Search results for: bio-medical sensors
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1673

Search results for: bio-medical sensors

53 Control of Doxorubicin Release Rate from Magnetic PLGA Nanoparticles Using a Non-Permanent Magnetic Field

Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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52 Model of Pharmacoresistant Blood-Brain Barrier In-vitro for Prediction of Transfer of Potential Antiepileptic Drugs

Authors: Emílie Kučerová, Tereza Veverková, Marina Morozovová, Eva Kudová, Jitka Viktorová

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The blood-brain barrier (BBB) is a key element regulating the transport of substances between the blood and the central nervous system (CNS). The BBB protects the CNS from potentially harmful substances and maintains a suitable environment for nervous activity in the CNS, but at the same time, it represents a significant obstacle to the entry of drugs into the CNS. Pharmacoresistant epilepsy is a form of epilepsy that cannot be suppressed using two (or more) appropriately chosen antiepileptic drugs. In many cases, pharmacoresistant epilepsy is characterized by an increased concentration of efflux pumps on the luminal sides of the endothelial cells that form the BBB and an increased number of drug-metabolizing enzymes in the BBB cells, thereby preventing the effective transport of antiepileptic drugs into the CNS. Currently, a number of scientific groups are focusing on the preparation and improvement of BBB models in vitro in order to study cell interactions or transport mechanisms. However, in pathological conditions such as pharmacoresistant epilepsy, there are changes in BBB structure, and current BBB models are insufficient for related research. Our goal is to develop a suitable BBB model for pharmacoresistant epilepsy in vitro and use it to test the transfer of potential antiepileptic drugs. This model is created by co-culturing immortalized human cerebral microvascular endothelial cells, human vascular pericytes and immortalized human astrocytes. The BBB in vitro is cultivated in the form of a 2D transwell model and the integrity of the barrier is verified by measuring transendothelial electrical resistance (TEER). From the current results, a contact cell arrangement with the cultivation of endothelial cells on the upper side of the insert and the co-cultivation of astrocytes and pericytes on the lower side of the insert is selected as the most promising for BBB model cultivation. The pharmacoresistance of the BBB model is achieved by long-term cultivation of endothelial cells in an increasing concentration of selected antiepileptic drugs, which should lead to increased production of efflux pumps and drug-metabolizing enzymes. The pharmacoresistant BBB model in vitro will be further used for the screening of substances that could act both as antiepileptics and at the same time as inhibitors of efflux pumps in endothelial cells. This project was supported by the Technology Agency of the Czech Republic (TACR), Personalized Medicine: Translational research towards biomedical applications, No. TN02000109 and by the Academy of Sciences of the Czech Republic (AS CR) – grant RVO 61388963.

Keywords: antiepileptic drugs, blood-brain barrier, efflux transporters, pharmacoresistance

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51 Modified Polysaccharide as Emulsifier in Oil-in-Water Emulsions

Authors: Tatiana Marques Pessanha, Aurora Perez-Gramatges, Regina Sandra Veiga Nascimento

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Emulsions are commonly used in applications involving oil/water dispersions, where handling of interfaces becomes a crucial aspect. The use of emulsion technology has greatly evolved in the last decades to suit the most diverse uses, ranging from cosmetic products and biomedical adjuvants to complex industrial fluids. The stability of these emulsions is influenced by factors such as the amount of oil, size of droplets and emulsifiers used. While commercial surfactants are typically used as emulsifiers to reduce interfacial tension, and therefore increase emulsion stability, these organic amphiphilic compounds are often toxic and expensive. A suitable alternative for emulsifiers can be obtained from the chemical modification of polysaccharides. Our group has been working on modification of polysaccharides to be used as additives in a variety of fluid formulations. In particular, we have obtained promising results using chitosan, a natural and biodegradable polymer that can be easily modified due to the presence of amine groups in its chemical structure. In this way, it is possible to increase both the hydrophobic and hydrophilic character, which renders a water-soluble, amphiphilic polymer that can behave as an emulsifier. The aim of this work was the synthesis of chitosan derivatives structurally modified to act as surfactants in stable oil-in-water. The synthesis of chitosan derivatives occurred in two steps, the first being the hydrophobic modification with the insertion of long hydrocarbon chains, while the second step consisted in the cationization of the amino groups. All products were characterized by infrared spectroscopy (FTIR) and carbon magnetic resonance (13C-NMR) to evaluate the cationization and hydrofobization degrees. These modified polysaccharides were used to formulate oil-in water (O:W) emulsions with different oil/water ratios (i.e 25:75, 35:65, 60:40) using mineral paraffinic oil. The formulations were characterized according to the type of emulsion, density and rheology measurements, as well as emulsion stability at high temperatures. All emulsion formulations were stable for at least 30 days, at room temperature (25°C), and in the case of the high oil content emulsion (60:40), the formulation was also stable at temperatures up to 100°C. Emulsion density was in the range of 0.90-0.87 s.g. The rheological study showed a viscoelastic behaviour in all formulations at room temperature, which is in agreement with the high stability showed by the emulsions, since the polymer acts not only reducing interfacial tension, but also forming an elastic membrane at the oil/water interface that guarantees its integrity. The results obtained in this work are a strong evidence of the possibility of using chemically modified polysaccharides as environmentally friendly alternatives to commercial surfactants in the stabilization of oil-in water formulations.

Keywords: emulsion, polymer, polysaccharide, stability, chemical modification

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50 Biosensor for Determination of Immunoglobulin A, E, G and M

Authors: Umut Kokbas, Mustafa Nisari

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Immunoglobulins, also known as antibodies, are glycoprotein molecules produced by activated B cells that transform into plasma cells and result in them. Antibodies are critical molecules of the immune response to fight, which help the immune system specifically recognize and destroy antigens such as bacteria, viruses, and toxins. Immunoglobulin classes differ in their biological properties, structures, targets, functions, and distributions. Five major classes of antibodies have been identified in mammals: IgA, IgD, IgE, IgG, and IgM. Evaluation of the immunoglobulin isotype can provide a useful insight into the complex humoral immune response. Evaluation and knowledge of immunoglobulin structure and classes are also important for the selection and preparation of antibodies for immunoassays and other detection applications. The immunoglobulin test measures the level of certain immunoglobulins in the blood. IgA, IgG, and IgM are usually measured together. In this way, they can provide doctors with important information, especially regarding immune deficiency diseases. Hypogammaglobulinemia (HGG) is one of the main groups of primary immunodeficiency disorders. HGG is caused by various defects in B cell lineage or function that result in low levels of immunoglobulins in the bloodstream. This affects the body's immune response, causing a wide range of clinical features, from asymptomatic diseases to severe and recurrent infections, chronic inflammation and autoimmunity Transient infant hypogammaglobulinemia (THGI), IgM deficiency (IgMD), Bruton agammaglobulinemia, IgA deficiency (SIgAD) HGG samples are a few. Most patients can continue their normal lives by taking prophylactic antibiotics. However, patients with severe infections require intravenous immune serum globulin (IVIG) therapy. The IgE level may rise to fight off parasitic infections, as well as a sign that the body is overreacting to allergens. Also, since the immune response can vary with different antigens, measuring specific antibody levels also aids in the interpretation of the immune response after immunization or vaccination. Immune deficiencies usually occur in childhood. In Immunology and Allergy clinics, apart from the classical methods, it will be more useful in terms of diagnosis and follow-up of diseases, if it is fast, reliable and especially in childhood hypogammaglobulinemia, sampling from children with a method that is more convenient and uncomplicated. The antibodies were attached to the electrode surface via the poly hydroxyethyl methacrylamide cysteine nanopolymer. It was used to evaluate the anodic peak results obtained in the electrochemical study. According to the data obtained, immunoglobulin determination can be made with a biosensor. However, in further studies, it will be useful to develop a medical diagnostic kit with biomedical engineering and to increase its sensitivity.

Keywords: biosensor, immunosensor, immunoglobulin, infection

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49 Impact of Autoclave Sterilization of Gelatin on Endotoxin Level and Physical Properties Compared to Surfactant Purified Gelatins

Authors: Jos Olijve

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Introduction and Purpose: Endotoxins are found in the outer membrane of gram-negative bacteria and have profound in vitro and in vivo responses. They can trigger strong immune responses and negatively affect various cellar activities particular cells expressing toll-like receptors. They are therefore unwanted contaminants of biomaterials sourced from natural raw materials, and their activity must be as low as possible. Collagen and gelatin are natural extracellular matrix components and have, due to their low allergenic potential, suitable biological properties, and tunable physical characteristics, high potential in biomedical applications. The purpose of this study was to determine the influence of autoclave sterilization of gelatin on physical properties and endotoxin level compared to surfactant purified gelatin. Methods: Type A gelatin from Sigma-Aldrich (G1890) with endotoxin level of 35000 endotoxin units (EU) per gram gelatin and type A gelatins from Rousselot Gent with endotoxin activity of 30000 EU per gram were used. A 10 w/w% G1890 gelatin solution was autoclave sterilized during 30 minutes at 121°C and 1 bar over pressure. The physical properties and the endotoxin level of the sterilized G1890 gelatin were compared to a type A gelatin from Rousselot purified with Triton X100 surfactant. The Triton X100 was added to a concentration of 0.5 w/w% which is above the critical micellar concentration. The gelatin surfactant mixtures were kept for 30-45 minutes under constant stirring at 55-60°C. The Triton X100 was removed by active carbon filtration. The endotoxin levels of the gelatins were measured using the Endozyme recombinant factor C method from Hyglos GmbH (Germany). Results and Discussion: Autoclave sterilization significantly affect the physical properties of gelatin. Molecular weight of G1890 decreased from 140 to 50kDa, and gel strength decreased from 300 to 40g. The endotoxin level of the gelatin reduced after sterilization from 35000 EU/g to levels of 400-500 EU/g. These endotoxin levels are however still far above the upper endotoxin level of 0.05 EU/ml, which resembles 5 EU/g gelatin based on a 1% gelatin solution, to avoid cell proliferation alteration. Molecular weight and gel strength of Rousselot gelatin was not altered after Triton X100 purification and remained 150kDa and 300g respectively. The endotoxin levels of Triton X100 purified Rousselot gelatin was < 5EU/g gelatin. Conclusion: Autoclave sterilization of gelatin is, in comparison to Triton X100 purification, not efficient to inactivate endotoxin levels in gelatin to levels below the upper limit to avoid cell proliferation alteration. Autoclave sterilization gave a significant decrease in molecular weight and gel strength which makes autoclave sterilized gelatin, in comparison to Triton X100 purified gelatin, not suitable for 3D printing.

Keywords: endotoxin, gelatin, molecular weight, sterilization, Triton X100

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48 Magnetic Navigation of Nanoparticles inside a 3D Carotid Model

Authors: E. G. Karvelas, C. Liosis, A. Theodorakakos, T. E. Karakasidis

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Magnetic navigation of the drug inside the human vessels is a very important concept since the drug is delivered to the desired area. Consequently, the quantity of the drug required to reach therapeutic levels is being reduced while the drug concentration at targeted sites is increased. Magnetic navigation of drug agents can be achieved with the use of magnetic nanoparticles where anti-tumor agents are loaded on the surface of the nanoparticles. The magnetic field that is required to navigate the particles inside the human arteries is produced by a magnetic resonance imaging (MRI) device. The main factors which influence the efficiency of the usage of magnetic nanoparticles for biomedical applications in magnetic driving are the size and the magnetization of the biocompatible nanoparticles. In this study, a computational platform for the simulation of the optimal gradient magnetic fields for the navigation of magnetic nanoparticles inside a carotid artery is presented. For the propulsion model of the particles, seven major forces are considered, i.e., the magnetic force from MRIs main magnet static field as well as the magnetic field gradient force from the special propulsion gradient coils. The static field is responsible for the aggregation of nanoparticles, while the magnetic gradient contributes to the navigation of the agglomerates that are formed. Moreover, the contact forces among the aggregated nanoparticles and the wall and the Stokes drag force for each particle are considered, while only spherical particles are used in this study. In addition, gravitational forces due to gravity and the force due to buoyancy are included. Finally, Van der Walls force and Brownian motion are taken into account in the simulation. The OpenFoam platform is used for the calculation of the flow field and the uncoupled equations of particles' motion. To verify the optimal gradient magnetic fields, a covariance matrix adaptation evolution strategy (CMAES) is used in order to navigate the particles into the desired area. A desired trajectory is inserted into the computational geometry, which the particles are going to be navigated in. Initially, the CMAES optimization strategy provides the OpenFOAM program with random values of the gradient magnetic field. At the end of each simulation, the computational platform evaluates the distance between the particles and the desired trajectory. The present model can simulate the motion of particles when they are navigated by the magnetic field that is produced by the MRI device. Under the influence of fluid flow, the model investigates the effect of different gradient magnetic fields in order to minimize the distance of particles from the desired trajectory. In addition, the platform can navigate the particles into the desired trajectory with an efficiency between 80-90%. On the other hand, a small number of particles are stuck to the walls and remains there for the rest of the simulation.

Keywords: artery, drug, nanoparticles, navigation

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47 Medication Side Effects: Implications on the Mental Health and Adherence Behaviour of Patients with Hypertension

Authors: Irene Kretchy, Frances Owusu-Daaku, Samuel Danquah

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Hypertension is the leading risk factor for cardiovascular diseases, and a major cause of death and disability worldwide. This study examined whether psychosocial variables influenced patients’ perception and experience of side effects of their medicines, how they coped with these experiences and the impact on mental health and medication adherence to conventional hypertension therapies. Methods: A hospital-based mixed methods study, using quantitative and qualitative approaches was conducted on hypertensive patients. Participants were asked about side effects, medication adherence, common psychological symptoms, and coping mechanisms with the aid of standard questionnaires. Information from the quantitative phase was analyzed with the Statistical Package for Social Sciences (SPSS) version 20. The interviews from the qualitative study were audio-taped with a digital audio recorder, manually transcribed and analyzed using thematic content analysis. The themes originated from participant interviews a posteriori. Results: The experiences of side effects – such as palpitations, frequent urination, recurrent bouts of hunger, erectile dysfunction, dizziness, cough, physical exhaustion - were categorized as no/low (39.75%), moderate (53.0%) and high (7.25%). Significant relationships between depression (x 2 = 24.21, P < 0.0001), anxiety (x 2 = 42.33, P < 0.0001), stress (x 2 = 39.73, P < 0.0001) and side effects were observed. A logistic regression model using the adjusted results for this association are reported – depression [OR = 1.9 (1.03 – 3.57), p = 0.04], anxiety [OR = 1.5 (1.22 – 1.77), p = < 0.001], and stress [OR = 1.3 (1.02 – 1.71), p = 0.04]. Side effects significantly increased the probability of individuals to be non-adherent [OR = 4.84 (95% CI 1.07 – 1.85), p = 0.04] with social factors, media influences and attitudes of primary caregivers further explaining this relationship. The personal adoption of medication modifying strategies, espousing the use of complementary and alternative treatments, and interventions made by clinicians were the main forms of coping with side effects. Conclusions: Results from this study show that contrary to a biomedical approach, the experience of side effects has biological, social and psychological interrelations. The result offers more support for the need for a multi-disciplinary approach to healthcare where all forms of expertise are incorporated into health provision and patient care. Additionally, medication side effects should be considered as a possible cause of non-adherence among hypertensive patients, thus addressing this problem from a Biopsychosocial perspective in any intervention may improve adherence and invariably control blood pressure.

Keywords: biopsychosocial, hypertension, medication adherence, psychological disorders

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46 Dangerous Words: A Moral Economy of HIV/AIDS in Swaziland

Authors: Robin Root

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A fundamental premise of medical anthropology is that clinical phenomena are simultaneously cultural, political, and economic: none more so than the linked acronyms HIV/AIDS. For the medical researcher, HIV/AIDS signals an epidemiological pandemic and a pathophysiology. For persons diagnosed with an HIV-related condition, the acronym often conjures dread, too often marking and marginalizing the afflicted irretrievably. Critical medical anthropology is uniquely equipped to theorize the linkages that bind individual and social wellbeing to global structural and culture-specific phenomena. This paper reports findings from an anthropological study of HIV/AIDS in Swaziland, site of the highest HIV prevalence in the world. The project, initiated in 2005, has documented experiences of HIV/AIDS, religiosity, and treatment and care as well as drought and famine. Drawing on interviews with Swazi religious and traditional leaders about their experiences of leadership amidst worsening economic conditions, environmental degradation, and an ongoing global health crisis, the paper provides uncommon insights for global health practitioners whose singular paradigm for designing and delivering interventions is biomedically-based. In contrast, this paper details the role of local leaders in mediating extreme social suffering and resilience in ways that medical science cannot model but which radically impact how sickness is experienced and health services are delivered and accessed. Two concepts help to organize the paper’s argument. First, a ‘moral economy of language’ is central to showing up the implicit ‘technologies of knowledge’ that inhere in scientific and religious discourses of HIV/AIDS; people draw upon these discourses strategically to navigate highly vulnerable conditions. Second, Paulo Freire’s ethnographic focus on a culture’s 'dangerous words' opens up for examination how ‘sex’ is dangerous for religion and ‘god’ is dangerous for science. The paper interrogates hegemonic and ‘lived’ discourses, both biomedical and religious, and contributes to an important literature on the moral economies of health, a framework of explication and, importantly, action appropriate to a wide-range of contemporary global health phenomena. The paper concludes by asserting that it is imperative that global health planners reflect upon and ‘check’ their hegemonic policy platforms by, one, collaborating with local authoritative agents of ‘what sickness means and how it is best treated,’ and, two, taking account of the structural barriers to achieving good health.

Keywords: Africa, biomedicine, HIV/AIDS, qualitative research , religion

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45 Analysis of Epileptic Electroencephalogram Using Detrended Fluctuation and Recurrence Plots

Authors: Mrinalini Ranjan, Sudheesh Chethil

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Epilepsy is a common neurological disorder characterised by the recurrence of seizures. Electroencephalogram (EEG) signals are complex biomedical signals which exhibit nonlinear and nonstationary behavior. We use two methods 1) Detrended Fluctuation Analysis (DFA) and 2) Recurrence Plots (RP) to capture this complex behavior of EEG signals. DFA considers fluctuation from local linear trends. Scale invariance of these signals is well captured in the multifractal characterisation using detrended fluctuation analysis (DFA). Analysis of long-range correlations is vital for understanding the dynamics of EEG signals. Correlation properties in the EEG signal are quantified by the calculation of a scaling exponent. We report the existence of two scaling behaviours in the epileptic EEG signals which quantify short and long-range correlations. To illustrate this, we perform DFA on extant ictal (seizure) and interictal (seizure free) datasets of different patients in different channels. We compute the short term and long scaling exponents and report a decrease in short range scaling exponent during seizure as compared to pre-seizure and a subsequent increase during post-seizure period, while the long-term scaling exponent shows an increase during seizure activity. Our calculation of long-term scaling exponent yields a value between 0.5 and 1, thus pointing to power law behaviour of long-range temporal correlations (LRTC). We perform this analysis for multiple channels and report similar behaviour. We find an increase in the long-term scaling exponent during seizure in all channels, which we attribute to an increase in persistent LRTC during seizure. The magnitude of the scaling exponent and its distribution in different channels can help in better identification of areas in brain most affected during seizure activity. The nature of epileptic seizures varies from patient-to-patient. To illustrate this, we report an increase in long-term scaling exponent for some patients which is also complemented by the recurrence plots (RP). RP is a graph that shows the time index of recurrence of a dynamical state. We perform Recurrence Quantitative analysis (RQA) and calculate RQA parameters like diagonal length, entropy, recurrence, determinism, etc. for ictal and interictal datasets. We find that the RQA parameters increase during seizure activity, indicating a transition. We observe that RQA parameters are higher during seizure period as compared to post seizure values, whereas for some patients post seizure values exceeded those during seizure. We attribute this to varying nature of seizure in different patients indicating a different route or mechanism during the transition. Our results can help in better understanding of the characterisation of epileptic EEG signals from a nonlinear analysis.

Keywords: detrended fluctuation, epilepsy, long range correlations, recurrence plots

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44 Learning from Long COVID: How Healthcare Needs to Change for Contested Illnesses

Authors: David Tennison

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In the wake of the Covid-19 pandemic, a new chronic illness emerged onto the global stage: Long Covid. Long Covid presents with several symptoms commonly seen in other poorly-understood illnesses, such as fibromyalgia (FM) and myalgic encephalomyelitis/ chronic fatigue syndrome (ME/CFS). However, while Long Covid has swiftly become a recognised illness, FM and ME/CFS are still seen as contested, which impacts patient care and healthcare experiences. This study aims to examine what the differences are between Long Covid and FM; and if the Long Covid case can provide guidance for how to address the healthcare challenge of contested illnesses. To address this question, this study performed comprehensive research into the history of FM; our current biomedical understanding of it; and available healthcare interventions (within the context of the UK NHS). Analysis was undertaken of the stigma and stereotypes around FM, and a comparison made between FM and the emerging Long Covid literature, along with the healthcare response to Long Covid. This study finds that healthcare for chronic contested illnesses in the UK is vastly insufficient - in terms of pharmaceutical and holistic interventions, and the provision of secondary care options. Interestingly, for Long Covid, many of the treatment suggestions are pulled directly from those used for contested illnesses. The key difference is in terms of funding and momentum – Long Covid has generated exponentially more interest and research in a short time than there has been in the last few decades of contested illness research. This stands to help people with FM and ME/CFS – for example, research has recently been funded into “brain fog”, a previously elusive and misunderstood symptom. FM is culturally regarded as a “women’s disease” and FM stigma stems from notions of “hysteria”. A key finding is that the idea of FM affecting women disproportionally is not reflected in modern population studies. Emerging data on Long Covid also suggests a slight leaning towards more female patients, however it is less feminised, potentially due to it emerging in the global historical moment of the pandemic. Another key difference is that FM is rated as an extremely low-prestige illness by healthcare professionals, while it was in large part due to the advocacy of affected healthcare professionals that Long Covid was so quickly recognised by science and medicine. In conclusion, Long Covid (and the risk of future pandemics and post-viral illnesses) highlight a crucial need for implementing new, and reinforcing existing, care networks for chronic illnesses. The difference in how contested illnesses like FM, and new ones like Long Covid are treated have a lot to do with the historical moment in which they emerge – but cultural stereotypes, from within and without medicine, need updating. Particularly as they contribute to disease stigma that causes genuine harm to patients. However, widespread understanding and acceptance of Long Covid could help fight contested illness stigma, and the attention, funding and research into Long Covid may actually help raise the profile of contested illnesses and uncover answers about their symptomatology.

Keywords: long COVID, fibromyalgia, myalgic encephalomyelitis, chronic fatigue syndrome, NHS, healthcare, contested illnesses, chronic illnesses, COVID-19 pandemic

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43 Drug Delivery Cationic Nano-Containers Based on Pseudo-Proteins

Authors: Sophio Kobauri, Temur Kantaria, Nina Kulikova, David Tugushi, Ramaz Katsarava

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The elaboration of effective drug delivery vehicles is still topical nowadays since targeted drug delivery is one of the most important challenges of the modern nanomedicine. The last decade has witnessed enormous research focused on synthetic cationic polymers (CPs) due to their flexible properties, in particular as non-viral gene delivery systems, facile synthesis, robustness, not oncogenic and proven gene delivery efficiency. However, the toxicity is still an obstacle to the application in pharmacotherapy. For overcoming the problem, creation of new cationic compounds including the polymeric nano-size particles – nano-containers (NCs) loading with different pharmaceuticals and biologicals is still relevant. In this regard, a variety of NCs-based drug delivery systems have been developed. We have found that amino acid-based biodegradable polymers called as pseudo-proteins (PPs), which can be cleared from the body after the fulfillment of their function are highly suitable for designing pharmaceutical NCs. Among them, one of the most promising are NCs made of biodegradable Cationic PPs (CPPs). For preparing new cationic NCs (CNCs), we used CPPs composed of positively charged amino acid L-arginine (R). The CNCs were fabricated by two approaches using: (1) R-based homo-CPPs; (2) Blends of R-based CPPs with regular (neutral) PPs. According to the first approach NCs we prepared from CPPs 8R3 (composed of R, sebacic acid and 1,3-propanediol) and 8R6 (composed of R, sebacic acid and 1,6-hexanediol). The NCs prepared from these CPPs were 72-101 nm in size with zeta potential within +30 ÷ +35 mV at a concentration 6 mg/mL. According to the second approach, CPPs 8R6 was blended in organic phase with neutral PPs 8L6 (composed of leucine, sebacic acid and 1,6-hexanediol). The NCs prepared from the blends were 130-140 nm in size with zeta potential within +20 ÷ +28 mV depending on 8R6/8L6 ratio. The stability studies of fabricated NCs showed that no substantial change of the particle size and distribution and no big particles’ formation is observed after three months storage. In vitro biocompatibility study of the obtained NPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed both type cathionic NCs are biocompatible. The obtained data allow concluding that the obtained CNCs are promising for the application as biodegradable drug delivery vehicles. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 'New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications'.

Keywords: biodegradable polymers, cationic pseudo-proteins, nano-containers, drug delivery vehicles

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42 Stability Study of Hydrogel Based on Sodium Alginate/Poly (Vinyl Alcohol) with Aloe Vera Extract for Wound Dressing Application

Authors: Klaudia Pluta, Katarzyna Bialik-Wąs, Dagmara Malina, Mateusz Barczewski

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Hydrogel networks, due to their unique properties, are highly attractive materials for wound dressing. The three-dimensional structure of hydrogels provides tissues with optimal moisture, which supports the wound healing process. Moreover, a characteristic feature of hydrogels is their absorption properties which allow for the absorption of wound exudates. For the fabrication of biomedical hydrogels, a combination of natural polymers ensuring biocompatibility and synthetic ones that provide adequate mechanical strength are often used. Sodium alginate (SA) is one of the polymers widely used in wound dressing materials because it exhibits excellent biocompatibility and biodegradability. However, due to poor strength properties, often alginate-based hydrogel materials are enhanced by the addition of another polymer such as poly(vinyl alcohol) (PVA). This paper is concentrated on the preparation methods of sodium alginate/polyvinyl alcohol hydrogel system incorporating Aloe vera extract and glycerin for wound healing material with particular focus on the role of their composition on structure, thermal properties, and stability. Briefly, the hydrogel preparation is based on the chemical cross-linking method using poly(ethylene glycol) diacrylate (PEGDA, Mn = 700 g/mol) as a crosslinking agent and ammonium persulfate as an initiator. In vitro degradation tests of SA/PVA/AV hydrogels were carried out in Phosphate-Buffered Saline (pH – 7.4) as well as in distilled water. Hydrogel samples were firstly cut into half-gram pieces (in triplicate) and immersed in immersion fluid. Then, all specimens were incubated at 37°C and then the pH and conductivity values were measurements at time intervals. The post-incubation fluids were analyzed using SEC/GPC to check the content of oligomers. The separation was carried out at 35°C on a poly(hydroxy methacrylate) column (dimensions 300 x 8 mm). 0.1M NaCl solution, whose flow rate was 0.65 ml/min, was used as the mobile phase. Three injections with a volume of 50 µl were made for each sample. The thermogravimetric data of the prepared hydrogels were collected using a Netzsch TG 209 F1 Libra apparatus. The samples with masses of about 10 mg were weighed separately in Al2O3 crucibles and then were heated from 30°C to 900°C with a scanning rate of 10 °C∙min−1 under a nitrogen atmosphere. Based on the conducted research, a fast and simple method was developed to produce potential wound dressing material containing sodium alginate, poly(vinyl alcohol) and Aloe vera extract. As a result, transparent and flexible SA/PVA/AV hydrogels were obtained. The degradation experiments indicated that most of the samples immersed in PBS as well as in distilled water were not degraded throughout the whole incubation time.

Keywords: hydrogels, wound dressings, sodium alginate, poly(vinyl alcohol)

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41 Poly(ε-Caprolactone)-Based Bilayered Scaffolds Prepared by Electrospinning for Tissue Engineering of Small-Diameter Vascular Grafts

Authors: Mohammed Fayez Al Rez

Abstract:

Nowadays, there is an unmet clinical need for new small-diameter vascular grafts to overcome the drawbacks of traditional methods used for treatment of widespread cardiovascular diseases. Vascular tissue engineering (VTE) is a promising approach that can be utilized to develop viable vascular grafts by in vitro seeding of functional cells onto a scaffold allowing them to attach, proliferate and differentiate. To achieve this purpose, the scaffold should provide cells with the initial necessary extracellular matrix environment and structure until being able to reconstruct the required vascular tissue. Therefore, producing scaffolds with suitable features is crucial for guiding cells properly to develop the desired tissue-engineered vascular grafts for clinical applications. The main objective of this work is fabrication and characterization of tubular small-diameter ( < 6 mm) bilayered scaffolds for VTE. The scaffolds were prepared via mixing electrospinning approach of biodegradable poly(ε-caprolactone) (PCL) polymer – due to its favorable physicochemical properties – to mimic the natural environment-extracellular matrix. Firstly, tubular nanofibrous construct with inner diameter of 3, 4 or 5 mm was electrospun as inner layer, and secondly, microfibrous construct was electrospun as outer layer directly on the first produced inner layer. To improve the biological properties of PCL, a group of the electrospun scaffolds was immersed in type-1 collagen solution. The morphology and structure of the resulting fibrous scaffolds were investigated by scanning electron microscope. The electrospun nanofibrous inner layer contained fibers measuring 219±35 nm in diameter, while the electrospun microfibrous outer layer contained fibers measuring 1011 ± 150 nm. Furthermore, mechanical, thermal and physical tests were conducted with both electrospun bilayered scaffold types where revealed improved properties. Biological investigations using endothelial, smooth muscle and fibroblast cell line showed good biocompatibility of both tested electrospun scaffolds. Better attachment and proliferation were obviously found when cells were cultured on the scaffolds immersed with collagen due to increasing the hydrophilicity of the PCL. The easy, inexpensive and versatile electrospinning approach used in this work was able to successfully produce double layered tubular elastic structures containing both nanofibers and microfibers to imitate the native vascular structure. The PCL – as a suitable and approved biomaterial for many biomedical and tissue engineering applications – can ensure favorable mechanical properties of scaffolds used for VTE. The VTE approach using electrospun bilayered scaffolds offers optimal solutions and holds significant promises for treatment of many cardiovascular diseases.

Keywords: electrospinning, poly(ε-caprolactone) (PCL), tissue-engineered vascular graft, tubular bilayered scaffolds, vascular cells

Procedia PDF Downloads 266
40 Modeling of Alpha-Particles’ Epigenetic Effects in Short-Term Test on Drosophila melanogaster

Authors: Z. M. Biyasheva, M. Zh. Tleubergenova, Y. A. Zaripova, A. L. Shakirov, V. V. Dyachkov

Abstract:

In recent years, interest in ecogenetic and biomedical problems related to the effects on the population of radon and its daughter decay products has increased significantly. Of particular interest is the assessment of the consequence of irradiation at hazardous radon areas, which includes the Almaty region due to the large number of tectonic faults that enhance radon emanation. In connection with the foregoing, the purpose of this work was to study the genetic effects of exposure to supernormal radon doses on the alpha-radiation model. Irradiation does not affect the growth of the cell, but rather its ability to differentiate. In addition, irradiation can lead to somatic mutations, morphoses and modifications. These damages most likely occur from changes in the composition of the substances of the cell. Such changes are epigenetic since they affect the regulatory processes of ontogenesis. Variability in the expression of regulatory genes refers to conditional mutations that modify the formation of signs of intraspecific similarity. Characteristic features of these conditional mutations are the dominant type of their manifestation, phenotypic asymmetry and their instability in the generations. Currently, the terms “morphosis” and “modification” are used to describe epigenetic variability, which are maintained in Drosophila melanogaster cultures using linkaged X- chromosomes, and the mutant X-chromosome is transmitted along the paternal line. In this paper, we investigated the epigenetic effects of alpha particles, whose source in nature is mainly radon and its daughter decay products. In the experiment, an isotope of plutonium-238 (Pu238), generating radiation with an energy of about 5500 eV, was used as a source of alpha particles. In an experiment in the first generation (F1), deformities or morphoses were found, which can be called "radiation syndromes" or mutations, the manifestation of which is similar to the pleiotropic action of genes. The proportion of morphoses in the experiment was 1.8%, and in control 0.4%. In this experiment, the morphoses in the flies of the first and second generation looked like black spots, or melanomas on different parts of the imago body; "generalized" melanomas; curled, curved wings; shortened wing; bubble on one wing; absence of one wing, deformation of thorax, interruption and violation of tergite patterns, disruption of distribution of ocular facets and bristles; absence of pigmentation of the second and third legs. Statistical analysis by the Chi-square method showed the reliability of the difference in experiment and control at P ≤ 0.01. On the basis of this, it can be considered that alpha particles, which in the environment are mainly generated by radon and its isotopes, have a mutagenic effect that manifests itself, mainly in the formation of morphoses or deformities.

Keywords: alpha-radiation, genotoxicity, morphoses, radioecology, radon

Procedia PDF Downloads 117
39 Multi-Objective Optimization (Pareto Sets) and Multi-Response Optimization (Desirability Function) of Microencapsulation of Emamectin

Authors: Victoria Molina, Wendy Franco, Sergio Benavides, José M. Troncoso, Ricardo Luna, Jose R. PéRez-Correa

Abstract:

Emamectin Benzoate (EB) is a crystal antiparasitic that belongs to the avermectin family. It is one of the most common treatments used in Chile to control Caligus rogercresseyi in Atlantic salmon. However, the sea lice acquired resistance to EB when it is exposed at sublethal EB doses. The low solubility rate of EB and its degradation at the acidic pH in the fish digestive tract are the causes of the slow absorption of EB in the intestine. To protect EB from degradation and enhance its absorption, specific microencapsulation technologies must be developed. Amorphous Solid Dispersion techniques such as Spray Drying (SD) and Ionic Gelation (IG) seem adequate for this purpose. Recently, Soluplus® (SOL) has been used to increase the solubility rate of several drugs with similar characteristics than EB. In addition, alginate (ALG) is a widely used polymer in IG for biomedical applications. Regardless of the encapsulation technique, the quality of the obtained microparticles is evaluated with the following responses, yield (Y%), encapsulation efficiency (EE%) and loading capacity (LC%). In addition, it is important to know the percentage of EB released from the microparticles in gastric (GD%) and intestinal (ID%) digestions. In this work, we microencapsulated EB with SOL (EB-SD) and with ALG (EB-IG) using SD and IG, respectively. Quality microencapsulation responses and in vitro gastric and intestinal digestions at pH 3.35 and 7.8, respectively, were obtained. A central composite design was used to find the optimum microencapsulation variables (amount of EB, amount of polymer and feed flow). In each formulation, the behavior of these variables was predicted with statistical models. Then, the response surface methodology was used to find the best combination of the factors that allowed a lower EB release in gastric conditions, while permitting a major release at intestinal digestion. Two approaches were used to determine this. The desirability approach (DA) and multi-objective optimization (MOO) with multi-criteria decision making (MCDM). Both microencapsulation techniques allowed to maintain the integrity of EB in acid pH, given the small amount of EB released in gastric medium, while EB-IG microparticles showed greater EB release at intestinal digestion. For EB-SD, optimal conditions obtained with MOO plus MCDM yielded a good compromise among the microencapsulation responses. In addition, using these conditions, it is possible to reduce microparticles costs due to the reduction of 60% of BE regard the optimal BE proposed by (DA). For EB-GI, the optimization techniques used (DA and MOO) yielded solutions with different advantages and limitations. Applying DA costs can be reduced 21%, while Y, GD and ID showed 9.5%, 84.8% and 2.6% lower values than the best condition. In turn, MOO yielded better microencapsulation responses, but at a higher cost. Overall, EB-SD with operating conditions selected by MOO seems the best option, since a good compromise between costs and encapsulation responses was obtained.

Keywords: microencapsulation, multiple decision-making criteria, multi-objective optimization, Soluplus®

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38 Exploring the Social Health and Well-Being Factors of Hydraulic Fracturing

Authors: S. Grinnell

Abstract:

A PhD Research Project exploring the Social Health and Well-Being Impacts associated with Hydraulic Fracturing, with an aim to produce a Best Practice Support Guidance for those anticipating dealing with planning applications or submitting Environmental Impact Assessments (EIAs). Amid a possible global energy crisis, founded upon a number of factors, including unstable political situations, increasing world population growth, people living longer, it is perhaps inevitable that Hydraulic Fracturing (commonly referred to as ‘fracking’) will become a major player within the global long-term energy and sustainability agenda. As there is currently no best practice guidance for governing bodies the Best Practice Support Document will be targeted at a number of audiences including, consultants undertaking EIAs, Planning Officers, those commissioning EIAs Industry and interested public stakeholders. It will offer a robust, evidence-based criteria and recommendations which provide a clear narrative and consistent and shared approach to the language used along with containing an understanding of the issues identified. It is proposed that the Best Practice Support Document will also support the mitigation of health impacts identified. The Best Practice Support Document will support the newly amended Environmental Impact Assessment Directive (2011/92/EU), to be transposed into UK law by 2017. A significant amendment introduced focuses on, ‘higher level of protection to the environment and health.’ Methodology: A qualitative research methods approach is being taken with this research. It will have a number of key stages. A literature review has been undertaken and been critically reviewed and analysed. This was followed by a descriptive content analysis of a selection of international and national policies, programmes and strategies along with published Environmental Impact Assessments and associated planning guidance. In terms of data collection, a number of stakeholders were interviewed as well as a number of focus groups of local community groups potentially affected by fracking. These were determined from across the UK. A theme analysis of all the data collected and the literature review will be undertaken, using NVivo. Best Practice Supporting Document will be developed based on the outcomes of the analysis and be tested and piloted in the professional fields, before a live launch. Concluding statement: Whilst fracking is not a new concept, the technology is now driving a new force behind the use of this engineering to supply fuels. A number of countries have pledged moratoria on fracking until further investigation from the impacts on health have been explored, whilst other countries including Poland and the UK are pushing to support the use of fracking. If this should be the case, it will be important that the public’s concerns, perceptions, fears and objections regarding the wider social health and well-being impacts are considered along with the more traditional biomedical health impacts.

Keywords: fracking, hydraulic fracturing, socio-economic health, well-being

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37 Electrohydrodynamic Patterning for Surface Enhanced Raman Scattering for Point-of-Care Diagnostics

Authors: J. J. Rickard, A. Belli, P. Goldberg Oppenheimer

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Medical diagnostics, environmental monitoring, homeland security and forensics increasingly demand specific and field-deployable analytical technologies for quick point-of-care diagnostics. Although technological advancements have made optical methods well-suited for miniaturization, a highly-sensitive detection technique for minute sample volumes is required. Raman spectroscopy is a well-known analytical tool, but has very weak signals and hence is unsuitable for trace level analysis. Enhancement via localized optical fields (surface plasmons resonances) on nanoscale metallic materials generates huge signals in surface-enhanced Raman scattering (SERS), enabling single molecule detection. This enhancement can be tuned by manipulation of the surface roughness and architecture at the sub-micron level. Nevertheless, the development and application of SERS has been inhibited by the irreproducibility and complexity of fabrication routes. The ability to generate straightforward, cost-effective, multiplex-able and addressable SERS substrates with high enhancements is of profound interest for SERS-based sensing devices. While most SERS substrates are manufactured by conventional lithographic methods, the development of a cost-effective approach to create nanostructured surfaces is a much sought-after goal in the SERS community. Here, a method is established to create controlled, self-organized, hierarchical nanostructures using electrohydrodynamic (HEHD) instabilities. The created structures are readily fine-tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements. HEHD pattern formation enables the fabrication of multiscale 3D structured arrays as SERS-active platforms. Importantly, each of the HEHD-patterned individual structural units yield a considerable SERS enhancement. This enables each single unit to function as an isolated sensor. Each of the formed structures can be effectively tuned and tailored to provide high SERS enhancement, while arising from different HEHD morphologies. The HEHD fabrication of sub-micrometer architectures is straightforward and robust, providing an elegant route for high-throughput biological and chemical sensing. The superior detection properties and the ability to fabricate SERS substrates on the miniaturized scale, will facilitate the development of advanced and novel opto-fluidic devices, such as portable detection systems, and will offer numerous applications in biomedical diagnostics, forensics, ecological warfare and homeland security.

Keywords: hierarchical electrohydrodynamic patterning, medical diagnostics, point-of care devices, SERS

Procedia PDF Downloads 317
36 Biocompatibility assessment of different origin Barrier Membranes for Guided Bone Regeneration

Authors: Antonio Munar-Frau, Sascha Klismoch, Manfred Schmolz, Federico Hernandez-Alfaro, Jordi Caballe-Serrano

Abstract:

Introduction: Biocompatibility of biomaterials has been proposed as one of the main criteria for treatment success. For guided bone regeneration (GBR), barrier membranes present a conflict given the number of origins and modifications of these materials. The biologic response to biomaterials is orchestrated by a series of events leading to the integration or rejection of the biomaterial, posing questions such as if a longer occlusive property may trigger an inflammatory reaction. Whole blood cultures are a solution to study the immune response to drugs or biomaterials during the first 24-48 hours. The aim of this study is to determine the early immune response of different origins and chemical modifications of barrier membranes. Materials & Methods: 5 different widely used barrier membranes were included in this study: Acellular dermal matrix (AlloDerm, LifeCell®), Porcine Peritoneum (BioGide, Geistlich Pharma®), Porcine Pericardium (Jason, Botiss Biomaterials GmbH®), Porcine Cross-linked collagen (Ossix Plus, Datum Dental®) and d-PTFE (Cytoplast TXT, Osteogenics Biomedical®). Blood samples were extracted from 3 different healthy donors and incubated with the different samples of barrier membranes for 24 hours. After the incubation time, serum samples were obtained and analyzed by means of biocompatibility assays taking into account 42 markers. Results: In an early stage of the inflammatory response, the Acellular dermal matrix, porcine peritoneum and porcine cross-linked collagen expressed similar patterns of cytokine expression with a great manifestation of ENA 78. Porcine pericardium and d-PTFE presented similar cytokine activation, especially for MMP-3 and MMP-9, although other cytokines were highlighted with lower expression. For the later immune response, Porcine peritoneum and acellular dermal matrix MCP-1 and IL-15 were evident. Porcine pericardium, porcine cross-linked collagen and d-PTFE presented a high expression of IL-16 and lower manifestation of other cytokines. Different behaviors depending on an earlier or later stage of the inflammation process were observed. Barrier membrane inflammatory expression does not only differ depending on the origin, variables such as treatment of the collagen and polymers may also have a great impact on the cytokine expression of the studied barrier membranes during inflammation. Conclusions: Surface treatment and modifications might affect the biocompatibility of the membranes, as different cytokine expressions were evidently depending on the origin of the biomaterial. This study is only a brushstroke regarding the biocompatibility of materials, as it is one of the pioneer studies for ex vivo barrier membranes assays. Studies regarding surface modification are needed in order to clarify mystifications of barrier membrane science.

Keywords: biomaterials, bone regeneration, biocompatibility, inflammation

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35 Listening to Voices: A Meaning-Focused Framework for Supporting People with Auditory Verbal Hallucinations

Authors: Amar Ghelani

Abstract:

People with auditory verbal hallucinations (AVH) who seek support from mental health services commonly report feeling unheard and invalidated in their interactions with social workers and psychiatric professionals. Current mental health training and clinical approaches have proven to be inadequate in addressing the complex nature of voice hearing. Childhood trauma is a key factor in the development of AVH and can render people more vulnerable to hearing both supportive and/or disturbing voices. Lived experiences of racism, poverty, and immigration are also associated with development of what is broadly classified as psychosis. Despite evidence affirming the influence of environmental factors on voice hearing, the Western biomedical system typically conceptualizes this experience as a symptom of genetically-based mental illnesses which requires diagnosis and treatment. Overemphasis on psychiatric medications, referrals, and directive approaches to people’s problems has shifted clinical interventions away from assessing and addressing problems directly related to AVH. The Maastricht approach offers voice hearers and mental health workers an alternative and respectful starting point for understanding and coping with voices. The approach was developed by voice hearers in partnership with mental health professionals and entails an innovative method to assess and create meaning from voice hearing and related life stressors. The objectives of the approach are to help people who hear voices: (1) understand the problems and/or people the voices may represent in their history, and (2) cope with distress and find solutions to related problems. The Maastricht approach has also been found to help voice hearers integrate emotional conflicts, reduce avoidance or fear associated with AVH, improve therapeutic relationships, and increase a sense of control over internal experiences. The proposed oral presentation will be guided by a recovery-oriented theoretical framework which suggests healing from psychological wounds occurs through social connections and community support systems. The presentation will start with a brainstorming exercise to identify participants pre-existing knowledge of the subject matter. This will lead into a literature review on the relations between trauma, intersectionality, and AVH. An overview of the Maastricht approach and review of research related to its therapeutic risks and benefits will follow. Participants will learn trauma-informed coping skills and questions which can help voice hearers make meaning from their experiences. The presentation will conclude with a review of resources and learning opportunities where participants can expand their knowledge of the Hearing Voices Movement and Maastricht approach.

Keywords: Maastricht interview, recovery, therapeutic assessment, voice hearing

Procedia PDF Downloads 82
34 Classification of ECG Signal Based on Mixture of Linear and Non-Linear Features

Authors: Mohammad Karimi Moridani, Mohammad Abdi Zadeh, Zahra Shahiazar Mazraeh

Abstract:

In recent years, the use of intelligent systems in biomedical engineering has increased dramatically, especially in the diagnosis of various diseases. Also, due to the relatively simple recording of the electrocardiogram signal (ECG), this signal is a good tool to show the function of the heart and diseases associated with it. The aim of this paper is to design an intelligent system for automatically detecting a normal electrocardiogram signal from abnormal one. Using this diagnostic system, it is possible to identify a person's heart condition in a very short time and with high accuracy. The data used in this article are from the Physionet database, available in 2016 for use by researchers to provide the best method for detecting normal signals from abnormalities. Data is of both genders and the data recording time varies between several seconds to several minutes. All data is also labeled normal or abnormal. Due to the low positional accuracy and ECG signal time limit and the similarity of the signal in some diseases with the normal signal, the heart rate variability (HRV) signal was used. Measuring and analyzing the heart rate variability with time to evaluate the activity of the heart and differentiating different types of heart failure from one another is of interest to the experts. In the preprocessing stage, after noise cancelation by the adaptive Kalman filter and extracting the R wave by the Pan and Tampkinz algorithm, R-R intervals were extracted and the HRV signal was generated. In the process of processing this paper, a new idea was presented that, in addition to using the statistical characteristics of the signal to create a return map and extraction of nonlinear characteristics of the HRV signal due to the nonlinear nature of the signal. Finally, the artificial neural networks widely used in the field of ECG signal processing as well as distinctive features were used to classify the normal signals from abnormal ones. To evaluate the efficiency of proposed classifiers in this paper, the area under curve ROC was used. The results of the simulation in the MATLAB environment showed that the AUC of the MLP and SVM neural network was 0.893 and 0.947, respectively. As well as, the results of the proposed algorithm in this paper indicated that the more use of nonlinear characteristics in normal signal classification of the patient showed better performance. Today, research is aimed at quantitatively analyzing the linear and non-linear or descriptive and random nature of the heart rate variability signal, because it has been shown that the amount of these properties can be used to indicate the health status of the individual's heart. The study of nonlinear behavior and dynamics of the heart's neural control system in the short and long-term provides new information on how the cardiovascular system functions, and has led to the development of research in this field. Given that the ECG signal contains important information and is one of the common tools used by physicians to diagnose heart disease, but due to the limited accuracy of time and the fact that some information about this signal is hidden from the viewpoint of physicians, the design of the intelligent system proposed in this paper can help physicians with greater speed and accuracy in the diagnosis of normal and patient individuals and can be used as a complementary system in the treatment centers.

Keywords: neart rate variability, signal processing, linear and non-linear features, classification methods, ROC Curve

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33 A Variational Reformulation for the Thermomechanically Coupled Behavior of Shape Memory Alloys

Authors: Elisa Boatti, Ulisse Stefanelli, Alessandro Reali, Ferdinando Auricchio

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Thanks to their unusual properties, shape memory alloys (SMAs) are good candidates for advanced applications in a wide range of engineering fields, such as automotive, robotics, civil, biomedical, aerospace. In the last decades, the ever-growing interest for such materials has boosted several research studies aimed at modeling their complex nonlinear behavior in an effective and robust way. Since the constitutive response of SMAs is strongly thermomechanically coupled, the investigation of the non-isothermal evolution of the material must be taken into consideration. The present study considers an existing three-dimensional phenomenological model for SMAs, able to reproduce the main SMA properties while maintaining a simple user-friendly structure, and proposes a variational reformulation of the full non-isothermal version of the model. While the considered model has been thoroughly assessed in an isothermal setting, the proposed formulation allows to take into account the full nonisothermal problem. In particular, the reformulation is inspired to the GENERIC (General Equations for Non-Equilibrium Reversible-Irreversible Coupling) formalism, and is based on a generalized gradient flow of the total entropy, related to thermal and mechanical variables. Such phrasing of the model is new and allows for a discussion of the model from both a theoretical and a numerical point of view. Moreover, it directly implies the dissipativity of the flow. A semi-implicit time-discrete scheme is also presented for the fully coupled thermomechanical system, and is proven unconditionally stable and convergent. The correspondent algorithm is then implemented, under a space-homogeneous temperature field assumption, and tested under different conditions. The core of the algorithm is composed of a mechanical subproblem and a thermal subproblem. The iterative scheme is solved by a generalized Newton method. Numerous uniaxial and biaxial tests are reported to assess the performance of the model and algorithm, including variable imposed strain, strain rate, heat exchange properties, and external temperature. In particular, the heat exchange with the environment is the only source of rate-dependency in the model. The reported curves clearly display the interdependence between phase transformation strain and material temperature. The full thermomechanical coupling allows to reproduce the exothermic and endothermic effects during respectively forward and backward phase transformation. The numerical tests have thus demonstrated that the model can appropriately reproduce the coupled SMA behavior in different loading conditions and rates. Moreover, the algorithm has proved effective and robust. Further developments are being considered, such as the extension of the formulation to the finite-strain setting and the study of the boundary value problem.

Keywords: generalized gradient flow, GENERIC formalism, shape memory alloys, thermomechanical coupling

Procedia PDF Downloads 196
32 Green Production of Chitosan Nanoparticles and their Potential as Antimicrobial Agents

Authors: L. P. Gomes, G. F. Araújo, Y. M. L. Cordeiro, C. T. Andrade, E. M. Del Aguila, V. M. F. Paschoalin

Abstract:

The application of nanoscale materials and nanostructures is an emerging area, these since materials may provide solutions to technological and environmental challenges in order to preserve the environment and natural resources. To reach this goal, the increasing demand must be accompanied by 'green' synthesis methods. Chitosan is a natural, nontoxic, biopolymer derived by the deacetylation of chitin and has great potential for a wide range of applications in the biological and biomedical areas, due to its biodegradability, biocompatibility, non-toxicity and versatile chemical and physical properties. Chitosan also presents high antimicrobial activities against a wide variety of pathogenic and spoilage microorganisms. Ultrasonication is a common tool for the preparation and processing of polymer nanoparticles. It is particularly effective in breaking up aggregates and in reducing the size and polydispersity of nanoparticles. High-intensity ultrasonication has the potential to modify chitosan molecular weight and, thus, alter or improve chitosan functional properties. The aim of this study was to evaluate the influence of sonication intensity and time on the changes of commercial chitosan characteristics, such as molecular weight and its potential antibacterial activity against Gram-negative bacteria. The nanoparticles (NPs) were produced from two commercial chitosans, of medium molecular weight (CS-MMW) and low molecular weight (CS-LMW) from Sigma-Aldrich®. These samples (2%) were solubilized in 100 mM sodium acetate pH 4.0, placed on ice and irradiated with an ultrasound SONIC ultrasonic probe (model 750 W), equipped with a 1/2" microtip during 30 min at 4°C. It was used on constant duty cycle and 40% amplitude with 1/1s intervals. The ultrasonic degradation of CS-MMW and CS-LMW were followed up by means of ζ-potential (Brookhaven Instruments, model 90Plus) and dynamic light scattering (DLS) measurements. After sonication, the concentrated samples were diluted 100 times and placed in fluorescence quartz cuvettes (Hellma 111-QS, 10 mm light path). The distributions of the colloidal particles were calculated from the DLS and ζ-potential are measurements taken for the CS-MMW and CS-LMW solutions before and after (CS-MMW30 and CS-LMW30) sonication for 30 min. Regarding the results for the chitosan sample, the major bands can be distinguished centered at Radius hydrodynamic (Rh), showed different distributions for CS-MMW (Rh=690.0 nm, ζ=26.52±2.4), CS-LMW (Rh=607.4 and 2805.4 nm, ζ=24.51±1.29), CS-MMW30 (Rh=201.5 and 1064.1 nm, ζ=24.78±2.4) and CS-LMW30 (Rh=492.5, ζ=26.12±0.85). The minimal inhibitory concentration (MIC) was determined using different chitosan samples concentrations. MIC values were determined against to E. coli (106 cells) harvested from an LB medium (Luria-Bertani BD™) after 18h growth at 37 ºC. Subsequently, the cell suspension was serially diluted in saline solution (0.8% NaCl) and plated on solid LB at 37°C for 18 h. Colony-forming units were counted. The samples showed different MICs against E. coli for CS-LMW (1.5mg), CS-MMW30 (1.5 mg/mL) and CS-LMW30 (1.0 mg/mL). The results demonstrate that the production of nanoparticles by modification of their molecular weight by ultrasonication is simple to be performed and dispense acid solvent addition. Molecular weight modifications are enough to provoke changes in the antimicrobial potential of the nanoparticles produced in this way.

Keywords: antimicrobial agent, chitosan, green production, nanoparticles

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31 Soybean Oil Based Phase Change Material for Thermal Energy Storage

Authors: Emre Basturk, Memet Vezir Kahraman

Abstract:

In many developing countries, with the rapid economic improvements, energy shortage and environmental issues have become a serious problem. Therefore, it has become a very critical issue to improve energy usage efficiency and also protect the environment. Thermal energy storage system is an essential approach to match the thermal energy claim and supply. Thermal energy can be stored by heating, cooling or melting a material with the energy and then enhancing accessible when the procedure is reversed. The overall thermal energy storage techniques are sorted as; latent heat or sensible heat thermal energy storage technology segments. Among these methods, latent heat storage is the most effective method of collecting thermal energy. Latent heat thermal energy storage depend on the storage material, emitting or discharging heat as it undergoes a solid to liquid, solid to solid or liquid to gas phase change or vice versa. Phase change materials (PCMs) are promising materials for latent heat storage applications due to their capacities to accumulate high latent heat storage per unit volume by phase change at an almost constant temperature. Phase change materials (PCMs) are being utilized to absorb, collect and discharge thermal energy during the cycle of melting and freezing, converting from one phase to another. Phase Change Materials (PCMs) can generally be arranged into three classes: organic materials, salt hydrates and eutectics. Many kinds of organic and inorganic PCMs and their blends have been examined as latent heat storage materials. Organic PCMs are rather expensive and they have average latent heat storage per unit volume and also have low density. Most organic PCMs are combustible in nature and also have a wide range of melting point. Organic PCMs can be categorized into two major categories: non-paraffinic and paraffin materials. Paraffin materials have been extensively used, due to their high latent heat and right thermal characteristics, such as minimal super cooling, varying phase change temperature, low vapor pressure while melting, good chemical and thermal stability, and self-nucleating behavior. Ultraviolet (UV)-curing technology has been generally used because it has many advantages, such as low energy consumption , high speed, high chemical stability, room-temperature operation, low processing costs and environmental friendly. For many years, PCMs have been used for heating and cooling industrial applications including textiles, refrigerators, construction, transportation packaging for temperature-sensitive products, a few solar energy based systems, biomedical and electronic materials. In this study, UV-curable, fatty alcohol containing soybean oil based phase change materials (PCMs) were obtained and characterized. The phase transition behaviors and thermal stability of the prepared UV-cured biobased PCMs were analyzed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The heating process phase change enthalpy is measured between 30 and 68 J/g, and the freezing process phase change enthalpy is found between 18 and 70 J/g. The decomposition of UVcured PCMs started at 260 ºC and reached a maximum of 430 ºC.

Keywords: fatty alcohol, phase change material, thermal energy storage, UV curing

Procedia PDF Downloads 338
30 Characterization of Surface Microstructures on Bio-Based PLA Fabricated with Nano-Imprint Lithography

Authors: D. Bikiaris, M. Nerantzaki, I. Koliakou, A. Francone, N. Kehagias

Abstract:

In the present study, the formation of structures in poly(lactic acid) (PLA) has been investigated with respect to producing areas of regular, superficial features with dimensions comparable to those of cells or biological macromolecules. Nanoimprint lithography, a method of pattern replication in polymers, has been used for the production of features ranging from tens of micrometers, covering areas up to 1 cm², down to hundreds of nanometers. Both micro- and nano-structures were faithfully replicated. Potentially, PLA has wide uses within biomedical fields, from implantable medical devices, including screws and pins, to membrane applications, such as wound covers, and even as an injectable polymer for, for example, lipoatrophy. The possibility of fabricating structured PLA surfaces, with structures of the dimensions associated with cells or biological macro- molecules, is of interest in fields such as cellular engineering. Imprint-based technologies have demonstrated the ability to selectively imprint polymer films over large areas resulting in 3D imprints over flat, curved or pre-patterned surfaces. Here, we compare nano-patterned with nano-patterned by nanoimprint lithography (NIL) PLA film. A silicon nanostructured stamp (provided by Nanotypos company) having positive and negative protrusions was used to pattern PLA films by means of thermal NIL. The polymer film was heated from 40°C to 60°C above its Tg and embossed with a pressure of 60 bars for 3 min. The stamp and substrate were demolded at room temperature. Scanning electron microscope (SEM) images showed good replication fidelity of the replicated Si stamp. Contact-angle measurements suggested that positive microstructuring of the polymer (where features protrude from the polymer surface) produced a more hydrophilic surface than negative micro-structuring. The ability to structure the surface of the poly(lactic acid), allied to the polymer’s post-processing transparency and proven biocompatibility. Films produced in this were also shown to enhance the aligned attachment behavior and proliferation of Wharton’s Jelly Mesenchymal Stem cells, leading to the observed growth contact guidance. The bacterial attachment patterns of some bacteria, highlighted that the nano-patterned PLA structure can reduce the propensity for the bacteria to attach to the surface, with a greater bactericidal being demonstrated activity against the Staphylococcus aureus cells. These biocompatible, micro- and nanopatterned PLA surfaces could be useful for polymer– cell interaction experiments at dimensions at, or below, that of individual cells. Indeed, post-fabrication modification of the microstructured PLA surface, with materials such as collagen (which can further reduce the hydrophobicity of the surface), will extend the range of applications, possibly through the use of PLA’s inherent biodegradability. Further study is being undertaken to examine whether these structures promote cell growth on the polymer surface.

Keywords: poly(lactic acid), nano-imprint lithography, anti-bacterial properties, PLA

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29 Kidney Supportive Care in Canada: A Constructivist Grounded Theory of Dialysis Nurses’ Practice Engagement

Authors: Jovina Concepcion Bachynski, Lenora Duhn, Idevania G. Costa, Pilar Camargo-Plazas

Abstract:

Kidney failure is a life-limiting condition for which treatment, such as dialysis (hemodialysis and peritoneal dialysis), can exact a tremendously high physical and psychosocial symptom burden. Kidney failure can be severe enough to require a palliative approach to care. The term supportive care can be used in lieu of palliative care to avoid the misunderstanding that palliative care is synonymous with end-of-life or hospice care. Kidney supportive care, encompassing advance care planning, is an approach to care that improves the quality of life for people receiving dialysis through early identification and treatment of symptoms throughout the disease trajectory. Advanced care planning involves ongoing conversations about the values, goals, and preferences for future care between individuals and their healthcare teams. Kidney supportive care is underutilized and often initiated late in this population. There is evidence to indicate nurses are not providing the necessary elements of supportive kidney care. Dialysis nurses’ delay or lack of engagement in supportive care until close to the end of life may result in people dying without receiving optimal palliative care services. Using Charmaz’s constructivist grounded theory, the purpose of this doctoral study is to develop a substantive theory that explains the process of engagement in supportive care by nurses working in dialysis settings in Canada. Through initial purposeful and subsequent theoretical sampling, 23 nurses with current or recent work experience in outpatient hemodialysis, home hemodialysis, and peritoneal dialysis settings drawn from across Canada were recruited to participate in two intensive interviews using the Zoom© teleconferencing platform. Concurrent data collection and data analysis, constant comparative analysis of initial and focused codes until the attainment of theoretical saturation, and memo-writing, as well as researcher reflexivity, have been undertaken to aid the emergence of concepts, categories, and, ultimately, the constructed theory. At the time of abstract submission, data analysis is currently at the second level of coding (i.e., focused coding stage) of the research study. Preliminary categories include: (a) focusing on biomedical care; (b) multi-dimensional challenges to having the conversation; (c) connecting and setting boundaries with patients; (d) difficulty articulating kidney-supportive care; and (e) unwittingly practising kidney-supportive care. For the conference, the resulting theory will be presented. Nurses working in dialysis are well-positioned to ensure the delivery of quality kidney-supportive care. This study will help to determine the process and the factors enabling and impeding nurse engagement in supportive care in dialysis to effect change for normalizing advance care planning conversations in the clinical setting. This improved practice will have substantive beneficial implications for the many individuals living with kidney failure and their supporting loved ones.

Keywords: dialysis, kidney failure, nursing, supportive care

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28 Cyber-Med: Practical Detection Methodology of Cyber-Attacks Aimed at Medical Devices Eco-Systems

Authors: Nir Nissim, Erez Shalom, Tomer Lancewiki, Yuval Elovici, Yuval Shahar

Abstract:

Background: A Medical Device (MD) is an instrument, machine, implant, or similar device that includes a component intended for the purpose of the diagnosis, cure, treatment, or prevention of disease in humans or animals. Medical devices play increasingly important roles in health services eco-systems, including: (1) Patient Diagnostics and Monitoring; Medical Treatment and Surgery; and Patient Life Support Devices and Stabilizers. MDs are part of the medical device eco-system and are connected to the network, sending vital information to the internal medical information systems of medical centers that manage this data. Wireless components (e.g. Wi-Fi) are often embedded within medical devices, enabling doctors and technicians to control and configure them remotely. All these functionalities, roles, and uses of MDs make them attractive targets of cyber-attacks launched for many malicious goals; this trend is likely to significantly increase over the next several years, with increased awareness regarding MD vulnerabilities, the enhancement of potential attackers’ skills, and expanded use of medical devices. Significance: We propose to develop and implement Cyber-Med, a unique collaborative project of Ben-Gurion University of the Negev and the Clalit Health Services Health Maintenance Organization. Cyber-Med focuses on the development of a comprehensive detection framework that relies on a critical attack repository that we aim to create. Cyber-Med will allow researchers and companies to better understand the vulnerabilities and attacks associated with medical devices as well as providing a comprehensive platform for developing detection solutions. Methodology: The Cyber-Med detection framework will consist of two independent, but complementary detection approaches: one for known attacks, and the other for unknown attacks. These modules incorporate novel ideas and algorithms inspired by our team's domains of expertise, including cyber security, biomedical informatics, and advanced machine learning, and temporal data mining techniques. The establishment and maintenance of Cyber-Med’s up-to-date attack repository will strengthen the capabilities of Cyber-Med’s detection framework. Major Findings: Based on our initial survey, we have already found more than 15 types of vulnerabilities and possible attacks aimed at MDs and their eco-system. Many of these attacks target individual patients who use devices such pacemakers and insulin pumps. In addition, such attacks are also aimed at MDs that are widely used by medical centers such as MRIs, CTs, and dialysis engines; the information systems that store patient information; protocols such as DICOM; standards such as HL7; and medical information systems such as PACS. However, current detection tools, techniques, and solutions generally fail to detect both the known and unknown attacks launched against MDs. Very little research has been conducted in order to protect these devices from cyber-attacks, since most of the development and engineering efforts are aimed at the devices’ core medical functionality, the contribution to patients’ healthcare, and the business aspects associated with the medical device.

Keywords: medical device, cyber security, attack, detection, machine learning

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27 Conceptualizing a Biomimetic Fablab Based on the Makerspace Concept and Biomimetics Design Research

Authors: Petra Gruber, Ariana Rupp, Peter Niewiarowski

Abstract:

This paper presents a concept for a biomimetic fablab as a physical space for education, research and development of innovation inspired by nature. Biomimetics as a discipline finds increasing recognition in academia and has started to be institutionalized at universities in programs and centers. The Biomimicry Research and Innovation Center was founded in 2012 at the University of Akron as an interdisciplinary venture for the advancement of innovation inspired by nature and is part of a larger community fostering the approach of bioimimicry in the Great Lakes region of the US. With 30 faculty members the center has representatives from Colleges of Arts and Sciences (e.g., biology, chemistry, geoscience, and philosophy) Engineering (e.g., mechanical, civil, and biomedical), Polymer Science, and Myers School of Arts. A platform for training PhDs in Biomimicry (17 students currently enrolled) is co-funded by educational institutions and industry partners. Research at the center touches on many areas but is also currently biased towards materials and structures, with highlights being materials based on principles found in spider silk and gecko attachment mechanisms. As biomimetics is also a novel scientific discipline, there is little standardisation in programming and the equipment of research facilities. As a field targeting innovation, design and prototyping processes are fundamental parts of the developments. For experimental design and prototyping, MIT's maker space concept seems to fit well to the requirements, but facilities need to be more specialised in terms of accessing biological systems and knowledge, specific research, production or conservation requirements. For the education and research facility BRIC we conceptualize the concept of a biomimicry fablab, that ties into the existing maker space concept and creates the setting for interdisciplinary research and development carried out in the program. The concept takes on the process of biomimetics as a guideline to define core activities that shall be enhanced by the allocation of specific spaces and tools. The limitations of such a facility and the intersections to further specialised labs housed in the classical departments are of special interest. As a preliminary proof of concept two biomimetic design courses carried out in 2016 are investigated in terms of needed tools and infrastructure. The spring course was a problem based biomimetic design challenge in collaboration with an innovation company interested in product design for assisted living and medical devices. The fall course was a solution based biomimetic design course focusing on order and hierarchy in nature with the goal of finding meaningful translations into art and technology. The paper describes the background of the BRIC center, identifies and discusses the process of biomimetics, evaluates the classical maker space concept and explores how these elements can shape the proposed research facility of a biomimetic fablab by examining two examples of design courses held in 2016.

Keywords: biomimetics, biomimicry, design, biomimetic fablab

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26 Development of an Automatic Control System for ex vivo Heart Perfusion

Authors: Pengzhou Lu, Liming Xin, Payam Tavakoli, Zhonghua Lin, Roberto V. P. Ribeiro, Mitesh V. Badiwala

Abstract:

Ex vivo Heart Perfusion (EVHP) has been developed as an alternative strategy to expand cardiac donation by enabling resuscitation and functional assessment of hearts donated from marginal donors, which were previously not accepted. EVHP parameters, such as perfusion flow (PF) and perfusion pressure (PP) are crucial for optimal organ preservation. However, with the heart’s constant physiological changes during EVHP, such as coronary vascular resistance, manual control of these parameters is rendered imprecise and cumbersome for the operator. Additionally, low control precision and the long adjusting time may lead to irreversible damage to the myocardial tissue. To solve this problem, an automatic heart perfusion system was developed by applying a Human-Machine Interface (HMI) and a Programmable-Logic-Controller (PLC)-based circuit to control PF and PP. The PLC-based control system collects the data of PF and PP through flow probes and pressure transducers. It has two control modes: the RPM-flow mode and the pressure mode. The RPM-flow control mode is an open-loop system. It influences PF through providing and maintaining the desired speed inputted through the HMI to the centrifugal pump with a maximum error of 20 rpm. The pressure control mode is a closed-loop system where the operator selects a target Mean Arterial Pressure (MAP) to control PP. The inputs of the pressure control mode are the target MAP, received through the HMI, and the real MAP, received from the pressure transducer. A PID algorithm is applied to maintain the real MAP at the target value with a maximum error of 1mmHg. The precision and control speed of the RPM-flow control mode were examined by comparing the PLC-based system to an experienced operator (EO) across seven RPM adjustment ranges (500, 1000, 2000 and random RPM changes; 8 trials per range) tested in a random order. System’s PID algorithm performance in pressure control was assessed during 10 EVHP experiments using porcine hearts. Precision was examined through monitoring the steady-state pressure error throughout perfusion period, and stabilizing speed was tested by performing two MAP adjustment changes (4 trials per change) of 15 and 20mmHg. A total of 56 trials were performed to validate the RPM-flow control mode. Overall, the PLC-based system demonstrated the significantly faster speed than the EO in all trials (PLC 1.21±0.03, EO 3.69±0.23 seconds; p < 0.001) and greater precision to reach the desired RPM (PLC 10±0.7, EO 33±2.7 mean RPM error; p < 0.001). Regarding pressure control, the PLC-based system has the median precision of ±1mmHg error and the median stabilizing times in changing 15 and 20mmHg of MAP are 15 and 19.5 seconds respectively. The novel PLC-based control system was 3 times faster with 60% less error than the EO for RPM-flow control. In pressure control mode, it demonstrates a high precision and fast stabilizing speed. In summary, this novel system successfully controlled perfusion flow and pressure with high precision, stability and a fast response time through a user-friendly interface. This design may provide a viable technique for future development of novel heart preservation and assessment strategies during EVHP.

Keywords: automatic control system, biomedical engineering, ex-vivo heart perfusion, human-machine interface, programmable logic controller

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25 An Economic Way to Toughen Poly Acrylic Acid Superabsorbent Polymer Using Hyper Branched Polymer

Authors: Nazila Dehbari, Javad Tavakoli, Yakani Kambu, Youhong Tang

Abstract:

Superabsorbent hydrogels (SAP), as an enviro-sensitive material have been widely used for industrial and biomedical applications due to their unique structure and capabilities. Poor mechanical properties of SAPs - which is extremely related to their large volume change – count as a great weakness in adopting for high-tech applications. Therefore, improving SAPs’ mechanical properties via toughening methods by mixing different types of cross-linked polymer or introducing energy-dissipating mechanisms is highly focused. In this work, in order to change the intrinsic brittle character of commercialized Poly Acrylic Acid (here as SAP) to be semi-ductile, a commercial available highly branched tree-like dendritic polymers with numerous –OH end groups known as hyper-branched polymer (HB) has been added to PAA-SAP system in a single step, cost effective and environment friendly solvent casting method. Samples were characterized by FTIR, SEM and TEM and their physico-chemical characterization including swelling capabilities, hydraulic permeability, surface tension and thermal properties had been performed. Toughness energy, stiffness, elongation at breaking point, viscoelastic properties and samples extensibility were mechanical properties that had been performed and characterized as a function of samples lateral cracks’ length in different HB concentration. Addition of HB to PAA-SAP significantly improved mechanical and surface properties. Increasing equilibrium swelling ratio by about 25% had been experienced by the SAP-HB samples in comparison with SAPs; however, samples swelling kinetics remained without changes as initial rate of water uptake and equilibrium time haven’t been subjected to any changes. Thermal stability analysis showed that HB is participating in hybrid network formation while improving mechanical properties. Samples characterization by TEM showed that, the aggregated HB polymer binders into nano-spheres with diameter in range of 10–200 nm. So well dispersion in the SAP matrix occurred as it was predictable due to the hydrophilic character of the numerous hydroxyl groups at the end of HB which enhance the compatibility of HB with PAA-SAP. As the profused -OH groups in HB could react with -COOH groups in the PAA-SAP during the curing process, the formation of a 2D structure in the SAP-HB could be attributed to the strong interfacial adhesion between HB and the PAA-SAP matrix which hinders the activity of PAA chains (SEM analysis). FTIR spectra introduced new peaks at 1041 and 1121 cm-1 that attributed to the C–O(–OH) stretching hydroxyl and O–C stretching ester groups of HB polymer binder indicating the incorporation of HB polymer into the SAP structure. SAP-HB polymer has significant effects on the final mechanical properties. The brittleness of PAA hydrogels are decreased by introducing HB as the fracture energies of hydrogels increased from 8.67 to 26.67. PAA-HBs’ stretch ability enhanced about 10 folds while reduced as a function of different notches depth.

Keywords: superabsorbent polymer, toughening, viscoelastic properties, hydrogel network

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24 Preparation of Biodegradable Methacrylic Nanoparticles by Semicontinuous Heterophase Polymerization for Drugs Loading: The Case of Acetylsalicylic Acid

Authors: J. Roberto Lopez, Hened Saade, Graciela Morales, Javier Enriquez, Raul G. Lopez

Abstract:

Implementation of systems based on nanostructures for drug delivery applications have taken relevance in recent studies focused on biomedical applications. Although there are several nanostructures as drugs carriers, the use of polymeric nanoparticles (PNP) has been widely studied for this purpose, however, the main issue for these nanostructures is the size control below 50 nm with a narrow distribution size, due to they must go through different physiological barriers and avoid to be filtered by kidneys (< 10 nm) or the spleen (> 100 nm). Thus, considering these and other factors, it can be mentioned that drug-loaded nanostructures with sizes varying between 10 and 50 nm are preferred in the development and study of PNP/drugs systems. In this sense, the Semicontinuous Heterophase Polymerization (SHP) offers the possibility to obtain PNP in the desired size range. Considering the above explained, methacrylic copolymer nanoparticles were obtained under SHP. The reactions were carried out in a jacketed glass reactor with the required quantities of water, ammonium persulfate as initiator, sodium dodecyl sulfate/sodium dioctyl sulfosuccinate as surfactants, methyl methacrylate and methacrylic acid as monomers with molar ratio of 2/1, respectively. The monomer solution was dosed dropwise during reaction at 70 °C with a mechanical stirring of 650 rpm. Nanoparticles of poly(methyl methacrylate-co-methacrylic acid) were loaded with acetylsalicylic acid (ASA, aspirin) by a chemical adsorption technique. The purified latex was put in contact with a solution of ASA in dichloromethane (DCM) at 0.1, 0.2, 0.4 or 0.6 wt-%, at 35°C during 12 hours. According to the boiling point of DCM, as well as DCM and water densities, the loading process is completed when the whole DCM is evaporated. The hydrodynamic diameter was measured after polymerization by quasi-elastic light scattering and transmission electron microscopy, before and after loading procedures with ASA. The quantitative and qualitative analyses of PNP loaded with ASA were measured by infrared spectroscopy, differential scattering calorimetry and thermogravimetric analysis. Also, the molar mass distributions of polymers were determined in a gel permeation chromatograph apparatus. The load capacity and efficiency were determined by gravimetric analysis. The hydrodynamic diameter results for methacrylic PNP without ASA showed a narrow distribution with an average particle size around 10 nm and a composition methyl methacrylate/methacrylic acid molar ratio equal to 2/1, same composition of Eudragit S100, which is a commercial compound widely used as excipient. Moreover, the latex was stabilized in a relative high solids content (around 11 %), a monomer conversion almost 95 % and a number molecular weight around 400 Kg/mol. The average particle size in the PNP/aspirin systems fluctuated between 18 and 24 nm depending on the initial percentage of aspirin in the loading process, being the drug content as high as 24 % with an efficiency loading of 36 %. These average sizes results have not been reported in the literature, thus, the methacrylic nanoparticles here reported are capable to be loaded with a considerable amount of ASA and be used as a drug carrier.

Keywords: aspirin, biocompatibility, biodegradable, Eudragit S100, methacrylic nanoparticles

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