Search results for: biomedical

Authors: Andrea Zielke-Nadkarni

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Pain management is a question of quality of life and an indicator for nursing quality. Chronic pain which is predominant in oncology and palliative nursing situations is perceived today as a multifactorial, individual emotional experience with specific characteristics including the sociocultural dimension when dealing with migrant patients. This dimension of chronic pain is of major importance in professional nursing of migrant patients in hospices or palliative care units. Objectives of the study are: 1. To find out more about the sociocultural views on pain and nursing care, on customs and nursing practices connected with pain of both Turkish Muslim and German Christian women, 2. To improve individual and family oriented nursing practice with view to sociocultural needs of patients in severe pain in palliative care. In a qualitative-explorative comparative study 4 groups of women, Turkish Muslims immigrants (4 from the first generation, 5 from the second generation) and German Christian women of two generations (5 of each age group) of the same age groups as the Turkish women and with similar educational backgrounds were interviewed (semistructured ethnographic interviews using Spradley, 1979) on their perceptions and experiences of pain and nursing care within their families. For both target groups the presentation will demonstrate the following results in detail: Utterance of pain as well as “private” and “public” pain vary within different societies and cultures. Permitted forms of pain utterance are learned in childhood and determine attitudes and expectations in adulthood. Language, especially when metaphors and symbols are used, plays a major role for misunderstandings. The sociocultural context of illness may include specific beliefs that are important to the patients and yet seem more than far-fetched from a biomedical perspective. Pain can be an influential factor in family relationships where respect or hierarchies do not allow the direct utterance of individual needs. Specific resources are often, although not exclusively, linked to religious convictions and are significantly helpful in reducing pain. The discussion will evaluate the results of the study with view to the relevant literature and present nursing interventions and instruments beyond medication that are helpful when dealing with patients from various socio-cultural backgrounds in painful end-oflife situations.

Keywords: pain management, migrants, sociocultural context, palliative care

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Authors: Siti Aisya Gany, Swee Ching Tan, Sook Yee Gan

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Diminished antioxidant defense or increased production of reactive oxygen species in the biological system can result in oxidative stress which may lead to various neurodegenerative diseases including Alzheimer’s disease (AD). Microglial activation also contributes to the progression of AD by producing several pro-inflammatory cytokines, nitric oxide (NO), and prostaglandin E2 (PGE2). Oxidative stress and inflammation have been reported to be possible pathophysiological mechanisms underlying AD. In addition, the cholinergic hypothesis postulates that memory impairment in patient with AD is also associated with the deficit of cholinergic function in the brain. Although a number of drugs have been approved for the treatment of AD, most of these synthetic drugs have diverse side effects and yield relatively modest benefits. Marine algae have great potential in pharmaceutical and biomedical applications as they are valuable sources of bioactive properties such as anti-coagulation, anti-microbial, anti-oxidative, anti-cancer and anti-inflammatory. Hence, this study aimed to provide an overview of the properties of Malaysian seaweeds (Padina australis, Sargassum polycystum and Caulerpa racemosa) in inhibiting oxidative stress, neuroinflammation and cholinesterase enzymes. All tested samples significantly exhibit potent DPPH and moderate Superoxide anion radical scavenging ability (P<0.05). Hexane and methanol extracts of S. polycystum exhibited the most potent radical scavenging ability with IC50 values of 0.1572 ± 0.004 mg/ml and 0.8493 ± 0.02 for DPPH and ABTS assays, respectively. Hexane extract of C. racemosa gave the strongest superoxide radical inhibitory effect (IC50 of 0.3862± 0.01 mg/ml). Most seaweed extracts significantly inhibited the production of cytokine (IL-6, IL-1 β, TNFα) and NO in a concentration-dependent manner without causing significant cytotoxicity to the lipopolysaccharide (LPS)-stimulated microglia cells (P<0.05). All extracts suppressed cytokine and NO level by more than 80% at the concentration of 0.4mg/ml. In addition, C. racemosa and S. polycystum also showed anti-acetylcholinesterase activities with the IC50 values ranging from 0.086-0.115 mg/ml. Moreover, C. racemosa and P. australis were also found to be active against butyrylcholinesterase with IC50 values ranging from 0.118-0.287 mg/ml.

Keywords: anti-cholinesterase, anti-oxidative, neuroinflammation, seaweeds

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Authors: Yemane Hailu Fissuh, Zhongzhan Zhang

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a systematic observation from a defined time of origin up to certain failure or censor is known as survival data. Survival analysis is a major area of interest in biostatistics and biomedical researches. At the heart of understanding, the most scientific and medical research inquiries lie for a causality analysis. Thus, the main concern of this study is to investigate the causal effect of treatment on survival time conditional to the possibly time-varying covariates. The theory of causality often differs from the simple association between the response variable and predictors. A causal estimation is a scientific concept to compare a pragmatic effect between two or more experimental arms. To evaluate an average treatment effect on survival outcome, the estimating equation was adjusted for time-varying covariates under the semi-parametric transformation models. The proposed model intuitively obtained the consistent estimators for unknown parameters and unspecified monotone transformation functions. In this article, the proposed method estimated an unbiased average causal effect of treatment on survival time of interest. The modified estimating equations of semiparametric transformation models have the advantage to include the time-varying effect in the model. Finally, the finite sample performance characteristics of the estimators proved through the simulation and Stanford heart transplant real data. To this end, the average effect of a treatment on survival time estimated after adjusting for biases raised due to the high correlation of the left-truncation and possibly time-varying covariates. The bias in covariates was restored, by estimating density function for left-truncation. Besides, to relax the independence assumption between failure time and truncation time, the model incorporated the left-truncation variable as a covariate. Moreover, the expectation-maximization (EM) algorithm iteratively obtained unknown parameters and unspecified monotone transformation functions. To summarize idea, the ratio of cumulative hazards functions between the treated and untreated experimental group has a sense of the average causal effect for the entire population.

Keywords: a modified estimation equation, causal effect, semiparametric transformation models, survival analysis, time-varying covariate

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Authors: William E. Bauta, Jennifer Rebeles, Reggie Jacob

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Porphyrins are noteworthy in biomedical science for their cancer tissue accumulation and photophysical properties. The preferential accumulation of some porphyrins in cancerous tissue has been known for many years. This, combined with their characteristic photophysical and photochemical properties, including their strong fluorescence and their ability to generate reactive oxygen species in vivo upon laser irradiation, has led to much research into the application of porphyrins as cancer diagnostic and therapeutic agents. Porphyrins have been used as dyes to detect cancer cells both in vivo and, less commonly, in vitro. In one example, human sputum samples from lung cancer patients and patients without the disease were dissociated and stained with the porphyrin TCPP (5,10,15,20-tetrakis-(4-carboxyphenyl)-porphine). Cells were analyzed by flow cytometry. Cancer samples were identified by their higher TCPP fluorescence intensity relative to the no-cancer controls. However, quantitative analysis of fluorescence in cell suspensions stained with multiple fluorophores requires particles stained with each of the individual fluorophores as controls. Fluorescent control particles must be compatible in size with flow cytometer fluidics and have favorable hydrodynamic properties in suspension. They must also display fluorescence comparable to the cells of interest and be stable upon storage amine-functionalized spherical polystyrene beads in the 5 to 20-micron diameter range that was reacted with TCPP and EDC in aqueous pH six buffer overnight to form amide bonds. Beads were isolated by centrifugation and tested by flow cytometry. The 10-micron amine-functionalized beads displayed the best combination of fluorescence intensity and hydrodynamic properties, such as lack of clumping and remaining in suspension during the experiment. These beads were further optimized by varying the stoichiometry of EDC and TCPP relative to the amine. The reaction was accompanied by the formation of a TCPP-related particulate, which was removed, after bead centrifugation, using a microfiltration process. The resultant TCPP-functionalized beads were compatible with flow cytometry conditions and displayed a fluorescence comparable to that of stained cells, which allowed their use as fluorescence standards. The beads were stable in refrigerated storage in the dark for more than eight months. This work demonstrates the first preparation of porphyrin-functionalized flow cytometry control beads.

Keywords: tetraaryl porphyrin, polystyrene beads, flow cytometry, peptide coupling

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Authors: Ariadna Manresa, Ines Ferrer

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Introduction: Ultrasonic moulding process (USM) is a recent injection technology used to manufacture micro components. It is able to melt small amounts of material so the waste of material is certainly reduced comparing to microinjection molding. This is an important advantage when the materials are expensive like medical biopolymers. Micro-scaled components are involved in a variety of uses, such as biomedical applications. It is required replication fidelity so it is important to stabilize the process and minimize the variability of the responses. The aim of this research is to investigate the influence of the main process parameters on the filling behaviour, the dimensional accuracy and the cavity pressure when a micro-plate is manufactured by biomaterials such as PLA and PCL. Methodology or Experimental Procedure: The specimens are manufactured using a Sonorus 1G Ultrasound Micro Molding Machine. The used geometry is a rectangular micro-plate of 15x5mm and 1mm of thickness. The materials used for the investigation are PLA and PCL due to biocompatible and degradation properties. The experimentation is divided into two phases. Firstly, the influence of process parameters (vibration amplitude, sonotrodo velocity, ultrasound time and compaction force) on filling behavior is analysed, in Phase 1. Next, when filling cavity is assured, the influence of both cooling time and force compaction on the cavity pressure, part temperature and dimensional accuracy is instigated, which is done in Phase. Results and Discussion: Filling behavior depends on sonotrodo velocity and vibration amplitude. When the ultrasonic time is higher, more ultrasonic energy is applied and the polymer temperature increases. Depending on the cooling time, it is possible that when mold is opened, the micro-plate temperature is too warm. Consequently, the polymer relieve its stored internal energy (ultrasonic and thermal) expanding through the easier direction. This fact is reflected on dimensional accuracy, causing micro-plates thicker than the mold. It has also been observed the most important fact that affects cavity pressure is the compaction configuration during the manufacturing cycle. Conclusions: This research demonstrated the influence of process parameters on the final micro-plated manufactured. Future works will be focused in manufacturing other geometries and analysing the mechanical properties of the specimens.

Keywords: biomaterial, biopolymer, micro injection molding, ultrasound

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Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

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Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

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Authors: Cathal Merz, Gareth O’Donnell

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Coil reinforced thin-walled (CRTW) tubes are used in medicine to treat problems affecting blood vessels within the body through minimally invasive procedures. The CRTW tube considered in this research makes up part of such a device and is inserted into the patient via their femoral or brachial arteries and manually navigated to the site in need of treatment. This procedure replaces the requirement to perform open surgery but is limited by reduction of blood vessel lumen diameter and increase in tortuosity of blood vessels deep in the brain. In order to maximize the capability of these procedures, CRTW tube devices are being manufactured with decreasing wall thicknesses in order to deliver treatment deeper into the body and to allow passage of other devices through its inner diameter. This introduces significant stresses to the device materials which have resulted in an observed increase in the breaking of the proximal segment of the device into two separate pieces after it has failed by buckling. As there is currently no international standard for measuring the mechanical properties of these CRTW tube devices, it is difficult to accurately analyze this problem. The aim of the current work is to address this discrepancy in the biomedical device industry by developing a measurement system that can be used to quantify the effect of process and design changes on CRTW tube performance, aiding in the development of better performing, next generation devices. Using materials testing frames, micro-computed tomography (micro-CT) imaging, experiment planning, analysis of variance (ANOVA), T-tests and regression analysis, test methods have been developed for assessing the impact of process and design changes on the device. The major findings of this study have been an insight into the suitability of buckle and three-point bend tests for the measurement of the effect of varying processing factors on the device’s performance, and guidelines for interpreting the output data from the test methods. The findings of this study are of significant interest with respect to verifying and validating key process and design changes associated with the device structure and material condition. Test method integrity evaluation is explored throughout.

Keywords: neurovascular catheter, coil reinforced tube, buckling, three-point bend, tensile

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Authors: Christine Y. Yeh, Brian D. Piening, Sarah M. Totten, Kimberly Kukurba, Wenyu Zhou, Kevin P. F. Contrepois, Gucci J. Gu, Sharon Pitteri, Michael Snyder

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Three million deaths worldwide are attributed to obesity. However, the biomolecular mechanisms that describe the link between adiposity and subsequent disease states are poorly understood. Insulin resistance characterizes approximately half of obese individuals and is a major cause of obesity-mediated diseases such as Type II diabetes, hypertension and other cardiovascular diseases. This study makes use of longitudinal quantitative and high-throughput multi-omics (genomics, epigenomics, transcriptomics, glycoproteomics etc.) methodologies on blood samples to develop multigenic and multi-analyte signatures associated with weight gain and insulin resistance. Participants of this study underwent a 30-day period of weight gain via excessive caloric intake followed by a 60-day period of restricted dieting and return to baseline weight. Blood samples were taken at three different time points per patient: baseline, peak-weight and post weight loss. Patients were characterized as either insulin resistant (IR) or insulin sensitive (IS) before having their samples processed via longitudinal multi-omic technologies. This comparative study revealed a wealth of biomolecular changes associated with weight gain after using methods in machine learning, clustering, network analysis etc. Pathways of interest included those involved in lipid remodeling, acute inflammatory response and glucose metabolism. Some of these biomolecules returned to baseline levels as the patient returned to normal weight whilst some remained elevated. IR patients exhibited key differences in inflammatory response regulation in comparison to IS patients at all time points. These signatures suggest differential metabolism and inflammatory pathways between IR and IS patients. Biomolecular differences associated with weight gain and insulin resistance were identified on various levels: in gene expression, epigenetic change, transcriptional regulation and glycosylation. This study was not only able to contribute to new biology that could be of use in preventing or predicting obesity-mediated diseases, but also matured novel biomedical informatics technologies to produce and process data on many comprehensive omics levels.

Keywords: insulin resistance, multi-omics, next generation sequencing, proteogenomics, type ii diabetes

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Authors: Laura Rueda-Gensini, Jader Rodríguez, Juan C. Cruz, Carolina Munoz-Camargo

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There is an emerging interest in botanicals and plant extracts for medicinal practices due to their widely reported health benefits. A large variety of phytochemicals found in plants have been correlated with antioxidant, immunomodulatory, and analgesic properties, which makes plant-derived products promising candidates for modulating the progression and treatment of numerous diseases. Non-centrifugal cane sugar (NCS), in particular, has been known for its high antioxidant and nutritional value, but composition-wise variability due to changing environmental and processing conditions have considerably limited its use in the nutraceutical and biomedical fields. This work is therefore aimed at assessing the effect of thermal exposure during NCS production over its bioactive composition and, in turn, its therapeutic value. Accordingly, two modified dehydration methods are proposed that employ: (i) vacuum-aided evaporation, which reduces the necessary temperatures to dehydrate the sample, and (ii) window refractance evaporation, which reduces thermal exposure time. The biochemical composition of NCS produced under these two methods was compared to traditionally-produced NCS by estimating their total polyphenolic and protein content with Folin-Ciocalteu and Bradford assays, as well as identifying the major phenolic compounds in each sample via HPLC-coupled mass spectrometry. Their antioxidant activities were also compared as measured by their scavenging potential of ABTS and DPPH radicals. Results show that the two modified production methods enhance polyphenolic and protein yield in resulting NCS samples when compared to traditional production methods. In particular, reducing employed temperatures with vacuum-aided evaporation demonstrated to be superior at preserving polyphenolic compounds, as evidenced both in the total and individual polyphenol concentrations. However, antioxidant activities were not significantly different between these. Although additional studies should be performed to determine if the observed compositional differences affect other therapeutic activities (e.g., anti-inflammatory, analgesic, and immunoprotective), these results suggest that reducing thermal exposure holds great promise for the production of natural products with enhanced nutritional value.

Keywords: non-centrifugal cane sugar, polyphenolic compounds, thermal processing, antioxidant activity

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

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Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection

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Authors: Damian Stanislaw Nakonieczny, Grazyna Simha Martynkova, Marianna Hundakova, G. Kratosová, Karla Cech Barabaszova

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The main aim of the research was to functionalize the surface of spherical aluminum silicates in the form of so-called cenospheres. Cenospheres are light ceramic particles with a density between 0.45 and 0.85 kgm-3 hat can be obtained as a result of separation from fly ash from coal combustion. However, their occurrence is limited to about 1% by weight of dry ash mainly derived from anthracite. Hence they are very rare and desirable material. Cenospheres are characterized by complete chemical inertness. Mohs hardness in range of 6 and completely smooth surface. Main idea was to prepare the surface by chemical etching, among others hydrofluoric acid (HF) and hydrogen peroxide, caro acid, silanization using (3-aminopropyl) triethoxysilane (APTES) and tetraethyl orthosilicate (TEOS) to obtain the maximum development and functionalization of the surface to improve chemical and mechanical connection with biomedically used polymers, i.e., polyacrylic methacrylate (PMMA) and polyetheretherketone (PEEK). These polymers are used medically mainly as a material for fixed and removable dental prostheses and PEEK spinal implants. The problem with their use is the decrease in mechanical properties over time and bacterial infections fungal during implantation and use of dentures. Hence, the use of a ceramic filler that will significantly improve the mechanical properties, improve the fluidity of the polymer during shape formation, and in the future, will be able to support bacteriostatic substances such as silver and zinc ions seem promising. In order to evaluate our laboratory work, several instrumental studies were performed: chemical composition and morphology with scanning electron microscopy with Energy-Dispersive X-Ray Probe (SEM/EDX), determination of characteristic functional groups of Fourier Transform Infrared Spectroscopy (FTIR), phase composition of X-ray Diffraction (XRD) and thermal analysis of Thermo Gravimetric Analysis/differentia thermal analysis (TGA/DTA), as well as assessment of isotherm of adsorption with Brunauer-Emmett-Teller (BET) surface development. The surface was evaluated for the future application of additional bacteria and static fungus layers. Based on the experimental work, it was found that orated methods can be suitable for the functionalization of the surface of cenosphere ceramics, and in the future it can be suitable as a bacteriostatic filler for biomedical polymers, i.e., PEEK or PMMA.

Keywords: bioceramics, composites, functionalization, surface development

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

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Authors: Sudip Mondal, Biswanath Mondal, Sudit S. Mukhopadhyay, Apurba Dey

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Bioactive materials improve devices for a long lifespan but have mechanical limitations. Mechanical characterization is one of the very important characteristics to evaluate the life span and functionality of the scaffold material. After implantation of scaffold material the primary stage rejection of scaffold occurs due to non biocompatible effect of host body system. The second major problems occur due to the effect of mechanical failure. The mechanical and biocompatibility failure of the scaffold materials can be overcome by the prior evaluation of the scaffold materials. In this study chemically treated Labeo rohita scale is used for synthesizing hydroxyapatite (HAp) biomaterial. Thermo-gravimetric and differential thermal analysis (TG-DTA) is carried out to ensure thermal stability. The chemical composition and bond structures of wet ball-milled calcined HAp powder is characterized by Fourier Transform Infrared spectroscopy (FTIR), X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Transmission Electron Microscopy (TEM), Energy Dispersive X-ray (EDX) analysis. Fish scale derived apatite materials consists of nano-sized particles with Ca/P ratio of 1.71. The biocompatibility through cytotoxicity evaluation and MTT assay are carried out in MG63 osteoblast cell lines. In the cell attachment study, the cells are tightly attached with HAp scaffolds developed in the laboratory. The result clearly suggests that HAp material synthesized in this study do not have any cytotoxic effect, as well as it has a natural binding affinity for mammalian cell lines. The synthesized HAp powder further successfully used to develop porous scaffold material with suitable mechanical property of ~0.8GPa compressive stress, ~1.10 GPa a hardness and ~ 30-35% porosity which is acceptable for implantation in trauma region for animal model. The histological analysis also supports the bio-affinity of processed HAp biomaterials in Wistar rat model for investigating the contact reaction and stability at the artificial or natural prosthesis interface for biomedical function. This study suggests the natural sourced fish scale-derived HAp material could be used as a suitable alternative biomaterial for tissue engineering application in near future.

Keywords: biomaterials, hydroxyapatite, scaffold, mechanical property, tissue engineering

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Authors: Axel Thallemer, Aleksandar Kostadinov, Abel Fam, Alex Teo

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For centuries, the forming processes in nature served as a source of inspiration for both architects and designers. It seems as most human artifacts are based on ideas which stem from the observation of the biological world and its principles of growth. As a fact, in the cultural history of Homo faber, materials have been mostly used in their solid state: From hand axe to computer mouse, the principle of employing matter has not changed ever since the first creation. In the scope of history only recently and by the help of additive-generative fabrication processes through Computer Aided Design (CAD), designers were enabled to deconstruct solid artifacts into an outer skin and an internal lattice structure. The intention behind this approach is to create a new topology which reduces resources and integrates functions into an additively manufactured component. However, looking at the currently employed lattice structures, it is very clear that those lattice structure geometries have not been thoroughly designed, but rather taken out of basic-geometry libraries which are usually provided by the CAD. In the here presented study, a group of 20 industrial design students created new and unique lattice structures using natural paragons as their models. The selected natural models comprise both the animate and inanimate world, with examples ranging from the spiraling of narwhal tusks, off-shooting of mangrove roots, minimal surfaces of soap bubbles, up to the rhythmical arrangement of molecular geometry, like in the case of SiOC (Carbon-Rich Silicon Oxicarbide). This ideation process leads to a design of a geometric cell, which served as a basic module for the lattice structure, whereby the cell was created in visual analogy to its respective natural model. The spatial lattices were fabricated additively in mostly [X]3 by [Y]3 by [Z]3 units’ volumes using selective powder bed melting in polyamide with (z-axis) 50 mm and 100 µm resolution and subdued to mechanical testing of their elastic zone in a biomedical laboratory. The results demonstrate that additively manufactured lattice structures can acquire different properties when they are designed in analogy to natural models. Several of the lattices displayed the ability to store and return kinetic energy, while others revealed a structural failure which can be exploited for purposes where a controlled collapse of a structure is required. This discovery allows for various new applications of functional lattice structures within industrially created objects.

Keywords: bio-inspired, biomimetic, lattice structures, additive manufacturing

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Authors: I. Irska, S. Paszkiewicz, D. Pawlikowska, E. Piesowicz, A. Linares, T. A. Ezquerra

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Due to the number of advantages such as high tensile strength, sensitivity to hydrolytic degradation, and biocompatibility poly(lactic acid) (PLA) is one of the most common polyesters for biomedical and pharmaceutical applications. However, PLA is a rigid, brittle polymer with low heat distortion temperature and slow crystallization rate. In order to broaden the range of PLA applications, it is necessary to improve these properties. In recent years a number of new strategies have been evolved to obtain PLA-based materials with improved characteristics, including manipulation of crystallinity, plasticization, blending, and incorporation into block copolymers. Among the other methods, synthesis of aliphatic-aromatic copolyesters has been attracting considerable attention as they may combine the mechanical performance of aromatic polyesters with biodegradability known from aliphatic ones. Given the need for highly flexible biodegradable polymers, in this contribution, a series of aromatic-aliphatic based on poly(butylene terephthalate) and poly(lactic acid) (PBT-b-PLA) copolyesters exhibiting superior mechanical properties were copolymerized with an additional poly(tetramethylene oxide) (PTMO) soft block. The structure and properties of both series were characterized by means of attenuated total reflectance – Fourier transform infrared spectroscopy (ATR-FTIR), nuclear magnetic resonance spectroscopy (¹H NMR), differential scanning calorimetry (DSC), wide-angle X-ray scattering (WAXS) and dynamic mechanical, thermal analysis (DMTA). Moreover, the related changes in tensile properties have been evaluated and discussed. Lastly, the viscoelastic properties of synthesized poly(ester-ether) copolymers were investigated in detail by step cycle tensile tests. The block lengths decreased with the advance of treatment, and the block-random diblock terpolymers of (PBT-ran-PLA)-b-PTMO were obtained. DSC and DMTA analysis confirmed unambiguously that synthesized poly(ester-ether) copolymers are microphase-separated systems. The introduction of polyether co-units resulted in a decrease in crystallinity degree and melting temperature. X-ray diffraction patterns revealed that only PBT blocks are able to crystallize. The mechanical properties of (PBT-ran-PLA)-b-PTMO copolymers are a result of a unique arrangement of immiscible hard and soft blocks, providing both strength and elasticity.

Keywords: aliphatic-aromatic copolymers, multiblock copolymers, phase behavior, thermoplastic elastomers

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Authors: Elizalde D. Bana

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Healing restores continuity and form through cell replication; hence, conserving structural integrity. In response to the worldwide pressing problem of chronic wounds in the healthcare delivery system, the researcher aims to provide effective intervention to preserve the structural integrity of the person. The wound healing effects of cryopreserved and lyophilized amniotic membrane (AM) of a term fetus embedded into two (2) concentrations (1.5 % and 1.0 %) of absorption-based ointment has been evaluated in vivo using the excision wound healing model 1x1 cm size. The total protein concentration in full term fetus was determined by the Biuret and Bradford methods, which are based on UV-visible spectroscopy. The percentages of protein presence in 9.5 mg (Mass total sample) of Amniotic membrane ranges between 14.77 – 14.46 % in Bradford method, while slightly lower to 13.78 – 13.80 % concentration in Biuret method, respectively. Bradford method evidently showed higher sensitivity for proteins than Biuret test. Overall, the amniotic membrane is composed principally of proteins in which a copious amount of literature substantially proved its healing abilities. After which, an area of 1 cm by 1 cm skin tissue was excised to its full thickness from the dorsolateral aspect of the isogenic mice and was applied twice a day with the ointment formulation having two (2) concentrations for the diabetic group and non-diabetic group. The wounds of each animal were left undressed and its area was measured every other day by a standard measurement formula from day 2,4,6,8,10,12 and 14. By the 14th day, the ointment containing 1.5 % of AM in absorption-based ointment applied to non-diabetic and diabetic group showed 100 % healing. The wound areas in the animals treated with the standard antibiotic, Mupirocin Ointment (Brand X) showed a 100% healing by the 14th day but with traces of scars, indicating that AM prepared from cryopreservation and lyophilization, at that given concentration, had a better wound healing property than the standard antibiotic. Four (4) multivariate tests were used which showed a significant interaction between days and treatments, meaning that the ointments prepared in two differing concentrations and induced in different groups of the mice had a significant effect on the percent of contraction over time. Furthermore, the evaluations of its effectiveness to wound healing were all significant although in differing degrees. It is observed that the higher the concentrations of amniotic membrane, the more effective are the results.

Keywords: wounds, healing, amniotic membrane ointments, biomedical, stem cell

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Authors: Arzu Karahan, Loriano Ballarin, Baruch Rinkevich

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Marine invertebrates, the highly diverse phyla of multicellular organisms, represent phenomena that are either not found or highly restricted in the vertebrates. These include phenomena like budding, fission, a fusion of ramets, and high regeneration power, such as the ability to create whole new organisms from either tiny parental fragment, many of which are controlled by totipotent, pluripotent, and multipotent stem cells. Thus, there is very much that can be learned from these organisms on the practical and evolutionary levels, further resembling Darwin's words, “It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change”. The ‘stem cell’ notion highlights a cell that has the ability to continuously divide and differentiate into various progenitors and daughter cells. In vertebrates, adult stem cells are rare cells defined as lineage-restricted (multipotent at best) with tissue or organ-specific activities that are located in defined niches and further regulate the machinery of homeostasis, repair, and regeneration. They are usually categorized by their morphology, tissue of origin, plasticity, and potency. The above description not always holds when comparing the vertebrates with marine invertebrates’ stem cells that display wider ranges of plasticity and diversity at the taxonomic and the cellular levels. While marine/aquatic invertebrates stem cells (MISC) have recently raised more scientific interest, the know-how is still behind the attraction they deserve. MISC, not only are highly potent but, in many cases, are abundant (e.g., 1/3 of the entire animal cells), do not locate in permanent niches, participates in delayed-aging and whole-body regeneration phenomena, the knowledge of which can be clinically relevant. Moreover, they have massive hidden potential for the discovery of new bioactive molecules that can be used for human health (antitumor, antimicrobial) and biotechnology. The MARISTEM COST action (Stem Cells of Marine/Aquatic Invertebrates: From Basic Research to Innovative Applications) aims to connect the European fragmented MISC community. Under this scientific umbrella, the action conceptualizes the idea for adult stem cells that do not share many properties with the vertebrates’ stem cells, organizes meetings, summer schools, and workshops, stimulating young researchers, supplying technical and adviser support via short-term scientific studies, making new bridges between the MISC community and biomedical disciplines.

Keywords: aquatic/marine invertebrates, adult stem cell, regeneration, cell cultures, bioactive molecules

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Authors: Kanika Gupta, Ashok Kumar

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Biofilms are dense, highly hydrated cell clusters that are irreversibly attached to a substratum, to an interface or to each other, and are embedded in a self-produced gelatinous matrix composed of extracellular polymeric substances. Research in biofilm field has become very significant, as biofilm has shown high mechanical resilience and resistance to antibiotic treatment and constituted as a significant problem in both healthcare and other industry related to microorganisms. The massive information both stated and hidden in the biofilm literature are growing exponentially therefore it is not possible for researchers and practitioners to automatically extract and relate information from different written resources. So, the current work proposes and discusses the use of text mining techniques for the extraction of information from biofilm literature corpora containing 34306 documents. It is very difficult and expensive to obtain annotated material for biomedical literature as the literature is unstructured i.e. free-text. Therefore, we considered unsupervised approach, where no annotated training is necessary and using this approach we developed a system that will classify the text on the basis of growth and development, drug effects, radiation effects, classification and physiology of biofilms. For this, a two-step structure was used where the first step is to extract keywords from the biofilm literature using a metathesaurus and standard natural language processing tools like Rapid Miner_v5.3 and the second step is to discover relations between the genes extracted from the whole set of biofilm literature using pubmed.mineR_v1.0.11. We used unsupervised approach, which is the machine learning task of inferring a function to describe hidden structure from 'unlabeled' data, in the above-extracted datasets to develop classifiers using WinPython-64 bit_v3.5.4.0Qt5 and R studio_v0.99.467 packages which will automatically classify the text by using the mentioned sets. The developed classifiers were tested on a large data set of biofilm literature which showed that the unsupervised approach proposed is promising as well as suited for a semi-automatic labeling of the extracted relations. The entire information was stored in the relational database which was hosted locally on the server. The generated biofilm vocabulary and genes relations will be significant for researchers dealing with biofilm research, making their search easy and efficient as the keywords and genes could be directly mapped with the documents used for database development.

Keywords: biofilms literature, classifiers development, text mining, unsupervised learning approach, unstructured data, relational database

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Authors: Mari A. Virtanen, Elina Haavisto, Eeva Liikanen, Maria Kääriäinen

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Rapid technological development and digitalization has affected also on higher education. During last twenty years multiple of electronic and mobile learning (e-learning, m-learning) platforms have been developed and have become prevalent in many universities and in the all fields of education. Ubiquitous learning (u-learning) is not that widely known or used. Ubiquitous learning environments (ULE) are the new era of computer-assisted learning. They are based on ubiquitous technology and computing that fuses the learner seamlessly into learning process by using sensing technology as tags, badges or barcodes and smart devices like smartphones and tablets. ULE combines real-life learning situations into virtual aspects and can be flexible used in anytime and anyplace. The aim of this study was to assess the effects of ubiquitous 360 o learning environment on higher education students’ clinical histotechnology competence. A quasi-experimental study design was used. 57 students in biomedical laboratory science degree program was assigned voluntarily to experiment (n=29) and to control group (n=28). Experimental group studied via ubiquitous 360o learning environment and control group via traditional web-based learning environment (WLE) in a 8-week educational intervention. Ubiquitous 360o learning environment (ULE) combined authentic learning environment (histotechnology laboratory), digital environment (virtual laboratory), virtual microscope, multimedia learning content, interactive communication tools, electronic library and quick response barcodes placed into authentic laboratory. Web-based learning environment contained equal content and components with the exception of the use of mobile device, interactive communication tools and quick response barcodes. Competence of clinical histotechnology was assessed by using knowledge test and self-report developed for this study. Data was collected electronically before and after clinical histotechnology course and analysed by using descriptive statistics. Differences among groups were identified by using Wilcoxon test and differences between groups by using Mann-Whitney U-test. Statistically significant differences among groups were identified in both groups (p<0.001). Competence scores in post-test were higher in both groups, than in pre-test. Differences between groups were very small and not statistically significant. In this study the learning environment have developed based on 360o technology and successfully implemented into higher education context. And students’ competence increases when ubiquitous learning environment were used. In the future, ULE can be used as a learning management system for any learning situation in health sciences. More studies are needed to show differences between ULE and WLE.

Keywords: competence, higher education, histotechnology, ubiquitous learning, u-learning, 360o

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Authors: Z. Terzopoulou, I. Koliakou, D. Bikiaris

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Tissue engineering offers a new approach to regenerate diseased or damaged tissues such as bone. Great effort is devoted to eliminating the need of removing non-degradable implants at the end of their life span, with biodegradable polymers playing a major part. Poly(ε-caprolactone) (PCL) is one of the best candidates for this purpose due to its high permeability, good biodegradability and exceptional biocompatibility, which has stimulated extensive research into its potential application in the biomedical fields. However, PCL degrades much slower than other known biodegradable polymers and has a total degradation of 2-4 years depending on the initial molecular weight of the device. This is due to its relatively hydrophobic character and high crystallinity. Consequently, much attention has been given to the tunable degradation of PCL to meet the diverse requirements of biomedicine. Poly(ε-caprolactone) (PCL) is a biodegradable polyester that lacks bioactivity, so when used in bone tissue engineering, new bone tissue cannot bond tightly on the polymeric surface. Therefore, it is important to incorporate reinforcing fillers into PCL matrix in order to result in a promising combination of bioactivity, biodegradability, and strength. Natural clay halloysite nanotubes (HNTs) were incorporated into PCL polymeric matrix, via in situ ring-opening polymerization of caprolactone, in concentrations 0.5, 1 and 2.5 wt%. Both unmodified and modified with aminopropyltrimethoxysilane (APTES) HNTs were used in this study. The effect of nanofiller concentration and functionalization with end-amino groups on the physicochemical properties of the prepared nanocomposites was studied. Mechanical properties were found enhanced after the incorporation of nanofillers, while the modification increased further the values of tensile and impact strength. Thermal stability of PCL was not affected by the presence of nanofillers, while the crystallization rate that was studied by Differential Scanning Calorimetry (DSC) and Polarized Light Optical Microscopy (POM) increased. All materials were subjected to enzymatic hydrolysis in phosphate buffer in the presence of lipases. Due to the hydrophilic nature of HNTs, the biodegradation rate of nanocomposites was higher compared to neat PCL. In order to confirm the effect of hydrophilicity, contact angle measurements were also performed. In vitro biomineralization test confirmed that all samples were bioactive as mineral deposits were detected by X-ray diffractometry after incubation in SBF. All scaffolds were tested in relevant cell culture using osteoblast-like cells (MG-63) to demonstrate their biocompatibility

Keywords: biomaterials, nanocomposites, scaffolds, tissue engineering

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Authors: A. G. Pershina, P. S. Postnikov, M. E. Trusova, D. O. Burlakova, A. E. Sazonov

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Invention of magnetic-fluorescent nanocomposites is a rapidly developing area of research. The magnetic-fluorescent nanocomposite attractiveness is connected with the ability of simultaneous management and control of such nanocomposites by two independent methods based on different physical principles. These nanocomposites are applied for the solution of various essential scientific and experimental biomedical problems. The aim of this research is development of principle approach to nanobiohybrid structures with magnetic and fluorescent properties design. The surface of carbon-coated iron nanoparticles (Fe@C) were covalently modified by 4-carboxy benzenediazonium tosylate. Recombinant fluorescent protein TagGFP2 (Eurogen) was obtained in E. coli (Rosetta DE3) by standard laboratory techniques. Immobilization of TagGFP2 on the nanoparticles surface was provided by the carbodiimide activation. The amount of COOH-groups on the nanoparticle surface was estimated by elemental analysis (Elementar Vario Macro) and TGA-analysis (SDT Q600, TA Instruments. Obtained nanocomposites were analyzed by FTIR spectroscopy (Nicolet Thermo 5700) and fluorescence microscopy (AxioImager M1, Carl Zeiss). Amount of the protein immobilized on the modified nanoparticle surface was determined by fluorimetry (Cary Eclipse) and spectrophotometry (Unico 2800) with the help of preliminary obtained calibration plots. In the FTIR spectra of modified nanoparticles the adsorption band of –COOH group around 1700 cm-1 and bands in the region of 450-850 cm-1 caused by bending vibrations of benzene ring were observed. The calculated quantity of active groups on the surface was equal to 0,1 mmol/g of material. The carbodiimide activation of COOH-groups on nanoparticles surface results to covalent immobilization of TagGFP2 fluorescent protein (0.2 nmol/mg). The success of immobilization was proved by FTIR spectroscopy. Protein characteristic adsorption bands in the region of 1500-1600 cm-1 (amide I) were presented in the FTIR spectrum of nanocomposite. The fluorescence microscopy analysis shows that Fe@C-TagGFP2 nanocomposite possesses fluorescence properties. This fact confirms that TagGFP2 protein retains its conformation due to immobilization on nanoparticles surface. Magnetic-fluorescent nanocomposite was obtained as a result of unique design solution implementation – the fluorescent protein molecules were fixed to the surface of superparamagnetic carbon-coated iron nanoparticles using original diazonium salts.

Keywords: carbon-coated iron nanoparticles, diazonium salts, fluorescent protein, immobilization

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Authors: Umedov Mekhroz, Griaznova Svetlana

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In connection with the growth of oncological diseases, the design of centers for diagnostics and the production of radiopharmaceuticals is the most relevant area of healthcare facilities. The design of new nuclear medicine centers should be carried out from the standpoint of solving the following tasks: the availability of medical care, functionality, environmental friendliness, sustainable development, improving the safety of drugs, the use of which requires special care, reducing the rate of environmental pollution, ensuring comfortable conditions for the internal microclimate, adaptability. The purpose of this article is to substantiate architectural and planning solutions, formulate recommendations and principles for the design of nuclear medicine centers and determine the connections between the production and medical functions of a building. The advantages of combining the production of radiopharmaceuticals and the department of medical care: less radiation activity is accumulated, the cost of the final product is lower, and there is no need to hire a transport company with a special license for transportation. A medical imaging department is a structural unit of a medical institution in which diagnostic procedures are carried out in order to gain an idea of the internal structure of various organs of the body for clinical analysis. Depending on the needs of a particular institution, the department may include various rooms that provide medical imaging using radiography, ultrasound diagnostics, and the phenomenon of nuclear magnetic resonance. The production of radiopharmaceuticals is an object intended for the production of a pharmaceutical substance containing a radionuclide and intended for introduction into the human body or laboratory animal for the purpose of diagnosis, evaluation of the effectiveness of treatment, or for biomedical research. The research methodology includes the following subjects: study and generalization of international experience in scientific research, literature, standards, teaching aids, and design materials on the topic of research; An integrated approach to the study of existing international experience of PET / CT scan centers and the production of radiopharmaceuticals; Elaboration of graphical analysis and diagrams based on the system analysis of the processed information; Identification of methods and principles of functional zoning of nuclear medicine centers. The result of the research is the identification of the design principles of nuclear medicine centers with the functions of the production of radiopharmaceuticals and the department of medical imaging. This research will be applied to the design and construction of healthcare facilities in the field of nuclear medicine.

Keywords: architectural planning solutions, functional zoning, nuclear medicine, PET/CT scan, production of radiopharmaceuticals, radiotherapy

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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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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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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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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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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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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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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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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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