Search results for: implantable biomedical devices

Authors: Reza Nematirad, Anil Pahwa, Balasubramaniam Natarajan

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Time series data consist of successive data points collected over a period of time. Accurate prediction of future values is essential for informed decision-making in several real-world applications, including electricity load demand forecasting, lifetime estimation of industrial machinery, traffic planning, weather prediction, and the stock market. Due to their critical relevance and wide application, there has been considerable interest in time series forecasting in recent years. However, the proliferation of sensors and IoT devices, real-time monitoring systems, and high-frequency trading data introduce significant intricate temporal variations, rapid changes, noise, and non-linearities, making time series forecasting more challenging. Classical methods such as Autoregressive integrated moving average (ARIMA) and Exponential Smoothing aim to extract pre-defined temporal variations, such as trends and seasonality. While these methods are effective for capturing well-defined seasonal patterns and trends, they often struggle with more complex, non-linear patterns present in real-world time series data. In recent years, deep learning has made significant contributions to time series forecasting. Recurrent Neural Networks (RNNs) and their variants, such as Long short-term memory (LSTMs) and Gated Recurrent Units (GRUs), have been widely adopted for modeling sequential data. However, they often suffer from the locality, making it difficult to capture local trends and rapid fluctuations. Convolutional Neural Networks (CNNs), particularly Temporal Convolutional Networks (TCNs), leverage convolutional layers to capture temporal dependencies by applying convolutional filters along the temporal dimension. Despite their advantages, TCNs struggle with capturing relationships between distant time points due to the locality of one-dimensional convolution kernels. Transformers have revolutionized time series forecasting with their powerful attention mechanisms, effectively capturing long-term dependencies and relationships between distant time points. However, the attention mechanism may struggle to discern dependencies directly from scattered time points due to intricate temporal patterns. Lastly, Multi-Layer Perceptrons (MLPs) have also been employed, with models like N-BEATS and LightTS demonstrating success. Despite this, MLPs often face high volatility and computational complexity challenges in long-horizon forecasting. To address intricate temporal variations in time series data, this study introduces Times2D, a novel framework that parallelly integrates 2D spectrogram and derivative heatmap techniques. The spectrogram focuses on the frequency domain, capturing periodicity, while the derivative patterns emphasize the time domain, highlighting sharp fluctuations and turning points. This 2D transformation enables the utilization of powerful computer vision techniques to capture various intricate temporal variations. To evaluate the performance of Times2D, extensive experiments were conducted on standard time series datasets and compared with various state-of-the-art algorithms, including DLinear (2023), TimesNet (2023), Non-stationary Transformer (2022), PatchTST (2023), N-HiTS (2023), Crossformer (2023), MICN (2023), LightTS (2022), FEDformer (2022), FiLM (2022), SCINet (2022a), Autoformer (2021), and Informer (2021) under the same modeling conditions. The initial results demonstrated that Times2D achieves consistent state-of-the-art performance in both short-term and long-term forecasting tasks. Furthermore, the generality of the Times2D framework allows it to be applied to various tasks such as time series imputation, clustering, classification, and anomaly detection, offering potential benefits in any domain that involves sequential data analysis.

Keywords: derivative patterns, spectrogram, time series forecasting, times2D, 2D representation

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Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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Authors: Elizabeth J. Currie, Fernando Ortega Perez

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—‘MEDICINE’ is a new project funded under the EC Horizon 2020 Marie-Sklodowska Curie Actions, to determine concepts of health and healing from a culturally specific indigenous context, using a framework of interdisciplinary methods which integrates archaeological-historical, ethnographic and modern health sciences approaches. The study will generate new theoretical and methodological approaches to model how peoples survive and adapt their traditional belief systems in a context of alien cultural impacts. In the immediate wake of the conquest of Peru by invading Spanish armies and ideology, native Andeans responded by forming the Taki Onkoy millenarian movement, which rejected European philosophical and ontological teachings, claiming “you make us sick”. The study explores how people’s experience of their world and their health beliefs within it, is fundamentally shaped by their inherent beliefs about the nature of being and identity in relation to the wider cosmos. Cultural and health belief systems and related rituals or behaviors sustain a people’s sense of identity, wellbeing and integrity. In the event of dislocation and persecution these may change into devolved forms, which eventually inter-relate with ‘modern’ biomedical systems of health in as yet unidentified ways. The development of new conceptual frameworks that model this process will greatly expand our understanding of how people survive and adapt in response to cultural trauma. It will also demonstrate the continuing role, relevance and use of TM in present-day indigenous communities. Studies will first be made of relevant pre-Colombian material culture, and then of early colonial period ethnohistorical texts which document the health beliefs and ritual practices still employed by indigenous Andean societies at the advent of the 17^th century Jesuit campaigns of persecution - ‘Extirpación de las Idolatrías’. Core beliefs drawn from these baseline studies will then be used to construct a questionnaire about current health beliefs and practices to be taken into the study population of indigenous Quechua peoples in the northern Andean region of Ecuador. Their current systems of knowledge and medicine have evolved within complex historical contexts of both the conquest by invading Inca armies in the late 15^th century, followed a generation later by Spain, into new forms. A new model will be developed of contemporary  Andean concepts of health, illness and healing demonstrating  the way these have changed through time. With this, a ‘policy tool’ will be constructed as a bridhging facility into contemporary global scenarios relevant to other Indigenous, First Nations, and migrant peoples to provide a means through which their traditional health beliefs and current needs may be more appropriately understood and met. This paper presents findings from the first analytical phases of the work based upon the study of the literature and the archaeological records. The study offers a novel perspective and methods in the development policies sensitive to indigenous and minority people’s health needs.

Keywords: Andean ethnomedicine, Andean health beliefs, health beliefs models, traditional medicine

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Authors: Achraf Al Faraj, Asma Sultana Shaik, Baraa Al Sayed

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Specific and effective targeting of drug delivery systems (DDS) to cancerous sites remains a major challenge for a better diagnostic and therapy. Recently, SWCNTs with their unique physicochemical properties and the ability to cross the cell membrane show promising in the biomedical field. The purpose of this study was first to develop a biocompatible iron oxide tagged SWCNTs as diagnostic nanoprobes to allow their noninvasive detection using MRI and their preferential targeting in a breast cancer murine model by placing an optimized flexible magnet over the tumor site. Magnetic targeting was associated to specific antibody-conjugated SWCNTs active targeting. The therapeutic efficacy of doxorubicin-conjugated SWCNTs was assessed, and the superiority of diffusion-weighted (DW-) MRI as sensitive imaging biomarker was investigated. Short Polyvinylpyrrolidone (PVP) stabilized water soluble SWCNTs were first developed, tagged with iron oxide nanoparticles and conjugated with Endoglin/CD105 monoclonal antibodies. They were then conjugated with doxorubicin drugs. SWCNTs conjugates were extensively characterized using TEM, UV-Vis spectrophotometer, dynamic light scattering (DLS) zeta potential analysis and electron spin resonance (ESR) spectroscopy. Their MR relaxivities (i.e. r1 and r2*) were measured at 4.7T and their iron content and metal impurities quantified using ICP-MS. SWCNTs biocompatibility and drug efficacy were then evaluated both in vitro and in vivo using a set of immunological assays. Luciferase enhanced bioluminescence 4T1 mouse mammary tumor cells (4T1-Luc2) were injected into the right inguinal mammary fat pad of Balb/c mice. Tumor bearing mice received either free doxorubicin (DOX) drug or SWCNTs with or without either DOX or iron oxide nanoparticles. A multi-pole 10x10mm high-energy flexible magnet was maintained over the tumor site during 2 hours post-injections and their properties and polarity were optimized to allow enhanced magnetic targeting of SWCNTs toward the primary tumor site. Tumor volume was quantified during the follow-up investigation study using a fast spin echo MRI sequence. In order to detect the homing of SWCNTs to the main tumor site, susceptibility-weighted multi-gradient echo (MGE) sequence was used to generate T2* maps. Apparent diffusion coefficient (ADC) measurements were also performed as a sensitive imaging biomarker providing early and better assessment of disease treatment. At several times post-SWCNT injection, histological analysis were performed on tumor extracts and iron-loaded SWCNT were quantified using ICP-MS in tumor sites, liver, spleen, kidneys, and lung. The optimized multi-poles magnet revealed an enhanced targeting of magnetic SWCNTs to the primary tumor site, which was found to be much higher than the active targeting achieved using antibody-conjugated SWCNTs. Iron-loading allowed their sensitive noninvasive tracking after intravenous administration using MRI. The active targeting of doxorubicin through magnetic antibody-conjugated SWCNTs nanoprobes was found to considerably decrease the primary tumor site and may have inhibited the development of metastasis in the tumor-bearing mice lung. ADC measurements in DW-MRI were found to significantly increase in a time-dependent manner after the injection of DOX-conjugated SWCNTs complexes.

Keywords: single-walled carbon nanotubes, nanomedicine, magnetic resonance imaging, cancer diagnosis and therapy

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

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Polymeric nanoparticles-based drug delivery systems and therapeutics have a great potential in the treatment of a numerous diseases, due to they are characterizing the flexible properties which is giving possibility to modify their structures with a complex definition over their structures, compositions and properties. Important characteristics of the polymeric nanoparticles (PNPs) used as drug carriers are high particle’s stability, high carrier capacity, feasibility of encapsulation of both hydrophilic and hydrophobic drugs, and feasibility of variable routes of administration, including oral application and inhalation; NPs are especially effective for intracellular drug delivery since they penetrate into the cells’ interior though endocytosis. A variety of PNPs based drug delivery systems including charged and neutral, degradable and non-degradable polymers of both natural and synthetic origin have been developed. Among these huge varieties the biodegradable PNPs which can be cleared from the body after the fulfillment of their function could be considered as one of the most promising. For intracellular uptake it is highly desirable to have positively charged PNPs since they can penetrate deep into cell membranes. For long-lasting circulation of PNPs in the body it is important they have so called “stealth coatings” to protect them from the attack of immune system of the organism. One of the effective ways to render the PNPs “invisible” for immune system is their PEGylation which represent the process of pretreatment of polyethylene glycol (PEG) on the surface of PNPs. The present work deals with constructing PNPs from amino acid based biodegradable polymers – regular poly(ester amide) (PEA) composed of sebacic acid, leucine and 1,6-hexandiol (labeled as 8L6), cationic PEA composed of sebacic acid, arginine and 1,6-hexandiol (labeled as 8R6), and comb-like co-PEA composed of sebacic acid, malic acid, leucine and 1,6-hexandiol (labeled as PEG-PEA). The PNPs were fabricated using the polymer deposition/solvent displacement (nanoprecipitation) method. The regular PEA 8L6 form stable negatively charged (zeta-potential within 2-12 mV) PNPs of desired size (within 150-200 nm) in the presence of various surfactants (Tween 20, Tween 80, Brij 010, etc.). Blending the PEAs 8L6 and 8R6 gave the 130-140 nm sized positively charged PNPs having zeta-potential within +20 ÷ +28 mV depending 8L6/8R6 ratio. The PEGylating PEA PEG-PEA was synthesized by interaction of epoxy-co-PEA [8L6]0,5-[tES-L6]0,5 with mPEG-amine-2000 The stable and positively charged PNPs were fabricated using pure PEG-PEA as a surfactant. A firm anchoring of the PEG-PEA with 8L6/8R6 based PNPs (owing to a high afinity of the backbones of all three PEAs) provided good stabilization of the NPs. In vitro biocompatibility study of the new PNPs with four different stable cell lines: A549 (human), U-937 (human), RAW264.7 (murine), Hepa 1-6 (murine) showed they are biocompatible. Considering high stability and cell compatibility of the elaborated PNPs one can conclude that they are promising for subsequent therapeutic applications. This work was supported by the joint grant from the Science and Technology Center in Ukraine and Shota Rustaveli National Science Foundation of Georgia #6298 “New biodegradable cationic polymers composed of arginine and spermine-versatile biomaterials for various biomedical applications”.

Keywords: biodegradable poly(ester amide)s, cationic poly(ester amide), pegylating poly(ester amide), nanoparticles

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Authors: Farideh Namvar, Rosfarizan Mohamed

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In the field of nanotechnology, the use of various biological units instead of toxic chemicals for the reduction and stabilization of nanoparticles, has received extensive attention. This use of biological entities to create nanoparticles has designated as “Green” synthesis and it is considered to be far more beneficial due to being economical, eco-friendly and applicable for large-scale synthesis as it operates on low pressure, less input of energy and low temperatures. The lack of toxic byproducts and consequent decrease in degradation of the product renders this technique more preferable over physical and classical chemical methods. The variety of biomass having reduction properties to produce nanoparticles makes them an ideal candidate for fabrication. Metal oxide nanoparticles have been said to represent a "fundamental cornerstone of nanoscience and nanotechnology" due to their variety of properties and potential applications. However, this also provides evidence of the fact that metal oxides include many diverse types of nanoparticles with large differences in chemical composition and behaviour. In this study, iron oxide nanoparticles (Fe3O4-NPs) were synthesized using a rapid, single step and completely green biosynthetic method by reduction of ferric chloride solution with brown seaweed (Sargassum muticum) water extract containing polysaccharides as a main factor which acts as reducing agent and efficient stabilizer. Antimicrobial activity against six microorganisms was tested using well diffusion method. The resulting S-IONPs are crystalline in nature, with a cubic shape. The average particle diameter, as determined by TEM, was found to be 18.01 nm. The S-IONPs were efficiently inhibited the growth of Listeria monocytogenes, Escherichia coli and Candida species. Our favorable results suggest that S-IONPs could be a promising candidate for development of future antimicrobial therapies. The nature of biosynthesis and the therapeutic potential by S-IONPs could pave the way for further research on design of green synthesis therapeutic agents, particularly nanomedicine, to deal with treatment of infections. Further studies are needed to fully characterize the toxicity and the mechanisms involved with the antimicrobial activity of these particles. Antioxidant activity of S-IONPs synthesized by green method was measured by ABTS (2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (IC50= 1000µg) radical scavenging activity. Also, with the increasing concentration of S-IONPs, catalase gene expression compared to control gene GAPDH increased. For anti-angiogenesis study the Ross fertilized eggs were divided into four groups; the control and three experimental groups. The gelatin sponges containing albumin were placed on the chorioalantoic membrane and soaked with different concentrations of S-IONPs. All the cases were photographed using a photo stereomicroscope. The number and the lengths of the vessels were measured using Image J software. The crown rump (CR) and weight of the embryo were also recorded. According to the data analysis, the number and length of the blood vessels, as well as the CR and weight of the embryos reduced significantly compared to the control (p < 0.05), dose dependently. The total hemoglobin was quantified as an indicator of the blood vessel formation, and in the treated samples decreased, which showed its inhibitory effect on angiogenesis.

Keywords: anti-angiogenesis, antimicrobial, antioxidant, biosynthesis, iron oxide (fe3o4) nanoparticles, sargassum muticum, seaweed

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Authors: M. C. O. Ezeibe, F. I. O. Ezeibe

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Reasons viral diseases (including AI, HIV/AIDS, and COVID-19), tumors (including Cancers and Prostrate enlargement), and antimicrobial-resistant infections (AMR) are difficult to cure are features of the pathogens which normal cells do not have or need (biomedical markers) have not been identified; medicines that can counter the markers have not been invented; strategies and mechanisms for their treatments have not been developed. When cells become abnormal, they acquire negative electrical charges, and viruses are either positively charged or negatively charged, while normal cells remain neutral (without electrical charges). So, opposite charges' electrostatic attraction is a treatment mechanism for viral diseases and tumors. Medicines that have positive electrical charges would mop abnormal (infected and tumor) cells and DNA viruses (negatively charged), while negatively charged medicines would mop RNA viruses (positively charged). Molecules of Aluminum-magnesium silicate [AMS: Al₂Mg₃ (SiO₄)₃], an approved medicine and pharmaceutical stabilizing agent, consist of nanoparticles which have both positive electrically charged ends and negative electrically charged ends. The very small size (0.96 nm) of the nanoparticles allows them to reach all cells in every organ. By stabilizing antimicrobials, AMS reduces the rate at which the body metabolizes them so that they remain at high concentrations for extended periods. When drugs remain at high concentrations for longer periods, their efficacies improve. Again, nanoparticles enhance the delivery of medicines to effect targets. Both remaining at high concentrations for longer periods and better delivery to effect targets improve efficacy and make lower doses achieve desired effects so that side effects of medicines are reduced to allow the immunity of patients to be enhanced. Silicates also enhance the immune responses of treated patients. Improving antimicrobial efficacies and enhancing patients` immunity terminate infections so that none remains that could develop resistance. Some countries do not have natural deposits of AMS, but they may have Aluminum silicate (AS: Al₄ (SiO₄)₃) and Magnesium silicate (MS: Mg₂SiO₄), which are also approved medicines. So, AS and MS were used to formulate an AMS-brand, named Medicinal synthetic AMS {Al₄ (SiO₄)₃ + 3Mg₂SiO₄ → 2Al₂Mg₃ (SiO₄)₃}. To overcome the challenge of AMS, AS, and MS being un-absorbable, Dextrose monohydrate is incorporated in MSAMS-formulations for the simple sugar to convey the electrically charged nanoparticles into blood circulation by the principle of active transport so that MSAMS-antimicrobial formulations function systemically. In vitro, MSAMS reduced (P≤0.05) titers of viruses, including Avian influenza virus and HIV. When used to treat virus-infected animals, it cured Newcastle disease and Infectious bursa disease of chickens, Parvovirus disease of dogs, and Peste des petits ruminants disease of sheep and goats. A number of HIV/AIDS patients treated with it have been reported to become HIV-negative (antibody and antigen). COVID-19 patients are also reported to recover and test virus negative when treated with MSAMS. PSA titers of prostate cancer/enlargement patients normalize (≤4) following treatment with MSAMS. MSAMS has also potentiated ampicillin trihydrate, sulfadimidin, cotrimoxazole, piparazine citrate and chloroquine phosphate to achieve ≥ 95 % infection-load reductions (AMR-prevention). At 75 % of doses of ampicillin, cotrimoxazole, and streptomycin, supporting MSAMS-formulations' treatments with antioxidants led to the termination of even already resistant infections.

Keywords: electrical charges, viruses, abnormal cells, aluminum-magnesium silicate

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