Search results for: drug delivery to the brain

Authors: Julia Brudzinski, Ashley Croswell, Jade Mardin, Hannah Shilling, Jennifer Berg-Carnegie

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Adults with brain injuries and mental illnesses commonly experience cognitive impairments that interfere with their participation in activities of daily living (ADLs). Prior research states that electronic reminder systems can support adults with cognitive impairments; however, previous studies focus primarily on one-way reminder systems. Research on adults with chronic diseases reported that two-way reminder systems yield better health outcomes and disease self-management compared to one-way reminder systems. Literature was identified through systematically searching 7 databases and hand-searching relevant reference lists. Retrieved studies were independently screened and reviewed by at least two members of the research team. Data was extracted on study design, participant characteristics, intervention details, study objectives, outcome measures, and important results. 574 articles were screened and reviewed. Nine articles met all inclusion criteria and were included. The literature focused on three main areas: system feasibility (n=8), stakeholder satisfaction (n=6), and efficacy of the two-way reminder systems (n=6). Participants in eight of the studies had brain injuries, with participants in only one study having a mental illness (i.e., schizophrenia). Two-way reminder systems were used to support participation in a wide range of ADLs. The current literature on two-way reminder systems to support ADLs for adults with cognitive impairments focuses on feasibility, stakeholder satisfaction, and system efficacy. Future research should focus on addressing the barriers to accessing and implementing two-way reminder systems and identifying specific client characteristics that would benefit most from using these systems.

Keywords: brain injury, digital health, occupational therapy, activities of daily living, two-way reminder systems

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Authors: Aydin Sipahioglu, Gokhan Celik

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Helicopter routing problem (HRP) is finding good tours for helicopter so as to pick up and deliver personnel or material among specified nodes, mutually. It can be encountered in case of being lots of supply and demand points for different commodities and requiring delivering commodities with helicopter. For instance, to deliver personnel or material from shore to oil rig is a good example. In fact, HRP is a branch of vehicle routing problem with pickup and delivery (VRPPD). However, it has additional constraints such that fuel capacity, performance of helicopter in different altitude and temperature, and the number of maximum takeoff and landing allowed. This kind of pickup and delivery problems can be classified into 3 groups, basically. 1-1 (one to one), M-M (many to many) and 1-M-1 (one to many to one). 1-1 means each commodity has only one supply and one demand point. M-M means there can be more than one supply and demand points for each kind of commodity. 1-M-1 means commodities at depot are delivered to demand points and commodities at customers are delivered to depot. In this case helicopter takes off from its own base, complete its tour and return to its own base. In this study, we define 1-M-M-1 type HRP. That means helicopter takes off from its home base, deliver commodities among the nodes as well as between depot and customers and return to its home base. These problems have NP-hard nature. Therefore, obtaining a good solution in a reasonable time is not easy. In this study, a model is offered for 1-M-M-1 type HRP. It is shown on small scale test instances that the model can find the optimal solution.

Keywords: helicopter routing problem, vehicle routing with pickup and delivery, integer programming

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Authors: Yuri V. Bykov, V. A. Baturin

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Aim of the study: The aim of the study was to perform a comparative analysis of the levels of autoantibodies (AAB) to the S-100 protein as well as to the dopamine and NMDA receptors in children with type 1 diabetes mellitus (DM) in therapeutic remission. Materials and methods: Blood serum obtained from 42 children ages 4 to 17 years (20 boys and 22 girls) was analyzed. Twenty-one of these children had a diagnosis of type 1 DM and were in therapeutic remission (study group). The mean duration of disease in children with type 1 DM was 9.6±0.36 years. Children without DM were included in a group of "apparently healthy children" (21 children, comparison group). AAB to the S-100 protein, the dopamine, and NMDA receptors were measured by ELISA. The normal range of IgG AAB was specified as up to 10 µg/mL. In order to compare the central parameters of the groups, the following parametric and non-parametric methods were used: Student's t-test or Mann-Whitney U test. The level of significance for inter-group comparisons was set at p<0.05. Results: The mean levels of AAB to the S-100B protein were significantly higher (p=0.0045) in children with DM (16.84±1.54 µg/mL) when compared with "apparently healthy children" (2.09±0.05 µg/mL). The detected elevated levels of AAB to NMDA receptors may indicate that in children with type 1 DM, there is a change in the activity of the glutamatergic system, which in its turn suggests the presence of excitotoxicity. The mean levels of AAB to dopamine receptors were higher (p=0.0082) in patients comprising the study group than in the children of the comparison group (40.47±2.31 µg/mL and 3.91±0.09 µg/mL). The detected elevated levels of AAB to dopamine receptors suggest an altered activity of the dopaminergic system in children with DM. This can also be viewed as indirect evidence of altered activity of the brain's glutamatergic system. The mean levels of AAB to NMDA receptors were higher in patients with type 1 DM compared with the "apparently healthy children," at 13.16±2.07 µg/mL and 1.304±0.05 µg/mL, respectively (p=0.0021). The elevated mean levels of AAB to the S-100B protein may indicate damage to brain tissue in children with type 1 DM. A difference was also detected between the mean values of the measured AABs, and this difference depended on the duration of the disease: mean AAB values were significantly higher in patients whose disease had lasted more than five years. Conclusions: The elevated mean levels of AAB to the S-100B protein may indicate damage to brain tissue in the setting of excitotoxicity in children with type 1 DM. The discovered elevation of the levels of AAB to NMDA and dopamine receptors may indicate the activation of the glutamatergic and dopaminergic systems. The observed abnormalities indicate the presence of central nervous system damage in children with type 1 DM, with a tendency towards the elevation of the levels of the studied AABs with disease progression.

Keywords: autoantibodies, brain damage, children, diabetes mellitus

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Authors: Suliman Khan, Rabeea Siddique, Mengzhou Xue

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Background: Patients with neurological disorders often display altered circadian rhythms. The disrupted circadian rhythms through chronic jetlag or shiftwork are thought to increase the risk and severity of human disease, including cancer, psychiatric, and related brain diseases. In this study, we investigated the impact of shiftwork or chronic jetlag (CJL) like conditions on mice’s brains. Transcriptome profiling based on RNA sequencing revealed that genes associated with serious neurological disorders were differentially expressed in the nucleus accumbens (NAc) and prefrontal cortex (PFC). According to the qPCR analysis, several key regulatory genes associated with neurological disorders were significantly altered in the NAc, PFC, hypothalamus, hippocampus, and striatum. Serotonin levels and the expression levels of serotonin transporters and receptors were significantly altered in mice treated with CJL. Overall, these results indicate that CJL may increase the risk of neurological disorders by disrupting the key regulatory genes, biological functions, serotonin, and corticosterone. These molecular linkages can further be studied to investigate the mechanism underlying CJL or shiftwork-mediated neurological disorders in order to develop treatment strategies.

Keywords: chronic jetlag, molecular profiles, brain disorders, circadian rhythms

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Authors: Stefan Bauer, Josef Frysak

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According to the scientific information management literature, the improper use of information technology (e.g. personal computers) by employees are one main cause for operational and information security loss events. Therefore, organizations implement information security awareness programs to increase employees’ awareness to further prevention of loss events. However, in many cases these information security awareness programs consist of conventional delivery methods like posters, leaflets, or internal messages to make employees aware of information security policies. We assume that a viral information security awareness video might be more effective medium than conventional methods commonly used by organizations. The purpose of this research is to develop a viral video artifact to improve employee security behavior concerning information technology.

Keywords: information security awareness, delivery methods, viral videos, employee security behavior

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Authors: Md. Danish Eqbal, Venkat Gundabala

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Microparticles and microcapsules are basically used as a carrier for cells, tissues, drugs, and chemicals. Due to its biocompatibility, non-toxicity and biodegradability, alginate based microparticles have numerous applications in drug delivery, tissue engineering, organ repair and transplantation, etc. The production of uniform monodispersed microparticles was a challenge for the past few decades. However, emergence of microfluidics has provided controlled methods for the generation of the uniform monodispersed microparticles. In this work, we present a successful method for the generation of both microparticles and microcapsules (single and double core) using merging approach of two droplets, completely inside the microfluidic device. We have fabricated hybrid glass- PDMS (polydimethylsiloxane) based microfluidic device which has coflow geometry as well as the T junction channel. Coflow is used to generate the single as well as double oil-alginate emulsion in oil and T junction helps to form the calcium chloride droplets in oil. The basic idea is to match the frequency of the alginate droplets and calcium chloride droplets perfectly for controlled generation. Using the merging of droplets technique, we have successfully generated the microparticles and the microcapsules having single core as well as double and multiple cores. The cores in the microcapsules are very stable, well separated from each other and very intact as seen through cross-sectional confocal images. The size and the number of the cores along with the thickness of the shell can be easily controlled by controlling the flowrate of the liquids.

Keywords: double-core, droplets, microcapsules, microparticles

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Authors: A. Wahid Uddin

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Obstetric anal sphincter injury carries significant morbidity for a woman and affects the quality of life to the extent of permanent damage to anal sphincter musculature. The study was undertaken in a district general hospital by retrospectively reviewing random 63 case notes of patients diagnosed with a significant third or fourth-degree perineal tear admitted between the year of 2015 to 2018. The observations were collected by a pre-designed questionnaire. All variables were expressed as percentages. The major risk factors noted were nulliparity (37%), instrumental delivery (25%), and birth weight of more than 4 kg (14%). Forceps delivery with or without episiotomy was the major contributing factor (75%). In the majority of the cases (71%), no record of any perineal protection measures undertaken. The study concluded that recommended perineal protection measures should be adopted as a routine practise.

Keywords: forceps, obstetrics, perineal, sphincter

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Authors: F. Kashanian, M. M. Masoudi, A. Akbari, A. Shamloo, M. R. Zand, S. S. Salehi

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Nano-sized materials present new opportunities in biology and medicine and they are used as biomedical tools for investigation, separation of molecules and cells. To achieve more effective cancer therapy, it is essential to select cancer cells exactly. This research suggests that using the antibody-functionalized nontoxic Arginine-doped magnetic nanoparticles (A-MNPs), has been prosperous in detection, capture, and magnetic separation of circulating tumor cells (CTCs) in tumor tissue. In this study, A-MNPs were synthesized via a simple precipitation reaction and directly immobilized Ep-CAM EBA-1 antibodies over superparamagnetic A-MNPs for Mucin BCA-225 in breast cancer cell. The samples were characterized by vibrating sample magnetometer (VSM), FT-IR spectroscopy, Tunneling Electron Microscopy (TEM) and Scanning Electron Microscopy (SEM). These antibody-functionalized nontoxic A-MNPs were used to capture breast cancer cell. Through employing a strong permanent magnet, the magnetic separation was achieved within a few seconds. Antibody-Conjugated nontoxic Arginine-doped Fe₃O₄ nanoparticles have the potential for the future study to capture CTCs which are released from tumor tissue and for drug delivery, and these results demonstrate that the antibody-conjugated A-MNPs can be used in magnetic hyperthermia techniques for cancer treatment.

Keywords: tumor tissue, antibody, magnetic nanoparticle, CTCs capturing

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Authors: Wei-Ju Huang, Hung-Pin Hsu

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[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

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Authors: Anil Kumar Pandey

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Power plane noise is the most significant source of signal integrity (SI) issues in a high-speed digital design. In this paper, power integrity (PI) analysis of multiple power planes in a power delivery system of a 12-layer high-speed FPGA board is presented. All 10 power planes of HSD board are analyzed separately by using 3D Electromagnetic based PI solver, then the transient simulation is performed on combined PI data of all planes along with voltage regulator modules (VRMs) and 70 current drawing chips to get the board level power noise coupling on different high-speed signals. De-coupling capacitors are placed between power planes and ground to reduce power noise coupling with signals.

Keywords: power integrity, power-aware signal integrity analysis, electromagnetic simulation, channel simulation

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Authors: Luc Conti, Dimitry Dumont-Fillon, Harald van Lintel, Eric Chappel

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Flow control valves comprise a silicon flexible membrane that deflects against a substrate, usually made of glass, containing pillars, an outlet hole, and anti-stiction features. However, there is a strong interest in using silicon instead of glass as substrate material, as it would simplify the process flow by allowing the use of well controlled anisotropic etching. Moreover, specific devices demanding a bending of the substrate would also benefit from the inherent outstanding mechanical strength of monocrystalline silicon. Unfortunately, direct Si-Si bonding is not easily achieved with highly structured wafers since residual stress may prevent the good adhesion between wafers. Using a thermoplastic polymer, such as parylene, as intermediate layer is not well adapted to this design as the wafer-to-wafer alignment is critical. An alternative anodic bonding method using an intermediate borosilicate layer has been successfully tested. This layer has been deposited onto the silicon substrate. The bonding recipe has been adapted to account for the presence of the SOI buried oxide and intermediate glass layer in order not to exceed the breakdown voltage. Flow control valves dedicated to infusion of viscous fluids at very high pressure have been made and characterized. The results are compared to previous data obtained using the standard anodic bonding method.

Keywords: anodic bonding, evaporated glass, flow control valve, drug delivery

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Authors: Abdollah Aliesmaeili

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The purpose of this research is to present a different perspective on the basic math teaching method called meta-instruction, which reverses the learning path. Meta-instruction is a method of teaching in which the teaching trajectory starts from brain education into learning. This research focuses on the behavior of the mind during learning. In this method, students are not instructed in mathematics, but they are educated. Another goal of the research is to "criticize Bloom's classification in the cognitive domain and reverse it", because it cannot meet the educational and instructional needs of the new generation and "substituting math education instead of math teaching". This is an indirect method of teaching. The method of research is longitudinal through four years. Statistical samples included students ages 6 to 11. The research focuses on improving the mental abilities of children to explore mathematical rules and operations by playing only with eight measurements (any years 2 examinations). The results showed that there is a significant difference between groups in remembering, understanding, and applying. Moreover, educating math is more effective than instructing in overall learning abilities.

Keywords: applying, Bloom's taxonomy, brain education, mathematics teaching method, meta-instruction, remembering, starmath method, understanding

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Authors: Panatda Intanin, Sangutid Thongsawad, Chirapha Tannanonta, Todsaporn Fuangrod

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Stereotactic radiosurgery (SRS) is a highly precision delivery technique that requires comprehensive quality assurance (QA) tests prior to treatment delivery. An isocenter of delivery beam plays a critical role that affect the treatment accuracy. The uncertainty of isocenter is traditionally accessed using circular cone equipment, Winston-Lutz (WL) phantom and film. This technique is considered time consuming and highly dependent on the observer. In this work, the development of multileaf collimator (MLC)-based isocenter verification tool using electronic portal imaging device (EPID) was proposed and evaluated. A mechanical isocenter alignment with ball bearing diameter 5 mm and circular cone diameter 10 mm fixed to gantry head defines the radiation field was set as the conventional WL test method. The conventional setup was to compare to the proposed setup; using MLC (10 x 10 mm) to define the radiation filed instead of cone. This represents more realistic delivery field than using circular cone equipment. The acquisition from electronic portal imaging device (EPID) and radiographic film were performed in both experiments. The gantry angles were set as following: 0°, 90°, 180° and 270°. A software tool was in-house developed using MATLAB/SIMULINK programming to determine the centroid of radiation field and shadow of WL phantom automatically. This presents higher accuracy than manual measurement. The deviation between centroid of both cone-based and MLC-based WL tests were quantified. To compare between film and EPID image, the deviation for all gantry angle was 0.26±0.19mm and 0.43±0.30 for cone-based and MLC-based WL tests. For the absolute deviation calculation on EPID images between cone and MLC-based WL test was 0.59±0.28 mm and the absolute deviation on film images was 0.14±0.13 mm. Therefore, the MLC-based isocenter verification using EPID present high sensitivity tool for SRS QA.

Keywords: isocenter verification, quality assurance, EPID, SRS

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Authors: Andreia Guimaraes Farnese, Mateus Fernandes Reu Urban, Leandro Procopio, Renato Zangaro, Regiane Albertini

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Senescence changes include postural balance, inferring the risk of falls, and can lead to fractures, bedridden, and the risk of death. Physical activity, e.g., cardiovascular exercises, is notable for improving balance due to brain cell stimulations, but fine coordination exercises also elevate cell brain metabolism. This study aimed to verify whether the elderly person who performs fine motor activity has a balance similar to that of those who practice physical activity. The subjects were divided into three groups according to the activity practice: control group (CG) with seven participants for the sedentary individuals, motor coordination group (MCG) with six participants, and activity practitioner group (PAG) with eight participants. Data comparisons were from the Berg balance scale, Time up and Go test, and stabilometric analysis. Descriptive statistical and ANOVA analyses were performed for data analysis. The results reveal that including fine motor activities can improve the balance of the elderly and indirectly decrease the risk of falls.

Keywords: balance, barapodometer, coordination, elderly

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Authors: Vandana T. Gawande, Kailash G. Bothara, Chandani O. Satija

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The present research work was aimed to determine stability of cefprozil monohydrate (CEFZ) as per various stress degradation conditions recommended by International Conference on Harmonization (ICH) guideline Q1A (R2). Forced degradation studies were carried out for hydrolytic, oxidative, photolytic and thermal stress conditions. The drug was found susceptible for degradation under all stress conditions. Separation was carried out by using High Performance Thin Layer Chromatographic System (HPTLC). Aluminum plates pre-coated with silica gel 60F254 were used as the stationary phase. The mobile phase consisted of ethyl acetate: acetone: methanol: water: glacial acetic acid (7.5:2.5:2.5:1.5:0.5v/v). Densitometric analysis was carried out at 280 nm. The system was found to give compact spot for cefprozil monohydrate (0.45 Rf). The linear regression analysis data showed good linear relationship in the concentration range 200-5.000 ng/band for cefprozil monohydrate. Percent recovery for the drug was found to be in the range of 98.78-101.24. Method was found to be reproducible with % relative standard deviation (%RSD) for intra- and inter-day precision to be < 1.5% over the said concentration range. The method was validated for precision, accuracy, specificity and robustness. The method has been successfully applied in the analysis of drug in tablet dosage form. Three unknown degradation products formed under various stress conditions were isolated by preparative HPTLC and characterized by mass spectroscopic studies.

Keywords: cefprozil monohydrate, degradation products, HPTLC, stress study, stability indicating method

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Authors: Khaled Alshammari

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Ciprofloxacin (CIP) is a common antibiotic drug used as a strudy electron donor that interacts with dynamic π -acceptors such as 2,3-dinitrosalsylic acid (HDNS) and Tetracyanoethylene (TCNE) for synthesizing a new model of charge transfer (CT) complexes. The synthesized complexes were identified using diverse analytical methods such as UV–vis spectra, photometric titration measurements, FT-IR, HNMR Spectroscopy, and thermogravimetric analysis techniques (TGA/DTA). The stoichiometries for all the formed complexes were found to be a 1:1 M ratio between the reactants. The characteristic spectroscopic properties such as transition dipole moment (µ), oscillator strength (f), formation constant (KCT), ionization potential (ID), standard free energy (∆G), and energy of interaction (ECT) for the CT-complexes were collected. The developed CT complexes were tested for their toxicity on main organs, antimicrobial activity, antioxidant activity, and biofilm formation.

Keywords: biological, biofilm, toxicity, thermal analysis, charge transfer, spectroscopy

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Authors: Carol Yue-En Ong, Angelina Hui-Min Tan, Quan Liu, Paul Chi-Lui Ho

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A public general hospital in Singapore has recently implemented an automated unit-dose machine in their inpatient dispensary, Swisslog, with the objective of reducing human error and improving patient safety. However, a concern in stability arises as tablets are removed from their original packaging (bottled loose tablets/capsules) and are repackaged into individual, clear plastic wrappers as unit doses in the system. Drugs that are light-sensitive and hygroscopic would be more susceptible to degradation as the wrapper does not offer full protection. Hence, this study was carried out to study the stability of haloperidol tablets and phenytoin capsules that are light-sensitive and hygroscopic respectively. Validated HPLC-UV assays were first established for quantification of these two compounds. The medications involved were put in the Swisslog and sampled every week for one month. The collected data was analysed and showed no degradation over time. This study also explored an alternative approach for drug stability determination-Raman spectroscopy. The advantage of Raman spectroscopy is its high time efficiency and non-destructive nature. The results suggest that drug degradation can indeed be detected using Raman microscopy, but further research is needed to establish this approach for quantification or qualification of compounds. NanoRam®, a portable Raman spectrocope was also used alongside Raman microscopy but was unsuccessful in detecting degradation in this study.

Keywords: drug stability, haloperidol, HPLC, phenytoin, raman spectroscopy, Swisslog

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Sun Zhe, Ruggero Micheletto

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The research of neural network is very important for the development of advanced next generation intelligent devices and the medical treatment. The most important part of the neural network research is the learning. The process of learning in our brain is essentially several adjustment processes of connection strength between neurons. It is very difficult to figure out how this mechanism works in the complex network and how the connection strength influences brain functions. For this reason, we made a model with only two coupled neurons and studied the influence of connection strength between them. To emulate the neuronal activity of realistic neurons, we prefer to use the Izhikevich neuron model. This model can simulate the neuron variables accurately and it’s simplicity is very suitable to implement on computers. In this research, the parameter ρ is used to estimate the correlation coefficient between spike train of two coupling neurons.We think the results is very important for figuring out the mechanism between synchronization of coupling neurons and synaptic plasticity. The result also presented the importance of the spike frequency adaptation in complex systems.

Keywords: neural networks, noise, stochastic processes, coupled neurons, correlation coefficient, synchronization, pacemaker, synaptic plasticity

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Authors: Venkat Garigapati

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To date, more than a dozen oligonucleotide products are approved as injectable products for clinical use. However, there is no single oligo nucleotide product approved for clinical use. Oral delivery of oligo nucleotides is patient friendly administration however, many challenges involved in the development of oral formulation. Over the course of last twenty plus years, the research in this space aimed to address these challenges. This paper describes the issues involved in solubility, stability, enzymatic (nuclease) induced degradation, and permeation of nucleotides in the Gastrointestinal (GI) and how to overcome these challenges. Also, the translation of in vitro data to in vivo models hinders the formulation development. This paper describes the challenges involved in the development of Oligo Nucleotide products for oral administration. It also discusses the chemistry and formulation strategies for oral administration of oligonucleotides.

Keywords: oral adminstration, oligo nucleotides, stability, permeation, gastrointestinal tract

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Authors: Ivy Rose Mathew

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The purpose of this study is to outline the efficacy of technology and the opportunities it can bring to implement a successful delivery model in Distance Learning. Distance Learning has proliferated over the past few years across the world. Some of the current challenges faced by current students of distance education include lack of motivation, a sense of isolation and a need for greater and improved communication. Hence the author proposes a creative technology supported model for distance learning exactly mirrored on the traditional face to face learning that can be adopted by distance learning providers. This model suggests the usage of a range of technologies and social networking facilities, with the aim of creating a more engaging and sustaining learning environment to help overcome the isolation often noted by distance learners. While discussing the possibilities, the author also highlights the complexity and practical challenges of implementing such a model. Design/methodology/approach: Theoretical issues from previous research related to successful models for distance learning providers will be considered. And also the analysis of a case study from one of the largest private tertiary institution in Botswana, Botho University will be included. This case study illustrates important aspects of the distance learning delivery model and provides insights on how curriculum development is planned, quality assurance is done, and learner support is assured for successful distance learning experience. Research limitations/implications: While some of the aspects of this study may not be applicable to other contexts, a number of new providers of distance learning can adapt the key principles of this delivery model.

Keywords: distance learning, efficacy, learning experience, technology supported model

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Authors: Nabil A. Albaser

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Background: There is a serious problem with adverse drug reactions (ADRs) everywhere, including Yemen. Since it helps with the detection, assessment, reporting and prevention of ADRs, pharmacovigilance (PV) is an essential part of the healthcare system. The unbiased reporting of ADRs remains the foundation of PV. Students majoring in healthcare should acquire the knowledge and skills necessary to conduct PV in a range of clinical settings. The primary objective of this study was to evaluate the understanding and attitudes of final-year Pharmacy, Nursing, and Midwifery students at Al-Razi University in Sana'a, Yemen, regarding PV and ADRs reporting. Methods: The study followed descriptive cross-sectional approach. A validated, self-administered questionnaire with three parts—demographic information, knowledge, and perceptions of Pharmacovigilance was online distributed to final-year Pharmacy, Nursing, and Midwifery students. The questionnaire was given to 175 students; 122 of them responded with a percentage (69.7%). Results: The majority of respondents were male (79.5%). More than the tow-third of the students, 68.9%, were beyond the age of 23. Although the majority of students, 80%, heard about the terms of ADRs and PV, but only 50% and 57.4% of the respondents, respectively, could define the both terms correctly. However, only 11.48 % of them, nevertheless, took a PV course. More than a half of them (56.6%) had a positive perceptions towards pharmacovigilance and ADR reporting and had a moderate degree of knowledge (68.9%). Conclusion: The study demonstrated that the participants lacked sufficient knowledge of pharmacovigilance and ADR reporting. They showed a moderate level of understanding of reporting ADRs as well as a favorable opinion of dealing with and reporting ADRs. Yemen's health care curriculum should include lessons on pharmacovigilance.

Keywords: adverse drug reaction reporting, pharmacovigilance, yemen, knowlegde

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Authors: Valencia Fernandes, Dharmendra Kumar Khatri, Shashi Bala Singh

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Background and Aim: Epigenetics are the inaudible signatures of several pathological processes in the brain. This study understands the influence of DNA methylation, a major epigenetic modification, in the prefrontal cortex and hippocampus of the diabetic brain and its notable effect on the cellular chaperones and synaptic proteins. Method: Chronic high fat diet and STZ-induced diabetic mice were studied for cognitive dysfunction, and global DNA methylation, as well as DNA methyltransferase (DNMT) activity, were assessed. Further, the cellular chaperones and synaptic proteins were examined using DNMT inhibitor, 5-aza-2′-deoxycytidine (5-aza-dC)-via intracerebroventricular injection. Moreover, % methylation of these synaptic proteins were also studied so as to correlate its epigenetic involvement. Computationally, its interaction with the DNMT enzyme were also studied using bioinformatic tools. Histological studies for morphological alterations and neuronal degeneration were also studied. Neurogenesis, a characteristic marker for new learning and memory formation, was also assessed via the BrdU staining. Finally, the most important behavioral studies, including the Morris water maze, Y maze, passive avoidance, and Novel object recognition test, were performed to study its cognitive functions. Results: Altered global DNA methylation and increased levels of DNMTs within the nucleus were confirmed in the cortex and hippocampus of the diseased mice, suggesting hypermethylation at a genetic level. Treatment with AzadC, a global DNA demethylating agent, ameliorated the protein and gene expression of the cellular chaperones and synaptic fidelity. Furthermore, the methylation analysis profile showed hypermethylation of the hsf1 protein, a master regulator for chaperones and thus, confirmed the epigenetic involvement in the diseased brain. Morphological improvements and decreased neurodegeneration, along with enhanced neurogenesis in the treatment group, suggest that epigenetic modulations do participate in learning and memory. This is supported by the improved behavioral test battery seen in the treatment group. Conclusion: DNA methylation could possibly accord in dysregulating the memory-associated proteins at chronic stages in type 2 diabetes. This could suggest a substantial contribution to the underlying pathophysiology of several metabolic syndromes like insulin resistance, obesity and also participate in transitioning this damage centrally, such as cognitive dysfunction.

Keywords: epigenetics, cognition, chaperones, DNA methylation

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Authors: Chang-Hwan Oh, Young-Jong Lee

Abstract:

In April, 2015, the Ministry of Food and Drug Safety’s announcement that only 10 of the 207 products that list Cynanchum Wilfordii Radix among their ingredients were confirmed to actually contain “iyeobupiso” the counterfeit version of the “baeksuo” raised a fog to consumers who purchased health/functional foods supposedly containing the herbal medicinal material, “baeksuo” in Korean. Baeksuo is the main ingredient of the product “EstroG-100” that contain Phlomis umbrosa and Angelica gigas too (NaturalEndoTech, S.Korea). The hot water extract of the herbal medicinal materials (HMM) was approved as a product specific Health/Functional Food (HFF) having a helpful function to women reaching menopause by Korea Food & Drug Administration (Ministry of Food & Drug Safety at present). The origin of “baeksuo” is the root of Cynanchum wilfordii Hemsley in Korea (But “iyeobupiso, the root of Cynanchum auriculatum Royle ex Wight is considered as the origin of “baeksuo” in China). In Korea, about 116 HMMs are listed as the food materials in Korea Food Code among the total 187 HMMs could be used for food and medicine purpose simultaneously. But there are some chances of the HMMs (shared use for food and medicine purpose) could be misused by the part and HMMs not permitted for HFF such as the “baeksuo” case. In this study, some of HMMs (shared use for food and medicine purpose) are examined to alleviate the misuse chance of HMMs for HFFs in Korea. For the purpose of this study, the origin, shape, edible parts, efficacy and the side effects of the similar HMMs to be misused for HFF are investigated.

Keywords: herbal medicinal materials, healthy/functional foods, misuse, shared use

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Authors: Seolah Lee, Yoohyk Jang, Soyoung Lee, Kon Chu, Sang Kun Lee

Abstract:

Objective: The International League Against Epilepsy (ILAE) currently suggests a topiramate serum level range of 5-20 mg/L. However, numerous institutions have observed substantial drug response at lower levels. This study aims to investigate the correlation between topiramate serum levels, drug responsiveness, and adverse events to establish a more accurate and tailored therapeutic range. Methods: We retrospectively analyzed topiramate serum samples collected between January 2017 and January 2022 at Seoul National University Hospital. Clinical data, including serum levels, antiseizure regimens, seizure frequency, and adverse events, were collected. Patient responses were categorized as "insufficient" (reduction in seizure frequency <50%) or "sufficient" (reduction ≥ 50%). Within the "sufficient" group, further subdivisions included seizure-free and tolerable seizure subgroups. A population pharmacokinetic model estimated serum levels from spot measurements. ROC curve analysis determined the optimal serum level cut-off. Results: A total of 389 epilepsy patients, with 555 samples, were reviewed, having a mean dose of 178.4±117.9 mg/day and a serum level of 3.9±2.8 mg/L. Out of the samples, only 5.6% (n=31) exhibited insufficient response, with a mean serum level of 3.6±2.5 mg/L. In contrast, 94.4% (n=524) of samples demonstrated sufficient response, with a mean serum level of 4.0±2.8 mg/L. This difference was not statistically significant (p = 0.45). Among the 78 reported adverse events, logistic regression analysis identified a significant association between ataxia and serum concentration (p = 0.04), with an optimal cut-off value of 6.5 mg/L. In the subgroup of patients receiving monotherapy, those in the tolerable seizure group exhibited a significantly higher serum level compared to the seizure-free group (4.8±2.0 mg/L vs 3.4±2.3 mg/L, p < 0.01). Notably, patients in the tolerable seizure group displayed a higher likelihood of progressing into drug-resistant epilepsy during follow-up visits compared to the seizure-free group. Significance: This study proposed an optimal therapeutic concentration for topiramate based on the patient's responsiveness to the drug and the incidence of adverse effects. We employed a population pharmacokinetic model and analyzed topiramate serum levels to recommend a serum level below 6.5 mg/L to mitigate the risk of ataxia-related side effects. Our findings also indicated that topiramate dose elevation is unnecessary for suboptimal responders, as the drug's effectiveness plateaus at minimal doses.

Keywords: topiramate, therapeutic range, low dos, antiseizure effect

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Authors: Arvind Aggarwal

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We have developed a comprehensive global healthcare delivery System based on information technology. It has medical consultation system where a virtual consultant can give medical consultation to the patients and Doctors at the digital medical centre after reviewing the patient’s EMR file consisting of patient’s history, investigations in the voice, images and data format. The system has the surgical operation system too, where a remote robotic consultant can conduct surgery at the robotic surgical centre. The instant speech and text translation is incorporated in the software where the patient’s speech and text (language) can be translated into the consultant’s language and vice versa. A consultant of any specialty (surgeon or Physician) based in any country can provide instant health care consultation, to any patient in any country without loss of time. Robotic surgeons based in any country in a tertiary care hospital can perform remote robotic surgery, through patient friendly telemedicine and tele-surgical centres. The patient EMR, financial data and data of all the consultants and robotic surgeons shall be stored in cloud. It is a complete comprehensive business model with healthcare medical and surgical delivery system. The whole system is self-financing and can be implemented in any country. The entire system uses paperless, filmless techniques. This eliminates the use of all consumables thereby reduces substantial cost which is incurred by consumables. The consultants receive virtual patients, in the form of EMR, thus the consultant saves time and expense to travel to the hospital to see the patients. The consultant gets electronic file ready for reporting & diagnosis. Hence time spent on the physical examination of the patient is saved, the consultant can, therefore, spend quality time in studying the EMR/virtual patient and give his instant advice. The time consumed per patient is reduced and therefore can see more number of patients, the cost of the consultation per patients is therefore reduced. The additional productivity of the consultants can be channelized to serve rural patients devoid of doctors.

Keywords: e-health, telemedicine, telecare, IT-based healthcare

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Authors: Wei-Han Wang, Hsiang-Yu Yu, Mau-Sun Hua

Abstract:

Theory of Mind (ToM) refers to the ability to infer another’s mental state. With appropriate ToM, one can behave well in social interactions. A growing body of evidence has demonstrated that patients with temporal lobe epilepsy (TLE) may have damaged ToM due to impact on regions of the underlying neural network of ToM. However, the question of whether there is cerebral laterality for ToM functions remains open. This study aimed to examine whether there is cerebral lateralization for ToM abilities in TLE patients. Sixty-seven adult TLE patients and 30 matched healthy controls (HC) were recruited. Patients were classified into right (RTLE), left (LTLE), and bilateral (BTLE) TLE groups on the basis of a consensus panel review of their seizure semiology, EEG findings, and brain imaging results. All participants completed an intellectual test and four tasks measuring basic and advanced ToM. The results showed that, on all ToM tasks; (1)each patient group performed worse than HC; (2)there were no significant differences between LTLE and RTLE groups; (3)the BTLE group performed the worst. It appears that the neural network responsible for ToM is distributed evenly between the cerebral hemispheres.

Keywords: cerebral lateralization, social cognition, temporal lobe epilepsy, theory of mind

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Authors: Takashi Kaburagi, Takamasa Komura, Yosuke Kurihara

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Absolute pitch is the ability to identify a musical note without a reference tone. Training for absolute pitch often occurs in preschool education. It is necessary to clarify how well the trainee can make use of synesthesia in order to evaluate the effect of the training. To the best of our knowledge, there are no existing methods for objectively confirming whether the subject is using synesthesia. Therefore, in this study, we present a method to distinguish the use of color-auditory synesthesia from the separate use of color and audition during absolute pitch training. This method measures blood volume in the prefrontal cortex using functional Near-infrared spectroscopy (fNIRS) and assumes that the cognitive step has two parts, a non-linear step and a linear step. For the linear step, we assume a second order ordinary differential equation. For the non-linear part, it is extremely difficult, if not impossible, to create an inverse filter of such a complex system as the brain. Therefore, we apply a method based on a self-organizing map (SOM) and are guided by the available data. The presented method was tested using 15 subjects, and the estimation accuracy is reported.

Keywords: absolute pitch, functional near-infrared spectroscopy, prefrontal cortex, synesthesia

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Authors: Mohan L. Jayatiake, Judd Storrs, Jing-Huei Lee

Abstract:

The optimal MRI resolution relies on a homogeneous magnetic field. However, local susceptibility variations can lead to field inhomogeneities that cause artifacts such as image distortion and signal loss. The effects of local susceptibility variation notoriously increase with magnetic field strength. Active shimming improves homogeneity by applying corrective fields generated from shim coils, but requires calculation of optimal current for each shim coil. FASTMAP (fast automatic shimming technique by mapping along projections) is an effective technique for finding optimal currents works well at high-field, but is restricted to shimming spherical regions of interest. The 3D gradient-echo pulse sequence was modified to reduce sensitivity to eddy currents and used to obtain susceptibility field maps at 4T. Measured fields were projected onto first-and second-order spherical harmonic functions corresponding to shim hardware. A spherical phantom was used to calibrate the shim currents. Susceptibility maps of a volunteer’s brain with and without FASTMAP shimming were obtained. Simulations indicate that optimal shim currents derived from the field map may provide better overall shimming of the human brain.

Keywords: shimming, high-field, active, passive

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Authors: Paresh M. Patel, Amit A. Patel, R. H. Parikh

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The present investigation was undertaken to fabricate modified transport fluconazole that belongs to BCS class II and have a poor applicability on topical infection. So to improve topical application, transdermal spray could play a vital role by using ethyl cellulose and Eudragit® S100 as film-forming polymers. Concentration of Eudragit® S100, ethyl cellulose and permeation enhancer (camphor and menthol) were selected as independent variables, whereas drying time, viscosity and in-vitro drug release were selected as dependent variables in factorial design. The viscosity, drying time and in-vitro drug release of the optimize batch B15 was 40.1 cps, 47 sec. and 90.79% respectively. The film of optimized batch was flexible and dermal-adhesive.

Keywords: Eudragit, ethyl cellulose, fluconazole, transdermal spray

Procedia PDF Downloads 456