Search results for: chimeric drug delivery vehicles

Authors: M. Moharami Gargari, S. Javdani Zamani, A. Mohammadnejad, S. Abuali

Abstract:

As maritime container transport is developing fast, the need arises for efficient operations at container terminals. One of the most important determinants of container handling efficiency is the productivity of quay cranes and internal transportation vehicles, which are responsible transporting of containers for unloading and loading operations for container vessels. For this reason, this paper presents an integrated mathematical model formulation for discrete berths with quay cranes and internal transportations vehicles. The problems have received increasing attention in the literature and the present paper deals with the integration of these interrelated problems. A new mixed integer linear formulation is developed for the Berth Allocation Problem (BAP), Quay Crane Assignment and Scheduling Problem (QCASP) and Internal Transportation Scheduling (ITS), which accounts for cranes and trucks positioning conditions.

Keywords: discrete berths, container terminal, truck scheduling, dynamic vessel arrival

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Authors: Sean Hall

Abstract:

Prior to COVID-19, the world was preoccupied with opioids, effectiveness versus risk, and specifically toxicity versus abuse. Historically underpinning opioid use was a concept of safety. As use over time and real-world data evolved, a pursuit for efficacy associated with non-opioid alternatives became mainstream. On January 8, 2021, the US signed back into the opioid problem, with these two fundamental questions still unresolved. The author will share the current progression of a lead non-opioid cancer bone pain candidate, NanaBis™. NanaBis™ represents two innovative factors: The active ingredients are from cannabinoids; these ingredients are in a proprietary sub-micron delivery platform, NanoCelle®. The author will offer an opinion piece, potentiating the future role of delivery platforms in medicine to increase both patient safety and compliance.

Keywords: NanaBis, nanoCelle, opioids, toxicity

Procedia PDF Downloads 76

Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon

Abstract:

The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.

Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling

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Authors: Vijayakameswara Rao Neralla, Jueun Jeon, Jae Hyung Park

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To develop a potential nanocarrier for diagnosis and treatment of rheumatoid arthritis (RA), we prepared a hyaluronic acid (HA)-5β-cholanic acid (CA) conjugate with an acid-labile ketal linker. This conjugate could self-assemble in aqueous conditions to produce pH-responsive HA-CA nanoparticles as potential carriers of the anti-inflammatory drug methotrexate (MTX). MTX was rapidly released from nanoparticles under inflamed synovial tissue in RA. In vitro cytotoxicity data showed that pH-responsive HA-CA nanoparticles were non-toxic to RAW 264.7 cells. In vivo biodistribution results confirmed that, after their systemic administration, pH-responsive HA-CA nanoparticles selectively accumulated in the inflamed joints of collagen-induced arthritis mice. These results indicate that pH-responsive HA-CA nanoparticles represent a promising candidate as a drug carrier for RA therapy.

Keywords: rheumatoid arthritis, hyaluronic acid, nanocarrier, self-assembly, MTX

Procedia PDF Downloads 277

Authors: Shashi Sharma, V. K. Katiyar, Uaday Singh

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The ability to manipulate magnetic particles in fluid flows by means of inhomogeneous magnetic fields is used in a wide range of biomedical applications including magnetic drug targeting (MDT). In MDT, magnetic carrier particles bounded with drug molecules are injected into the vascular system up-stream from the malignant tissue and attracted or retained at the specific region in the body with the help of an external magnetic field. Although the concept of MDT has been around for many years, however, wide spread acceptance of the technique is still looming despite the fact that it has shown some promise in both in vivo and clinical studies. This is because traditional MDT has some inherent limitations. Typically, the magnetic force is not very strong and it is also very short ranged. Since the magnetic force must overcome rather large hydrodynamic forces in the body, MDT applications have been limited to sites located close to the surface of the skin. Even in this most favorable situation, studies have shown that it is difficult to collect appreciable amounts of the MDCPs at the target site. To overcome these limitations of the traditional MDT approach, Ritter and co-workers reported the implant assisted magnetic drug targeting (IA-MDT). In IA-MDT, the magnetic implants are placed strategically at the target site to greatly and locally increase the magnetic force on MDCPs and help to attract and retain the MDCPs at the targeted region. In the present work, we develop a mathematical model to study the capturing of magnetic nanoparticles flowing in a fluid in an implant assisted cylindrical channel under the magnetic field. A coil of ferromagnetic SS 430 has been implanted inside the cylindrical channel to enhance the capturing of magnetic nanoparticles under the magnetic field. The dominant magnetic and drag forces, which significantly affect the capturing of nanoparticles, are incorporated in the model. It is observed through model results that capture efficiency increases from 23 to 51 % as we increase the magnetic field from 0.1 to 0.5 T, respectively. The increase in capture efficiency by increase in magnetic field is because as the magnetic field increases, the magnetization force, which is attractive in nature and responsible to attract or capture the magnetic particles, increases and results the capturing of large number of magnetic particles due to high strength of attractive magnetic force.

Keywords: capture efficiency, implant assisted-magnetic drug targeting (IA-MDT), magnetic nanoparticles, modelling

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Authors: Mehrnaz Mostafavi

Abstract:

Nanoliposomes, minute lipid-based vesicles at the nano-scale, show promise in the realm of photothermal therapy (PTT). This study presents an extensive overview of nanoliposomes in PTT, exploring their distinct attributes and the significant progress in this therapeutic methodology. The research delves into the fundamental traits of nanoliposomes, emphasizing their adaptability, compatibility with biological systems, and their capacity to encapsulate diverse therapeutic substances. Specifically, it examines the integration of light-absorbing materials, like gold nanoparticles or organic dyes, into nanoliposomal formulations, enabling their efficacy as proficient agents for photothermal treatment Additionally, this paper elucidates the mechanisms involved in nanoliposome-mediated PTT, highlighting their capability to convert light energy into localized heat, facilitating the precise targeting of diseased cells or tissues. This precise regulation of light absorption and heat generation by nanoliposomes presents a non-invasive and precisely focused therapeutic approach, particularly in conditions like cancer. The study explores advancements in nanoliposomal formulations aimed at optimizing PTT outcomes. These advancements include strategies for improved stability, enhanced drug loading, and the targeted delivery of therapeutic agents to specific cells or tissues. Furthermore, the paper discusses multifunctional nanoliposomal systems, integrating imaging components or targeting elements for real-time monitoring and improved accuracy in PTT. Moreover, the review highlights recent preclinical and clinical trials showcasing the effectiveness and safety of nanoliposome-based PTT across various disease models. It also addresses challenges in clinical implementation, such as scalability, regulatory considerations, and long-term safety assessments. In conclusion, this paper underscores the substantial potential of nanoliposomes in advancing PTT as a promising therapeutic approach. Their distinctive characteristics, combined with their precise ability to convert light into heat, offer a tailored and efficient method for treating targeted diseases. The encouraging outcomes from preclinical studies pave the way for further exploration and potential clinical applications of nanoliposome-based PTT.

Keywords: nanoliposomes, photothermal therapy, light absorption, heat conversion, therapeutic agents, targeted delivery, cancer therapy

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Authors: Huafeng Wei

Abstract:

Dementia in Alzheimer’s Disease (AD) is the number one cause of dementia internationally, without effective treatments. Increasing evidence suggest that disruption of intracellular calcium homeostasis, primarily pathological elevation of cytosol and mitochondria but reduction of endoplasmic reticulum (ER) calcium concentrations, play critical upstream roles on multiple pathologies and associated neurodegeneration, impaired neurogenesis, synapse, and cognitive dysfunction in various AD preclinical studies. The last federal drug agency (FDA) approved drug for AD dementia treatment, memantine, exert its therapeutic effects by ameliorating N-methyl-D-aspartate (NMDA) glutamate receptor overactivation and subsequent calcium dysregulation. More research works are needed to develop other drugs targeting calcium dysregulation at multiple pharmacological acting sites for future effective AD dementia treatment. Particularly, calcium channel blockers for the treatment of hypertension and dantrolene for the treatment of muscle spasm and malignant hyperthermia can be repurposed for this purpose. In our own research work, intranasal administration of dantrolene significantly increased its brain concentrations and durations, rendering it a more effective therapeutic drug with less side effects for chronic AD dementia treatment. This review summarizesthe progress of various studies repurposing drugs targeting calcium dysregulation for future effective AD dementia treatment as potentially disease-modifying drugs.

Keywords: alzheimer, calcium, cognitive dysfunction, dementia, neurodegeneration, neurogenesis

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Authors: Loredana Elena Nita, Maria Bercea, Aurica P. Chiriac, Iordana Neamtu

Abstract:

The paper is devoted to the behavior of gels based on poly(itaconic anhydride-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) copolymers, with different ratio between the comonomers, and hyaluronic acid (HA). The gel formation was investigated by small-amplitude oscillatory shear measurements following the viscoelastic behavior as a function of gel composition, temperature and shear conditions. Hyaluronic acid was investigated in the same conditions and its rheological behavior is typical to viscous fluids. In the case of the copolymers, the ratio between the two comonomers influences the viscoelastic behavior, a higher content of itaconic anhydride favoring the gel formation. Also, the sol-gel transition was evaluated according to Winter-Chambon criterion that identifies the gelation point when the viscoelastic moduli (G’ and G”) behave similarly as a function of oscillation frequency. From rheological measurements, an optimum composition was evidenced for which the system presents a typical gel-like behavior at 37 °C: the elastic modulus is higher than the viscous modulus and they are not dependent on the oscillation frequency. The formation of the 3D macroporous network was also evidenced by FTIR spectra, SEM microscopy and chemical imaging. These hydrogels present a high potential as drug delivery systems.

Keywords: copolymer, viscoelasticity, gelation, 3D network

Procedia PDF Downloads 273

Authors: Reza Bahboodian

Abstract:

One of the most important factors in the use of construction machinery is the fuel consumption cost of this equipment. The use of diesel engines in off-road vehicles is an important source of nitrogen oxides and particulate matter. Emissions of nitrogen oxides and particulate matter 10 in off-road vehicles (construction and mining) may be high. Due to the high cost of fuel, it is necessary to minimize fuel consumption. Factors affecting the fuel consumption of these cars are very diverse. Climate changes such as changes in pressure, temperature, humidity, fuel type selection, type of gearbox used in the car are effective in fuel consumption and pollution, and engine efficiency. In this paper, methods for reducing fuel consumption and pollutants by considering valid European and European standards are examined based on new methods such as hybridization, optimal gear change, adding hydrogen to diesel fuel, determining optimal working fluids, and using oxidation catalysts.

Keywords: improve fuel consumption, construction machinery, pollutant reduction, determining the optimal working cycle

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Authors: Ramalan Musa Yerima

Abstract:

The paper titled “loading by number” explained a strategy developed recently by Zonal Commanding Officer of the Federal Road Safety Corps of Nigeria, covering Sokoto, Kebbi and Zamfara States of Northern Nigeria. The strategy is aimed at reducing competition, which will invariably leads to the reduction in speed, reduction in dangerous driving, reduction in crash rate, reduction in injuries, reduction in property damages and reduction in death through road traffic crashes (RTC). This research paper presents a study focused on enhancing the safety of commercial vehicles. The background of this study highlights the alarming statistics related to commercial vehicle crashes in Nigeria with focus on Sokoto, Kebbi and Zamfara States, which often result in significant damage to property, loss of lives, and economic costs. The significance and aims is to investigate and propose effective strategy to enhance the safety of commercial vehicles. The study recognizes the pressing need for heightened safety measures in commercial transportation, as it impacts not only the well-being of drivers and passengers but also the overall public safety. To achieve the objectives, an examination of accident data, including causes and contributing factors, was performed to identify critical areas for improvement. The major finding of the study reveals that when competition comes into play within the realm of commercial driving, it has detrimental effects on road safety and resource management. Commercial drivers are pushed to complete their routes quickly, deliver goods on time or they pushed themselves to arrive quickly for more passengers and new contracts. This competitive environment, fuelled by internal and external pressures such as tight deadlines, poverty and greed, often leads to sad endings. The study recommend that if a strategy called loading by number is integrated with other multiple safety measures such as driver training programs, regulatory enforcement, and infrastructure improvements, commercial vehicle safety can be significantly enhanced. "Loading by Number” approach is design to ensure that the sequence of departure of drivers from motor park ‘A’ would be communicated to motor park officials of park ‘B’, which would be considered sequentially when giving them returning passengers, regardless of the first to arrive. In conclusion, this paper underscores the significance of improving the safety measures of commercial vehicles, as they are often larger and heavier than other vehicles on the road. Whenever they are involved in accidents, the consequences can be more severe. Commercial vehicles are also frequently involved in long-haul or interstate transportation, which means they cover longer distances and spend more time on the road. This increased exposure to driving conditions increases the probability of accidents occurring. By implementing the suggested measures, policymakers, transportation authorities, and industry stakeholders can work collectively towards ensuring a safer commercial transportation system.

Keywords: commercial, safety, strategy, transportation

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Authors: Huayang Yu, Nicola Ingram, David C. Green, Paul D. Thornton

Abstract:

The dual stimuli-controlled release of doxorubicin from gel-embedded nanoparticles is reported. Non-cytotoxic polymer nanoparticles are formed from poly(ethylene glycol)-b-poly(benzyl glutamate) that, uniquely, contain a central ester link. This connection renders the nanoparticles pH-responsive, enabling extensive doxorubicin release in acidic solutions (pH 6.5), but not in solutions of physiological pH (pH 7.4). Doxorubicin loaded nanoparticles were found to be stable for at least 31 days and lethal against the three breast cancer cell lines tested. Furthermore, doxorubicin-loaded nanoparticles could be incorporated within a thermoresponsive poly(2-hydroxypropyl methacrylate) gel depot, which forms immediately upon injection of poly(2-hydroxypropyl methacrylate) into aqueous solution. The combination of the poly(2-hydroxypropyl methacrylate) gel and poly(ethylene glycol)-b-poly(benzyl glutamate) nanoparticles yields an injectable doxorubicin delivery system that facilities near-complete drug release when maintained at elevated temperatures (37 °C) in acidic solution (pH 6.5). In contrast, negligible payload release occurs when the material is stored at room temperature in a non-acidic solution (pH 7.4). The system has great potential as a vehicle for the prolonged, site-specific release of chemotherapeutics.

Keywords: biodegradable, nanoparticle, polymer, thermoresponsive

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

Abstract:

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

Keywords: artery, drug, nanoparticles, navigation

Procedia PDF Downloads 98

Authors: Ramalan Musa Yerima

Abstract:

The paper titled “Loading by number” explained a strategy developed recently by the Zonal Commanding Officer of the Federal Road Safety Corps of Nigeria, covering Sokoto, Kebbi and Zamfara States of Northern Nigeria. The strategy is aimed at reducing competition, which will invariably lead to a reduction in speed, reduction in dangerous driving, reduction in crash rate, reduction in injuries, reduction in property damages and reduction in death through road traffic crashes (RTC). This research paper presents a study focused on enhancing the safety of commercial vehicles. The background of this study highlights the alarming statistics related to commercial vehicle crashes in Nigeria with a focus on Sokoto, Kebbi and Zamfara States, which often result in significant damage to property, loss of lives, and economic costs. The significance and aims is to investigate and propose an effective strategy to enhance the safety of commercial vehicles. The study recognizes the pressing need for heightened safety measures in commercial transportation, as it impacts not only the well-being of drivers and passengers but also the overall public safety. To achieve the objectives, an examination of accident data, including causes and contributing factors, was performed to identify critical areas for improvement. The major finding of the study reveals that when competition comes into play within the realm of commercial driving, it has detrimental effects on road safety and resource management. Commercial drivers are pushed to complete their routes quickly and deliver goods on time, or they push themselves to arrive quickly for more passengers and new contracts. This competitive environment, fuelled by internal and external pressures such as tight deadlines, poverty and greed, often leads to sad endings. The study recommends that if a strategy called loading by number is integrated with other multiple safety measures, such as driver training programs, regulatory enforcement, and infrastructure improvements, commercial vehicle safety can be significantly enhanced. "Loading by Number” approach is designed to ensure that the sequence of departure of drivers from the motor park ‘A’ would be communicated to motor park officials of park ‘B’, which would be considered sequentially when giving them returning passengers, regardless of the first to arrive. In conclusion, this paper underscores the significance of improving the safety measures of commercial vehicles, as they are often larger and heavier than other vehicles on the road. Whenever they are involved in accidents, the consequences can be more severe. Commercial vehicles are also frequently involved in long-haul or interstate transportation, which means they cover longer distances and spend more time on the road. This increased exposure to driving conditions increases the probability of accidents occurring. By implementing the suggested measures, policymakers, transportation authorities, and industry stakeholders can work collectively toward ensuring a safer commercial transportation system.

Keywords: commercial, safety, strategy, transport

Procedia PDF Downloads 47

Authors: Gail Louw, Helena Boshoff, Taeksun Song, Clifton Barry

Abstract:

Drug resistance in Mycobacterium tuberculosis is primarily attributed to mutations in target genes. These mutations incur a fitness cost and result in bacterial generations that are less fit, which subsequently acquire compensatory mutations to restore fitness. We hypothesize that mutations in specific drug target genes influence bacterial metabolism and cellular function, which affects its ability to develop subsequent resistance to additional agents. We aim to determine whether the sequential acquisition of drug resistance and specific mutations in a well-defined clinical M. tuberculosis strain promotes or limits the development of additional resistance. In vitro mutants resistant to pretomanid, linezolid, moxifloxacin, rifampicin and kanamycin were generated from a pan-susceptible clinical strain from the Beijing lineage. The resistant phenotypes to the anti-TB agents were confirmed by the broth microdilution assay and genetic mutations were identified by targeted gene sequencing. Growth of mono-resistant mutants was done in enriched medium for 14 days to assess in vitro fitness. Double resistant mutants were generated against anti-TB drug combinations at concentrations 5x and 10x the minimum inhibitory concentration. Subsequently, mutation frequencies for these anti-TB drugs in the different mono-resistant backgrounds were determined. The initial level of resistance and the mutation frequencies observed for the mono-resistant mutants were comparable to those previously reported. Targeted gene sequencing revealed the presence of known and clinically relevant mutations in the mutants resistant to linezolid, rifampicin, kanamycin and moxifloxacin. Significant growth defects were observed for mutants grown under in vitro conditions compared to the sensitive progenitor. Mutation frequencies determination in the mono-resistant mutants revealed a significant increase in mutation frequency against rifampicin and kanamycin, but a significant decrease in mutation frequency against linezolid and sutezolid. This suggests that these mono-resistant mutants are more prone to develop resistance to rifampicin and kanamycin, but less prone to develop resistance against linezolid and sutezolid. Even though kanamycin and linezolid both inhibit protein synthesis, these compounds target different subunits of the ribosome, thereby leading to different outcomes in terms of fitness in the mutants with impaired cellular function. These observations showed that oxazolidinone treatment is instrumental in limiting the development of multi-drug resistance in M. tuberculosis in vitro.

Keywords: oxazolidinones, mutations, resistance, tuberculosis

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Authors: Bhumika Wadhwa, Fayaz Malik

Abstract:

The serine/threonine protein kinase B (PKB) also known as Akt, is one of the multifaceted kinase in human kinome, existing in three isoforms. Akt plays a vital role in phosphoinositide 3-kinase (PI3K) mediated oncogenesis in various malignancies and is one of the attractive targets for cancer drug discovery. The functional significance of an individual isoform of Akt is not redundant in cancer cell proliferation and metastasis instead Akt isoforms play distinct roles during metastasis; thereby regulating EMT. This study aims to determine isoform specific functions of Akt in cancer. The results obtained suggest that Akt1 restrict tumor invasion, whereas Akt2 promotes cell migration and invasion by various techniques like MTT, wound healing and invasion assay. Similarly, qRT-PCR also revealed that Akt3 has shown promising results in promoting cancer cell migration. Contrary to pro-oncogenic properties attributed to Akt, it is to be understood how various isoforms of Akt compensates each other in the regulation of common pathways during cancer progression and drug resistance. In conclusion, this study aims to target selective isoforms which is essential to inhibit cancer. However, the question now is whether, and how much, Akt inhibition will be tolerated in the clinic remains to be answered and the experiments will have to address the question of which combinations of newly devised Akt isoform specific inhibitors exert a favourable therapeutic effect in in vivo models of cancer to provide the therapeutic window with minimal toxicity.

Keywords: Akt isoforms, cancer, drug resistance, epithelial mesenchymal transition

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Authors: Sarika Gupta, Harshika Khanna, Ajay K Verma, Surya Kant

Abstract:

Background: Drug-resistant tuberculosis (DR-TB) is a growing health challenge to global TB control efforts. Pediatric DR-TB is one of the neglected infectious diseases. In our previously published report, we have notified an increased prevalence of DR-TB in the pediatric population at a tertiary health care centre in North India which was estimated as 17.4%, 15.1%, 18.4%, and 20.3% in (%) in the year 2018, 2019, 2020, and 2021. Limited evidence exists about a pattern of drug resistance, side effect profile and programmatic outcomes of Paediatric DR-TB treatment. Therefore, this study was done to find out the pattern of resistance, side effect profile and treatment outcome. Methodology: This was a prospective cohort study conducted at the nodal drug-resistant tuberculosis centre of a tertiary care hospital in North India from January 2021 to December 2022. Subjects included children aged between 0-18 years of age with a diagnosis of DR-TB, on the basis of GeneXpert (rifampicin [RIF] resistance detected), line probe assay and drug sensitivity testing (DST) of M. tuberculosis (MTB) grown on a culture of body fluids. Children were classified as monoresistant TB, polyresistant TB (resistance to more than 1 first-line anti-TB drug, other than both INH and RIF), MDR-TB, pre-XDR-TB and XDR-TB, as per the WHO classification. All the patients were prescribed DR TB treatment as per the standard guidelines, either shorter oral DR-TB regimen or a longer all-oral MDR/XDR-TB regimen (age below five years needed modification). All the patients were followed up for side effects of treatment once per month. The patient outcomes were categorized as good outcomes if they had completed treatment and cured or were improving during the course of treatment, while bad outcomes included death or not improving during the course of treatment. Results: Of the 50 pediatric patients included in the study, 34 were females (66.7%) and 16 were male (31.4%). Around 33 patients (64.7%) were suffering from pulmonary TB, while 17 (33.3%) were suffering from extrapulmonary TB. The proportions of monoresistant TB, polyresistant TB, MDR-TB, pre-XDR-TB and XDR-TB were 2.0%, 0%, 50.0%, 30.0% and 18.0%, respectively. Good outcome was reported in 40 patients (80.0%). The 10 bad outcomes were 7 deaths (14%) and 3 (6.0%) children who were not improving. Adverse events (single or multiple) were reported in all the patients, most of which were mild in nature. The most common adverse events were metallic taste 16(31.4%), rash and allergic reaction 15(29.4%), nausea and vomiting 13(26.0%), arthralgia 11 (21.6%) and alopecia 11 (21.6%). Serious adverse event of QTc prolongation was reported in 4 cases (7.8%), but neither arrhythmias nor symptomatic cardiac side effects occurred. Vestibular toxicity was reported in 2(3.9%), and psychotic symptoms in 4(7.8%). Hepatotoxicity, hypothyroidism, peripheral neuropathy, gynaecomastia, and amenorrhea were reported in 2 (4.0%), 4 (7.8%), 2 (3.9%), 1(2.0%), and 2 (3.9%) respectively. None of the drugs needed to be withdrawn due to uncontrolled adverse events. Conclusion: Paediatric DR TB treatment achieved favorable outcomes in a large proportion of children. DR TB treatment regimen drugs were overall well tolerated in this cohort.

Keywords: pediatric, drug-resistant, tuberculosis, adverse events, treatment

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Authors: Ghada S. Moussa

Abstract:

Vehicle classification is an important task in traffic surveillance and intelligent transportation systems. Classification of vehicle images is facing several problems such as: high intra-class vehicle variations, occlusion, shadow, illumination. These problems and others must be considered to develop a reliable vehicle classification system. In this study, a reliable multi-type vehicle classification system based on Bag-of-Words (BoW) paradigm is developed. Our proposed system used and compared four well-known classifiers; Linear Discriminant Analysis (LDA), Support Vector Machine (SVM), k-Nearest Neighbour (KNN), and Decision Tree to classify vehicles into four categories: motorcycles, small, medium and large. Experiments on a large dataset show that our approach is efficient and reliable in classifying vehicles with accuracy of 95.7%. The SVM outperforms other classification algorithms in terms of both accuracy and robustness alongside considerable reduction in execution time. The innovativeness of developed system is it can serve as a framework for many vehicle classification systems.

Keywords: vehicle classification, bag-of-words technique, SVM classifier, LDA classifier, KNN classifier, decision tree classifier, SIFT algorithm

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Authors: Zhixiang Li, Shuguang Yao, Wen Ma

Abstract:

Coupler rubber buffer has been widely applied on the high-speed trains and the main function of the rubber buffer is dissipating the impact energy between vehicles. The rubber buffer consists of two groups of rubbers, which are both pre-compressed and then installed into the frame body. This work focuses on the energy absorption capacity of each group of buffers particularly. The quasi-static compression tests were carried out to obtain the pre-compression force and the load-defection response of the buffers. Then a finite element (FE) model was constructed using Ls_dyna program. The rubber material was modeled with a tabulated method easily, in which no more material constants need to be fitted. The simulation results agreed with the experimental results well. Numerical study of the buffers was performed using the validated FE model and the influence of the initial pressure on the buffers was obtained. In addition, the interaction between the two groups of buffers was also investigated and the optimum distribution of the two was found.

Keywords: initial pressure, rubber buffer, simulation, tabulated method

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Authors: Sunitha Sampathi, Pankaj Kumar Tiriya, Sonia Gera, Sravanthi Reddy Pailla, V. Likhitha, A. J. Maruthi

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Surgical site infections (SSIs) are the most common nosocomial infections localized at the incision site. With an estimated 27 million surgical procedures each year in USA, approximately 2-5% rate of SSIs are predicted to occur annually. SSIs are treated with antibiotic medication. Current trend suggest that the direct drug delivery from the suture to the scared tissue can improve patient comfort and wound recovery. For that reason coating the surface of the medical device such as suture and catguts with broad spectrum antibiotics can prevent the formation of bactierial colonies with out comprimising the mechanical properties of the sutures.Hence, the present study was aimed to develop and evaluate a surgical suture coated with an antibiotic Ciprofloxacin hydrochloride loaded on gold nanoparticles. Gold nanoparticles were synthesized by chemical reduction method and conjugated with ciprofloxacin using Polyvinylpyrolidone as stabilizer and gold as carrier. Ciprofloxacin conjugated gold nanoparticles were coated over an absorbable surgical suture made of Polyglactan using sodium alginate as an immobilising agent by slurry dipping technique. The average particle size and Polydispersity Index of drug conjugated gold NPs were found to be 129±2.35 nm and 0.243±0.36 respectively. Gold nanoparticles are characterized by UV-Vis absorption spectroscopy, Fourier Transform Infrared Spectroscopy (FT-IR), Scanning electron microscopy and Transmission electron microscopy. FT-IR revealed that there is no chemical interaction between drug and polymer. Antimicrobial activity for coated sutures was evaluated by disc diffusion method on culture plates of both gram negative (E-coli) and gram positive bacteria (Staphylococcus aureus) and results found to be satisfactory. In vivo studies for coated sutures was performed on Swiss albino mice and histological evaluation of intestinal wound healing parameters such as wound edges in mucosa, muscularis, presence of necrosis, exudates, granulation tissue, granulocytes, macrophages, restoration, and repair of mucosal epithelium and muscularis propria on day 7 after surgery were studied. The control animal group, sutured with plain suture (uncoated suture) showed signs of restoration and repair, but presence of necrosis, heamorraghic infiltration and granulation tissue was still noticed. Whereas the animal group treated with ciprofloxacin and ciprofloxacin gold nanoparticle coated sutures has shown promising decrease in terms of haemorraghic infiltration, granulation tissue, necrosis and better repaired muscularis layers on comparision with plain coated sutures indicating faster rate of repair and less chance of sepsis. Hence coating of sutures with broad spectrum antibiotics can be an alternate technique to reduce SSIs.

Keywords: ciprofloxacin hydrochloride, gold nanoparticles, surgical site infections, sutures

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Authors: Garzon V., Bustos R., Salvador J. P., Marco M. P., Pinacho D. G.

Abstract:

Bacterial resistance to antimicrobial treatment has increased significantly in recent years, making it a public health problem. Large numbers of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last line” antimicrobial drug therapies for the treatment of multi-resistant bacteria. Some of the chemical groups of antimicrobials most used for the treatment of infections caused by multiresistant bacteria in the clinic are Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin) and Carbapenem (Meropenem). Molecules that require therapeutic drug monitoring (TDM). Due to the above, a methodology based on nanobiotechnology based on an optical and electrochemical biosensor is being developed, which allows the evaluation of the plasmatic levels of some antimicrobials such as glycopeptide, polymyxin, lipopeptide and carbapenem quickly, at a low cost, with a high specificity and sensitivity and that can be implemented in the future in public and private health hospitals. For this, the project was divided into five steps i) Design of specific anti-drug antibodies, produced in rabbits for each of the types of antimicrobials, evaluating the results by means of an immunoassay analysis (ELISA); ii) quantification by means of an electrochemical biosensor that allows quantification with high sensitivity and selectivity of the reference antimicrobials; iii) Comparison of antimicrobial quantification with an optical type biosensor; iv) Validation of the methodologies used with biosensor by means of an immunoassay. Finding as a result that it is possible to quantify antibiotics by means of the optical and electrochemical biosensor at concentrations on average of 1,000ng/mL, the antibodies being sensitive and specific for each of the antibiotic molecules, results that were compared with immunoassays and HPLC chromatography. Thus, contributing to the safe use of these drugs commonly used in clinical practice and new antimicrobial drugs.

Keywords: antibiotics, electrochemical biosensor, optical biosensor, therapeutic drug monitoring

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Authors: Akwu N. A., Naidoo Y., Salau V. F., Olofinsan K. A.

Abstract:

Grewia lasiocarpa E. Mey. ex Harv. (Malvaceae) is a Southern African medicinal plant indigenously used with other plants for birthing problems. The anti-diabetic properties of the hexane, chloroform, and methanol extracts of Grewia lasiocarpa stem bark were assessed using in vitro α-glucosidase enzyme inhibition assay. The predictive in silico drug-likeness and toxicity properties of the phytocompounds were conducted using the pKCSM, ADMElab, and SwissADME computer-aided online tools. The highest α-glucosidase percentage inhibition was observed in the hexane extract (86.76%, IC50= 0.24 mg/mL), followed by chloroform (63.08%, IC50= 4.87 mg/mL) and methanol (53.22%, IC50= 9.41 mg/mL); while acarbose, the standard anti-diabetic drug was (84.54%, IC50= 1.96 mg/mL). The α-glucosidase assay revealed that the hexane extract exhibited the strongest carbohydrate inhibiting capacity and is a better inhibitor than the standard reference drug-acarbose. The computational studies also affirm the results observed in the in vitroα-glucosidaseassay. Thus, the extracts of G. lasiocarpa may be considered a potential plant-sourced compound for treating type 2 diabetes mellitus. This is the first study on the anti-diabetic properties of Grewia lasiocarpa hexane, chloroform, and methanol extracts using in vitro and in silico models.

Keywords: grewia lasiocarpa, α-glucosidase inhibition, anti-diabetes, ADMET

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Authors: Ilaria Manca, Ilaria Manca, Francesca Pettinau, Ignazia Mocci, Elisabetta M. Usai, Barbara Pittau

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Lamotrigine is a phenyltriazine used in the treatment of epilepsy and bipolar disorder type I. The purpose of this study was to test and compare various solid forms of immediate release (IR) lamotrigine products, at different strenghts, in order to study their disaggregation and dissolution behavior. IR products are designed to release their active substance promptly after administration. Concentration of hydrochloric acid in gastric juice is about 0.1-0.001 M, so FDA (Food and Drug Administration) recommends, for lamotrigine regular tablets, dissolution tests in HCl 0.1 M.Toinvestigate the pH dependency of drug release in the entire gastrointestinal tract, we worked at two additional media with different pH values (4.5 and 6.8), that reflect conditions in it. To afford acceptable dissolution rates, tablets must disintegrate. Disaggregation of constituent particles increases the surface area and substantially increases the dissolution rate. For this reason availability of an active substance from tablets depends on its ability to disintegrate fast in dissolution media. pH of gastrointestinal fluid affects drug absorption by conditioning its solubility and dissolution, but also tablet disintegration may be influenced by it. To obtain information about the quantitative relationship between different mixture components, Nuclear Magnetic Resonance (NMR) spectroscopy was used. We also investigate tablet hardness. The investigation carried out confirms pH 1.2 as the ideal environment for the immediate availability of the active substance.

Keywords: dissolution, disaggregation, Lamotrigine, bioequivalence

Procedia PDF Downloads 440

Authors: Hari Bezwada, Michelle Cheon, Ryan Divan, Hannah Escritor, Michelle Kagramian, Isha Korgaonkar, Maya MacAdams, Udgita Pamidigantam, Richard Pilny, Eleanor Race, Angadh Singh, Nathan Zhang, LeeAnn Nguyen, Fina Liotta

Abstract:

Malaria is a deadly disease caused by the Plasmodium parasite, which continues to develop resistance to current antimalarial drugs. In this research project, the effectiveness of numerous thiazole derivatives was explored in inhibiting the PfPKG, a crucial part of the Plasmodium life cycle. This study involved the synthesis of six thiazole-derived amides to inhibit the PfPKG pathway. Nuclear Magnetic Resonance (NMR) spectroscopy and Infrared (IR) spectroscopy were used to characterize these compounds. Furthermore, AutoDocking software was used to predict binding affinities of these thiazole-derived amides in silico. In silico, compound 6 exhibited the highest predicted binding affinity to PfPKG, while compound 5 had the lowest affinity. Compounds 1-4 displayed varying degrees of predicted binding affinity. In-vitro, it was found that compound 4 had the best percent inhibition, while compound 5 had the worst percent inhibition. Overall, all six compounds had weak inhibition (approximately 30-39% at 10 μM), but these results provide a foundation for future drug discovery experiments.

Keywords: Medicinal Chemistry, Malaria, drug discovery, PfPKG, Thiazole, Plasmodium

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Authors: Si-Gwan Kim

Abstract:

In Delay Tolerant Networks (DTN), there may not exist an end-to-end path between source and destination at the time of message transmission. Employing ‘Store Carry and Forward’ delivery mechanism for message transmission in such networks usually incurs long message delays. In this paper, we present the modified Binary Spray and Wait (BSW) routing protocol that enhances the performance of the original one. Our proposed algorithm adjusts the number of forward messages depending on the number of neighbor nodes. By using beacon messages periodically, the number of neighbor nodes can be managed. The simulation using ONE simulator results shows that our modified version gives higher delivery ratio and less latency as compared to BSW.

Keywords: delay tolerant networks, store carry and forward, one simulator, binary spray and wait

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Authors: Jiheon Park, Taekwang Kim, Kwang Ryel Ryu

Abstract:

Electric automated guided vehicles (AGVs) are becoming popular in many automated container terminals nowadays because they are pollution-free and environmentally friendly vehicles for transporting the containers within the terminal. Since efficient operation of AGVs is critical for the productivity of the container terminal, the replacement of batteries of the AGVs must be conducted in a strategic way to minimize undesirable transportation interruptions. While a too frequent replacement may lead to a loss of terminal productivity by delaying container deliveries, missing the right timing of battery replacement can result in a dead AGV that causes a severer productivity loss due to the extra efforts required to finish post treatment. In this paper, we propose a strategy for battery replacement based on a scoring function of multiple criteria taking into account the current battery level, the distances to different battery stations, and the progress of the terminal job operations. The strategy is optimized using a genetic algorithm with the objectives of minimizing the total time spent for battery replacement as well as maximizing the terminal productivity.

Keywords: AGV operation, automated container terminal, battery replacement, electric AGV, strategy optimization

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Authors: Dogaru-Ulieru Valentin, Sălișteanu Ioan Corneliu, Ardeleanu Mihăiță Nicolae, Broscăreanu Ștefan, Sălișteanu Bogdan, Mihai Mihail

Abstract:

The SiaMOTO system is a communications and data processing platform for vehicle traffic. The human factor is the most important factor in the generation of this data, as the driver is the one who dictates the trajectory of the vehicle. Like any trajectory, specific parameters refer to position, speed and acceleration. Constant knowledge of these parameters allows complex analyses. Roadways allow many vehicles to travel through their confined space, and the overlapping trajectories of several vehicles increase the likelihood of collision events, known as road accidents. Any such event has causes that lead to its occurrence, so the conditions for its occurrence are known. The human factor is predominant in deciding the trajectory parameters of the vehicle on the road, so monitoring it by knowing the events reported by the DiaMOTO device over time, will generate a guide to target any potentially high-risk driving behavior and reward those who control the driving phenomenon well. In this paper, we have focused on detailing the communication infrastructure of the DiaMOTO device with the traffic data collection server, the infrastructure through which the database that will be used for complex AI/DLM analysis is built. The central element of this description is the data string in CODEC-8 format sent by the DiaMOTO device to the SiaMOTO collection server database. The data presented are specific to a functional infrastructure implemented in an experimental model stage, by installing on a number of 50 vehicles DiaMOTO unique code devices, integrating ADAS and GPS functions, through which vehicle trajectories can be monitored 24 hours a day.

Keywords: DiaMOTO, Codec-8, ADAS, GPS, driver monitoring

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Authors: Abubakar Sa’adatu Mohammed

Abstract:

This paper reports on a study of problem solving differences between expert and novice Problem solvers for effective physics teaching. Significant differences were found both at the conceptual level and at the level of critical thinking, creative thinking and reasoning. It is suggested for a successful solution of a problem, conceptual knowledge alone may not be sufficient. There is the need of the knowledge of how the conceptual knowledge should be applied (problem solving skills). It is hoped that this research might contribute to efforts of exploring ways for students to acquire a powerful conceptual toolkit based on experts like problem solvers approach for effective teaching delivery.

Keywords: conceptual knowledge, procedural knowledge, critical thinking, creative thinking, reasoning ability

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Authors: Sahar Elsaleh, Ghada Farhat, Shaikha Al-Derham, Fasih Alam

Abstract:

Background: Cesarean section (CS) delivery is one of the major concerns both in developing and developed countries. The rate of CS deliveries are on the rise globally, and especially in Qatar. Many socio-economic, demographic, clinical and institutional factors play an important role for cesarean sections. This study aims to investigate factors affecting the prevalence of CS among women in Qatar using the UNICEF’s Multiple Indicator Cluster Survey (MICS) 2012 database. Methods: The study has focused on the women’s questionnaire of the MICS, which was successfully distributed to 5699 participants. Following study inclusion and exclusion criteria, a final sample of 761 women aged 19- 49 years who had at least one delivery of giving birth in their lifetime before the survey were included. A number of socio-economic, demographic, clinical and institutional factors, identified through literature review and available in the data, were considered for the analyses. Bivariate and multivariate logistic regression models, along with a multi-level modeling to investigate clustering effect, were undertaken to identify the factors that affect CS prevalence in Qatar. Results: From the bivariate analyses the study has shown that, a number of categorical factors are statistically significantly associated with the dependent variable (CS). When identifying the factors from a multivariate logistic regression, the study found that only three categorical factors -‘age of women’, ‘place at delivery’ and ‘baby weight’ appeared to be significantly affecting the CS among women in Qatar. Although the MICS dataset is based on a cluster survey, an exploratory multi-level analysis did not show any clustering effect, i.e. no significant variation in results at higher level (households), suggesting that all analyses at lower level (individual respondent) are valid without any significant bias in results. Conclusion: The study found a statistically significant association between the dependent variable (CS delivery) and age of women, frequency of TV watching, assistance at birth and place of birth. These results need to be interpreted cautiously; however, it can be used as evidence-base for further research on cesarean section delivery in Qatar.

Keywords: cesarean section, factors, multiple indicator cluster survey, MICS database, Qatar

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Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

Abstract:

The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

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Authors: Geetakshi Arora, Danish Malhotra

Abstract:

Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

Procedia PDF Downloads 110