome of keeping a LTPA record on LTPA behavior is statistically significant, although actual differences may not be practically important.

Keywords: behavioural regulation in exercise questionnaire–2, Godin leisure–time exercise questionnaire, online physical activity log, perceived competence scale, self-determination theory

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153 Effect of Internet Addiction on Dietary Behavior and Lifestyle Characteristics among University Students

Authors: Hafsa Kamran, Asma Afreen, Zaheer Ahmed

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Internet addiction, an emerging mental health disorder from last two decades, is manifested by the inability in the controlled use of internet leading to academics, social, physiological and/or psychological difficulties. The present study aimed to assess the levels of internet addiction among university students in Lahore and to explore the effects of internet addiction on their dietary behavior and lifestyle. It was an analytical cross-sectional study. Data was collected from October to December 2016 from students of four universities selected through two-stage sampling method. The numbers of participants were 500 and 13 questionnaires were rejected due to incomplete information. Levels of Internet Addiction (IA) were calculated using Young Internet Addiction Test (YIAT). Data was also collected on students’ demographics, lifestyle factors and dietary behavior using self-reported questionnaire. Data was analyzed using SPSS (version 21). Chi-square test was applied to evaluate the relationship between variables. Results of the study revealed that 10% of the population had severe internet addiction while moderate Internet Addiction was present in 42%. High prevalence was found among males (11% vs. 8%), private sector university students (p = 0.008) and engineering students (p = 0.000). The lifestyle habits of internet addicts were significantly of poorer quality than normal users (p = 0.05). Internet addiction was found associated with lesser physically activity (p = 0.025), had shorter duration of physical activity (p = 0.016), had more disorganized sleep pattern (p = 0.023), had less duration of sleep (p = 0.019), reported being more tired and sleepy in class (p = 0.033) and spending more time on internet as compared to normal users. Severe and moderate internet addicts also found to be more overweight and obese than normal users (p = 0.000). The dietary behavior of internet addicts was significantly poorer than normal users. Internet addicts were found to skip breakfast more than a normal user (p = 0.039). Common reasons for meal skipping were lack of time and snacking between meals (p = 0.000). They also had increased meal size (p = 0.05) and habit of snacking while using the internet (p = 0.027). Fast food (p = 0.016) and fried items (p = 0.05) were most consumed snacks, while carbonated beverages (p = 0.019) were most consumed beverages among internet addicts. Internet Addicts were found to consume less than recommended daily servings of dairy (p = 0.008) and fruits (p = 0.000) and more servings of meat group (p = 0.025) than their no internet addict counterparts. In conclusion, in this study, it was demonstrated that internet addicts have unhealthy dietary behavior and inappropriate lifestyle habits. University students should be educated regarding the importance of balanced diet and healthy lifestyle, which are critical for effectual primary prevention of numerous chronic degenerative diseases. Furthermore, it is necessary to raise awareness concerning adverse effects of internet addiction among youth and their parents.

Keywords: dietary behavior, internet addiction, lifestyle, university students

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152 Nutritional Education in Health Resort Institutions in the Face of Demographic and Epidemiological Changes in Poland

Authors: J. Woźniak-Holecka, T. Holecki, S. Jaruga

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Spa treatment is an important area of the health care system in Poland due to the increasing needs of the population and the context of historical conditions for this form of therapy. It extends the range of financing possibilities of the outlets and increases the potential of spa services, which is very important in the context of demographic and epidemiological changes. The main advantages of spa treatment services include its relatively wide availability, low risk of side effects, good patient tolerance, long-lasting curative effect and a relatively low cost. In addition, patients should be provided with a proper diet and enable participation in health education and health promotion classes aimed at health problems consistent with the treatment profile. Challenges for global health care systems include a sharp increase in spending on benefits, dynamic development of health technologies and growing social expectations. This requires extending the competences of health resort facilities for health promotion. Within each type of health resort institutions in Poland, nutritional education services are implemented, aimed at creating and consolidating proper eating habits. Choosing the right diet can speed up recovery or become one of the methods to alleviate the symptoms of chronic diseases. During spa treatment patient learns the principles of rational nutrition and adequate dietotherapy to his diseases. The aim of the project is to assess the frequency and quality of nutritional education provided to patients in health resort facilities in a nationwide perspective. The material for the study will be data obtained as part of an in-depth interview conducted among Heads of Nutrition Departments of selected institutions. The use of nutritional education in a health resort may be an important goal of implementing the state health policy as a useful tool to reduce the risk of diet-related diseases. Recognizing nutritional education in health resort institutions as a type of full-value health service can be effective system support for health policy, including seniors, due to demographic changes currently occurring in the Polish population. Furthermore, it is necessary to increase the interest and motivation of patients to follow the recommendations of nutritional education, because it will bring tangible benefits for the long-term effects of therapy and care should be taken for the form and methodology of nutrition education implemented in health resort institutions. Finally it is necessary to construct an educational offer in terms of selected groups of patients with the highest health needs: the elderly and the disabled. In conclusion, it can be said that the system of nutritional education implemented in polish health resort institutions should be subjected to global changes and strong systemic correction.

Keywords: health care system, nutritional education, public health, spa and treatment

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151 Numerical Analysis of Mandible Fracture Stabilization System

Authors: Piotr Wadolowski, Grzegorz Krzesinski, Piotr Gutowski

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The aim of the presented work is to recognize the impact of mini-plate application approach on the stress and displacement within the stabilization devices and surrounding bones. The mini-plate osteosynthesis technique is widely used by craniofacial surgeons as an improved replacement of wire connection approach. Many different types of metal plates and screws are used to the physical connection of fractured bones. Below investigation is based on a clinical observation of patient hospitalized with mini-plate stabilization system. Analysis was conducted on a solid mandible geometry, which was modeled basis on the computed tomography scan of the hospitalized patient. In order to achieve most realistic connected system behavior, the cortical and cancellous bone layers were assumed. The temporomandibular joint was simplified to the elastic element to allow physiological movement of loaded bone. The muscles of mastication system were reduced to three pairs, modeled as shell structures. Finite element grid was created by the ANSYS software, where hexahedral and tetrahedral variants of SOLID185 element were used. A set of nonlinear contact conditions were applied on connecting devices and bone common surfaces. Properties of particular contact pair depend on screw - mini-plate connection type and possible gaps between fractured bone around osteosynthesis region. Some of the investigated cases contain prestress introduced to the mini-plate during the application, what responds the initial bending of the connecting device to fit the retromolar fossa region. Assumed bone fracture occurs within the mandible angle zone. Due to the significant deformation of the connecting plate in some of the assembly cases the elastic-plastic model of titanium alloy was assumed. The bone tissues were covered by the orthotropic material. As a loading were used the gauge force of magnitude of 100N applied in three different locations. Conducted analysis shows significant impact of mini-plate application methodology on the stress distribution within the miniplate. Prestress effect introduces additional loading, which leads to locally exceed the titanium alloy yield limit. Stress in surrounding bone increases rapidly around the screws application region, exceeding assumed bone yield limit, what indicate the local bone destruction. Approach with the doubled mini-plate shows increased stress within the connector due to the too rigid connection, where the main path of loading leads through the mini-plates instead of plates and connected bones. Clinical observations confirm more frequent plate destruction of stiffer connections. Some of them could be an effect of decreased low cyclic fatigue capability caused by the overloading. The executed analysis prove that the mini-plate system provides sufficient support to mandible fracture treatment, however, many applicable solutions shifts the entire system to the allowable material limits. The results show that connector application with the initial loading needs to be carefully established due to the small material capability tolerances. Comparison to the clinical observations allows optimizing entire connection to prevent future incidents.

Keywords: mandible fracture, mini-plate connection, numerical analysis, osteosynthesis

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150 Deep Convolutional Neural Network for Detection of Microaneurysms in Retinal Fundus Images at Early Stage

Authors: Goutam Kumar Ghorai, Sandip Sadhukhan, Arpita Sarkar, Debprasad Sinha, G. Sarkar, Ashis K. Dhara

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Diabetes mellitus is one of the most common chronic diseases in all countries and continues to increase in numbers significantly. Diabetic retinopathy (DR) is damage to the retina that occurs with long-term diabetes. DR is a major cause of blindness in the Indian population. Therefore, its early diagnosis is of utmost importance towards preventing progression towards imminent irreversible loss of vision, particularly in the huge population across rural India. The barriers to eye examination of all diabetic patients are socioeconomic factors, lack of referrals, poor access to the healthcare system, lack of knowledge, insufficient number of ophthalmologists, and lack of networking between physicians, diabetologists and ophthalmologists. A few diabetic patients often visit a healthcare facility for their general checkup, but their eye condition remains largely undetected until the patient is symptomatic. This work aims to focus on the design and development of a fully automated intelligent decision system for screening retinal fundus images towards detection of the pathophysiology caused by microaneurysm in the early stage of the diseases. Automated detection of microaneurysm is a challenging problem due to the variation in color and the variation introduced by the field of view, inhomogeneous illumination, and pathological abnormalities. We have developed aconvolutional neural network for efficient detection of microaneurysm. A loss function is also developed to handle severe class imbalance due to very small size of microaneurysms compared to background. The network is able to locate the salient region containing microaneurysms in case of noisy images captured by non-mydriatic cameras. The ground truth of microaneurysms is created by expert ophthalmologists for MESSIDOR database as well as private database, collected from Indian patients. The network is trained from scratch using the fundus images of MESSIDOR database. The proposed method is evaluated on DIARETDB1 and the private database. The method is successful in detection of microaneurysms for dilated and non-dilated types of fundus images acquired from different medical centres. The proposed algorithm could be used for development of AI based affordable and accessible system, to provide service at grass root-level primary healthcare units spread across the country to cater to the need of the rural people unaware of the severe impact of DR.

Keywords: retinal fundus image, deep convolutional neural network, early detection of microaneurysms, screening of diabetic retinopathy

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149 Biocultural Biographies and Molecular Memories: A Study of Neuroepigenetics and How Trauma Gets under the Skull

Authors: Elsher Lawson-Boyd

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In the wake of the Human Genome Project, the life sciences have undergone some fascinating changes. In particular, conventional beliefs relating to gene expression are being challenged by advances in postgenomic sciences, especially by the field of epigenetics. Epigenetics is the modification of gene expression without changes in the DNA sequence. In other words, epigenetics dictates that gene expression, the process by which the instructions in DNA are converted into products like proteins, is not solely controlled by DNA itself. Unlike gene-centric theories of heredity that characterized much of the 20th Century (where the genes were considered as having almost god-like power to create life), gene expression in epigenetics insists on environmental ‘signals’ or ‘exposures’, a point that radically deviates from gene-centric thinking. Science and Technology Studies (STS) scholars have shown that epigenetic research is having vast implications for the ways in which chronic, non-communicable diseases are conceptualized, treated, and governed. However, to the author’s knowledge, there have not yet been any in-depth sociological engagements with neuroepigenetics that examine how the field is affecting mental health and trauma discourse. In this paper, the author discusses preliminary findings from a doctoral ethnographic study on neuroepigenetics, trauma, and embodiment. Specifically, this study investigates the kinds of causal relations neuroepigenetic researchers are making between experiences of trauma and the development of mental illnesses like complex post-traumatic stress disorder (PTSD), both throughout a human’s lifetime and across generations. Using qualitative interviews and nonparticipant observation, the author focuses on two public-facing research centers based in Melbourne: Florey Institute of Neuroscience and Mental Health (FNMH), and Murdoch Children’s Research Institute (MCRI). Preliminary findings indicate that a great deal of ambiguity characterizes this infant field, particularly when animal-model experiments are employed and the results are translated into human frameworks. Nevertheless, researchers at the FNMH and MCRI strongly suggest that adverse and traumatic life events have a significant effect on gene expression, especially when experienced during early development. Furthermore, they predict that neuroepigenetic research will have substantial implications for the ways in which mental illnesses like complex PTSD are diagnosed and treated. These preliminary findings shed light on why medical and health sociologists have good reason to be chiming in, engaging with and de-black-boxing ideations emerging from postgenomic sciences, as they may indeed have significant effects for vulnerable populations not only in Australia but other developing countries in the Global South.

Keywords: genetics, mental illness, neuroepigenetics, trauma

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148 Systematic Review of Technology-Based Mental Health Solutions for Modelling in Low and Middle Income Countries

Authors: Mukondi Esther Nethavhakone

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In 2020 World Health Organization announced the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as Coronavirus disease 2019 (COVID-19) pandemic. To curb or contain the spread of the novel coronavirus (COVID 19), global governments implemented social distancing and lockdown regulations. Subsequently, it was no longer business as per usual, life as we knew it had changed, and so many aspects of people's lives were negatively affected, including financial and employment stability. Mainly, because companies/businesses had to put their operations on hold, some had to shut down completely, resulting in the loss of income for many people globally. Finances and employment insecurities are some of the issues that exacerbated many social issues that the world was already faced with, such as school drop-outs, teenage pregnancies, sexual assaults, gender-based violence, crime, child abuse, elderly abuse, to name a few. Expectedly the majority of the population's mental health state was threatened. This resulted in an increased number of people seeking mental healthcare services. The increasing need for mental healthcare services in Low and Middle-income countries proves to be a challenge because it is a well-known fact due to financial constraints and not well-established healthcare systems, mental healthcare provision is not as prioritised as the primary healthcare in these countries. It is against this backdrop that the researcher seeks to find viable, cost-effective, and accessible mental health solutions for low and middle-income countries amid the pressures of any pandemic. The researcher will undertake a systematic review of the technology-based mental health solutions that have been implemented/adopted by developed countries during COVID 19 lockdown and social distancing periods. This systematic review study aims to determine if low and middle-income countries can adopt the cost-effective version of digital mental health solutions for the healthcare system to adequately provide mental healthcare services during critical times such as pandemics (when there's an overwhelming diminish in mental health globally). The researcher will undertake a systematic review study through mixed methods. It will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The mixed-methods uses findings from both qualitative and quantitative studies in one review study. It will be beneficial to conduct this kind of study using mixed methods because it is a public health topic that involves social interventions and it is not purely based on medical interventions. Therefore, the meta-ethnographic (qualitative data) analysis will be crucial in understanding why and which digital methods work and for whom does it work, rather than only the meta-analysis (quantitative data) providing what digital mental health methods works. The data collection process will be extensive, involving the development of a database, table of summary of evidence/findings, and quality assessment process lastly, The researcher will ensure that ethical procedures are followed and adhered to, ensuring that sensitive data is protected and the study doesn't pose any harm to the participants.

Keywords: digital, mental health, covid, low and middle-income countries

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147 Organ Donation after Medical Aid in Dying: A Critical Study of Clinical Processes and Legal Rules in Place

Authors: Louise Bernier

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Under some jurisdictions (including Canada), eligible patients can request and receive medical assistance in dying (MAiD) through lethal injections, inducing their cardiocirculatory death. Those same patients can also wish to donate their organs in the process. If they qualify as organ donors, a clinical and ethical rule called the 'dead donor rule' (DDR) requires the transplant teams to wait after cardiocirculatory death is confirmed, followed by a 'no touch' period (5 minutes in Canada) before they can proceed with organ removal. The medical procedures (lethal injections) as well as the delays associated with the DDR can damage organs (mostly thoracic organs) due to prolonged anoxia. Yet, strong scientific evidences demonstrate that operating differently and reconsidering the DDR would result in more organs of better quality available for transplant. This idea generates discomfort and resistance, but it is also worth considering, especially in a context of chronic shortage of available organs. One option that could be examined for MAiD’ patients who wish and can be organ donors would be to remove vital organs while patients are still alive (and under sedation). This would imply accepting that patient’s death would occur through organ donation instead of lethal injections required under MAiD’ legal rules. It would also mean that patients requesting MAiD and wishing to be organ donors could aspire to donate better quality organs, including their heart, an altruistic gesture that carries important symbolic value for many donors and their families. Following a patient centered approach, our hypothesis is that preventing vital organ donation from a living donor in all circumstance is neither perfectly coherent with how legal mentalities have evolved lately in the field of fundamental rights nor compatible with the clinical and ethical frameworks that shape the landscape in which those complex medical decisions unfold. Through a study of the legal, ethical, and clinical rules in place, both at the national and international levels, this analysis raises questions on the numerous inconsistencies associated with respecting the DDR with patients who have chosen to die through MAiD. We will begin with an assessment of the erosion of certain national legal frameworks that pertain to the sacred nature of the right to life which now also includes the right to choose how one wishes to die. We will then study recent innovative clinical protocols tested in different countries to help address acute organ shortage problems in creative ways. We will conclude this analysis with an ethical assessment of the situation, referring to principles such as justice, autonomy, altruism, beneficence, and non-malfeasance. This study will build a strong argument in favor of starting to allow vital organ donations from living donors in countries where MAiD is already permitted.

Keywords: altruism, autonomy, dead donor rule, medical assistance in dying, non-malfeasance, organ donation

Procedia PDF Downloads 152
146 Estimating the Efficiency of a Meta-Cognitive Intervention Program to Reduce the Risk Factors of Teenage Drivers with Attention Deficit Hyperactivity Disorder While Driving

Authors: Navah Z. Ratzon, Talia Glick, Iris Manor

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Attention Deficit Hyperactivity Disorder (ADHD) is a chronic disorder that affects the sufferer’s functioning throughout life and in various spheres of activity, including driving. Difficulties in cognitive functioning and executive functions are often part and parcel of the ADHD diagnosis, and thus form a risk factor in driving. Studies examining the effectiveness of intervention programs for improving and rehabilitating driving in typical teenagers have been conducted in relatively small numbers; while studies on similar programs for teenagers with ADHD have been especially scarce. The aim of the present study has been to examine the effectiveness of a metacognitive occupational therapy intervention program for reducing risk factors in driving among teenagers with ADHD. The present study included 37 teenagers aged 17 to 19. They included 23 teenagers with ADHD divided into experimental (11) and control (12) groups; as well as 14 non-ADHD teenagers forming a second control group. All teenagers taking part in the study were examined in the Tel Aviv University driving lab, and underwent cognitive diagnoses and a driving simulator test. Every subject in the intervention group took part in 3 assessment meetings, and two metacognitive treatment meetings. The control groups took part in two assessment meetings with a follow-up meeting 3 months later. In all the study’s groups, the treatment’s effectiveness was tested by comparing monitoring results on the driving simulator at the first and second evaluations. In addition, the driving of 5 subjects from the intervention group was monitored continuously from a month prior to the start of the intervention, a month during the phase of the intervention and another month until the end of the intervention. In the ADHD control group, the driving of 4 subjects was monitored from the end of the first evaluation for a period of 3 months. The study’s findings were affected by the fact that the ADHD control group was different from the two other groups, and exhibited ADHD characteristics manifested by impaired executive functions and lower metacognitive abilities relative to their peers. The study found partial, moderate, non-significant correlations between driving skills and cognitive functions, executive functions, and perceptions and attitudes towards driving. According to the driving simulator test results and the limited sampling results of actual driving, it was found that a metacognitive occupational therapy intervention may be effective in reducing risk factors in driving among teenagers with ADHD relative to their peers with and without ADHD. In summary, the results of the present study indicate a positive direction that speaks to the viability of using a metacognitive occupational therapy intervention program for reducing risk factors in driving. A further study is required that will include a bigger number of subjects, add actual driving monitoring hours, and assign subjects randomly to the various groups.

Keywords: ADHD, driving, driving monitoring, metacognitive intervention, occupational therapy, simulator, teenagers

Procedia PDF Downloads 281
145 Comprehensive Literature Review of the Humanistic Burden of Clostridium (Clostridiodes) difficile Infection

Authors: Caroline Seo, Jennifer Stephens, Kirstin H. Heinrich

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Background: Clostridiodes (formerly Clostridium) difficile infection (CDI) is an anaerobic, spore-forming bacterium with manifestations including diarrhea, pseudomembranous colitis and toxic megacolon. Despite general understanding that CDI may be associated with marked burden on patients’ health, there has been limited information available on the humanistic burden of CDI. The objective of this literature review was to summarize the published data on the humanistic burden of CDI globally, in order to better inform future research efforts and increase awareness of the patient perspective in this disease. Methods: A comprehensive literature review of the past 15 years (2002-2017) was conducted using MEDLINE, Embase and Cumulative Index of Nursing and Allied Health Literature. Additional searches were conducted from conference proceedings (2015-2017). Articles selected were studies specifically designed to examine the humanistic burden of illness associated with adult patients with CDI. Results: Of 3,325 articles or abstracts identified, 33 remained after screening and full text review. Sixty percent (60%) were published in 2016 or 2017. Data from the United States or Western Europe were most common. Data from Brazil, Canada, China and Spain also exist. Thirteen (13) studies used validated patient-reported outcomes instruments, mostly EQ-5D utility and SF-36 generic instruments. Three (3) studies used CDI-specific instruments (CDiff32, CDI-DaySyms). The burden of CDI impacts patients in multiple health-related quality of life (HRQOL) domains. SF-36 domains with the largest decrements compared to other GI diarrheal diseases (IBS-D and Crohn’s) were role physical, physical functioning, vitality, social functioning, and role emotional. Reported EQ-5D utilities for CDI ranged from 0.35-0.42 compared to 0.65 in Crohn’s and 0.72 in IBS-D. The majority of papers addressed physical functioning and mental health domains (67% for both). Across various studies patients reported weakness, lack of appetite, sleep disturbance, functional dependence, and decreased activities of daily lives due to the continuous diarrhea. Due to lack of control over this infection, CDI also impacts the psychological and emotional quality of life of the patients. Patients reported feelings of fear, anxiety, frustration, depression, and embarrassment. Additionally, the type of disease (primary vs. recurrent) may impact mental health. One study indicated that there is a decrement in SF-36 mental scores in patients with recurrent CDI, in comparison to patients with primary CDI. Other domains highlighted by these studies include pain (27%), social isolation (27%), vitality and fatigue (24%), self-care (9%), and caregiver burden (0%). Two studies addressed work productivity, with 1 of these studies reporting that CDI patients had the highest work productivity and activity impairment scores among the gastrointestinal diseases. No study specifically included caregiver self-report. However, 3 studies did provide mention of patients’ worry on how their diagnosis of CDI would impact family, caregivers, and/or friends. Conclusions: Despite being a serious public health issue there has been a paucity of research on the HRQOL among those with CDI. While progress is being made, gaps exist in understanding the burden on patients, caregivers, and families. Future research is warranted to aid understanding of the CDI patient perspective.

Keywords: burden, Clostridiodes, difficile, humanistic, infection

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144 Saco Sweet Cherry: Phenolic Profile and Biological Activity of Coloured and Non-Coloured Fractions

Authors: Catarina Bento, Ana Carolina Gonçalves, Fábio Jesus, Luís Rodrigues Silva

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Increasing evidence suggests that a diet rich in fruits and vegetables plays important roles in the prevention of chronic diseases, such as heart disease, cancer, stroke, diabetes, Alzheimer’s disease, among others. Fruits and vegetables gained prominence due their richness in bioactive compounds, being the focus of many studies due to their biological properties acting as health promoters. Prunus avium Linnaeus (L.), commonly known as sweet cherry has been the centre of attention due to its health benefits, and has been highly studied. In Portugal, most of the cherry production comes from the Fundão region. The Saco is one of the most important cultivar produced in this region, attributed with geographical protection. In this work, we prepared 3 extracts through solid-phase extraction (SPE): a whole extract, fraction I (non-coloured phenolics) and fraction II (coloured phenolics). The three extracts were used to determine the phenolic profile of Saco cultivar by liquid chromatography with diode array detection (LC-DAD) technique. This was followed by the evaluation of their biological potential, testing the extracts’ capacity to scavenge free-radicals (DPPH•, nitric oxide (•NO) and superoxide radical (O2●-)) and to inhibit α-glucosidase enzyme of all extracts. Additionally, we evaluated, for the first time, the protective effects against peroxyl radical (ROO•)-induced hemoglobin oxidation and hemolysis in human erythrocytes. A total of 16 non-coloured phenolics were detected, 3-O-caffeoylquinic and ρ-coumaroylquinic acids were the main ones, and 6 anthocyanins were found, among which cyanidin-3-O-rutinoside represented the majority. In respect to antioxidant activity, Saco showed great antioxidant potential in a concentration-dependent manner, demonstrated through the DPPH•,•NO and O2●-radicals, and greater ability to inhibit the α-glucosidase enzyme in comparison to the regular drug acarbose used to treat diabetes. Additionally, Saco proved to be effective to protect erythrocytes against oxidative damage in a concentration-dependent manner against hemoglobin oxidation and hemolysis. Our work demonstrated that Saco cultivar is an excellent source of phenolic compounds which are natural antioxidants that easily capture reactive species, such as ROO• before they can attack the erythrocytes’ membrane. In a general way, the whole extract showed the best efficiency, most likely due to a synergetic interaction between the different compounds. Finally, comparing the two separate fractions, the coloured fraction showed the most activity in all the assays, proving to be the biggest contributor of Saco cherries’ biological activity.

Keywords: biological potential, coloured phenolics, non-coloured phenolics, sweet cherry

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143 A Computational Framework for Load Mediated Patellar Ligaments Damage at the Tropocollagen Level

Authors: Fadi Al Khatib, Raouf Mbarki, Malek Adouni

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In various sport and recreational activities, the patellofemoral joint undergoes large forces and moments while accommodating the significant knee joint movement. In doing so, this joint is commonly the source of anterior knee pain related to instability in normal patellar tracking and excessive pressure syndrome. One well-observed explanation of the instability of the normal patellar tracking is the patellofemoral ligaments and patellar tendon damage. Improved knowledge of the damage mechanism mediating ligaments and tendon injuries can be a great help not only in rehabilitation and prevention procedures but also in the design of better reconstruction systems in the management of knee joint disorders. This damage mechanism, specifically due to excessive mechanical loading, has been linked to the micro level of the fibred structure precisely to the tropocollagen molecules and their connection density. We argue defining a clear frame starting from the bottom (micro level) to up (macro level) in the hierarchies of the soft tissue may elucidate the essential underpinning on the state of the ligaments damage. To do so, in this study a multiscale fibril reinforced hyper elastoplastic Finite Element model that accounts for the synergy between molecular and continuum syntheses was developed to determine the short-term stresses/strains patellofemoral ligaments and tendon response. The plasticity of the proposed model is associated only with the uniaxial deformation of the collagen fibril. The yield strength of the fibril is a function of the cross-link density between tropocollagen molecules, defined here by a density function. This function obtained through a Coarse-graining procedure linking nanoscale collagen features and the tissue level materials properties using molecular dynamics simulations. The hierarchies of the soft tissues were implemented using the rule of mixtures. Thereafter, the model was calibrated using a statistical calibration procedure. The model then implemented into a real structure of patellofemoral ligaments and patellar tendon (OpenKnee) and simulated under realistic loading conditions. With the calibrated material parameters the calculated axial stress lies well with the experimental measurement with a coefficient of determination (R2) equal to 0.91 and 0.92 for the patellofemoral ligaments and the patellar tendon respectively. The ‘best’ prediction of the yielding strength and strain as compared with the reported experimental data yielded when the cross-link density between the tropocollagen molecule of the fibril equal to 5.5 ± 0.5 (patellofemoral ligaments) and 12 (patellar tendon). Damage initiation of the patellofemoral ligaments was located at the femoral insertions while the damage of the patellar tendon happened in the middle of the structure. These predicted finding showed a meaningful correlation between the cross-link density of the tropocollagen molecules and the stiffness of the connective tissues of the extensor mechanism. Also, damage initiation and propagation were documented with this model, which were in satisfactory agreement with earlier observation. To the best of our knowledge, this is the first attempt to model ligaments from the bottom up, predicted depending to the tropocollagen cross-link density. This approach appears more meaningful towards a realistic simulation of a damaging process or repair attempt compared with certain published studies.

Keywords: tropocollagen, multiscale model, fibrils, knee ligaments

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142 Baricitinib Lipid-based Nanosystems as a Topical Alternative for Atopic Dermatitis Treatment

Authors: N. Garrós, P. Bustos, N. Beirampour, R. Mohammadi, M. Mallandrich, A.C. Calpena, H. Colom

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Atopic dermatitis (AD) is a persistent skin condition characterized by chronic inflammation caused by an autoimmune response. It is a prevalent clinical issue that requires continual treatment to enhance the patient's quality of life. Systemic therapy often involves the use of glucocorticoids or immunosuppressants to manage symptoms. Our objective was to create and assess topical liposomal formulations containing Baricitinib (BNB), a reversible inhibitor of Janus-associated kinase (JAK), which is involved in various immune responses. These formulations were intended to address flare-ups and improve treatment outcomes for AD. We created three distinct liposomal formulations by combining different amounts of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), cholesterol (CHOL), and ceramide (CER): (i) pure POPC, (ii) POPC mixed with CHOL (at a ratio of 8:2, mol/mol), and (iii) POPC mixed with CHOL and CER (at a ratio of 3.6:2.4:4.0 mol/mol/mol). We conducted various tests to determine the formulations' skin tolerance, irritancy capacity, and their ability to cause erythema and edema on altered skin. We also assessed the transepidermal water loss (TEWL) and skin hydration of rabbits to evaluate the efficacy of the formulations. Histological analysis, the HET-CAM test, and the modified Draize test were all used in the evaluation process. The histological analysis revealed that liposome POPC and POPC:CHOL avoided any damage to the tissues structures. The HET-CAM test showed no irritation effect caused by any of the three liposomes, and the modified Draize test showed a good Draize score for erythema and edema. Liposome POPC effectively counteracted the impact of xylol on the skin, and no erythema or edema was observed during the study. TEWL values were constant for all the liposomes with similar values to the negative control (within the range 8 - 15 g/h·m2, which means a healthy value for rabbits), whereas the positive control showed a significant increase. The skin hydration values were constant and followed the trend of the negative control, while the positive control showed a steady increase during the tolerance study. In conclusion, the developed formulations containing BNB exhibited no harmful or irritating effects, they did not demonstrate any irritant potential in the HET-CAM test and liposomes POPC and POPC:CHOL did not cause any structural alteration according to the histological analysis. These positive findings suggest that additional research is necessary to evaluate the efficacy of these liposomal formulations in animal models of the disease, including mutant animals. Furthermore, before proceeding to clinical trials, biochemical investigations should be conducted to better understand the mechanisms of action involved in these formulations.

Keywords: baricitinib, HET-CAM test, histological study, JAK inhibitor, liposomes, modified draize test

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141 Phenolic Composition and Contribution of Individual Compounds to Antioxidant Activity of Malus domestica Borkh Fruit Cultivars

Authors: Raudone Lina, Raudonis Raimondas, Liaudanskas Mindaugas, Pukalskas Audrius, Viskelis Pranas, Janulis Valdimaras

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Human health fortification, its protection and disease prophylaxis are the main problems of the health care systems. Plant origin materials and their preparations are applied for the prevention of the common diseases. Oxidative stress takes part in the pathogenesis of many autoimmune, neurodegenerative, tumor and ageing processes. The antioxidants are able to protect the human body from the free radicals and to stop the progression of numerous chronic diseases. The research of plant origin materials is relevant for the search of natural antioxidants. A group of compounds that gained scientific attention due to antioxidant properties and effects on human health are phenolic compounds. Phenolic compounds are widely abundant in various parts of plants, i.e. leaves, stems, roots, flowers and fruits. Most commonly consumed fruits all over the world are apples. It is very important to analyze the antioxidant activity of apples as they are extensively used in the prevention of various diseases. The aim of this study was to determine the antioxidant profiles of Malus domestica Borkh fruit cultivars (Aldas, Auksis, Connel Red, Ligol, Lodel, Rajka) and to identify the phenolic compounds with potent contribution to antioxidant activity. Nineteen constituents were identified in apple cultivars using ultra high performance liquid chromatography coupled to quadruple and time-of-flight mass spectrometers (UPLC–QTOF–MS). Phytochemical profile was constituted of phenolic acids, procyanidins, quercetin derivatives and dihydrochalcones. Reducing and radical scavenging activities of individual constituents were determined using high performance liquid chromatography (HPLC) coupled to post-column FRAP and ABTS assay, respectively. Significant differences of total radical scavenging and reducing activity (expressed as trolox equivalents, TE µmol/g) were determined between the investigated cultivars. Chlorogenic acid and complex of procyanidins were the main contributors to antioxidant activity determining up to 35 % and 55 % of total TE values, respectively. Determined phenolic composition and antioxidant activity significantly depend on apple cultivars. It is important to determine the individual compounds that are significant for antioxidant activity and that could be investigated in vivo systems. The identification of the antioxidants provides information for the further research of standardized extracts that could be used for pharmaceutical preparations with specific phenolic traits.

Keywords: FRAP, ABTS, antioxidant, phenolic, apples, chlorogenic acid

Procedia PDF Downloads 380
140 Implementation Research on the Singapore Physical Activity and Nutrition Program: A Mixed-Method Evaluation

Authors: Elaine Wong

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Introduction: The Singapore Physical Activity and Nutrition Study (SPANS) aimed to assess the effects of a community-based intervention on physical activity (PA) and nutrition behaviours as well as chronic disease risk factors for Singaporean women aged above 50 years. This article examines the participation, dose, fidelity, reach, satisfaction and reasons for completion and non-completion of the SPANS. Methods: The SPANS program integrated constructs of Social Cognitive Theory (SCT) and is composed of PA activities; nutrition workshops; dietary counselling coupled with motivational interviewing (MI) through phone calls; and text messages promoting healthy behaviours. Printed educational resources and health incentives were provided to participants. Data were collected via a mixed-method design strategy from a sample of 295 intervention participants. Quantitative data were collected using self-completed survey (n = 209); qualitative data were collected via research assistants’ notes, post feedback sessions and exit interviews with program completers (n = 13) and non-completers (n = 12). Results: Majority of participants reported high ‘satisfactory to excellent’ ratings for the program pace, suitability of interest and overall program (96.2-99.5%). Likewise, similar ratings for clarity of presentation; presentation skills, approachability, knowledge; and overall rating of trainers and program ambassadors were achieved (98.6-100%). Phone dietary counselling had the highest level of participation (72%) at less than or equal to 75% attendance rate followed by nutrition workshops (65%) and PA classes (60%). Attrition rate of the program was 19%; major reasons for withdrawal were personal commitments, relocation and health issues. All participants found the program resources to be colourful, informative and practical for their own reference. Reasons for program completion and maintenance were: desired health benefits; social bonding opportunities and to learn more about PA and nutrition. Conclusions: Process evaluation serves as an appropriate tool to identify recruitment challenges, effective intervention strategies and to ensure program fidelity. Program participants were satisfied with the educational resources, program components and delivery strategies implemented by the trainers and program ambassadors. The combination of printed materials and intervention components, when guided by the SCT and MI, were supportive in encouraging and reinforcing lifestyle behavioural changes. Mixed method evaluation approaches are integral processes to pinpoint barriers, motivators, improvements and effective program components in optimising the health status of Singaporean women.

Keywords: process evaluation, Singapore, older adults, lifestyle changes, program challenges

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139 Effects of Narghile Smoking in Tongue, Trachea and Lung

Authors: Sarah F. M. Pilati, Carolina S. Flausino, Guilherme F. Hoffmeister, Davi R. Tames, Telmo J. Mezadri

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The effects that may be related to narghile smoking in the tissues of the oral cavity, trachea and lung and associated inflammation has been the question raised lately. The objective of this study was to identify histopathological changes and the presence of inflammation through the exposure of mice to narghile smoking through a whole-body study. The animals were divided in 4 groups with 5 animals in each group, being: one control group, one with 7 days of exposure, 15 days and the last one with 30 days. The animals were exposed to the conventional hookah smoke from Mizo brand with 0.5% percentage of unwashed tobacco and the EcOco brand coconut fiber having a dimension of 2cm × 2cm. The duration of the session was 30 minutes / day per 7, 15 and 30 days. The tobacco smoke concentration at which test animals were exposed was 35 ml every two seconds while the remaining 58 seconds were pure air. Afterward, the mice were sacrificed and submitted to histological evaluation through slices. It was found in the tongue of the 7-day group the presence in epithelium areas with acanthosis, hyperkeratosis and epithelial projections. In-depth, more intense inflammation was observed. All alteration processes increased significantly as the days of exposure increased. In trachea, with the 7-day group, there was a decrease in thickening of the pseudostratified epithelium and a slight decrease in lashes, giving rise to the metaplasia process, a process that was established in the 31-day sampling when the epithelium became stratified. In the conjunctive tissue, it was observed the presence of defense cells and formation of new vessels, evidencing the chronic inflammatory process, which decreased in the course of the samples due to the deposition of collagen fibers as seen in the 15 and 31 days groups. Among the structures of the lung, the study focused on the bronchioles and alveoli. From the 7-day group, intra-alveolar septum thickness increased, alveolar space decreased, inflammatory infiltrate with mononuclear and defense cells and new vessels formation were observed, increasing the number of red blood cells in the region. The results showed that with the passing of the days a progressive increase of the signs of changes in the region was observed, a factor that shows that narghile smoking stimulates alterations mainly in the alveoli (place where gas exchanges occur that should not present alterations) calling attention to the harmful and aggressive effect of narghile smoking. These data also highlighted the harmful effect of smoking, since the presence of acanthosis, hyperkeratosis, epithelial projections and inflammation evidences the cellular alteration process for the tongue tissue protection. Also, the narghile smoking stimulates both epithelial and inflammatory changes in the trachea, in addition to a process of metaplasia, a factor that reinforces the harmful effect and the carcinogenic potential of the narghile smoking.

Keywords: metaplasia, inflammation, pathological constriction, hyperkeratosis

Procedia PDF Downloads 146
138 Triple Case Phantom Tumor of Lungs

Authors: Angelis P. Barlampas

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Introduction: The term phantom lung mass describes the ovoid collection of fluid within the interlobular fissure, which initially creates the impression of a mass. The problem of correct differential diagnosis is great, especially in plain radiography. A case is presented with three nodular pulmonary foci, the shape, location, and density of which, as well as the presence of chronic loculated pleural effusions, suggest the presence of multiple phantom tumors of the lung. Purpose: The aim of this paper is to draw the attention of non-experienced and non-specialized physicians to the existence of benign findings that mimic pathological conditions and vice versa. The careful study of a radiological examination and the comparison with previous exams or further control protect against quick wrong conclusions. Methods: A hospitalized patient underwent a non-contrast CT scan of the chest as part of the general control of her situation. Results: Computed tomography revealed pleural effusions, some of them loculated, increased cardiothoracic index, as well as the presence of three nodular foci, one in the left lung and two in the right with a maximum density of up to 18 Hounsfield units and a mean diameter of approximately five centimeters. Two of them are located in the characteristical anatomical position of the major interlobular fissure. The third one is located in the area of the right lower lobe’s posterior basal part, and it presents the same characteristics as the previous ones and is likely to be a loculated fluid collection, within an auxiliary interlobular fissure or a cyst, in the context of the patient's more general pleural entrapments and loculations. The differential diagnosis of nodular foci based on their imaging characteristics includes the following: a) rare metastatic foci with low density (liposarcoma, mucous tumors of the digestive or genital system, necrotic metastatic foci, metastatic renal cancer, etc.), b) necrotic multiple primary lung tumor locations (squamous epithelial cancer, etc. ), c) hamartomas of the lung, d) fibrotic tumors of the interlobular fissures, e) lipoid pneumonia, f) fluid concentrations within the interlobular fissures, g) lipoma of the lung, h) myelolipomas of the lung. Conclusions: The collection of fluid within the interlobular fissure of the lung can give the false impression of a lung mass, particularly on plain chest radiography. In the case of computed tomography, the ability to measure the density of a lesion, combined with the provided high anatomical details of the location and characteristics of the lesion, can lead relatively easily to the correct diagnosis. In cases of doubt or image artifacts, comparison with previous or subsequent examinations can resolve any disagreements, while in rare cases, intravenous contrast may be necessary.

Keywords: phantom mass, chest CT, pleural effusion, cancer

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137 Enabling Wire Arc Additive Manufacturing in Aircraft Landing Gear Production and Its Benefits

Authors: Jun Wang, Chenglei Diao, Emanuele Pagone, Jialuo Ding, Stewart Williams

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As a crucial component in aircraft, landing gear systems are responsible for supporting the plane during parking, taxiing, takeoff, and landing. Given the need for high load-bearing capacity over extended periods, 300M ultra-high strength steel (UHSS) is often the material of choice for crafting these systems due to its exceptional strength, toughness, and fatigue resistance. In the quest for cost-effective and sustainable manufacturing solutions, Wire Arc Additive Manufacturing (WAAM) emerges as a promising alternative for fabricating 300M UHSS landing gears. This is due to its advantages in near-net-shape forming of large components, cost-efficiency, and reduced lead times. Cranfield University has conducted an extensive preliminary study on WAAM 300M UHSS, covering feature deposition, interface analysis, and post-heat treatment. Both Gas Metal Arc (GMA) and Plasma Transferred Arc (PTA)-based WAAM methods were explored, revealing their feasibility for defect-free manufacturing. However, as-deposited 300M features showed lower strength but higher ductility compared to their forged counterparts. Subsequent post-heat treatments were effective in normalising the microstructure and mechanical properties, meeting qualification standards. A 300M UHSS landing gear demonstrator was successfully created using PTA-based WAAM, showcasing the method's precision and cost-effectiveness. The demonstrator, measuring Ф200mm x 700mm, was completed in 16 hours, using 7 kg of material at a deposition rate of 1.3kg/hr. This resulted in a significant reduction in the Buy-to-Fly (BTF) ratio compared to traditional manufacturing methods, further validating WAAM's potential for this application. A "cradle-to-gate" environmental impact assessment, which considers the cumulative effects from raw material extraction to customer shipment, has revealed promising outcomes. Utilising Wire Arc Additive Manufacturing (WAAM) for landing gear components significantly reduces the need for raw material extraction and refinement compared to traditional subtractive methods. This, in turn, lessens the burden on subsequent manufacturing processes, including heat treatment, machining, and transportation. Our estimates indicate that the carbon footprint of the component could be halved when switching from traditional machining to WAAM. Similar reductions are observed in embodied energy consumption and other environmental impact indicators, such as emissions to air, water, and land. Additionally, WAAM offers the unique advantage of part repair by redepositing only the necessary material, a capability not available through conventional methods. Our research shows that WAAM-based repairs can drastically reduce environmental impact, even when accounting for additional transportation for repairs. Consequently, WAAM emerges as a pivotal technology for reducing environmental impact in manufacturing, aiding the industry in its crucial and ambitious journey towards Net Zero. This study paves the way for transformative benefits across the aerospace industry, as we integrate manufacturing into a hybrid solution that offers substantial savings and access to more sustainable technologies for critical component production.

Keywords: WAAM, aircraft landing gear, microstructure, mechanical performance, life cycle assessment

Procedia PDF Downloads 126
136 Association of Depression with Physical Inactivity and Time Watching Television: A Cross-Sectional Study with the Brazilian Population PNS, 2013

Authors: Margareth Guimaraes Lima, Marilisa Berti A. Barros, Deborah Carvalho Malta

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The relationship between physical activity (PA) and depression has been investigated, in both, observational and clinical studies: PA can integrate the treatments for depression; the physical inactivity (PI) may contribute to increase depression symptoms; and on the other hand, emotional problems can decrease PA. The main of this study was analyze the association among leisure and transportation PI and time watching television (TV) according to depression (minor and major), evaluated with the Patient Health Questionnaire (PHQ-9). The association was also analyzed by gender. This is a cross-sectional study. Data were obtained from the National Health Survey 2013 (PNS), performed with representative sample of the Brazilian adult population, in 2013. The PNS collected information from 60,202 individuals, aged 18 years or more. The independent variable were: leisure time physical inactivity (LTPI), considering inactive or insufficiently actives (categories were linked for analyzes), those who do not performed a minimum of 150 or 74 minutes of moderate or vigorous LTPA, respectively, by week; transportation physical inactivity (TPI), individuals who did not reached 150 minutes, by week, travelling by bicycle or on foot to work or other activities; daily time watching TV > 5 hours. The principal independent variable was depression, identified by PHQ-9. Individuals were classified with major depression, with > 5 symptoms, more than seven days, but one of the symptoms was “depressive mood” or “lack of interest or pleasure”. The others had minor depression. The variables used to adjustment were gender, age, schooling and chronic disease. The prevalence of LTPI, TPI and TV time were estimated according to depression, and differences were tested with Chi-Square test. Adjusted prevalence ratios were estimated using multiple Poisson regression models. The analyzes also had stratification by gender. Mean age of the studied population was 42.9 years old (CI95%:42.6-43.2) and 52.9% were women. 77.5% and 68.1% were inactive or insufficiently active in leisure and transportation, respectively and 13.3% spent time watching TV 5 > hours. 6% and 4.1% of the Brazilian population were diagnosed with minor or major depression. LTPI prevalence was 5% and 9% higher among individuals with minor and major depression, respectively, comparing with no depression. The prevalence of TPI was 7% higher in those with major depression. Considering larger time watching TV, the prevalence was 45% and 74% higher among those with minor and major depression, respectively. Analyzing by gender, the associations were greater in men than women and TPI was note be associated, in women. The study detected the higher prevalence of leisure time physical inactivity and, especially, time spent watching TV, among individuals with major and minor depression, after to adjust for a number of potential confounding factors. TPI was only associated with major disorders and among men. Considering the cross-sectional design of the research, these associations can point out the importance of the mental problems control of the population to increase PA and decrease the sedentary lifestyle; on the other hand, the study highlight the need of interventions by encouraging people with depression, to practice PA, even to transportation.

Keywords: depression, physical activity, PHQ-9, sedentary lifestyle

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135 Railway Composite Flooring Design: Numerical Simulation and Experimental Studies

Authors: O. Lopez, F. Pedro, A. Tadeu, J. Antonio, A. Coelho

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The future of the railway industry lies in the innovation of lighter, more efficient and more sustainable trains. Weight optimizations in railway vehicles allow reducing power consumption and CO₂ emissions, increasing the efficiency of the engines and the maximum speed reached. Additionally, they reduce wear of wheels and rails, increase the space available for passengers, etc. Among the various systems that integrate railway interiors, the flooring system is one which has greater impact both on passenger safety and comfort, as well as on the weight of the interior systems. Due to the high weight saving potential, relative high mechanical resistance, good acoustic and thermal performance, ease of modular design, cost-effectiveness and long life, the use of new sustainable composite materials and panels provide the latest innovations for competitive solutions in the development of flooring systems. However, one of the main drawbacks of the flooring systems is their relatively poor resistance to point loads. Point loads in railway interiors can be caused by passengers or by components fixed to the flooring system, such as seats and restraint systems, handrails, etc. In this way, they can originate higher fatigue solicitations under service loads or zones with high stress concentrations under exceptional loads (higher longitudinal, transverse and vertical accelerations), thus reducing its useful life. Therefore, to verify all the mechanical and functional requirements of the flooring systems, many physical prototypes would be created during the design phase, with all of the high costs associated with it. Nowadays, the use of virtual prototyping methods by computer-aided design (CAD) and computer-aided engineering (CAE) softwares allow validating a product before committing to making physical test prototypes. The scope of this work was to current computer tools and integrate the processes of innovation, development, and manufacturing to reduce the time from design to finished product and optimise the development of the product for higher levels of performance and reliability. In this case, the mechanical response of several sandwich panels with different cores, polystyrene foams, and composite corks, were assessed, to optimise the weight and the mechanical performance of a flooring solution for railways. Sandwich panels with aluminum face sheets were tested to characterise its mechanical performance and determine the polystyrene foam and cork properties when used as inner cores. Then, a railway flooring solution was fully modelled (including the elastomer pads to provide the required vibration isolation from the car body) and perform structural simulations using FEM analysis to comply all the technical product specifications for the supply of a flooring system. Zones with high stress concentrations are studied and tested. The influence of vibration modes on the comfort level and stability is discussed. The information obtained with the computer tools was then completed with several mechanical tests performed on some solutions, and on specific components. The results of the numerical simulations and experimental campaign carried out are presented in this paper. This research work was performed as part of the POCI-01-0247-FEDER-003474 (coMMUTe) Project funded by Portugal 2020 through COMPETE 2020.

Keywords: cork agglomerate core, mechanical performance, numerical simulation, railway flooring system

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134 Ibrutinib and the Potential Risk of Cardiac Failure: A Review of Pharmacovigilance Data

Authors: Abdulaziz Alakeel, Roaa Alamri, Abdulrahman Alomair, Mohammed Fouda

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Introduction: Ibrutinib is a selective, potent, and irreversible small-molecule inhibitor of Bruton's tyrosine kinase (BTK). It forms a covalent bond with a cysteine residue (CYS-481) at the active site of Btk, leading to inhibition of Btk enzymatic activity. The drug is indicated to treat certain type of cancers such as mantle cell lymphoma (MCL), chronic lymphocytic leukaemia and Waldenström's macroglobulinaemia (WM). Cardiac failure is a condition referred to inability of heart muscle to pump adequate blood to human body organs. There are multiple types of cardiac failure including left and right-sided heart failure, systolic and diastolic heart failures. The aim of this review is to evaluate the risk of cardiac failure associated with the use of ibrutinib and to suggest regulatory recommendations if required. Methodology: Signal Detection team at the National Pharmacovigilance Center (NPC) of Saudi Food and Drug Authority (SFDA) performed a comprehensive signal review using its national database as well as the World Health Organization (WHO) database (VigiBase), to retrieve related information for assessing the causality between cardiac failure and ibrutinib. We used the WHO- Uppsala Monitoring Centre (UMC) criteria as standard for assessing the causality of the reported cases. Results: Case Review: The number of resulted cases for the combined drug/adverse drug reaction are 212 global ICSRs as of July 2020. The reviewers have selected and assessed the causality for the well-documented ICSRs with completeness scores of 0.9 and above (35 ICSRs); the value 1.0 presents the highest score for best-written ICSRs. Among the reviewed cases, more than half of them provides supportive association (four probable and 15 possible cases). Data Mining: The disproportionality of the observed and the expected reporting rate for drug/adverse drug reaction pair is estimated using information component (IC), a tool developed by WHO-UMC to measure the reporting ratio. Positive IC reflects higher statistical association while negative values indicates less statistical association, considering the null value equal to zero. The results of (IC=1.5) revealed a positive statistical association for the drug/ADR combination, which means “Ibrutinib” with “Cardiac Failure” have been observed more than expected when compared to other medications available in WHO database. Conclusion: Health regulators and health care professionals must be aware for the potential risk of cardiac failure associated with ibrutinib and the monitoring of any signs or symptoms in treated patients is essential. The weighted cumulative evidences identified from causality assessment of the reported cases and data mining are sufficient to support a causal association between ibrutinib and cardiac failure.

Keywords: cardiac failure, drug safety, ibrutinib, pharmacovigilance, signal detection

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133 Timely Screening for Palliative Needs in Ambulatory Oncology

Authors: Jaci Mastrandrea

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Background: The National Comprehensive Cancer Network (NCCN) recommends that healthcare institutions have established processes for integrating palliative care (PC) into cancer treatment and that all cancer patients be screened for PC needs upon initial diagnosis as well as throughout the entire continuum of care (National Comprehensive Cancer Network, 2021). Early PC screening is directly correlated with improved patient outcomes. The Sky Lakes Cancer Treatment Center (SLCTC) is an institution that has access to PC services yet does not have protocols in place for identifying patients with palliative needs or a standardized referral process. The aim of this quality improvement project is to improve early access to PC services by establishing a standardized screening and referral process for outpatient oncology patients. Method: The sample population included all adult patients with an oncology diagnosis who presented to the SLCTC for treatment during the project timeline from March 15th, 2022, to April 29th, 2022. The “Palliative and Supportive Needs Assessment'' (PSNA) screening tool was developed from validated and evidence-based PC referral criteria. The tool was initially implemented using paper forms and later was integrated into the Epic-Beacon EHR system. Patients were screened by registered nurses on the SLCTC treatment team. Nurses responsible for screening patients received an educational inservice prior to implementation. Patients with a PSNA score of three or higher were considered to be a positive screen. Scores of five or higher triggered a PC referral order in the patient’s EHR for the oncologist to review and approve. All patients with a positive screen received an educational handout on the topic of PC, and the EHR was flagged for follow-up. Results: Prior to implementation of the PSCNA screening tool, the SLCTC had zero referrals to PC in the past year, excluding referrals to hospice. Data was collected from the first 100 patient screenings completed within the eight-week data collection period. Seventy-three percent of patients met criteria for PC referral with a score greater than or equal to three. Of those patients who met referral criteria, 53.4% (39 patients) were referred for a palliative and supportive care consultation. Patients that were not referred to PC upon meeting the criteria were flagged in the EHR for re-screening within one to three months. Patients with lung cancer, chronic hematologic malignancies, breast cancer, and gastrointestinal malignancy most frequently met criteria for PC referral and scored highest overall on the scale of 0-12. Conclusion: The implementation of a standardized PC screening tool at the SLCTC significantly increased awareness of PC needs among cancer patients in the outpatient setting. Additionally, data derived from this quality improvement project supports the national recommendation for PC to be an integral component of cancer treatment across the entire continuum of care.

Keywords: oncology, palliative care, symptom management, symptom screening, ambulatory oncology, cancer, supportive care

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132 Integration of a Protective Film to Enhance the Longevity and Performance of Miniaturized Ion Sensors

Authors: Antonio Ruiz Gonzalez, Kwang-Leong Choy

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The measurement of electrolytes has a high value in the clinical routine. Ions are present in all body fluids with variable concentrations and are involved in multiple pathologies such as heart failures and chronic kidney disease. In the case of dissolved potassium, although a high concentration in the blood (hyperkalemia) is relatively uncommon in the general population, it is one of the most frequent acute electrolyte abnormalities. In recent years, the integration of thin films technologies in this field has allowed the development of highly sensitive biosensors with ultra-low limits of detection for the assessment of metals in liquid samples. However, despite the current efforts in the miniaturization of sensitive devices and their integration into portable systems, only a limited number of successful examples used commercially can be found. This fact can be attributed to a high cost involved in their production and the sustained degradation of the electrodes over time, which causes a signal drift in the measurements. Thus, there is an unmet necessity for the development of low-cost and robust sensors for the real-time monitoring of analyte concentrations in patients to allow the early detection and diagnosis of diseases. This paper reports a thin film ion-selective sensor for the evaluation of potassium ions in aqueous samples. As an alternative for this fabrication method, aerosol assisted chemical vapor deposition (AACVD), was applied due to cost-effectivity and fine control over the film deposition. Such a technique does not require vacuum and is suitable for the coating of large surface areas and structures with complex geometries. This approach allowed the fabrication of highly homogeneous surfaces with well-defined microstructures onto 50 nm thin gold layers. The degradative processes of the ubiquitously employed poly (vinyl chloride) membranes in contact with an electrolyte solution were studied, including the polymer leaching process, mechanical desorption of nanoparticles and chemical degradation over time. Rational design of a protective coating based on an organosilicon material in combination with cellulose to improve the long-term stability of the sensors was then carried out, showing an improvement in the performance after 5 weeks. The antifouling properties of such coating were assessed using a cutting-edge quartz microbalance sensor, allowing the quantification of the adsorbed proteins in the nanogram range. A correlation between the microstructural properties of the films with the surface energy and biomolecules adhesion was then found and used to optimize the protective film.

Keywords: hyperkalemia, drift, AACVD, organosilicon

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131 A Rare Case of Dissection of Cervical Portion of Internal Carotid Artery, Diagnosed Postpartum

Authors: Bidisha Chatterjee, Sonal Grover, Rekha Gurung

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Postpartum dissection of the internal carotid artery is a relatively rare condition and is considered as an underlying aetiology in 5% to 25% of strokes under the age of 30 to 45 years. However, 86% of these cases recover completely and 14% have mild focal neurological symptoms. Prognosis is generally good with early intervention. The risk quoted for a repeat carotid artery dissection in subsequent pregnancies is less than 2%. 36-year Caucasian primipara presented on postnatal day one of forceps delivery with tachycardia. In the intrapartum period she had a history of prolonged rupture of membranes and developed intrapartum sepsis and was treated with antibiotics. Postpartum ECG showed septal inferior T wave inversion and a troponin level of 19. Subsequently Echocardiogram ruled out post-partum cardiomyopathy. Repeat ECG showed improvement of the previous changes and in the absence of symptoms no intervention was warranted. On day 4 post-delivery, she had developed symptoms of droopy right eyelid, pain around the right eye and itching in the right ear. On examination, she had developed right sided ptosis, unequal pupils (Rt miotic pupil). Cranial nerve examination, reflexes, sensory examination and muscle power was normal. Apart from migraine, there was no medical or family history of note. In view of Horner’s on the right, she had a CT Angiogram and subsequently MR/MRA and was diagnosed with dissection of the cervical portion of the right internal carotid artery. She was discharged on a course of Aspirin 75mg. By 6 week post-natal follow up patient had recovered significantly with occasional episodes of unequal pupils and tingling of right toes which resolved spontaneously. Cervical artery dissection, including VAD and carotid artery dissection, are rare complications of pregnancy with an estimated annual incidence of 2.6–3 per 100,000 pregnancy hospitalizations. Aetiology remains unclear though trauma during straining at labour, underlying arterial disease and preeclampsia have been implicated. Hypercoagulable state during pregnancy and puerperium could also be an important factor. 60-90% cases present with severe headache and neck pain and generally precede neurological symptoms like ipsilateral Horner’s syndrome, retroorbital pain, tinnitus and cranial nerve palsy. Although rare, the consequences of delayed diagnosis and management can lead to severe and permanent neurological deficits. Patients with a strong index of suspicion should undergo an MRI or MRA of head and neck. Antithrombotic and antiplatelet therapy forms the mainstay of therapy with selected cases needing endovascular stenting. Long term prognosis is favourable with either complete resolution or minimal deficit if treatment is prompt. Patients should be counselled about the recurrence risk and possibility of stroke in future pregnancy. Coronary artery dissection is rare and treatable but needs early diagnosis and treatment. Post-partum headache and neck pain with neurological symptoms should prompt urgent imaging followed by antithrombotic and /or antiplatelet therapy. Most cases resolve completely or with minimal sequelae.

Keywords: postpartum, dissection of internal carotid artery, magnetic resonance angiogram, magnetic resonance imaging, antiplatelet, antithrombotic

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130 Switchable Lipids: From a Molecular Switch to a pH-Sensitive System for the Drug and Gene Delivery

Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

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Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

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