Search results for: neutron activation detectors

Authors: Nihan Nugay, Nur Cicek Kekec, Kalman Toth, Turgut Nugay, Joseph P. Kennedy

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In recent years, polyurethane structures are paving the way for elastomer usage in biology, human medicine, and biomedical application areas. Polyurethanes having a combination of high oxidative and hydrolytic stability and excellent mechanical properties are focused due to enhancing the usage of PUs especially for implantable medical device application such as cardiac-assist. Currently, unique polyurethanes consisting of polyisobutylenes as soft segments and conventional hard segments, named as PIB-based PUs, are developed with precise NCO/OH stoichiometry (∽1.05) for obtaining PIB-based PUs with enhanced properties (i.e., tensile stress increased from ∽11 to ∽26 MPa and elongation from ∽350 to ∽500%). Static and dynamic mechanical properties were optimized by examining stress-strain graphs, self-organization and crystallinity (XRD) traces, rheological (DMA, creep) profiles and thermal (TGA, DSC) responses. Annealing procedure was applied for PIB-based PUs. Annealed PIB-based PU shows ∽26 MPa tensile strength, ∽500% elongation, and ∽77 Microshore hardness with excellent hydrolytic and oxidative stability. The surface characters of them were examined with AFM and contact angle measurements. Annealed PIB-based PU exhibits the higher segregation of individual segments and surface hydrophobicity thus annealing significantly enhances hydrolytic and oxidative stability by shielding carbamate bonds by inert PIB chains. According to improved surface and microstructure characters, greater efforts are focused on analyzing protein adsorption and calcification profiles. In biomedical applications especially for cardiological implantations, protein adsorption inclination on polymeric heart valves is undesirable hence protein adsorption from blood serum is followed by platelet adhesion and subsequent thrombus formation. The protein adsorption character of PIB-based PU examines by applying Bradford assay in fibrinogen and bovine serum albumin solutions. Like protein adsorption, calcium deposition on heart valves is very harmful because vascular calcification has been proposed activation of osteogenic mechanism in the vascular wall, loss of inhibitory factors, enhance bone turnover and irregularities in mineral metabolism. The calcium deposition on films are characterized by incubating samples in simulated body fluid solution and examining SEM images and XPS profiles. PIB-based PUs are significantly more resistant to hydrolytic-oxidative degradation, protein adsorption and calcium deposition than ElastEonTM E2A, a commercially available PDMS-based PU, widely used for biomedical applications.

Keywords: biomedical application, calcification, polyisobutylene, polyurethane, protein adsorption

Procedia PDF Downloads 257

Authors: Ora Geiger

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Reading is a cognitive process of deciphering visual signs to produce meaning. During the reading process, written information of symbols and signs is received in the person’s eye and processed in the brain. This definition is relevant to both the reading of letters and the reading of musical notation. But while the letters of the alphabet are signs determined arbitrarily, notes are recorded systematically on a staff, with the location of each note on the staff indicating its relative pitch. In this paper, the researcher specifies the characteristics of alphabet reading in comparison to musical notation reading, and discusses the question whether a person diagnosed with dyslexia will necessarily have difficulty in reading musical notes. Dyslexia is a learning disorder that makes it difficult to acquire alphabet-reading skills due to difficulties expressed in the identification of letters, spelling, and other language deciphering skills. In order to read, one must be able to connect a symbol with a sound and to join the sounds into words. A person who has dyslexia finds it difficult to translate a graphic symbol into the sound that it represents. When teaching reading to children diagnosed with dyslexia, the multi-sensory approach, supporting the activation and involvement of most of the senses in the learning process, has been found to be particularly effective. According to this approach, when most senses participate in the reading learning process, it becomes more effective. During years of experience, the researcher, who is a music specialist, has been following the music reading learning process of elementary school age students, some of them diagnosed with Dyslexia, while studying to play soprano (descant) recorder. She argues that learning music reading while studying to play a musical instrument is a multi-sensory experience by its nature. The senses involved are: sight, hearing, touch, and the kinesthetic sense (motion), which provides the brain with information on the relative positions of the body. In this way, the learner experiences simultaneously visual, auditory, tactile, and kinesthetic impressions. The researcher concludes that there should be no contra-indication for teaching standard music reading to children with dyslexia if an appropriate process is offered. This conclusion is based on two main characteristics of music reading: (1) musical notation system is a systematic, logical, relative set of symbols written on a staff; and (2) music reading learning connected with playing a musical instrument is by its nature a multi-sensory activity since it combines sight, hearing, touch, and movement. This paper describes music reading teaching procedures and provides unique teaching methods that have been found to be effective for students who were diagnosed with Dyslexia. It provides theoretical explanations in addition to guidelines for music education practices.

Keywords: alphabet reading, dyslexia, multisensory teaching method, music reading, recorder playing

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Authors: Prateek Goyal, Archini Paruthi, Superb K. Misra

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Contamination of water resources has been a major concern, which has drawn attention to the need to develop new material models for treatment of effluents. Existing conventional waste water treatment methods remain ineffective sometimes and uneconomical in terms of remediating contaminants like heavy metal ions (mercury, arsenic, lead, cadmium and chromium); organic matter (dyes, chlorinated solvents) and high salt concentration, which makes water unfit for consumption. We believe that nanotechnology based strategy, where we use nanoparticles as a tool to remediate a class of pollutants would prove to be effective due to its property of high surface area to volume ratio, higher selectivity, sensitivity and affinity. In recent years, scientific advancement has been made to study the application of photocatalytic (ZnO, TiO2 etc.) nanomaterials and magnetic nanomaterials in remediating contaminants (like heavy metals and organic dyes) from water/wastewater. Our study focuses on the synthesis and monitoring remediation efficiency of ZnO, Fe3O4 and Fe3O4 coated ZnO nanoparticulate system for the removal of heavy metals and dyes simultaneously. Multitude of ZnO nanostructures (spheres, rods and flowers) using multiple routes (microwave & hydrothermal approach) offers a wide range of light active photo catalytic property. The phase purity, morphology, size distribution, zeta potential, surface area and porosity in addition to the magnetic susceptibility of the particles were characterized by XRD, TEM, CPS, DLS, BET and VSM measurements respectively. Further on, the introduction of crystalline defects into ZnO nanostructures can also assist in light activation for improved dye degradation. Band gap of a material and its absorbance is a concrete indicator for photocatalytic activity of the material. Due to high surface area, high porosity and affinity towards metal ions and availability of active surface sites, iron oxide nanoparticles show promising application in adsorption of heavy metal ions. An additional advantage of having magnetic based nanocomposite is, it offers magnetic field responsive separation and recovery of the catalyst. Therefore, we believe that ZnO linked Fe3O4 nanosystem would be efficient and reusable. Improved photocatalytic efficiency in addition to adsorption for environmental remediation has been a long standing challenge, and the nano-composite system offers the best of features which the two individual metal oxides provide for nanoremediation.

Keywords: adsorption, nanocomposite, nanoremediation, photocatalysis

Procedia PDF Downloads 238

Authors: Iliyasu Musa Omoyine, Musa Sunday Abraham, Oladele Sunday Blessing, Iliya Ibrahim Abdullahi, Ibegbu Augustine Oseloka, Nuhu Nana-Hawau, Animoku Abdulrazaq Amoto, Yusuf Abdullateef Onoruoiza, Sambo Sohnap James, Akpulu Steven Peter, Ajayi Abayomi

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The neuroprotective role of inflammation from detrimental intrinsic and extrinsic factors has been reported. However, the overactivation of astrocytes and microglia due to lead toxicity produce excessive pro-inflammatory cytokines, mediating neurodegenerative diseases. The present study investigated the mitigatory effects of quercetin on neuroinflammation, correlating with memory function in lead-exposed rats. In this study, Wistar rats were administered orally with Quercetin (Q: 60 mg/kg) and Succimer as a standard drug (S: 10 mg/kg) for 21 days after lead exposure (Pb: 125 mg/kg) of 21 days or in combination with Pb, once daily for 42 days. Working and reference memory was assessed using an Eight-arm radial water maze (8-ARWM). The changes in brain lead level, the neuronal nitric oxide synthase (nNOS) activity, and the level of neuroinflammatory markers such as tumour necrosis factor-alpha (TNF-α) and Interleukin 1 Beta (IL-1β) were determined. Immunohistochemically, astrocyte expression was evaluated. The results showed that the brain level of lead was increased significantly in lead-exposed rats. The expression of astrocytes increased in the CA3 and CA1 regions of the hippocampus, and the levels of brain TNF-α and IL-1β increased in lead-exposed rats. Lead impaired reference and working memory by increasing reference memory errors and working memory incorrect errors in lead-exposed rats. However, quercetin treatment effectively improved memory and inhibited neuroinflammation by reducing astrocytes’ expression and the levels of TNF-α and IL-1β. The expression of astrocytes and the levels of TNF-α and IL-1β correlated with memory function. The possible explanation for quercetin’s anti-neuroinflammatory effect is that it modulates the activity of cellular proteins involved in the inflammatory response; inhibits the transcription factor of nuclear factor-kappa B (NF-κB), which regulates the expression of proinflammatory molecules; inhibits kinases required for the synthesis of Glial fibrillary acidic protein (GFAP) and modifies the phosphorylation of some proteins, which affect the structure and function of intermediate filament proteins; and, lastly, induces Cyclic-AMP Response Element Binding (CREB) activation and neurogenesis as a compensatory mechanism for memory deficits and neuronal cell death. In conclusion, the levels of neuroinflammatory markers negatively correlated with memory function. Thus, quercetin may be a promising therapy in neuroinflammation and memory dysfunction in populations prone to lead exposure.

Keywords: lead, quercetin, neuroinflammation, memory

Procedia PDF Downloads 54

Authors: Justin Durham, Chanda Rooney, Robert Mather, Mickie Vanhoy

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The psychological construct of empathy is to understand a person’s cognitive perspective and experience the other person’s emotional state. Deciphering emotional states is conducive for interpreting vicarious pain. Observing others' physical pain activates neural networks related to the actual experience of pain itself. The study addresses empathy as a nonlinear dynamic process of simulation for individuals to understand the mental states of others and experience vicarious pain, exhibiting self-organized criticality. Such criticality follows from a combination of neural networks with an excitatory feedback loop generating bistability to resonate permutated empathy. Cortical networks exhibit diverse patterns of activity, including oscillations, synchrony and waves, however, the temporal dynamics of neurophysiological activities underlying empathic processes remain poorly understood. Mu rhythms are EEG oscillations with dominant frequencies of 8-13 Hz becoming synchronized when the body is relaxed with eyes open and when the sensorimotor system is in idle, thus, mu rhythm synchrony is expected to be highest in baseline conditions. When the sensorimotor system is activated either by performing or simulating action, mu rhythms become suppressed or desynchronize, thus, should be suppressed while observing video clips of painful injuries if previous research on mirror system activation holds. Twelve undergraduates contributed EEG data and survey responses to empathy and psychopathy scales in addition to watching consecutive video clips of sports injuries. Participants watched a blank, black image on a computer monitor before and after observing a video of consecutive sports injuries incidents. Each video condition lasted five-minutes long. A BIOPAC MP150 recorded EEG signals from sensorimotor and thalamocortical regions related to a complex neural network called the ‘pain matrix’. Physical and social pain are activated in this network to resonate vicarious pain responses to processing empathy. Five EEG single electrode locations were applied to regions measuring sensorimotor electrical activity in microvolts (μV) to monitor mu rhythms. EEG signals were sampled at a rate of 200 Hz. Mu rhythm desynchronization was measured via 8-13 Hz at electrode sites (F3 & F4). Data for each participant’s mu rhythms were analyzed via Fast Fourier Transformation (FFT) and multifractal time series analysis.

Keywords: desynchronization, dynamical systems theory, electroencephalography (EEG), empathy, multifractal time series analysis, mu waveform, neurophysiology, pain simulation, social cognition

Procedia PDF Downloads 283

Authors: Cezarina da Conceição Santinho Maurício, José Duque Vicente

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Established in 1987, the Erasmus Programme is a program for the exchange of higher education students. Its purposes are several. The mobility developed has contributed to the promotion of multiple learning, the internalization the feeling of belonging to a community, and the consolidation of cooperation between entities or universities. It also allows the experience of a European experience, considering multilingualism one of the bases of the European project and vehicle to achieve the union in diversity. The program has progressed and introduced changes Erasmus+ currently offers a wide range of opportunities for higher education, vocational education and training, school education, adult education, youth, and sport. These opportunities are open to students and other stakeholders, such as teachers. Portugal was one of the countries that readily adhered to this program, assuming itself as an instrument of internationalization of polytechnic and university higher education. Students and social work teachers have been involved in this mobility of learning and multicultural interactions. The presence and activation of this program was made possible by Portugal's joining the European Union. This event was reflected in the field of portuguese social work and contributes to its approach to the reality of european social work. Historically, the Portuguese social work has built a close connection with the Latin American world and, in particular, with Brazil. There are several examples that can be identified in the different historical stages. This is the case of the post-revolution period of 1974 and the presence of the reconceptualization movement, the struggle for enrollment in the higher education circuit, the process of winning a bachelor's degree, and postgraduate training (the first doctorates of social work were carried out in Brazilian universities). This influence is also found in the scope of the authors and the theoretical references used. This study examines the participation of graduates and students of social work in the Erasmus program. The following specific goals were outlined: to identify the host countries and universities; to investigate the dimension and type of mobility made, understand the learning and experiences acquired, identify the difficulties felt, capture their perspectives on social work and the contribution of this experience in training. In the methodological field, the option fell on a qualitative methodology, with the application of semi-structured interviews to graduates and students of social work with Erasmus mobility experience. Once the graduates agreed, the interviews were recorded and transcribed, analyzed according to the previously defined analysis categories. The findings emphasize the importance of this experience for students and graduates in informal and formal learning. The authors conclude with recommendations to reinforce this mobility, either at the individual level or as a project built for the group or collective.

Keywords: erasmus programme, graduates and students of social work, participation, social work

Procedia PDF Downloads 149

Authors: Hamed Yaghoubi, Esmaeil Salahi, Fateme Taati

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The effective shear and bulk viscosity, as well as dynamic viscosity, describe the rheological properties of the ceramic body during the liquid phase sintering process. The rheological parameters depend on the physical and thermomechanical characteristics of the material such as relative density, temperature, grain size, and diffusion coefficient and activation energy. The main goal of this research is to acquire a comprehensive understanding of the response of an incompressible viscose ceramic material during liquid phase sintering process such as stress-strain relations, sintering and hydrostatic stress, the prediction of anisotropic shrinkage and heterogeneous densification as a function of sintering time by including the simultaneous influence of gravity field, and frictional force. After raw materials analysis, the standard hard porcelain mixture as a ceramic body was designed and prepared. Three different experimental configurations were designed including midpoint deflection, sinter bending, and free sintering samples. The numerical method for the ceramic specimens during the liquid phase sintering process are implemented in the CREEP user subroutine code in ABAQUS. The numerical-experimental procedure shows the anisotropic behavior, the complete difference in spatial displacement through three directions, the incompressibility for ceramic samples during the sintering process. The anisotropic shrinkage factor has been proposed to investigate the shrinkage anisotropy. It has been shown that the shrinkage along the normal axis of casting sample is about 1.5 times larger than that of casting direction, the gravitational force in pyroplastic deformation intensifies the shrinkage anisotropy more than the free sintering sample. The lowest and greatest equivalent creep strain occurs at the intermediate zone and around the central line of the midpoint distorted sample, respectively. In the sinter bending test sample, the equivalent creep strain approaches to the maximum near the contact area with refractory support. The inhomogeneity in Von-Misses, pressure, and principal stress intensifies the relative density non-uniformity in all samples, except in free sintering one. The symmetrical distribution of stress around the center of free sintering sample, cause to hinder the pyroplastic deformations. Densification results confirmed that the effective bulk viscosity was well-defined with relative density values. The stress analysis confirmed that the sintering stress is more than the hydrostatic stress from start to end of sintering time so, from both theoretically and experimentally point of view, the sintering process occurs completely.

Keywords: anisotropic shrinkage, ceramic material, liquid phase sintering process, rheological properties, numerical-experimental procedure

Procedia PDF Downloads 341

Authors: Eva Masson, Andrea Kübler

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Anxiety disorders (AD) are the most prevalent psychological disorders. However, far from most affected individuals are diagnosed and receive treatment. This gap is probably due to the diagnosis criteria, relying on symptoms (according to the DSM-5 definition) with no objective biomarker. Approach-avoidance conflict tasks are one common approach to simulate such disorders in a lab setting, with most of the paradigms focusing on the relationships between behavior and neurophysiology. Approach-avoidance conflict tasks typically place participants in a situation where they have to make a decision that leads to both positive and negative outcomes, thereby sending conflicting signals that trigger the Behavioral Inhibition System (BIS). Furthermore, behavioral validation of such paradigms adds credibility to the tasks – with overt conflict behavior, it is safer to assume that the task actually induced a conflict. Some of those tasks have linked asymmetrical frontal brain activity to induced conflicts and the BIS. However, there is currently no consensus for the direction of the frontal activation. The authors present here a modified version of the T-Maze paradigm, a motivational conflict desktop task, in which behavior is recorded simultaneously to the recording of high-density EEG (HD-EEG). Methods: In this within-subject design, HD-EEG and behavior of 35 healthy participants was recorded. EEG data was collected with a 128 channels sponge-based system. The motivational conflict desktop task consisted of three blocks of repeated trials. Each block was designed to record a slightly different behavioral pattern, to increase the chances of eliciting conflict. This variety of behavioral patterns was however similar enough to allow comparison of the number of trials categorized as ‘overt conflict’ between the blocks. Results: Overt conflict behavior was exhibited in all blocks, but always for under 10% of the trials, in average, in each block. However, changing the order of the paradigms successfully introduced a ‘reset’ of the conflict process, therefore providing more trials for analysis. As for the EEG correlates, the authors expect a different pattern for trials categorized as conflict, compared to the other ones. More specifically, we expect an elevated alpha frequency power in the left frontal electrodes at around 200ms post-cueing, compared to the right one (relative higher right frontal activity), followed by an inversion around 600ms later. Conclusion: With this comprehensive approach of a psychological mechanism, new evidence would be brought to the frontal asymmetry discussion, and its relationship with the BIS. Furthermore, with the present task focusing on a very particular type of motivational approach-avoidance conflict, it would open the door to further variations of the paradigm to introduce different kinds of conflicts involved in AD. Even though its application as a potential biomarker sounds difficult, because of the individual reliability of both the task and peak frequency in the alpha range, we hope to open the discussion for task robustness for neuromodulation and neurofeedback future applications.

Keywords: anxiety, approach-avoidance conflict, behavioral inhibition system, EEG

Procedia PDF Downloads 39

Authors: Hager Elsheikh

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Context: Pancreatitis is a condition characterized by inflammation in the pancreas, which can lead to serious complications if untreated. Both acute and chronic pancreatitis are associated with immune reactions and fibrosis, which further damage the pancreas. The type 2 immune response, primarily driven by alternative activated macrophages (AAMs), plays a significant role in the development of fibrosis. The IL-4/STAT6 pathway is a crucial signaling pathway for the activation of M2 macrophages. Pancreatic fibrosis is induced by dysregulated inflammatory responses and can result in the autodigestion and necrosis of pancreatic acinar cells. Research Aim: The aim of this study is to investigate the impact of STAT6, a crucial molecule in the IL-4/STAT6 pathway, on the severity and development of fibrosis during acute and chronic pancreatitis. The research also aims to understand the influence of the JAK/STAT6 signaling pathway on the balance between fibrosis and regeneration in the presence of different macrophage populations. Methodology: The research utilizes murine models of acute and chronic pancreatitis induced by cerulean injection. Animal models will be employed to study the effect of STAT6 knockout on disease severity and fibrosis. Isolation of acinar cells and cell culture techniques will be used to assess the impact of different macrophage populations on wound healing and regeneration. Various techniques such as PCR, histology, immunofluorescence, and transcriptomics will be employed to analyze the tissues and cells. Findings: The research aims to provide insights into the mechanisms underlying tissue fibrosis and wound healing during acute and chronic pancreatitis. By investigating the influence of the JAK/STAT6 signaling pathway and different macrophage populations, the study aims to understand their impact on tissue fibrosis, disease severity, and pancreatic regeneration. Theoretical Importance: This research contributes to our understanding of the role of specific signaling pathways, macrophage polarization, and the type 2 immune response in pancreatitis. It provides insights into the molecular mechanisms underlying tissue fibrosis and the potential for targeted therapies. Data Collection and Analysis Procedures: Data will be collected through the use of murine models, isolation and culture of acinar cells, and various experimental techniques such as PCR, histology, immunofluorescence, and transcriptomics. Data will be analyzed using appropriate statistical methods and techniques, and the findings will be interpreted in the context of the research objectives. Conclusion: By investigating the mechanisms of tissue fibrosis and wound healing during acute and chronic pancreatitis, this research aims to enhance our understanding of the disease progression and potential therapeutic targets. The findings have theoretical importance in expanding our knowledge of pancreatic fibrosis and the role of macrophage polarization in the context of the type 2 immune response.

Keywords: immunity in chronic diseases, pancreatitis, macrophages, immune response

Procedia PDF Downloads 34

Authors: Z. Karahaliloğlu, E. Yalçın, M. Demirbilek, E.B. Denkbaş

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Critical-sized bone defects caused by trauma, bone diseases, prosthetic implant revision or tumor excision cannot be repaired by physiological regenerative processes. Current orthopedic applications for critical-sized bone defects are to use autologous bone grafts, bone allografts, or synthetic graft materials. However, these strategies are unable to solve completely the problem, and motivate the development of novel effective biological scaffolds for tissue engineering applications and regenerative medicine applications. In particular, scaffolds combined with a variety of bio-agents as fundamental tools emerge to provide the regeneration of damaged bone tissues due to their ability to promote cell growth and function. In this study, a magnetic silk fibroin (SF) hydrogel scaffold was prepared by electrogelation process of the concentrated Bombxy mori silk fibroin (8 %wt) aqueous solution. For enhancement of osteoblast-like cells (SaOS-2) growth and adhesion, basal fibroblast growth factor (bFGF) were conjugated physically to the HSA-coated magnetic nanoparticles (Fe3O4) and magnetic SF e-gel scaffolds were prepared by incorporation of Fe3O4, HSA (human serum albumin)=Fe3O4 and HSA=Fe3O4-bFGF nanoparticles. HSA=Fe3O4, HSA=Fe3O4-bFGF loaded and bare SF e-gels scaffolds were characterized using scanning electron microscopy (SEM.) For cell studies, human osteoblast-like cell line (SaOS-2) was used and an MTT assay was used to assess the cytotoxicity of magnetic silk fibroin e-gel scaffolds and cell density on these surfaces. For the evaluation osteogenic activation, ALP (alkaline phosphatase), the amount of mineralized calcium, total protein and collagen were studied. Fe3O4 nanoparticles were successfully synthesized and bFGF was conjugated to HSA=Fe3O4 nanoparticles with %97.5 of binding yield which has a particle size of 71.52±2.3 nm. Electron microscopy images of the prepared HSA and bFGF incorporated SF e-gel scaffolds showed a 3D porous morphology. In terms of water uptake results, bFGF conjugated HSA=Fe3O4 nanoparticles has the best water absorbability behavior among all groups. In the in-vitro cell culture studies realized using SaOS-2 cell line, the coating of Fe3O4 nanoparticles surface with a protein enhance the cell viability and HSA coating and bFGF conjugation, the both have an inductive effect in the cell proliferation. One of the markers of bone formation and osteoblast differentiation, according to the ALP activity and total protein results, HSA=Fe3O4-bFGF loaded SF e-gels had significantly enhanced ALP activity. Osteoblast cultured HSA=Fe3O4-bFGF loaded SF e-gels deposited more calcium compared with SF e-gel. The proposed magnetic scaffolds seem to be promising for bone tissue regeneration and used in future work for various applications.

Keywords: basic fibroblast growth factor (bFGF), e-gel, iron oxide nanoparticles, silk fibroin

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

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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

Procedia PDF Downloads 160

Authors: Regis Pochon, Nicolas Stefaniak, Veronique Baltazart, Pamela Gobin

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Anxiety is known to have an impact on working memory. In reasoning or memory tasks, individuals with anxiety tend to show longer response times and poorer performance. Furthermore, there is a memory bias for negative information in anxiety. Given the crucial role of working memory in lexical learning, anxious students may encounter more difficulties in learning to read and spell. Anxiety could even affect an earlier learning, that is the activation of phonological representations, which are decisive for the learning of reading and writing. The aim of this study is to compare the access to phonological representations of beginning readers and writers according to their level of anxiety, using an auditory lexical decision task. Eighty students of 6- to 9-years-old completed the French version of the Revised Children's Manifest Anxiety Scale and were then divided into four anxiety groups according to their total score (Low, Median-Low, Median-High and High). Two set of eighty-one stimuli (words and non-words) have been auditory presented to these students by means of a laptop computer. Stimuli words were selected according to their emotional valence (positive, negative, neutral). Students had to decide as quickly and accurately as possible whether the presented stimulus was a real word or not (lexical decision). Response times and accuracy were recorded automatically on each trial. It was anticipated a) longer response times for the Median-High and High anxiety groups in comparison with the two others groups, b) faster response times for negative-valence words in comparison with positive and neutral-valence words only for the Median-High and High anxiety groups, c) lower response accuracy for Median-High and High anxiety groups in comparison with the two others groups, d) better response accuracy for negative-valence words in comparison with positive and neutral-valence words only for the Median-High and High anxiety groups. Concerning the response times, our results showed no difference between the four groups. Furthermore, inside each group, the average response times was very close regardless the emotional valence. Otherwise, group differences appear when considering the error rates. Median-High and High anxiety groups made significantly more errors in lexical decision than Median-Low and Low groups. Better response accuracy, however, is not found for negative-valence words in comparison with positive and neutral-valence words in the Median-High and High anxiety groups. Thus, these results showed a lower response accuracy for above-median anxiety groups than below-median groups but without specificity for the negative-valence words. This study suggests that anxiety can negatively impact the lexical processing in young students. Although the lexical processing speed seems preserved, the accuracy of this processing may be altered in students with moderate or high level of anxiety. This finding has important implication for the prevention of reading and spelling difficulties. Indeed, during these learnings, if anxiety affects the access to phonological representations, anxious students could be disturbed when they have to match phonological representations with new orthographic representations, because of less efficient lexical representations. This study should be continued in order to precise the impact of anxiety on basic school learning.

Keywords: anxiety, emotional valence, childhood, lexical access

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Authors: E. Steen, B. Dewulf, N. Müller, C. Vandycke, Y. Vandekerckhove

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Introduction: The care for a ST-elevation myocardial infarction (STEMI) patient is time-critical. Reperfusion therapy within 90 minutes of initial medical contact is mandatory in the improvement of the outcome. Primary percutaneous coronary intervention (PCI) without previous fibrinolytic treatment, is the preferred reperfusion strategy in patients with STEMI, provided it can be performed within guideline-mandated times. Aim of the study: During a one year period (January 2013 to December 2013) the files of all consecutive STEMI patients with urgent referral from non-PCI facilities for primary PCI were reviewed. Special attention was given to a subgroup of patients with prior out-of-hospital medical contact generated by the 112-system. In an effort to reduce out-of-hospital system delay to definitive care a change in pre-hospital 112 dispatch strategies is proposed for these time-critical patients. Actual time recordings were compared with travel time simulations for two suggested scenarios. A first scenario (SC1) involves the decision by the on scene ground EMS (GEMS) team to transport the out-of-hospital diagnosed STEMI patient straight forward to a PCI centre bypassing the nearest non-PCI hospital. Another strategy (SC2) explored the potential role of helicopter EMS (HEMS) where the on scene GEMS team requests a PCI-centre based HEMS team for immediate medical transfer to the PCI centre. Methods and Results: 49 (29,1% of all) STEMI patients were referred to our hospital for emergency PCI by a non-PCI facility. 1 file was excluded because of insufficient data collection. Within this analysed group of 48 secondary referrals 21 patients had an out-of-hospital medical contact generated by the 112-system. The other 27 patients presented at the referring emergency department without prior contact with the 112-system. The table below shows the actual time data from first medical contact to definitive care as well as the simulated possible gain of time for both suggested strategies. The PCI-team was always alarmed upon departure from the referring centre excluding further in-hospital delay. Time simulation tools were similar to those used by the 112-dispatch centre. Conclusion: Our data analysis confirms prolonged reperfusion times in case of secondary emergency referrals for STEMI patients even with the use of HEMS. In our setting there was no statistical difference in gain of time between the two suggested strategies, both reducing the secondary referral generated delay with about one hour and by this offering all patients PCI within the guidelines mandated time. However, immediate HEMS activation by the on scene ground EMS team for transport purposes is preferred. This ensures a faster availability of the local GEMS-team for its community. In case these options are not available and the guideline-mandated times for primary PCI are expected to be exceeded, primary fibrinolysis should be considered in a non-PCI centre.

Keywords: STEMI, system delay, HEMS, emergency medicine

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Authors: V. T. Gerov, D. I. Gerova, I. D. Micheva, N. F. Nazifova-Tasinova, M. N. Nikolova, M. G. Pasheva, B. T. Galunska

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Multiple myeloma (MM) is the most frequent plasma cell (PC) dyscrasia that involves the skeleton. Myeloma bone disease (MBD) is characterized by osteolytic bone lesions as a result of increased osteoclasts activity not followed by reactive bone formation due to osteoblasts suppression. Skeletal complications cause significant adverse effects on quality of life and lead to increased morbidity and mortality. Last decade studies revealed the implication of different proteins in osteoclast activation and osteoblast inhibition. The aim of the present study was to determine serum levels of periostin, sRANKL and osteopontin and to evaluate their role as bone markers in MBD. Materials and methods. Thirty-two newly diagnosed MM patients (mean age: 62.2 ± 10.7 years) and 33 healthy controls (mean age: 58.9 ± 7.5 years) were enrolled in the study. According to IMWG criteria 28 patients were with symptomatic MM and 4 with monoclonal gammopathy of undetermined significance (MGUS). In respect to their bone involvement all symptomatic patients were divided into two groups (G): 9 patients with 0-3 osteolytic lesions (G1) and 19 patients with >3 osteolytic lesions and/or pathologic fractures (G2). Blood samples were drawn for routine laboratory analysis and for measurement of periostin, sRANKL and osteopontin serum levels by ELISA kits (Shanghai Sunred Biological Technology, China). Descriptive analysis, Mann-Whitney test for assessment the differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Results. The median serum levels of periostin, sRANKL and osteopontin of ММ patients were significantly higher compared to controls (554.7pg/ml (IQR=424.0-720.6) vs 396.9pg/ml (IQR=308.6-471.9), p=0.0001; 8.9pg/ml (IQR=7.1-10.5) vs 5.6pg/ml (IQR=5.1-6.4, p<0.0001 and 514.0ng/ml (IQR=469.3-754.0) vs 387.0ng/ml (IQR=335.9-441.9), p<0.0001, respectively). for assessment of differences between groups and non-parametric correlation analysis were performed using GraphPad Prism v8.01. Statistical significance was found for all tested bone markers between symptomatic MM patients and controls: G1 vs controls (p<0.03), G2 vs controls (p<0.0001) for periostin; G1 vs controls (p<0.0001), G2 vs controls (p<0.0001) for sRANKL; G1 vs controls (p=0.002), G2 vs controls (p<0.0001) for osteopontin, as well between symptomatic MM patients and MGUS patients: G1 vs MGUS (p<0.003), G2 vs MGUS (p=0.003) for periostin; G1 vs MGUS (p<0.05), G2 vs MGUS (p<0.001) for sRANKL; G1 vs MGUS (p=0.011), G2 vs MGUS (p=0.0001) for osteopontin. No differences were detected between MGUS and controls and between patients in G1 and G2 groups. Spearman correlation analysis revealed moderate positive correlation between periostin and beta-2-microglobulin (r=0.416, p=0.018), percentage bone marrow myeloma PC (r=0.432, p=0.014), and serum total protein (r=0.427, p=0.015). Osteopontin levels were also positively related to beta-2-microglobulin (r=0.540, p=0.0014), percentage bone marrow myeloma PC (r=0.423, p=0.016), and serum total protein (r=0.413, p=0.019). Serum sRANKL was only related to beta-2-microglobulin levels (r=0.398, p=0.024). Conclusion: In the present study, serum levels of periostin, sRANKL and osteopontin in newly diagnosed MM patients were evaluated. They gradually increased from MGUS to more advanced stages of MM reflecting the severity of bone destruction. These results support the idea that some new protein markers could be used in monitoring the MBD as a most severe complication of MM.

Keywords: myeloma bone disease, periostin, sRANKL, osteopontin

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Authors: Sinan Yapici, Hayrettin Eroglu

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The discharge of the aqueous radionuclides wastes used for the diagnoses of diseases and treatments of patients in nuclear medicine can cause fatal health problems when the radionuclides and its stable daughter component mix with underground water. Tl-201, which is one of the radionuclides commonly used in the nuclear medicine, is a toxic substance and is converted to its stable daughter component Hg-201, which is also a poisonous heavy metal: Tl201 → Hg201 + Gamma Ray [135-167 Kev (12%)] + X Ray [69-83 Kev (88%)]; t1/2 = 73,1 h. The purpose of the present work was to remove Tl-201 radionuclides from aqueous solution by biosorption on the solid bio wastes of food and cosmetic industry as bio sorbents of prina from an olive oil plant, rose residue from a rose oil plant and tea residue from a tea plant, and to make a comparison of the biosorption efficiencies. The effects of the biosorption temperature, initial pH of the aqueous solution, bio sorbent dose, particle size and stirring speed on the biosorption yield were investigated in a batch process. It was observed that the biosorption is a rapid process with an equilibrium time less than 10 minutes for all the bio sorbents. The efficiencies were found to be close to each other and measured maximum efficiencies were 93,30 percent for rose residue, 94,1 for prina and 98,4 for tea residue. In a temperature range of 283 and 313 K, the adsorption decreased with increasing temperature almost in a similar way. In a pH range of 2-10, increasing pH enhanced biosorption efficiency up to pH=7 and then the efficiency remained constant in a similar path for all the biosorbents. Increasing stirring speed from 360 to 720 rpm enhanced slightly the biosorption efficiency almost at the same ratio for all bio sorbents. Increasing particle size decreased the efficiency for all biosorbent; however the most negatively effected biosorbent was prina with a decrease in biosorption efficiency from about 84 percent to 40 with an increase in the nominal particle size 0,181 mm to 1,05 while the least effected one, tea residue, went down from about 97 percent to 87,5. The biosorption efficiencies of all the bio sorbents increased with increasing biosorbent dose in the range of 1,5 to 15,0 g/L in a similar manner. The fit of the experimental results to the adsorption isotherms proved that the biosorption process for all the bio sorbents can be represented best by Freundlich model. The kinetic analysis showed that all the processes fit very well to pseudo second order rate model. The thermodynamics calculations gave ∆G values between -8636 J mol-1 and -5378 for tea residue, -5313 and -3343 for rose residue, and -5701 and -3642 for prina with a ∆H values of -39516 J mol-1, -23660 and -26190, and ∆S values of -108.8 J mol-1 K-1, -64,0, -72,0 respectively, showing spontaneous and exothermic character of the processes. An empirical biosorption model in the following form was derived for each biosorbent as function of the parameters and time, taking into account the form of kinetic model, with regression coefficients over 0.9990 where At is biosorbtion efficiency at any time and Ae is the equilibrium efficiency, t is adsorption period as s, ko a constant, pH the initial acidity of biosorption medium, w the stirring speed as s-1, S the biosorbent dose as g L-1, D the particle size as m, and a, b, c, and e are the powers of the parameters, respectively, E a constant containing activation energy and T the temperature as K.

Keywords: radiation, diosorption, thallium, empirical modelling

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Authors: Shahril Anuar Bahari, Mohd Azrie Mohd Kepli, Mohd Ariff Jamaludin, Kamarulzaman Nordin, Mohamad Jani Saad

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Formaldehyde release from wood-based panel composites can be very toxicity and may increase the risk of human health as well as environmental problems. A new bio-composites product without synthetic adhesive or resin is possible to be developed in order to reduce these problems. Apart from formaldehyde release, adhesive is also considered to be expensive, especially in the manufacturing of composite products. Natural bonded composites can be termed as a panel product composed with any type of cellulosic materials without the addition of synthetic resins. It is composed with chemical content activation in the cellulosic materials. Pulp and paper making method (chemical pulping) was used as a general guide in the composites manufacturing. This method will also generally reduce the manufacturing cost and the risk of formaldehyde emission and has potential to be used as an alternative technology in fiber composites industries. In this study, the natural bonded bamboo fiber composite was produced from virgin Malaysian bamboo fiber (Bambusa vulgaris). The bamboo culms were chipped and digested into fiber using this pulping method. The black liquor collected from the pulping process was used as a natural binding agent in the composition. Then the fibers were mixed and blended with black liquor without any resin addition. The amount of black liquor used per composite board was 20%, with approximately 37% solid content. The composites were fabricated using a hot press machine at two different board densities, 850 and 950 kg/m³, with two sets of hot pressing time, 25 and 35 minutes. Samples of the composites from different densities and hot pressing times were tested in flexural strength and internal bonding (IB) for strength performance according to British Standard. Modulus of elasticity (MOE) and modulus of rupture (MOR) was determined in flexural test, while tensile force perpendicular to the surface was recorded in IB test. Results show that the strength performance of the composites with 850 kg/m³ density were significantly higher than 950 kg/m³ density, especially for samples from 25 minutes hot pressing time. Strength performance of composites from 25 minutes hot pressing time were generally greater than 35 minutes. Results show that the maximum mean values of strength performance were recorded from composites with 850 kg/m³ density and 25 minutes pressing time. The maximum mean values for MOE, MOR and IB were 3251.84, 16.88 and 0.27 MPa, respectively. Only MOE result has conformed to high density fiberboard (HDF) standard (2700 MPa) in British Standard for Fiberboard Specification, BS EN 622-5: 2006. Microstructure characteristics of composites can also be related to the strength performance of the composites, in which, the observed fiber damage in composites from 950 kg/m³ density and overheat of black liquor led to the low strength properties, especially in IB test.

Keywords: bamboo fiber, natural bonded, black liquor, mechanical tests, microstructure observations

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Authors: Milu T. Cherian, Sergio C. Chai, Morgan A. Casal, Taosheng Chen

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This study aims to use CINPA1, a recently discovered small-molecule inhibitor of the xenobiotic receptor CAR (constitutive androstane receptor) for understanding the binding modes of CAR and to guide CAR-mediated gene expression profiling studies in human primary hepatocytes. CAR and PXR are xenobiotic sensors that respond to drugs and endobiotics by modulating the expression of metabolic genes that enhance detoxification and elimination. Elevated levels of drug metabolizing enzymes and efflux transporters resulting from CAR activation promote the elimination of chemotherapeutic agents leading to reduced therapeutic effectiveness. Multidrug resistance in tumors after chemotherapy could be associated with errant CAR activity, as shown in the case of neuroblastoma. CAR inhibitors used in combination with existing chemotherapeutics could be utilized to attenuate multidrug resistance and resensitize chemo-resistant cancer cells. CAR and PXR have many overlapping modulating ligands as well as many overlapping target genes which confounded attempts to understand and regulate receptor-specific activity. Through a directed screening approach we previously identified a new CAR inhibitor, CINPA1, which is novel in its ability to inhibit CAR function without activating PXR. The cellular mechanisms by which CINPA1 inhibits CAR function were also extensively examined along with its pharmacokinetic properties. CINPA1 binding was shown to change CAR-coregulator interactions as well as modify CAR recruitment at DNA response elements of regulated genes. CINPA1 was shown to be broken down in the liver to form two, mostly inactive, metabolites. The structure-activity differences of CINPA1 and its metabolites were used to guide computational modeling using the CAR-LBD structure. To rationalize how ligand binding may lead to different CAR pharmacology, an analysis of the docked poses of human CAR bound to CITCO (a CAR activator) vs. CINPA1 or the metabolites was conducted. From our modeling, strong hydrogen bonding of CINPA1 with N165 and H203 in the CAR-LBD was predicted. These residues were validated to be important for CINPA1 binding using single amino-acid CAR mutants in a CAR-mediated functional reporter assay. Also predicted were residues making key hydrophobic interactions with CINPA1 but not the inactive metabolites. Some of these hydrophobic amino acids were also identified and additionally, the differential coregulator interactions of these mutants were determined in mammalian two-hybrid systems. CINPA1 represents an excellent starting point for future optimization into highly relevant probe molecules to study the function of the CAR receptor in normal- and pathophysiology, and possible development of therapeutics (for e.g. use for resensitizing chemoresistant neuroblastoma cells).

Keywords: antagonist, chemoresistance, constitutive androstane receptor (CAR), multi-drug resistance, structure activity relationship (SAR), xenobiotic resistance

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Authors: S. Wiak, L. Szymanski, Z. Kolacinski, G. Raniszewski, L. Pietrzak, Z. Staniszewska

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The term ‘cancer’ is given to a collection of related diseases that may affect any part of the human body. It is a pathological behaviour of cells with the potential to undergo abnormal breakdown in the processes that control cell proliferation, differentiation, and death of particular cells. Although cancer is commonly considered as modern disease, there are beliefs that drastically growing number of new cases can be linked to the extensively prolonged life expectancy and enhanced techniques for cancer diagnosis. Magnetic hyperthermia therapy is a novel approach to cancer treatment, which may greatly contribute to higher efficiency of the therapy. Employing carbon nanotubes as nanocarriers for magnetic particles, it is possible to decrease toxicity and invasiveness of the treatment by surface functionalisation. Despite appearing in recent years, magnetic particle hyperthermia has already become of the highest interest in the scientific and medical environment. The reason why hyperthermia therapy brings so much hope for future treatment of cancer lays in the effect that it produces in malignant cells. Subjecting them to thermal shock results in activation of numerous degradation processes inside and outside the cell. The heating process initiates mechanisms of DNA destruction, protein denaturation and induction of cell apoptosis, which may lead to tumour shrinkage, and in some cases, it may even cause complete disappearance of cancer. The factors which have the major impact on the final efficiency of the treatment include temperatures generated inside the tissues, time of exposure to the heating process, and the character of an individual cancer cell type. The vast majority of cancer cells is characterised by lower pH, persistent hypoxia and lack of nutrients, which can be associated to abnormal microvasculature. Since in healthy tissues we cannot observe presence of these conditions, they should not be seriously affected by elevation of the temperature. The aim of this work is to investigate the influence of iron content in iron filled Carbon Nanotubes on the desired nanoparticles for cancer therapy. In the article, the development and demonstration of the method and the model device for hyperthermic selective destruction of cancer cells are presented. This method was based on the synthesis and functionalization of carbon nanotubes serving as ferromagnetic material nanocontainers. The methodology of the production carbon- ferromagnetic nanocontainers (FNCs) includes the synthesis of carbon nanotubes, chemical, and physical characterization, increasing the content of a ferromagnetic material and biochemical functionalization involving the attachment of the key addresses. The ferromagnetic nanocontainers were synthesised in CVD and microwave plasma system. The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013.

Keywords: hyperthermia, carbon nanotubes, cancer colon cells, radio frequency field

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Authors: Rania S. Hussein

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This research mainly focuses on examining engagement in social media brand communities. Engagement in social media has become a main focus in literature affirming that the role of social media in our daily lives is growing. (Akman and Mishra, 2017;Prado-Gascó et al., 2017). Social media has also become a key medium for brand communication and brand building relationships(Frimpong and McLean,2018;Dimitriu and Guesalaga, 2017). Engagement on social media has become a main focus of many researchers who tried to understand this concept further and draw a link between engagement and various social media activities (Cvijikj and Michahelles;2013), Andre,2015; Wang et al., 2015). According to Felix et al. (2017), the internet and social media have provided better digital resources to improve brand loyalty and customer interactions, thus leading to social media engagement within brand communities. The aim of this research is to highlight the importance of social media and why it is important to maintain engagement within social media. While the term ‘engagement’ is widely used in scholarly literature, there isn’t a common consensus about what the term exactly entails, according to Kidd, (2011). On one hand, it was seen as something that includes factors such as participation, activation, empowerment, devotion, trust, and productivity (Zhang et al, andBenyoucef, M. (2016), ). Other scholars held different viewpoints. For example, Lim et al. (2015) has chosen to break down engagement into three types: operational engagement, emotional engagement, and relational engagement. Chandler and Lusch (2015) further studied engagement as a means to measure commitment to a brand. Fernandes&Remelhe (2016) had a more technical view, measuring engagement through comments, following, subscribing, sharing, enjoying, writing, etc., in the social media context. ustomer engagement has become a research focus for understanding how consumer relationships are developed, retained, and improved within a digital context. Based on previous literature, it is evident that many customer engagement related studies are limited to the interaction between firms and consumers on social media. There is a clear gap in the literature regarding consumer-to-consumer interaction and user-generated content and its significance. While some researchers, such as Alversia et al. (2016), touched upon the importance of customer-based engagement, a gap still remains: there is no consistent and well-tested method for defining the factors that affect consumer interaction. Moreover, few scholarly research papers such as (Case, 2019; Riley, 2020;Habibi, 2014) provided to assist businesses understand their customers' interaction habits as well as the best ways to develop customer loyalty. Additionally, the majority of research on brand pages concentrated on the drivers of Consumer engagement, with just a few studies example, Lamberton, Cc(2016), Poorrezaei, (2016). (Jayasingh, 2019), looking into the implications. This study focuses on understanding the concept of engagement and its importance, specifically engagement within social media brand communities. It examines drivers as well as consequences of engagement, including brand knowledge, brand trust, entertainment, and brand page interactivity. Brand engagement is also expected to affect brand loyalty and word of the mouth.

Keywords: engagement, social media, brand communities, drivers

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Authors: Susan Hall, Gary D. Grant, Catherine McDermott, Devinder Arora

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Introduction /Aim: The kynurenine pathway is thought to play an important role in the pathophysiology of numerous neurodegenerative diseases including depression, Alzheimer’s disease, and Parkinson’s disease. Numerous neuroactive compounds, including the neurotoxic 3-hydroxyanthranilic acid, 3-hydroxykynurenine and quinolinic acid and the neuroprotective kynurenic acid and picolinic acid, are produced through the metabolism of kynurenine and are thought to be the causative agents responsible for neurodegeneration. The toxicity of 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid has been widely evaluated and demonstrated in primary cell cultures but to date only 3-hydroxykynurenine and 3-hydroxyanthranilic acid have been shown to cause toxicity in immortal tumour cells. The aim of this study was to evaluate the toxicity of kynurenine metabolites, both individually and in combination, on SH-SY5Y neuroblastoma cells after 24 and 72 h exposure in order to explore a cost-effective model to study their neurotoxic effects and potential protective agents. Methods: SH-SY5Y neuroblastoma cells were exposed to various concentrations of the neuroactive kynurenine metabolites, both individually and in combination, for 24 and 72 h, and viability was subsequently evaluated using the Resazurin (Alamar blue) proliferation assay. Furthermore, the effects of these compounds, alone and in combination, on specific death pathways including apoptosis, necrosis and free radical production was evaluated using various assays. Results: Consistent with literature, toxicity was shown with short-term 24-hour treatments at 1000 μM concentrations for both 3-hydroxykynurenine and 3-hydroxyanthranilic acid. Combinations of kynurenine metabolites showed modest toxicity towards SH-SY5Y neuroblastoma cells in a concentration-dependent manner. Specific cell death pathways, including apoptosis, necrosis and free radical production were shown to be increased after both 24 and 72 h exposure of SH-SY5Y neuroblastoma cells to 3-hydroxykynurenine and 3-hydroxyanthranilic acid and various combinations of neurotoxic kynurenine metabolites. Conclusion: It is well documented that neurotoxic kynurenine metabolites show toxicity towards primary human neurons in the nanomolar to low micromolar concentration range. Results show that the concentrations required to show significant cell death are in the range of 1000 µM for 3-hydroxykynurenine and 3-hydroxyanthranilic acid and toxicity of quinolinic acid towards SH-SY5Y was unable to be shown. This differs significantly from toxicities observed in primary human neurons. Combinations of the neurotoxic metabolites were shown to have modest toxicity towards these cells with increased toxicity and activation of cell death pathways observed after 72 h exposure. This study suggests that the 24 h model is unsuitable for use in neurotoxicity studies, however, the 72 h model better represents the observations of the studies using primary human neurons and may provide some benefit in providing a cost-effective model to assess possible protective agents against kynurenine metabolite toxicities.

Keywords: kynurenine metabolites, neurotoxicity, quinolinic acid, SH-SY5Y neuroblastoma

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Authors: Shahira M. Ezzat, Marwa I. Ezzat, Mona M. Okba, Esther T. Menze, Ashraf B. Abdel-Naim, Shahnas O. Mohamed

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Background: In order to decrease the burden of the high cost of synthetic drugs, it is important to focus on phytopharmaceuticals. The aim of our study was to search for the mechanism of ginger (Zingiber officinale Roscoe) anti-inflammatory potential and to correlate it to its biophytochemicals. Methods: Various extracts viz. water, 50%, 70%, 80%, and 90% ethanol were prepared from ginger rhizomes. Fractionation of the aqueous extract (AE) was accomplished using Diaion HP-20. In vitro anti-inflammatory activity of the different extracts and isolated compounds was evaluated by protein denaturation inhibition, membrane stabilization, protease inhibition, and anti-lipoxygenase assays. In vivo anti-inflammatory activity of AE was estimated by assessment of rat paw oedema after carrageenan injection. Prostaglandin E2 (PGE2), certain inflammation markers (TNF-α, IL-6, IL-1α, IL-1β, INFr, MCP-1MIP, RANTES, and Nox) levels and MPO activity in the paw edema exudates were measured. Total antioxidant capacity (TAC) was also determined. Histopathological alterations of paw tissues were scored. Results: All the tested extracts showed significant (p < 0.1) anti-inflammatory activities. The highest percentage of heat induced albumin denaturation (66%) was exhibited by the 50% ethanol (250 μg/ml). The 70 and 90% ethanol extracts (500 μg/ml) were more potent as membrane stabilizers (34.5 and 37%, respectively) than diclofenac (33%). The 80 and 90% ethanol extracts (500 μg/ml) showed maximum protease inhibition (56%). The strongest anti-lipoxygenase activity was observed for the AE. It showed more significant lipoxygenase inhibition activity than that of diclofenac (58% and 52%, respectively) at the same concentration (125 μg/ml). Fractionation of AE yielded four main fractions (Fr I-IV) which showed significant in vitro anti-inflammatory. Purification of Fr-III and IV led to the isolation of 6-poradol (G1), 6-shogaol (G2); methyl 6- gingerol (G3), 5-gingerol (G4), 6-gingerol (G5), 8-gingerol (G6), 10-gingerol (G7), and 1-dehydro-6-gingerol (G8). G2 (62.5 ug/ml), G1 (250 ug/ml), and G8 (250 ug/ml) exhibited potent anti-inflammatory activity in all studied assays, while G4 and G5 exhibited moderate activity. In vivo administration of AE ameliorated rat paw oedema in a dose-dependent manner. AE (at 200 mg/kg) showed significant reduction (60%) of PGE2 production. The AE at different doses (at 25-200 mg/kg) showed significant reduction in inflammatory markers except for IL-1α. AE (at 25 mg/kg) is superior to indomethacin in reduction of IL-1β. Treatment of animals with the AE (100, 200 mg/kg) or indomethacin (10 mg/kg) showed significant reduction in TNF-α, IL-6, MCP-1, and RANTES levels, and MPO activity by about (31, 57 and 32% ) (65, 60 and 57%) (27, 41 and 28%) (23, 32 and 23%) (66, 67 and 67%) respectively. AE at 100 and 200 mg/kg was equipotent to indomethacin in reduction of NOₓ level and in increasing the TAC. Histopathological examination revealed very few inflammatory cells infiltration and oedema after administration of AE (200 mg/kg) prior to carrageenan. Conclusion: Ginger anti-inflammatory activity is mediated by inhibiting macrophage and neutrophils activation as well as negatively affecting monocyte and leukocyte migration. Moreover, it produced dose-dependent decrease in pro-inflammatory cytokines and chemokines and replenished the total antioxidant capacity. We strongly recommend future investigations of ginger in the potential signal transduction pathways.

Keywords: anti-lipoxygenase activity, inflammatory markers, 1-dehydro-6-gingerol, 6-shogaol

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Authors: Thauane Silva, Gabrielle do Vale, Andre Ferreira, Marilda Siqueira, Thiago Moreno L. Souza, Milene D. Miranda

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The exposure of A(H1N1)pdm09-infected epithelial cells (HeLa) to HIV-1 viral particles, or its gp120, enhanced interferon-induced transmembrane protein (IFITM3) content, a viral restriction factor (RF), resulting in a decrease in influenza replication. The gp120 binds to CCR5 (R5) or CXCR4 (X4) cell receptors during HIV-1 infection. Then, it is possible that the endogenous ligands of these receptors also modulate the expression of IFITM3 and other cellular factors that restrict influenza virus replication. Thus, the aim of this study is to analyze the role of cellular receptors R5 and X4 in modulating RFs in order to inhibit the replication of the influenza virus. A549 cells were treated with 2x effective dose (ED50) of endogenous R5 or X4 receptor agonists, CCL3 (20 ng/ml), CCL4 (10 ng/ml), CCL5 (10 ng/ml) and CXCL12 (100 ng/mL) or exogenous agonists, gp120 Bal-R5, gp120 IIIB-X4 and its mutants (5 µg/mL). The interferon α (10 ng/mL) and oseltamivir (60 nM) were used as a control. After 24 h post agonists exposure, the cells were infected with virus influenza A(H3N2) at 2 MOI (multiplicity of infection) for 1 h. Then, 24 h post infection, the supernatant was harvested and, the viral titre was evaluated by qRT-PCR. To evaluate IFITM3 and SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 (SAMHD1) protein levels, A549 were exposed to agonists for 24 h, and the monolayer was lysed with Laemmli buffer for western blot (WB) assay or fixed for indirect immunofluorescence (IFI) assay. In addition to this, we analyzed other RFs modulation in A549, after 24 h post agonists exposure by customized RT² Profiler Polymerase Chain Reaction Array. We also performed a functional assay in which SAMHD1-knocked-down, by single-stranded RNA (siRNA), A549 cells were infected with A(H3N2). In addition, the cells were treated with guanosine to assess the regulatory role of dNTPs by SAMHD1. We found that R5 and X4 agonists inhibited influenza replication in 54 ± 9%. We observed a four-fold increase in SAMHD1 transcripts by RFs mRNA quantification panel. After 24 h post agonists exposure, we did not observe an increase in IFITM3 protein levels through WB or IFI assays, but we observed an upregulation up to three-fold in the protein content of SAMHD1, in A549 exposed to agonists. Besides this, influenza replication enhanced in 20% in cell cultures that SAMDH1 was knockdown. Guanosine treatment in cells exposed to R5 ligands further inhibited influenza virus replication, suggesting that the inhibitory mechanism may involve the activation of the SAMHD1 deoxynucleotide triphosphohydrolase activity. Thus, our data show for the first time a direct relationship of SAMHD1 and inhibition of influenza replication, and provides perspectives for new studies on the signaling modulation, through cellular receptors, to induce proteins of great importance in the control of relevant infections for public health.

Keywords: chemokine receptors, gp120, influenza, virus restriction factors

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Authors: Men An Pan, Hong Ren Chen, Chih Heng Shih, Hsing Yuan Yen

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Pingtung County is located in the southernmost region of Taiwan. During the winter season, pollutants due to insufficient dispersion caused by the downwash of the northeast monsoon lead to the poor air quality of the County. Through the implementation of various control methods, including the application of permits of air pollution, fee collection of air pollution, control oil fume of catering sectors, smoke detection of diesel vehicles, regular inspection of locomotives, and subsidies for low-polluting vehicles. Moreover, to further mitigate the air pollution, additional alternative controlling strategies are also carried out, such as construction site control, prohibition of open-air agricultural waste burning, improvement of river dust, and strengthening of road cleaning operations. The combined efforts have significantly reduced air pollutants in the County. However, in order to effectively and promptly monitor the ambient air quality, the County has subsequently deployed micro-sensors, with a total of 400 IoTs (Internet of Things) micro-sensors for PM2.5 and VOC detection and 3 air quality monitoring stations of the Environmental Protection Agency (EPA), covering 33 townships of the County. The covered area has more than 1,300 listed factories and 5 major industrial parks; thus forming an Internet of Things (IoTs) based multi-level air quality monitoring system. The results demonstrate that the IoTs multi-level air quality sensors combined with other strategies such as “sand and gravel dredging area technology monitoring”, “banning open burning”, “intelligent management of construction sites”, “real-time notification of activation response”, “nighthawk early bird plan with micro-sensors”, “unmanned aircraft (UAV) combined with land and air to monitor abnormal emissions”, and “animal husbandry odour detection service” etc. The satisfaction improvement rate of air control, through a 2021 public survey, reached a high percentage of 81%, an increase of 46% as compared to 2018. For the air pollution complaints for the whole year of 2021, the total number was 4213 in contrast to 7088 in 2020, a reduction rate reached almost 41%. Because of the spatial-temporal features of the air quality monitoring IoTs system by the application of microsensors, the system does assist and strengthen the effectiveness of the existing air quality monitoring network of the EPA and can provide real-time control of the air quality. Therefore, the hot spots and potential pollution locations can be timely determined for law enforcement. Hence, remarkable results were obtained for the two years. That is, both reduction of public complaints and better air quality are successfully achieved through the implementation of the present IoTs system for real-time air quality monitoring throughout Pingtung County.

Keywords: IoT, PM, air quality sensor, air pollution, environmental monitoring

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Authors: Siba Soren, Purnendu Parhi

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Today, the world is facing a severe challenge due to depletion of traditional fossil fuels. Scientists across the globe are working for a solution that involves a dramatic shift to practical and environmentally sustainable energy sources. High-capacity energy systems, such as metal-air batteries, fuel cells, are highly desirable to meet the urgent requirement of sustainable energies. Among the fuel cells, Direct methanol fuel cells (DMFCs) are recognized as an ideal power source for mobile applications and have received considerable attention in recent past. In this advanced electrochemical energy conversion technologies, Oxygen Reduction Reaction (ORR) is of utmost importance. However, the poor kinetics of cathodic ORR in DMFCs significantly hampers their possibilities of commercialization. The oxygen is reduced in alkaline medium either through a 4-electron (equation i) or a 2-electron (equation ii) reduction pathway at the cathode ((i) O₂ + 2H₂O + 4e⁻ → 4OH⁻, (ii) O₂ + H₂O + 2e⁻ → OH⁻ + HO₂⁻ ). Due to sluggish ORR kinetics the ability to control the reduction of molecular oxygen electrocatalytically is still limited. The electrocatalytic ORR starts with adsorption of O₂ on the electrode surface followed by O–O bond activation/cleavage and oxide removal. The reaction further involves transfer of 4 electrons and 4 protons. The sluggish kinetics of ORR, on the one hand, demands high loading of precious metal-containing catalysts (e.g., Pt), which unfavorably increases the cost of these electrochemical energy conversion devices. Therefore, synthesis of active electrocatalyst with an increase in ORR performance is need of the hour. In the recent literature, there are many reports on transition metal oxide (TMO) based ORR catalysts for their high activity TMOs are also having drawbacks like low electrical conductivity, which seriously affects the electron transfer process during ORR. It was found that 2D graphene layer is having high electrical conductivity, large surface area, and excellent chemical stability, appeared to be an ultimate choice as support material to enhance the catalytic performance of bare metal oxide. g-C₃N₄ is also another candidate that has been used by the researcher for improving the ORR performance of metal oxides. This material provides more active reaction sites than other N containing carbon materials. Rare earth oxide like CeO₂ is also a good candidate for studying the ORR activity as the metal oxide not only possess unique electronic properties but also possess catalytically active sites. Here we will discuss the ORR performance (in alkaline medium) of N-rGO/C₃N₄ supported nano Cerium Oxides hybrid synthesized by microwave assisted Solvothermal method. These materials exhibit superior electrochemical stability and methanol tolerance capability to that of commercial Pt/C.

Keywords: oxygen reduction reaction, electrocatalyst, cerium oxide, graphene

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Authors: Chih-Rong Shyr, Chi-Ping Huang

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Intravesical BCG is the gold-standard therapy for high risk non-muscle invasive bladder cancer (NMIBC) after TURBT, but if not responsive to BCG, these BCG unresponsive patients face cystectomy that causes morbidity and comes with a morality risk. To provide the bladder sparing options for patients with BCG-unresponsive NMIBC, several new treatments have been developed to salvage the bladders and prevent progression to muscle invasive or metastatic, but however, most approved or developed treatments still fail in a significant proportion of patients without long term success. Thus more treatment options and the combination of different therapeutic modalities are urgently needed to change the outcomes. Xenogeneic rejection has been proposed to a mechanism of action to induce anti-tumor immunity for the treatment of cancers due to the similarities between rejection mechanism to xenoantigens (proteins, glycans and lipids) and anti-tumor immunities to tumor specific antigens (neoantigens, tumor associated carbohydrates and lipids). Xenogeneic urothelial cells (XUC) of porcine origin have been shown to induce anti-tumor immune responses to inhibit bladder tumor progression in mouse bladder cancer models. To further demonstrate the efficacy of the distinct intravesical XUC treatment in NMIBC, and the combined effects with chemotherapy and immune checkpoint inhibitors (ICIs) as a alternate therapeutic option, this study investigated the therapeutic effects and mechanisms of intravesical XUC immunotherapy in an orthotopic mouse immune competent model of NMIBC, generated from a mouse bladder cancer cell line. We found that the tumor progression was inhibited by intravescial XUC treatment and there was a synergy between intravesical XUC with intravesical chemotherapeutic agent, gemcitabine or systemic ICI, anti-PD1 antibody treatment. The cancer cell proliferation was decreased but the cell death was increased by the intravecisal XUC treatment. Most importantly, the mechanisms of action of intravesical XUC immunotherapy were found to be linked to enhanced infiltration of CD4+ and CD8+ T-cell as well as NK cells, but decreased presence of myeloid immunosuppressive cells in XUC treated tumors. The increased stimulation of immune cells of XUC treated mice to xenogeneic urothelial cells and mouse bladder cancer cells in immune cell proliferation and cytokine secretion were observed both as a monotherapy and in combination with intravesical gemcitabine or systemic anti PD-L1 treatment. In sum, we identified the effects of intravesical XUC treatment in monotherapy and combined therapy on tumor progression and its cellular and molecular events related to immune activation to understand the anti-tumoral mechanisms behind intravesical XUC immunotherapy for NMIBC. These results contribute to the understanding of the mechanisms behind successful xenogeneic cell immunotherapy against NMIBC and characterize a novel therapeutic approach with a new xenogeneic cell modality for BCG-unresponsive NMIBC.

Keywords: xenoantigen, neoantigen, rejection, immunity

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Authors: Shaista Suhail

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As cancer populations is increasing sharply, the incidence of oral squamous cell carcinoma (OSCC) has also been expected to increase. Oral carcinogenesis is a highly complex, multistep process which involves accumulation of genetic alterations that lead to the induction of proteins promoting cell growth (encoded by oncogenes), increased enzymatic (telomerase) activity promoting cancer cell proliferation. The global increase in frequency and mortality, as well as the poor prognosis of oral squamous cell carcinoma, has intensified current research efforts in the field of prevention and early detection of this disease. The advances in the understanding of the molecular basis of oral cancer should help in the identification of new markers. The study of the carcinogenic process of the oral cancer, including continued analysis of new genetic alterations, along with their temporal sequencing during initiation, promotion and progression, will allow us to identify new diagnostic and prognostic factors, which will provide a promising basis for the application of more rational and efficient treatments. Telomerase activity has been readily found in most cancer biopsies, in premalignant lesions or germ cells. Activity of telomerase is generally absent in normal tissues. It is known to be induced upon immortalization or malignant transformation of human cells such as in oral cancer cells. Maintenance of telomeres plays an essential role during transformation of precancer to malignant stage. Mammalian telomeres, a specialized nucleoprotein structures are composed of large conctamers of the guanine-rich sequence 5_-TTAGGG-3_. The roles of telomeres in regulating both stability of genome and replicative immortality seem to contribute in essential ways in cancer initiation and progression. It is concluded that activity of telomerase can be used as a biomarker for diagnosis of malignant oral cancer and a target for inactivation in chemotherapy or gene therapy. Its expression will also prove to be an important diagnostic tool as well as a novel target for cancer therapy. The activation of telomerase may be an important step in tumorgenesis which can be controlled by inactivating its activity during chemotherapy. The expression and activity of telomerase are indispensable for cancer development. There are no drugs which can effect extremely to treat oral cancers. There is a general call for new emerging drugs or methods that are highly effective towards cancer treatment, possess low toxicity, and have a minor environment impact. Some novel natural products also offer opportunities for innovation in drug discovery. Natural compounds isolated from medicinal plants, as rich sources of novel anticancer drugs, have been of increasing interest with some enzyme (telomerase) blockage property. The alarming reports of cancer cases increase the awareness amongst the clinicians and researchers pertaining to investigate newer drug with low toxicity.

Keywords: oral carcinoma, telomere, telomerase, blockage

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Authors: Loren S. Bernal., Catalina Castillo, Carel E. Carvajal, José F. Ibla

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Plastic pollution, specifically microplastics, has become a significant issue in aquatic ecosystems worldwide. The large amount of plastic waste carried by water tributaries has resulted in the accumulation of microplastics in water bodies. The polymer aging process caused by environmental influences such as photodegradation and chemical degradation of additives leads to polymer embrittlement and properties change that require degradation or reduction procedures in rivers. However, there is a lack of such procedures for freshwater entities that develop over extended periods. The aim of this study is evaluate the potential of Pleurotus ostreatus a fungus, in reducing lowdensity polyethylene microplastics present in freshwater samples collected from the middle basin of the Magdalena River in Colombia. The study aims to evaluate this process both in vitro and in silico by identifying the growth capacity of Pleurotus ostreatus in the presence of microplastics and identifying the most likely interactions of Pleurotus ostreatus enzymes and their affinity energies. The study follows an engineering development methodology applied on an experimental basis. The in vitro evaluation protocol applied in this study focused on the growth capacity of Pleurotus ostreatus on microplastics using enzymatic inducers. In terms of in silico evaluation, molecular simulations were conducted using the Autodock 1.5.7 program to calculate interaction energies. The molecular dynamics were evaluated by using the myPresto Portal and GROMACS program to calculate radius of gyration and Energies.The results of the study showed that Pleurotus ostreatus has the potential to degrade low-density polyethylene microplastics. The in vitro evaluation revealed the adherence of Pleurotus ostreatus to LDPE using scanning electron microscopy. The best results were obtained with enzymatic inducers as a MnSO4 generating the activation of laccase or manganese peroxidase enzymes in the degradation process. The in silico modelling demonstrated that Pleurotus ostreatus was able to interact with the microplastics present in LDPE, showing affinity energies in molecular docking and molecular dynamics shown a minimum energy and the representative radius of gyration between each enzyme and its substract. The study contributes to the development of bioremediation processes for the removal of microplastics from freshwater sources using the fungus Pleurotus ostreatus. The in silico study provides insights into the affinity energies of Pleurotus ostreatus microplastic degrading enzymes and their interaction with low-density polyethylene. The study demonstrated that Pleurotus ostreatus can interact with LDPE microplastics, making it a good agent for the development of bioremediation processes that aid in the recovery of freshwater sources. The results of the study suggested that bioremediation could be a promising approach to reduce microplastics in freshwater systems.

Keywords: bioremediation, in silico modelling, microplastics, Pleurotus ostreatus

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Authors: Jie Lin, Yiwen Pan, Li Zhang, Zhangyong Xia

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Atherosclerosis is a chronic inflammatory disease characterized by the accumulation of lipids, immune cells, and extracellular matrix in the arterial walls. This pathological process can lead to the formation of plaques that can obstruct blood flow and trigger various cardiovascular diseases such as heart attack and stroke. The underlying molecular mechanisms still remain unclear, although many studies revealed the dysfunction of endothelial cells, recruitment and activation of monocytes and macrophages, and the production of pro-inflammatory cytokines and chemokines in atherosclerosis. This study aimed to identify hub genes involved in the progression of atherosclerosis and to analyze their biological function in silico, thereby enhancing our understanding of the disease’s molecular mechanisms. Through the analysis of microarray data, we examined the gene expression in media and neo-intima from plaques, as well as distant macroscopically intact tissue, across a cohort of 32 hypertensive patients. Initially, 112 differentially expressed genes (DEGs) were identified. Subsequent immune infiltration analysis indicated a predominant presence of 27 immune cell types in the atherosclerosis group, particularly noting an increase in monocytes and macrophages. In the Weighted gene co-expression network analysis (WGCNA), 10 modules with a minimum of 30 genes were defined as key modules, with blue, dark, Oliver green and sky-blue modules being the most significant. These modules corresponded respectively to monocyte, activated B cell, and activated CD4 T cell gene patterns, revealing a strong morphological-genetic correlation. From these three gene patterns (modules morphology), a total of 2509 key genes (Gene Significance >0.2, module membership>0.8) were extracted. Six hub genes (CD36, DPP4, HMOX1, PLA2G7, PLN2, and ACADL) were then identified by intersecting 2509 key genes, 102 DEGs with lipid-related genes from the Genecard database. The bio-functional analysis of six hub genes was estimated by a robust classifier with an area under the curve (AUC) of 0.873 in the ROC plot, indicating excellent efficacy in differentiating between the disease and control group. Moreover, PCA visualization demonstrated clear separation between the groups based on these six hub genes, suggesting their potential utility as classification features in predictive models. Protein-protein interaction (PPI) analysis highlighted DPP4 as the most interconnected gene. Within the constructed key gene-drug network, 462 drugs were predicted, with ursodeoxycholic acid (UDCA) being identified as a potential therapeutic agent for modulating DPP4 expression. In summary, our study identified critical hub genes implicated in the progression of atherosclerosis through comprehensive bioinformatic analyses. These findings not only advance our understanding of the disease but also pave the way for applying similar analytical frameworks and predictive models to other diseases, thereby broadening the potential for clinical applications and therapeutic discoveries.

Keywords: atherosclerosis, hub genes, drug prediction, bioinformatics

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Authors: Nicola Milani, Carla Bellissimo, Davide Pogliana, Davide Panzin, Luca Garlaschelli, Giulia Facchinetti, Claudia Casson, Luca Marazzina, Andrea Sartori, Simone Rivaroli, Jeff Konin

Abstract:

The patient is a 26 year-old male amateur football player from Milan, Italy; (81kg; 185cm; BMI 23.6 kg/m²). He sustained a non-contact anterior cruciate ligament tear to his right knee in June 2021. In September 2021, his right knee ligament was reconstructed using a semitendinosus graft. The injury occurred during a football match on natural grass with typical shoes on a warm day (32 degrees celsius). Playing as a defender he sustained the injury during a change of direction, where the foot was fixated on the grass. He felt pain and was unable to continue playing the match. The surgeon approved his rehabilitation to begin two weeks post-operative. The initial physiotherapist assessment determined performing two training sessions per day within the first three months. In the first three weeks, the pain was 4/10 on Numerical Rating Scale (NRS), no swelling, a range of motion was 0-110°, with difficulty fully extending his knee and minimal quadriceps activation. Crutches were discontinued at four weeks with improved walking. Active exercise, electrostimulator, physical therapy, massages, osteopathy, and passive motion were initiated. At week 6, he completed his first functional movement screen; the score was 16/21 with no pain and no swelling. At week 8, the isokinetic test showed a 23% differential deficit between the two legs in maximum strength (at 90°/s). At week 10, he improved to 15% of injury-induced deficit which suggested he was ready to start running. At week 12, the athlete sustained his first threshold test. At week 16, he performed his first return to sports movement assessment, which revealed a 10% stronger difference between the legs. At week 16, he had his second threshold test. At week 17, his first on-field test revealed a 5% differential deficit between the two legs in the hop test. At week 18, isokinetic test demonstrates that the uninjured leg was 7% stronger than the recovering leg in maximum strength (at 90°/s). At week 20, his second on-field test revealed a 2% difference in hop test; at week 21, his third isokinetic test demonstrated a difference of 5% in maximum strength (at 90°/s). At week 21, he performed his second return to sports movement assessment which revealed a 2% difference between the limbs. Since it was the end of the championship, the team asked him to partake in the playoffs; moreover the player was very motivated to participate in the playoffs also because he was the captain of the team. Together with the player and the team, we decided to let him play even though we were aware of a heightened risk of injury than what is reported in the literature because of two factors: biological recovery times and the results of the tests we performed. In the decision making process about the athlete’s recovery time, it is important to balance the information available from the literature with the desires of the patient to avoid frustration.

Keywords: ACL, football, rehabilitation, return to play

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Authors: Fangfang Wang, Tianjing Wang, Leyi Fu, Feng Yun, Ningning Xie, Jue Zhou, Fan Qu

Abstract:

Background: Ferroptosis, a recently discovered form of programmed cell death characterized by iron-dependent lipid peroxidation, may be linked to polycystic ovary syndrome (PCOS). Diseases marked by iron overload have been correlated with ferroptosis. Coincidently, investigations have revealed anomalies in iron metabolism among women with PCOS; however, there were inconsistencies in the evidence. Objective and Rationale: This review aimed to comprehensively explore the potential relationship between ferroptosis and PCOS by investigating the differences in iron metabolism among women with PCOS in comparison to a control group. Additionally, a narrative synthesis was provided on the past research status regarding the association between PCOS and ferroptosis. Methods: A systematic search of the literature was performed using PubMed, Embase, Web of Science from inception up to December 2022. Search terms relating to assisted PCOS, ferroptosis, and iron metabolism were used. PRISMA guidance was followed. RevMan 5.4 was utilized for conducting the meta-analysis, wherein the investigated outcomes included iron status (ferritin, iron, transferrin saturation) and a systemic iron-regulatory hormone (hepcidin). A narrative synthesis was performed to explore the correlation between PCOS and ferroptosis. Results: In the meta-analysis comprising a total of 16 studies, significant differences in serum ferritin levels between the PCOS group and the control group were observed (15 studies, standardized mean difference (SMD): 0.41, 95% CI: 0.22 to 0.59, P<0.01). This indicates elevated serum ferritin levels in PCOS patients compared to women without PCOS. The transferrin saturation in PCOS patients was significantly higher than that in the control group (3 studies, mean difference (MD): 4.39, 95% CI: 1.67 to 7.11, P<0.01). Regarding serum iron (6 studies, SMD: 0.05, 95% CI: -0.24 to 0.33, P=0.75) and serum hepcidin (4 studies, SMD: -0.44, 95% CI: -1.41 to 0.52, P=0.37), no statistically significant differences were observed between the PCOS group and the control group. Other studies have found that ferroptosis is involved in the occurrence and development of PCOS, offering valuable insights for guiding potential treatment measures and prognosis evaluation of PCOS. In addition, ferroptosis is involved in the miscarriage of PCOS-like rats; thus, controlling ferroptosis might improve pregnancy outcomes in PCOS. Conclusions: The observation of a significant elevation in serum ferritin and transferrin saturation levels in women with PCOS may suggest an underlying disturbance in iron metabolism, potentially inducing the activation of ferroptosis. Further research is imperative to elucidate the underlying pathophysiology, providing insights for potential preventive measures and therapeutic strategies. Limitation: There are some limitations as follows: First, due to limited extractable information, we excluded purely abstract publications and non-English publications. Second, the majority of original articles were case-control studies, making it difficult to determine the causal relationship between iron metabolism abnormalities and the onset of PCOS. Third, there is substantial heterogeneity in the definition of PCOS.

Keywords: polycystic ovary syndrome, ferroptosis, iron metabolism, systematic review and meta-analysis

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