Search results for: brain tumor
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1859

Search results for: brain tumor

599 Enhancing Sensitization of Cervical Cancer Cells to γ-Radiation Ellagic Acid

Authors: Vidhula Ahire, Amit Kumar, K. P. Mishra, Gauri Kulkarni

Abstract:

Herbal polyphenols have gained significance because of their increasing promise in prevention and treatment of cancer. Therefore, development of a dietary compound as an effective radiosensitizer and a radioprotector is highly warranted for cervical cancer patients undergoing therapy. This study describes the cytotoxic effects of the flavonoid, ellagic acid (EA) when administered either alone or in combination with gamma radiation on cervical cancer HeLa cells in vitro. Apoptotic index and proliferation were measured by using trypan blue assay. Reproductive cell death was analyzed by clonogenic assay. Propidium iodide staining for flowcytometry was performed to analyze cell cycle modulation. Nuclear and mitochondrial changes were studied with specific dyes. DNA repair kinetics was analyzed by immunofluorescence assay. Evaluation and comparison of EA effects were performed with other clinically used breast cancer drugs. When tumor cells were exposed to 2 and 4 Gy of irradiation in presence of EA (10 μM), it yielded a synergistic cytotoxic effect on cervical cancer cells whereas in NIH3T3 cells it reversed the injury caused by irradiation and abetted in the regaining of normal healthy cells. At 24h ~25foci/cell was observed and 2.6 fold decrease in the mitochondrial membrane potential. Up to 40% cell were arrested in the G1 phase and 20-36% cells exhibited apoptosis. Our results demonstrate the role of increased apoptosis and cell cycle modulation in the mechanism of EA mediated radiosensitization of cervical cancer cells and thus advocating EA as an adjuvant for preclinical trials in cancer chemo- radiotherapy.

Keywords: cervical cancer, ellagic acid, sensitization, radiation therapy

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598 CD133 and CD44 - Stem Cell Markers for Prediction of Clinically Aggressive Form of Colorectal Cancer

Authors: Ognen Kostovski, Svetozar Antovic, Rubens Jovanovic, Irena Kostovska, Nikola Jankulovski

Abstract:

Introduction:Colorectal carcinoma (CRC) is one of the most common malignancies in the world. The cancer stem cell (CSC) markers are associated with aggressive cancer types and poor prognosis. The aim of study was to determine whether the expression of colorectal cancer stem cell markers CD133 and CD44 could be significant in prediction of clinically aggressive form of CRC. Materials and methods: Our study included ninety patients (n=90) with CRC. Patients were divided into two subgroups: with metatstatic CRC and non-metastatic CRC. Tumor samples were analyzed with standard histopathological methods, than was performed immunohistochemical analysis with monoclonal antibodies against CD133 and CD44 stem cell markers. Results: High coexpression of CD133 and CD44 was observed in 71.4% of patients with metastatic disease, compared to 37.9% in patients without metastases. Discordant expression of both markers was found in 8% of the subgroup with metastatic CRC, and in 13.4% of the subgroup without metastatic CRC. Statistical analyses showed a significant association of increased expression of CD133 and CD44 with the disease stage, T - category and N - nodal status. With multiple regression analysis the stage of disease was designate as a factor with the greatest statistically significant influence on expression of CD133 (p <0.0001) and CD44 (p <0.0001). Conclusion: Our results suggest that the coexpression of CD133 and CD44 have an important role in prediction of clinically aggressive form of CRC. Both stem cell markers can be routinely implemented in standard pathohistological diagnostics and can be useful markers for pre-therapeutic oncology screening.

Keywords: colorectal carcinoma, stem cells, CD133+, CD44+

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597 Detecting Music Enjoyment Level Using Electroencephalogram Signals and Machine Learning Techniques

Authors: Raymond Feng, Shadi Ghiasi

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An electroencephalogram (EEG) is a non-invasive technique that records electrical activity in the brain using scalp electrodes. Researchers have studied the use of EEG to detect emotions and moods by collecting signals from participants and analyzing how those signals correlate with their activities. In this study, researchers investigated the relationship between EEG signals and music enjoyment. Participants listened to music while data was collected. During the signal-processing phase, power spectral densities (PSDs) were computed from the signals, and dominant brainwave frequencies were extracted from the PSDs to form a comprehensive feature matrix. A machine learning approach was then taken to find correlations between the processed data and the music enjoyment level indicated by the participants. To improve on previous research, multiple machine learning models were employed, including K-Nearest Neighbors Classifier, Support Vector Classifier, and Decision Tree Classifier. Hyperparameters were used to fine-tune each model to further increase its performance. The experiments showed that a strong correlation exists, with the Decision Tree Classifier with hyperparameters yielding 85% accuracy. This study proves that EEG is a reliable means to detect music enjoyment and has future applications, including personalized music recommendation, mood adjustment, and mental health therapy.

Keywords: EEG, electroencephalogram, machine learning, mood, music enjoyment, physiological signals

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596 Hybrid-Nanoengineering™: A New Platform for Nanomedicine

Authors: Mewa Singh

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Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

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595 The application of Gel Dosimeters and Comparison with other Dosimeters in Radiotherapy: A Literature Review

Authors: Sujan Mahamud

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Purpose: A major challenge in radiotherapy treatment is to deliver precise dose of radiation to the tumor with minimum dose to the healthy normal tissues. Recently, gel dosimetry has emerged as a powerful tool to measure three-dimensional (3D) dose distribution for complex delivery verification and quality assurance. These dosimeters act both as a phantom and detector, thus confirming the versatility of dosimetry technique. The aim of the study is to know the application of Gel Dosimeters in Radiotherapy and find out the comparison with 1D and 2D dimensional dosimeters. Methods and Materials: The study is carried out from Gel Dosimeter literatures. Secondary data and images have been collected from different sources such as different guidelines, books, and internet, etc. Result: Analyzing, verifying, and comparing data from treatment planning system (TPS) is determined that gel dosimeter is a very excellent powerful tool to measure three-dimensional (3D) dose distribution. The TPS calculated data were in very good agreement with the dose distribution measured by the ferrous gel. The overall uncertainty in the ferrous-gel dose determination was considerably reduced using an optimized MRI acquisition protocol and a new MRI scanner. The method developed for comparing measuring gel data with calculated treatment plans, the gel dosimetry method, was proven to be a useful for radiation treatment planning verification. In 1D and 2D Film, the depth dose and lateral for RMSD are 1.8% and 2%, and max (Di-Dj) are 2.5% and 8%. Other side 2D+ ( 3D) Film Gel and Plan Gel for RMSDstruct and RMSDstoch are 2.3% & 3.6% and 1% & 1% and system deviation are -0.6% and 2.5%. The study is investigated that the result fined 2D+ (3D) Film Dosimeter is better than the 1D and 2D Dosimeter. Discussion: Gel Dosimeters is quality control and quality assurance tool which will used the future clinical application.

Keywords: gel dosimeters, phantom, rmsd, QC, detector

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594 Usage of Cord Blood Stem Cells of Asphyxia Infants for Treatment

Authors: Ahmad Shah Farhat

Abstract:

Background: Prenatal asphyxia or birth asphyxia is the medical situation resulting from a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain. Human umbilical cord blood (UCB) is a well-established source of hematopoietic stem/progenitor cells (HSPCs) for allogeneic stem cell transplantation. These can be used clinically to care for children with malignant diseases. Low O2 can cause in proliferation and differentiation of stem cells. Method: the cord blood of 11 infants with 3-5 Apgar scores or need to cardiac pulmonary Resuscitation as an asphyxia group and ten normal infants with more than 8 Apgar scores as the normal group was collected, and after isolating hematopoietic stem cells, the cells were cultured in enriched media for 14 days to compare the numbers of colonies by microscope. Results: There was a significant difference in the number of RBC precursor colonies (red colonies) in cultured media with 107 cord blood hematopoietic stem cells of infants who were exposed to hypoxemia in two wells of palate. There was not a significant difference in the number of white cell colonies in the two groups in the two wells of the plate. Conclusion: Hypoxia in the perinatal period can cause the increase of hematopoietic stem cells of cord blood, special red precursor stem cells in vitro, like an increase of red blood cells in the body when exposed to low oxygen conditions. Thus, it will be usable.

Keywords: asphyxia, neonre, stem cell, red cell

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593 Artificial Intelligence in Disease Diagnosis

Authors: Shalini Tripathi, Pardeep Kumar

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The method of translating observed symptoms into disease names is known as disease diagnosis. The ability to solve clinical problems in a complex manner is critical to a doctor's effectiveness in providing health care. The accuracy of his or her expertise is crucial to the survival and well-being of his or her patients. Artificial Intelligence (AI) has a huge economic influence depending on how well it is applied. In the medical sector, human brain-simulated intellect can help not only with classification accuracy, but also with reducing diagnostic time, cost and pain associated with pathologies tests. In light of AI's present and prospective applications in the biomedical, we will identify them in the paper based on potential benefits and risks, social and ethical consequences and issues that might be contentious but have not been thoroughly discussed in publications and literature. Current apps, personal tracking tools, genetic tests and editing programmes, customizable models, web environments, virtual reality (VR) technologies and surgical robotics will all be investigated in this study. While AI holds a lot of potential in medical diagnostics, it is still a very new method, and many clinicians are uncertain about its reliability, specificity and how it can be integrated into clinical practice without jeopardising clinical expertise. To validate their effectiveness, more systemic refinement of these implementations, as well as training of physicians and healthcare facilities on how to effectively incorporate these strategies into clinical practice, will be needed.

Keywords: Artificial Intelligence, medical diagnosis, virtual reality, healthcare ethical implications 

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592 Epidemiology of Primary Bronchopulmonary Cancer in Tunisia

Authors: Melliti Rihab, Zaeid Sonia, Khechine Wiem, Daldoul Amira

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Introduction: Lung cancer is the leading cause of cancer death. Its incidence is increasing, and its prognosis remains pejorative. We present the clinical, pathological, and therapeutic characteristics of bronchopulmonary cancer (BPC) in Tunisia. Methods: Retrospective study including patients followed in the oncology department of the University Hospital of Monastir between April 2014 and December 2021 suffering from lung cancer. Results: These are 117 patients, including 86.3% men and 13.7% women (sex ratio 6.3). The average age was 64 years ± 9 (37-83), with 95.7% being over 50 years old. Patients were smokers in 82% of cases. The clinical signs were dominated by chest pain (27.5%) and dyspnea in 21.1% of cases. In 6 patients, an episode of COVID-19 infection revealed the diagnosis. Half of the patients had a PS between 0 and 1. Small cell lung cancer was present in 18 patients (15.4%). The majority of non small cell lung cancer was of the adenocarcinoma type (68.7%). The diagnosis was late (stage IV) in 62.4% of cases. BPC was metastatic to bone (52%), contralateral lung (25.9%), and brain (27.3%). Patients were oligometastatic in 26% of cases. Surgery and radiotherapy were performed respectively in 14.5% and 23.1% of cases. Three-quarters of the patients had had nutrition (75.2%). The ROS1 mutation was present in 1 patient. PDL-1 expression was >40% in 2 patients. Survival was mean eight months ± 7.4. Conclusion: Lung cancer is diagnosed at a late stage in Tunisia. The lack of molecular study for non-small cell PBC and the lack of marketing authorization for tyrosine kinase inhibitors in Tunisia make the management incomplete.

Keywords: SCLC, NCSLC, ROS1, PDL1

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591 The Effect of Endurance Training and Ginseng Consumption on VEGF and PDGF Plasma in Untrained Females

Authors: Barari Alireza, Seyed Hossein Alavi, Ghasemi Mohamad

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Objectives: VEGF and PDGF play central role in the processes of angiogenesis and vascular changes in most body tissues. The aim of the present study to determine effect of endurance training with ginseng on VEGF and PDGF levels is untrained female. Methods: Statistic society of this study was untraining male students of Azad University of Sari Branch in year of 2012-2013. Forty young untrained female (age 21.3 ± 0.90 year, height162.08±8.07cm , body weight 65.45± 7.6 kg and body mass index [BMI] 23.23 ± 2.64 kg/m2) were randomly divided into four groups: control(C), endurance(E), ginseng (G), endurance and ginseng (EG). Participants in training groups performed endurance training for 6 weeks and three sessions per week with 60-80% HRmax. Subjects perform endurance training and consumed ginseng for six weeks. Blood samples from the subjects before and after the test was performed. One wey ANOVA were used to test for differences between group and pair T-test were used for differences within groups. In all cases, P<0.05 was considered to be statistically significant. Results: A higher and significant Vo2 max was found in E and EG groups, while no change in other groups. BMI and Fat% were significantly decreased in EG group. No significant difference was found between and within groups in VEGF level. A higher and significant PDGF was only in endurance group, while there was significant reduction observed in G and EG groups. One-way ANOVA for PDGF showed significant difference between groups. Conclusion: The finding of the current study indicated that ginseng likely could through reducing of angiogenesis factors Such as VEGF and PDGF and reduced activity of tumor necrosis factor and inhibited inflammatory process.

Keywords: endurance, ginseng, VEGF, PDGF, untrained female

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590 Serum Levels of Plasminogen Activator Inhibitor-1 (PAI-1) Are Increased in Alzheimer’s Disease and MCI Patients and Correlate With Cognitive Deficits

Authors: Francesco Angelucci, Katerina Veverova, Alžbeta Katonová, Lydia Piendel, Martin Vyhnalek, Jakub Hort

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Alzheimer's disease (AD) is a central nervous system (CNS) disease characterized by loss of memory, cognitive functions and neurodegeneration. Plasmin is an enzyme degrading many plasma proteins. In the CNS, plasmin may reduce the accumulation of A, and have other actions relevant to AD pathophysiology. Brain plasmin synthesis is regulated by two enzymes: one activating, the tissue plasminogen activator (tPA), and the other inhibiting, the plasminogen activator inhibitor-1 (PAI-1). We investigated whether tPA and PAI-1 serum levels in AD and amnestic mild cognitive impairment (aMCI) patients are altered compared to cognitively healthy controls. Moreover, we examined the PAI-1/tPA ratio in these patient groups. 40 AD, 40 aMCI and 10 healthy controls were recruited. Venous blood was collected and PAI-1 and tPA serum concentrations were quantified by sandwich ELISAs. The results showed that PAI-1 levels increased in AD and aMCI patients. This increase negatively correlated with cognitive deficit measured by MMSE. Similarly, the ratio between tPA and PAI-1 gradually increases in aMCI and AD patients. This study demonstrates that AD and aMCI patients have altered PAI-1 serum levels and PAI-1/tPA ratio. Since these enzymes are CNS regulators of plasmin, PAI-1 serum levels could be a marker reflecting a cognitive decline in AD.

Keywords: Alzheimer disease, amnestic mild cognitive impairment, plasmin, tissue-type plasminogen activator

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589 Nitric Oxide: Role in Immunity and Therapeutics

Authors: Anusha Bhardwaj, Shekhar Shinde

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Nitric oxide (NO•) has been documented in research papers as one of the most versatile player in the therapeutics. It is identified as a biological multifunctional messenger molecule which is synthesized by the action of nitric oxide synthase (NOS) enzyme from L-arginine. The protective and the toxic effect in conjunction form the complete picture of the biological function of nitric oxide in humans. The dual nature is because of various factors such as concentration of NO, the isoform of NOS involved, type of cells in which it is synthesized, reaction partners like proteins, reactive oxygen intermediates, prosthetic groups, thiols etc., availability of the substrate L-arginine, intracellular environment in which NO is produced and generation of guanosine 3, 5’- cyclic monophosphate (cGMP). Activation of NOS through infection or trauma leads to one or more systemic effects including enhanced immune activity against invading pathogens, vaso/bronchodilatation in the cardiovascular and respiratory systems and altered neurotransmission which can be protective or toxic. Hence, NO affects the balance between healthy signaling and neurodegeneration in the brain. In lungs, it has beneficial effects on the function of airways as a bronchodilator and acts as the neurotransmitter of bronchodilator nerves. Whereas, on the other hand, NO may have deleterious effects by amplifying the asthmatic inflammatory response and also act as a vasodilator in the airways by increasing plasma exudation. But NOS Inhibitors and NO donors hamper the signalling pathway and hence a therapeutic application of NO is compromised.

Keywords: nitric oxide, multifunctional, dual nature, therapeutic applications

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588 Towards Overturning the Dismal Mathematics Performance in Schools by Capitalizing on the Overlooked Cognitive Prowess for Adolescents to Learn Mathematics

Authors: Dudu Ka Ruth Mkhize

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Adolescents are at the front and centre of poor mathematics performance in schools. Literature has concluded in some countries that there is a permanent and perpetual mathematics crisis in schools of the persistent poor performance in mathematics by teens. There is no shortage of interventions and research to solve this problem. However, none has capitalised on the cognitive prowess of adolescents, which was revealed at the turn of the century by the introduction of neuroimaging technologies such as structural and functional magnetic resonance imaging (sMRI and fMRI). This research found that brain growth during adolescence results in enhanced cognitive abilities essential for mathematics learning. This paper is based on the four-year case study of rural high school adolescents who had a negative attitude towards mathematics and hence were failing mathematics. But through a ten-day intervention where teaching revolved around invoking their cognitive ability, their attitude and motivation for mathematics changed for the better. The paper concludes that despite educational psychology being part of teacher education as well as education systems, there are numerous overlooked gems of psychological theories which have the potential to enhance academic achievement for youth in schools. A recommendation is made to take cues from positive psychology, whose establishment was a rejection of the dominance of the disease model in psychology. Similarly, the general perspective of poor mathematics performance can take a u-turn towards the cognitive ability acquired by adolescents because of their developmental stage.

Keywords: adolescence, cognitive growth, mathematics performance

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587 Comparing the Efficacy of Quantitative Electroencephalogram-Based Neurofeedback Therapy Program versus Organizational Skills Training Program to Reduce the Core Symptoms among Children Group of ADHD

Authors: Radwa R. El-Saadany , Medhat Abu Zeid, Tarek Omar, Marwa S. Maqsoud

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Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders characterized by attention deficit, hyperactivity, and impulsivity. Neurofeedback (NF) is one of the neurotherapy treatments that cause brain wave changes. Method: The current pseudo-experimental study with a pre–post-test design was conducted on a population of children with attention deficit hyperactivity disorder (ADHD).The sample size comprised of (30) children selected by random sampling method and assigned to two therapeutic groups: First therapeutic group received a neurofeedback program. Based on QEEG, it reached (10) children. The second therapeutic group received an organization skills training program, it reached (10) and the control group that did not receive programs, it reached (10) children. Results: There are significant differences between pre- and post-assessments among therapeutic groups in reducing the three core symptoms of ADHD in favor of post measurement. There are no significant differences between post-assessment and follow up measurement of the therapeutic groups.

Keywords: QEEG-based neurofeedback therapy program, organizational skills training program, attention deficit hyperactivity disorder

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586 Evaluation of Goji By-Product as a Value-Added Ingredient for the Functional Food Industry

Authors: Sanaa Ragaee, Paragyani Bora, Wee Teng Tan, Xin Hu

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Goji berry (Lycium barbarum) is a member of the family Solanaceae which is grown widely in China, Tibet, and other parts of Asia. Its fruits are 1–2 cm-long, bright orange-red ellipsoid berries and it has a long tradition as a food and medicinal plant. Goji berries are believed to boost immune system properties. The berries are considered an excellent source of macronutrients, micronutrients, vitamins, minerals and several bioactive components. Studies have shown effects of goji fruit on aging, neuroprotection, general well-being, fatigue/endurance, metabolism/energy expenditure, glucose control in diabetics and glaucoma, antioxidant properties, immunomodulation and anti-tumor activity. Goji berries are being used to prepare Goji beverage, and the remaining solid material is considered as by-product. The by-product is currently unused and disposed as waste despite its potential as a value-added food ingredient. Therefore, this study is intended to evaluate nutritional properties of Goji by-product and its potential applications in the baking industry. The Goji by-product was freeze dried and ground to pass through 1 mm screen prior to evaluation and food use. The Goji by-product was found to be a rich source of fiber (54%) and free phenolic components (1,307 µg/g), protein (13.6%), ash (3.3%) and fat (10%). Incorporation of the Goji by-product in muffins and cookies at various levels (10-40%) significantly improved the nutritional quality of the baked products. The baked products were generally accepted and highly rated by panelists at 20% replacement level. The results indicate the potential of Goji by-product as a value-added ingredient in particular as a source of dietary fiber and protein.

Keywords: Goji, by-product, phenolics, fibers, baked products

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585 Creative Potential of Children with Learning Disabilities

Authors: John McNamara

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Growing up creative is an important idea in today’s classrooms. As education seeks to prepare children for their futures, it is important that the system considers traditional as well as non-traditional pathways. This poster describes the findings of a research study investigating creative potential in children with learning disabilities. Children with learning disabilities were administered the Torrance Test of Creative Problem Solving along with subtests from the Comprehensive Test of Phonological Processing. A quantitative comparative analysis was computed using paired-sample t-tests. Results indicated statistically significant difference between children’s creative problem-solving skills and their reading-based skills. The results lend support to the idea that children with learning disabilities have inherent strengths in the area of creativity. It can be hypothesized that the success of these children may be associated with the notion that they are using a type of neurological processing that is not otherwise used in academic tasks. Children with learning disabilities, a presumed left-side neurological processing problem, process information with the right side of the brain – even with tasks that should be processed with the left side (i.e. language). In over-using their right hemisphere, it is hypothesized that children with learning disabilities have well-developed right hemispheres and, as such, have strengths associated with this type of processing, such as innovation and creativity. The current study lends support to the notion that children with learning disabilities may be particularly primed to succeed in areas that call on creativity and creative thinking.

Keywords: learning disabilities, educational psychology, education, creativity

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584 Fabrication of Drug-Loaded Halloysite Nanotubes Containing Sodium Alginate/Gelatin Composite Scaffolds

Authors: Masoumeh Haghbin Nazarpak, Hamidreza Tolabi, Aryan Ekhlasi

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Bone defects are mentioned as one of the most challenging clinical conditions, affecting millions of people each year. A fracture, osteoporosis, tumor, or infection usually causes these defects. At present, autologous and allogeneic grafts are used to correct bone defects, but these grafts have some difficulties, such as limited access, infection, disease transmission, and immune rejection. Bone tissue engineering is considered a new strategy for repairing bone defects. However, problems with scaffolds’ design with unique structures limit their clinical applications. In addition, numerous in-vitro studies have been performed on the behavior of bone cells in two-dimensional environments. Still, cells grow in physiological situations in the human body in a three-dimensional environment. As a result, the controlled design of porous structures with high structural complexity and providing the necessary flexibility to meet specific needs in bone tissue repair is beneficial. For this purpose, a three-dimensional composite scaffold based on gelatin and sodium alginate hydrogels is used in this research. In addition, the antibacterial drug-loaded halloysite nanotubes were introduced into the hydrogel scaffold structure to provide a suitable substrate for controlled drug release. The presence of halloysite nanotubes improved hydrogel’s properties, while the drug eliminated infection and disease transmission. Finally, it can be acknowledged that the composite scaffold prepared in this study for bone tissue engineering seems promising.

Keywords: halloysite nanotubes, bone tissue engineering, composite scaffold, controlled drug release

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583 Clinically-Based Improvement Project Focused on Reducing Risks Associated with Diabetes Insipidus, Syndrome of Inappropriate ADH, and Cerebral Salt Wasting in Paediatric Post-Neurosurgical and Traumatic Brain Injury Patients

Authors: Shreya Saxena, Felix Miller-Molloy, Phillipa Bowen, Greg Fellows, Elizabeth Bowen

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Background: Complex fluid balance abnormalities are well-established post-neurosurgery and traumatic brain injury (TBI). The triple-phase response requires fluid management strategies reactive to urine output and sodium homeostasis as patients shift between Diabetes Insipidus (DI) and Syndrome of Inappropriate ADH (SIADH). It was observed, at a tertiary paediatric center, a relatively high prevalence of the above complications within a cohort of paediatric post-neurosurgical and TBI patients. An audit of the clinical practice against set institutional guidelines was undertaken and analyzed to understand why this was occurring. Based on those results, new guidelines were developed with structured educational packages for the specialist teams involved. This was then reaudited, and the findings were compared. Methods: Two independent audits were conducted across two time periods, pre and post guideline change. Primary data was collected retrospectively, including both qualitative and quantitative data sets from the CQUIN neurosurgical database and electronic medical records. All paediatric patients post posterior fossa (PFT) or supratentorial surgery or with a TBI were included. A literature review of evidence-based practice, initial audit data, and stakeholder feedback was used to develop new clinical guidelines and nursing standard operation procedures. Compliance against these newly developed guidelines was re-assessed and a thematic, trend-based analysis of the two sets of results was conducted. Results: Audit-1 January2017-June2018, n=80; Audit-2 January2020-June2021, n=30 (reduced operative capacity due to COVID-19 pandemic). Overall, improvements in the monitoring of both fluid balance and electrolyte trends were demonstrated; 51% vs. 77% and 78% vs. 94%, respectively. The number of clear fluid management plans documented postoperatively also increased (odds ratio of 4), leading to earlier recognition and management of evolving fluid-balance abnormalities. The local paediatric endocrine team was involved in the care of all complex cases and notified sooner for those considered to be developing DI or SIADH (14% to 35%). However, significant Na fluctuations (>12mmol in 24 hours) remained similar – 5 vs six patients – found to be due to complex pituitary hypothalamic pathology – and the recommended adaptive fluid management strategy was still not always used. Qualitative data regarding useability and understanding of fluid-balance abnormalities and the revised guidelines were obtained from health professionals via surveys and discussion in the specialist teams providing care. The feedback highlighted the new guidelines provided a more consistent approach to the post-operative care of these patients and was a better platform for communication amongst the different specialist teams involved. The potential limitation to our study would be the small sample size on which to conduct formal analyses; however, this reflects the population that we were investigating, which we cannot control. Conclusion: The revised clinical guidelines, based on audited data, evidence-based literature review and stakeholder consultations, have demonstrated an improvement in understanding of the neuro-endocrine complications that are possible, as well as increased compliance to post-operative monitoring of fluid balance and electrolytes in this cohort of patients. Emphasis has been placed on preventative rather than treatment of DI and SIADH. Consequently, this has positively impacted patient safety for the center and highlighted the importance of educational awareness and multi-disciplinary team working.

Keywords: post-operative, fluid-balance management, neuro-endocrine complications, paediatric

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582 Targeting Calcium Dysregulation for Treatment of Dementia in Alzheimer's Disease

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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581 Patterns of Malignant and Benign Breast Lesions in Hail Region: A Retrospective Study at King Khalid Hospital

Authors: Laila Seada, Ashraf Ibrahim, Amjad Al Shammari

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Background and Objectives: Breast carcinoma is the most common cancer of females in Hail region, accounting for 31% of all diagnosed cancer cases followed by thyroid carcinoma (25%) and colorectal carcinoma (13%). Methods: In the present retrospective study, all cases of breast lesions received at the histopathology department in King Khalid Hospital, Hail, during the period from May 2011 to April 2016 have been retrieved from department files. For all cases, a trucut biopsy, lumpectomy, or modified radical mastectomy was available for histopathologic diagnosis, while 105/140 (75%) had, as well, preoperative fine needle aspirates (FNA). Results: 49 cases out of 140 (35%) breast lesions were carcinomas: 44/49 (89.75%) was invasive ductal, 2/49(4.1%) invasive lobular carcinomas, 1/49(2.05%) intracystic low grade papillary carcinoma and 2/49 (4.1%) ductal carcinoma in situ (DCIS). Mean age for malignant cases was 45.06 (+/-10.58): 32.6% were below the age of 40 and 30.6 below 50 years, 18.3% below 60 and 16.3% below 70 years. For the benign group, mean age was 32.52 (+/10.5) years. Benign lesions were in order of frequency: 34 fibroadenomas, 14 fibrocystic disease, 12 chronic mastitis, five granulomatous mastitis, three intraductal papillomas, and three benign phyllodes tumor. Tubular adenoma, lipoma, skin nevus, pilomatrixoma, and breast reduction specimens constituted the remaining specimens. Conclusion: Breast lesions are common in our series and invasive carcinoma accounts for more than 1/3rd of the lumps, with 63.2% incidence in pre-menopausal ladies, below the age of 50 years. FNA as a non-invasive procedure, proved to be an effective tool in diagnosing both benign and malignant/suspicious breast lumps and should continue to be used as a first assessment line of palpable breast masses.

Keywords: age incidence, breast carcinoma, fine needle aspiration, hail region

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580 Major Depressive Disorder: Diagnosis based on Electroencephalogram Analysis

Authors: Wajid Mumtaz, Aamir Saeed Malik, Syed Saad Azhar Ali, Mohd Azhar Mohd Yasin

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In this paper, a technique based on electroencephalogram (EEG) analysis is presented, aiming for diagnosing major depressive disorder (MDD) among a potential population of MDD patients and healthy controls. EEG is recognized as a clinical modality during applications such as seizure diagnosis, index for anesthesia, detection of brain death or stroke. However, its usability for psychiatric illnesses such as MDD is less studied. Therefore, in this study, for the sake of diagnosis, 2 groups of study participants were recruited, 1) MDD patients, 2) healthy people as controls. EEG data acquired from both groups were analyzed involving inter-hemispheric asymmetry and composite permutation entropy index (CPEI). To automate the process, derived quantities from EEG were utilized as inputs to classifier such as logistic regression (LR) and support vector machine (SVM). The learning of these classification models was tested with a test dataset. Their learning efficiency is provided as accuracy of classifying MDD patients from controls, their sensitivities and specificities were reported, accordingly (LR =81.7 % and SVM =81.5 %). Based on the results, it is concluded that the derived measures are indicators for diagnosing MDD from a potential population of normal controls. In addition, the results motivate further exploring other measures for the same purpose.

Keywords: major depressive disorder, diagnosis based on EEG, EEG derived features, CPEI, inter-hemispheric asymmetry

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579 Preparation and Antioxidant Activity of Heterocyclic Indole Derivatives

Authors: Tunca Gul Altuntas, Aziz Baydar, Cemre Acar, Sezen Yılmaz, Tulay Coban

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Free radicals, which are generated in many bioorganic redox processes, play a role in the pathogenesis of several diseases including cancer, arthritis, hemorrhagic shock, inflammatory, cardiovascular, neurodegenerative diseases and age-related degenerative brain diseases. Exposures of normal cell to free radical damages several structures, oxidizes nucleic acids, proteins, lipids, or DNA. Compounds interfere with the action of reactive oxygen species might be useful in prevention and treatment of these pathologies. A series of indole compounds containing piperazine ring were synthesized. Coupling of indole-2-carboxylic acid with monosubstituted piperazines was accomplished with 1,1’-carbonyldiimidazole (CDI) in a good yield. The structures of prepared compounds were verified in good agreement with their 1H NMR (nuclear magnetic resonance), MS (mass spectrophotometry), and IR (infrared spectrophotometry) characteristics. In this work, all synthetized indole derivatives were screened in vitro for their antioxidative potential against vitamin E (α-tocopherol) using different antioxidant assays such as superoxide anion formation, lipid peroxidation levels in rat liver, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable radical scavenging activity. The synthesized compounds showed various levels of inhibition compared to vitamin E. This may give promising results for the development of new antioxidant agents.

Keywords: antioxidant, indoles, piperazines, reactive oxygen species

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578 Behavioral Assessment of the Role of Brain 5-HT4 Receptors on the Memory and Cognitive Performance in a Rat Model of Alzheimer Disease

Authors: Siamak Shahidi, Nasrin Hashemi-Firouzi, Sara Soleimani-Asl, Alireza Komaki

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Introduction: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory and cognitive performance. Recently, an involvement of the serotonergic system and their receptors are suspected in the AD progression. In the present behavioral study, the effects of BIMU (selective 5-HT4 receptor agonist) on cognition and memory in the rat model of AD was investigated. Material and Methods: The animal model of the AD was induced by intracerebroventricular (Icv) injection of amyloid beta (Aβ) in adult male Wistar rats. Animals were divided into experimental groups included control, sham, Aβ, Aβ +BIMU groups. The treatment substances were icv injected (1 μg/μL) for thirty consecutive days. Then, novel object recognition (NOR) and passive avoidance learning (PAL) tests were applied to investigate memory and cognitive performance. Results: Aβ decrease the discrimination index of NOR test. Also, it increases the time spent in the dark compartment during PAL test, as compared with sham and control groups. In addition, compared to Aβ groups, BIMU significantly increased the discrimination index of NOR test and decreased the time spent in the dark compartment of PAL test. Conclusion: These findings suggest that 5-HT4 receptor activation prevents progression of memory and cognitive impairment in a rat model of AD.

Keywords: Alzheimer disease, cognition, memory, serotonin receptors

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577 The Great Mimicker: A Case of Disseminated Tuberculosis

Authors: W. Ling, Mohamed Saufi Bin Awang

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Introduction: Mycobacterium tuberculosis post a major health problem worldwide. Central nervous system (CNS) infection by mycobacterium tuberculosis is one of the most devastating complications of tuberculosis. Although with advancement in medical fields, we are yet to understand the pathophysiology of how mycobacterium tuberculosis was able to cross the blood-brain barrier (BBB) and infect the CNS. CNS TB may present with nonspecific clinical symptoms which can mimic other diseases/conditions; this is what makes the diagnosis relatively difficult and challenging. Public health has to be informed and educated about the spread of TB, and early identification of TB is important as it is a curable disease. Case Report: A young 21-year-old Malay gentleman was initially presented to us with symptoms of ear discharge, tinnitus, and right-sided headache for the past one year. Further history reveals that the symptoms have been mismanaged and neglected over the period of 1 year. Initial investigation reveals features of inflammation of the ear. Further imaging showed the feature of chronic inflammation of the otitis media and atypical right cerebral abscess, which has the same characteristic features and consistency. He further underwent a biopsy, and results reveal positive Mycobacterium tuberculosis of the otitis media. With the results and the available imaging, we were certain that this is likely a case of disseminated tuberculosis causing CNS TB. Conclusion: We aim to highlight the challenge and difficult face in our health care system and public health in early identification and treatment.

Keywords: central nervous system tuberculosis, intracranial tuberculosis, tuberculous encephalopathy, tuberculous meningitis

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576 Quality of Life and Self-Assessed Health of Buprenorphine–Maintained Opiate Addicts

Authors: Igna Brajević Gizdić, Gorka Vuletić

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Introduction: Addiction is a chronic brain relapsing disorder. Opioid Substitution Therapy (OST) using buprenorphine as a medical treatment option shows as a promising option for achieving and maintaining abstinence in opioid-addicted patients. This research aimed to determine and evaluate the quality of life (QoL) in opiate-addicted patients after five years of buprenorphine therapy. Method: The total sample included 44 buprenorphine-maintained opiate addicts in outpatient treatment. The participants were administered the QoL questionnaire (WHOQOL-BREF) at two-time points (T1 and T2) with an interval of at least five years. WHOQOL-BREF contains a total of 26 questions. The first two questions, related to overall QoL and general health status, and the remaining questions (3–26), which represented four domains—physical, psychological, social, and environmental health—were evaluated separately. Results: The results indicated no significant differences in overall self-assessed QoL nor in individual domains after five years (T2) of abstinence with OST buprenorphine- maintenance. Conclusion: These findings indicated no improvement in QoL of buprenorphine-maintenance opiate addicts in outpatient treatment. However, this might be due to the smaller sample size and participants' overall high scores in QoL at T1. This study suggests the importance of expectations when considering the QoL and general health of buprenorphine-maintenance opiate addicts in outpatient treatment.

Keywords: abstinence, addicts, buprenorphine, opioid substitution therapy, quality of life

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575 Large-Capacity Image Information Reduction Based on Single-Cue Saliency Map for Retinal Prosthesis System

Authors: Yili Chen, Xiaokun Liang, Zhicheng Zhang, Yaoqin Xie

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In an effort to restore visual perception in retinal diseases, an electronic retinal prosthesis with thousands of electrodes has been developed. The image processing strategies of retinal prosthesis system converts the original images from the camera to the stimulus pattern which can be interpreted by the brain. Practically, the original images are with more high resolution (256x256) than that of the stimulus pattern (such as 25x25), which causes a technical image processing challenge to do large-capacity image information reduction. In this paper, we focus on developing an efficient image processing stimulus pattern extraction algorithm by using a single cue saliency map for extracting salient objects in the image with an optimal trimming threshold. Experimental results showed that the proposed stimulus pattern extraction algorithm performs quite well for different scenes in terms of the stimulus pattern. In the algorithm performance experiment, our proposed SCSPE algorithm have almost five times of the score compared with Boyle’s algorithm. Through experiment s we suggested that when there are salient objects in the scene (such as the blind meet people or talking with people), the trimming threshold should be set around 0.4max, in other situations, the trimming threshold values can be set between 0.2max-0.4max to give the satisfied stimulus pattern.

Keywords: retinal prosthesis, image processing, region of interest, saliency map, trimming threshold selection

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574 Depressant Effects of 2-PMPA through Reduction of p-CREB (Ser133) and mGluR5 Level in Prefrontal Cortex of C57BL/6 Mice

Authors: Sang-Sun Yoon, Yea-Hyun Leem, Sangmee Ahn Jo

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The N-acetylated-alpha-linked-acidic (NAAG) peptidase inhibitor 2-phosphonomethyl pentanedioic acid (2-PMPA) has demonstrated to be neuroprotective against glutamate-mediated neuron degeneration and neurological disorders such as ischemia. Several studies have demonstrated impaired psychiatric function by altered glutamate carboxypeptidase II expression, although 2-PMPA has not yet been studied. Thus, we investigated effect of 2-PMPA on depressive-like phenotype using C57BL/6 mice. Treatment of 2-PMPA (10 mg/kg for 6 days/daily, ip injection) on C57BL/6 naïve mice showed depressive-like symptoms such as decreased social preference, but did not affect the immobility measured by tail suspension test. Reduction of phosphorylated cAMP-responsive element binding (p-CREB) known as a representative marker of depressive-like behavior was observed in layer 1 and piriform cortex subregions of the prefrontal cortex of 2-PMPA-treated mice. The immunoreactivity of metabotropic glutamate receptors 5 (mGluR5) that mediate phosphorylation of CREB was also decreased in layer 1 and piriform cortex subregions of the prefrontal cortex of 2-PMPA injected mice. Thus, our results suggest that dysregulation of the GCPII or NAAG by 2-PMPA treatment is likely to be associated with pathogenesis of depression and further studies are needed to understand whether the reduced NAAG level or enhanced glutamate level in the brain is involved in this response.

Keywords: depression, GCPII, 2-PMPA, p-CREB, mGluR5

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573 Mitochondrial DNA Copy Number in Egyptian Patients with Hepatitis C Virus Related Hepatocellular Carcinoma

Authors: Doaa Hashad, Amany Elyamany, Perihan Salem

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Introduction: Hepatitis C virus infection (HCV) constitutes a serious dilemma that has an impact on the health of millions of Egyptians. Hepatitis C virus related hepatocellular carcinoma (HCV-HCC) is a crucial consequence of HCV that represents the third cause of cancer-related deaths worldwide. Aim of the study: assess the use of mitochondrial DNA (mtDNA) content as a non-invasive molecular biomarker in hepatitis c virus related hepatocellular carcinoma (HCV-HCC). Methods: A total of 135 participants were enrolled in the study. Volunteers were assigned to one of three groups equally; a group of HCV related cirrhosis (HCV-cirrhosis), a group of HCV-HCC and a control group of age- and sex- matched healthy volunteers with no evidence of liver disease. mtDNA was determined using a quantitative real-time PCR technique. Results: mtDNA content was lowest in HCV-HCC cases. No statistically significant difference was observed between the group of HCV-cirrhosis and the control group as regards mtDNA level. HCC patients with multi-centric hepatic lesions had significantly lower mtDNA content. On using receiver operating characteristic curve analysis, a cutoff of 34 was assigned for mtDNA content to distinguish between HCV-HCC and HCV-cirrhosis patients who are not yet complicated by malignancy. Lower mtDNA was associated with greater HCC risk on using healthy controls, HCV-cirrhosis, or combining both groups as a reference group. Conclusions: mtDNA content might constitute a non-invasive molecular biomarker that reflects tumor burden in HCV-HCC cases and could be used as a predictor of HCC risk in patients of HCV-cirrhosis. In addition, the non significant difference of mtDNA level between HCV-cirrhosis patients and healthy controls could eliminate the grey zone created by the use of AFP in some cirrhotic patients.

Keywords: DNA copy number, HCC, HCV, mitochondrial

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572 Artificial Intelligence Approach to Water Treatment Processes: Case Study of Daspoort Treatment Plant, South Africa

Authors: Olumuyiwa Ojo, Masengo Ilunga

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Artificial neural network (ANN) has broken the bounds of the convention programming, which is actually a function of garbage in garbage out by its ability to mimic the human brain. Its ability to adopt, adapt, adjust, evaluate, learn and recognize the relationship, behavior, and pattern of a series of data set administered to it, is tailored after the human reasoning and learning mechanism. Thus, the study aimed at modeling wastewater treatment process in order to accurately diagnose water control problems for effective treatment. For this study, a stage ANN model development and evaluation methodology were employed. The source data analysis stage involved a statistical analysis of the data used in modeling in the model development stage, candidate ANN architecture development and then evaluated using a historical data set. The model was developed using historical data obtained from Daspoort Wastewater Treatment plant South Africa. The resultant designed dimensions and model for wastewater treatment plant provided good results. Parameters considered were temperature, pH value, colour, turbidity, amount of solids and acidity. Others are total hardness, Ca hardness, Mg hardness, and chloride. This enables the ANN to handle and represent more complex problems that conventional programming is incapable of performing.

Keywords: ANN, artificial neural network, wastewater treatment, model, development

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571 Fiber Optic Asparagine Biosensor for Fruit Juices by Co-Immobilization of L-Asparaginase and Phenol Red

Authors: Mandeep Kataria, Ritu Narula, Navneet Kaur

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Asparagine is vital amino acid which is required for the development of brain and it regulates the equilibrium of central nervous system. Asparagine is the chief amino acid that forms acrylamide in baked food by reacting with reducing sugars at high temperature ( Millard Reaction i.e. amino acids and sugars give new flavors at high temperature). It can also be a parameter of freshness in fruit juices because on storage of juices at 37°C caused an 87% loss in the total free amino acids and major decrease was recorded in asparagine contents. With this significance of monitoring asparagine, in the present work a biosensor for determining asparagine in fruit juices is developed. For the construction of biosensor L-asparaginase enzyme (0.5 IU) was co-immobilized with phenol red on TEOS chitosan sol-gel plastic disc and fixed on the fiber optic tip. Tip was immersed in a cell having 5ml of substrate and absorption was noted at response time of 5 min with 10-1 - 10-10 M concentrations of asparagine at 538 nm. L-asparaginase was extracted and from Solanum nigrum Asparagine biosensor was applied fruit juices on the monitoring asparagine contents. L-asparagine concentration found to be present in fruit juices like Guava Juice, Apple Juice, Mango Juice, Litchi juice, Strawberry juice, Pineapple juice Lemon juice, and Orange juice. Hence the developed biosensor has commercial aspects in quality insurance of fruit juices.

Keywords: fiber optic biosensor, chitosan, teos, l-asparaginase

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570 Lipid-Chitosan Hybrid Nanoparticles for Controlled Delivery of Cisplatin

Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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