Search results for: brain tumor
1192 Toward an Understanding of the Neurofunctional Dissociation between Animal and Tool Concepts: A Graph Theoretical Analysis
Authors: Skiker Kaoutar, Mounir Maouene
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Neuroimaging studies have shown that animal and tool concepts rely on distinct networks of brain areas. Animal concepts depend predominantly on temporal areas while tool concepts rely on fronto-temporo-parietal areas. However, the origin of this neurofunctional distinction for processing animal and tool concepts remains still unclear. Here, we address this question from a network perspective suggesting that the neural distinction between animals and tools might reflect the differences in their structural semantic networks. We build semantic networks for animal and tool concepts derived from Mc Rae and colleagues’s behavioral study conducted on a large number of participants. These two networks are thus analyzed through a large number of graph theoretical measures for small-worldness: centrality, clustering coefficient, average shortest path length, as well as resistance to random and targeted attacks. The results indicate that both animal and tool networks have small-world properties. More importantly, the animal network is more vulnerable to targeted attacks compared to the tool network a result that correlates with brain lesions studies.Keywords: animals, tools, network, semantics, small-world, resilience to damage
Procedia PDF Downloads 5381191 You Only Get One Brain: An Exploratory Retrospective Study On Life After Adolescent TBI
Authors: Mulligan T., Barker-Collo S., Gobson K., Jones K.
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There is a relatively scarce body of literature regarding adolescent experiences of traumatic brain injury (TBI). This qualitative study explored how sustaining a TBI at this unique stage of development might impact a young person as they navigate the challenges of adolescence and transition to adulthood, and what might support recovery. Thirteen young adults who sustained a mild-moderate TBI as an adolescent (aged 13 – 17 years), approximately 7.7 years (range = 6.7 – 8.0 years) prior, participated in the research. Semi-structured individual interviews were conducted to explore participants’ experiences surrounding and following their TBIs. Thematic analysis of interview data produced five key categories of findings: (1) Following their TBIs, many participants experienced problems with cognitive (e.g., forgetfulness, concentration difficulties), physical (e.g., migraines, fatigue) and emotional (e.g., depression, anxiety) functioning, which were often endured into adulthood. (2) TBI-related problems often adversely affected important areas of life for the participant, including school, work and friendships. (3) Changes following TBI commonly impacted identity formation. (4) Recovery processes evolved over time as the participants coped initially by just ‘getting on with it’, before learning to accept new limitations and, ultimately, growing from their TBI experiences. (5) While the presence of friends and family assisted recovery, struggles were often exacerbated by a lack of emotional support from others, in addition to the absence of any assistance or information-provision from professionals regarding what to expect following TBI. The findings suggest that even mild TBI sustained during adolescence can have consequences for an individual’s functioning, engagement in life and identity development, whilst also giving rise to post-traumatic growth. Recovery following adolescent TBI might be maximised by facilitating greater understanding of the injury and acknowledging its impacts on important areas of life, as well as the provision of emotional support and facilitating self-reflection and meaning-making.Keywords: adolescent, brain Injury, qualitative, post-traumatic growth
Procedia PDF Downloads 501190 The Use of Vasopressin in the Management of Severe Traumatic Brain Injury: A Narrative Review
Authors: Nicole Selvi Hill, Archchana Radhakrishnan
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Introduction: Traumatic brain injury (TBI) is a leading cause of mortality among trauma patients. In the management of TBI, the main principle is avoiding cerebral ischemia, as this is a strong determiner of neurological outcomes. The use of vasoactive drugs, such as vasopressin, has an important role in maintaining cerebral perfusion pressure to prevent secondary brain injury. Current guidelines do not suggest a preferred vasoactive drug to administer in the management of TBI, and there is a paucity of information on the therapeutic potential of vasopressin following TBI. Vasopressin is also an endogenous anti-diuretic hormone (AVP), and pathways mediated by AVP play a large role in the underlying pathological processes of TBI. This creates an overlap of discussion regarding the therapeutic potential of vasopressin following TBI. Currently, its popularity lies in vasodilatory and cardiogenic shock in the intensive care setting, with increasing support for its use in haemorrhagic and septic shock. Methodology: This is a review article based on a literature review. An electronic search was conducted via PubMed, Cochrane, EMBASE, and Google Scholar. The aim was to identify clinical studies looking at the therapeutic administration of vasopressin in severe traumatic brain injury. The primary aim was to look at the neurological outcome of patients. The secondary aim was to look at surrogate markers of cerebral perfusion measurements, such as cerebral perfusion pressure, cerebral oxygenation, and cerebral blood flow. Results: Eight papers were included in the final number. Three were animal studies; five were human studies, comprised of three case reports, one retrospective review of data, and one randomised control trial. All animal studies demonstrated the benefits of vasopressors in TBI management. One animal study showed the superiority of vasopressin in reducing intracranial pressure and increasing cerebral oxygenation over a catecholaminergic vasopressor, phenylephrine. All three human case reports were supportive of vasopressin as a rescue therapy in catecholaminergic-resistant hypotension. The retrospective review found vasopressin did not increase cerebral oedema in TBI patients compared to catecholaminergic vasopressors; and demonstrated a significant reduction in the requirements of hyperosmolar therapy in patients that received vasopressin. The randomised control trial results showed no significant differences in primary and secondary outcomes between TBI patients receiving vasopressin versus those receiving catecholaminergic vasopressors. Apart from the randomised control trial, the studies included are of low-level evidence. Conclusion: Studies favour vasopressin within certain parameters of cerebral function compared to control groups. However, the neurological outcomes of patient groups are not known, and animal study results are difficult to extrapolate to humans. It cannot be said with certainty whether vasopressin’s benefits stand above usage of other vasoactive drugs due to the weaknesses of the evidence. Further randomised control trials, which are larger, standardised, and rigorous, are required to improve knowledge in this field.Keywords: catecholamines, cerebral perfusion pressure, traumatic brain injury, vasopressin, vasopressors
Procedia PDF Downloads 661189 A System Dynamics Approach to Exploring Personality Traits in Young Children
Authors: Misagh Faezipour
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System dynamics is a systems engineering approach that can help address the complex challenges in different systems. Little is known about how the brain represents people to predict behavior. This work is based on how the brain simulates different personal behavior and responds to them in the case of young children ages one to five. As we know, children’s minds/brains are just as clean as a crystal, and throughout time, in their surroundings, families, and education center, they grow to develop and have different kinds of behavior towards the world and the society they live in. Hence, this work aims to identify how young children respond to various personality behavior and observes their reactions towards them from a system dynamics perspective. We will be exploring the Big Five personality traits in young children. A causal model is developed in support of the system dynamics approach. These models graphically present the factors and factor relationships that contribute to the big five personality traits and provide a better understanding of the entire behavior model. A simulator will be developed that includes a set of causal model factors and factor relationships. The simulator models the behavior of different factors related to personality traits and their impacts and can help make more informed decisions in a risk-free environment.Keywords: personality traits, systems engineering, system dynamics, causal model, behavior model
Procedia PDF Downloads 891188 De novo Transcriptome Assembly of Lumpfish (Cyclopterus lumpus L.) Brain Towards Understanding their Social and Cognitive Behavioural Traits
Authors: Likith Reddy Pinninti, Fredrik Ribsskog Staven, Leslie Robert Noble, Jorge Manuel de Oliveira Fernandes, Deepti Manjari Patel, Torstein Kristensen
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Understanding fish behavior is essential to improve animal welfare in aquaculture research. Behavioral traits can have a strong influence on fish health and habituation. To identify the genes and biological pathways responsible for lumpfish behavior, we performed an experiment to understand the interspecies relationship (mutualism) between the lumpfish and salmon. Also, we tested the correlation between the gene expression data vs. observational/physiological data to know the essential genes that trigger stress and swimming behavior in lumpfish. After the de novo assembly of the brain transcriptome, all the samples were individually mapped to the available lumpfish (Cyclopterus lumpus L.) primary genome assembly (fCycLum1.pri, GCF_009769545.1). Out of ~16749 genes expressed in brain samples, we found 267 genes to be statistically significant (P > 0.05) found only in odor and control (1), model and control (41) and salmon and control (225) groups. However, genes with |LogFC| ≥0.5 were found to be only eight; these are considered as differentially expressed genes (DEG’s). Though, we are unable to find the differential genes related to the behavioral traits from RNA-Seq data analysis. From the correlation analysis, between the gene expression data vs. observational/physiological data (serotonin (5HT), dopamine (DA), 3,4-Dihydroxyphenylacetic acid (DOPAC), 5-hydroxy indole acetic acid (5-HIAA), Noradrenaline (NORAD)). We found 2495 genes found to be significant (P > 0.05) and among these, 1587 genes are positively correlated with the Noradrenaline (NORAD) hormone group. This suggests that Noradrenaline is triggering the change in pigmentation and skin color in lumpfish. Genes related to behavioral traits like rhythmic, locomotory, feeding, visual, pigmentation, stress, response to other organisms, taxis, dopamine synthesis and other neurotransmitter synthesis-related genes were obtained from the correlation analysis. In KEGG pathway enrichment analysis, we find important pathways, like the calcium signaling pathway and adrenergic signaling in cardiomyocytes, both involved in cell signaling, behavior, emotion, and stress. Calcium is an essential signaling molecule in the brain cells; it could affect the behavior of fish. Our results suggest that changes in calcium homeostasis and adrenergic receptor binding activity lead to changes in fish behavior during stress.Keywords: behavior, De novo, lumpfish, salmon
Procedia PDF Downloads 1691187 High-Dose-Rate Brachytherapy for Cervical Cancer: The Effect of Total Reference Air Kerma on the Results of Single-Channel and Tri-Channel Applicators
Authors: Hossain A., Miah S., Ray P. K.
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Introduction: Single channel and tri-channel applicators are used in the traditional treatment of cervical cancer. Total reference air kerma (TRAK) and treatment outcomes in high-dose-rate brachytherapy for cervical cancer using single-channel and tri-channel applicators were the main objectives of this retrospective study. Material and Methods: Patients in the radiotherapy division who received brachytherapy, chemotherapy, and external radiotherapy (EBRT) using single and tri-channel applicators were the subjects of a retrospective cohort study from 2016 to 2020. All brachytherapy parameters, including TRAK, were calculated in accordance with the international protocol. The Kaplan Meier method was used to analyze survival rates using a log-rank test. Results and Discussions: Based on treatment times of 15.34 (10-20) days and 21.35 (6.5-28) days, the TRAK for the tri-channel applicator was 0.52 cGy.m² and for the single-channel applicator was 0.34 cGy.m². Based on TRAK, the rectum, bladder, and tumor had respective Pearson correlations of 0.082, 0.009, and 0.032. The 1-specificity and sensitivity were 0.70 and 0.30, respectively. At that time, AUC was 0.71. The log-rank test showed that tri-channel applicators had a survival rate of 95% and single-channel applicators had a survival rate of 85% (p=0.565). Conclusions: The relationship between TRAK and treatment duration and Pearson correlation for the tumor, rectum, and bladder suggests that TRAK should be taken into account for the proper operation of single channel and tri-channel applicators.Keywords: single-channel, tri-channel, high dose rate brachytherapy, cervical cancer
Procedia PDF Downloads 961186 Learning outside the Box by Using Memory Techniques Skill: Case Study in Indonesia Memory Sports Council
Authors: Muhammad Fajar Suardi, Fathimatufzzahra, Dela Isnaini Sendra
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Learning is an activity that has been used to do, especially for a student or academics. But a handful of people have not been using and maximizing their brains work and some also do not know a good brain work time in capturing the lessons, so that knowledge is absorbed is also less than the maximum. Indonesia Memory Sports Council (IMSC) is an institution which is engaged in the performance of the brain and the development of effective learning methods by using several techniques that can be used in considering the lessons and knowledge to grasp well, including: loci method, substitution method, and chain method. This study aims to determine the techniques and benefits of using the method given in learning and memorization by applying memory techniques taught by Indonesia Memory Sports Council (IMSC) to students and the difference if not using this method. This research uses quantitative research with survey method addressed to students of Indonesian Memory Sports Council (IMSC). The results of this study indicate that learn, understand and remember the lesson using the techniques of memory which is taught in Indonesia Memory Sport Council is very effective and faster to absorb the lesson than learning without using the techniques of memory, and this affects the academic achievement of students in each educational institution.Keywords: chain method, Indonesia memory sports council, loci method, substitution method
Procedia PDF Downloads 2831185 Molecular Portraits: The Role of Posttranslational Modification in Cancer Metastasis
Authors: Navkiran Kaur, Apoorva Mathur, Abhishree Agarwal, Sakshi Gupta, Tuhin Rashmi
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Aim: Breast cancer is the most common cancer in women worldwide, and resistance to the current therapeutics, often concurrently, is an increasing clinical challenge. Glycosylation of proteins is one of the most important post-translational modifications. It is widely known that aberrant glycosylation has been implicated in many different diseases due to changes associated with biological function and protein folding. Alterations in cell surface glycosylation, can promote invasive behavior of tumor cells that ultimately lead to the progression of cancer. In breast cancer, there is an increasing evidence pertaining to the role of glycosylation in tumor formation and metastasis. In the present study, an attempt has been made to study the disease associated sialoglycoproteins in breast cancer by using bioinformatics tools. The sequence will be retrieved from UniProt database. A database in the form of a word document was made by a collection of FASTA sequences of breast cancer gene sequence. Glycosylation was studied using yinOyang tool on ExPASy and Differential genes expression and protein analysis was done in context of breast cancer metastasis. The number of residues predicted O-glc NAc threshold containing 50 aberrant glycosylation sites or more was detected and recorded for individual sequence. We found that the there is a significant change in the expression profiling of glycosylation patterns of various proteins associated with breast cancer. Differential aberrant glycosylated proteins in breast cancer cells with respect to non-neoplastic cells are an important factor for the overall progression and development of cancer.Keywords: breast cancer, bioinformatics, cancer, metastasis, glycosylation
Procedia PDF Downloads 2891184 Mature Cystic Teratomas of Ovary: A Series of 19 Cases with Rare Malignant Transformation in Three
Authors: Parveen Kundu, Nitika Chawla, Ruchi Agarwal, Swaran Kaur
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Background: Mature cystic teratoma is a benign, most common tumor of the ovary occurring mostly in young and middle-aged females. This study consists of 19 cases of mature cystic teratomas which were received in the Department Of Pathology over a period of two years. There were malignant transformations observed in three cases, which makes it very important for pathologists to thoroughly examine the entire specimen of mature cystic teratomas. Material and Methods: Nineteen reported cases of mature cystic teratomas were received in Deptt. Of Pathology, BPS GMC Khanpur Kalan, Sonepat, over a two-year period from November 2020 to October 2022 and reviewed retrospectively. Data regarding age, size, laterality, gross, morphological features, and surgery performed were retrieved from pathological archives. Results: In our study, the most common age of presentation was the 20-40 year age group. The most common presenting complaint was fullness in the abdomen or abdominal distension. Four out of 19 cases studied cases presented with bilateral ovarian cysts. Tumor size ranged from 6 to 20 cm in diameter. In seven cases, cysts were greater than or equal to 10 cm in diameter. Three cases showed malignant transformation. Conclusion: It is very important to thoroughly examine the contralateral ovary to rule out bilateral presentation. A furthermost thorough examination is advised in tumors of size >10 cm and in tumors with solid areas to rule out any malignant transformation.Keywords: teratoma, ovary, malignant, transformation
Procedia PDF Downloads 761183 Early Diagnosis of Alzheimer's Disease Using a Combination of Images Processing and Brain Signals
Authors: E. Irankhah, M. Zarif, E. Mazrooei Rad, K. Ghandehari
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Alzheimer's prevalence is on the rise, and the disease comes with problems like cessation of treatment, high cost of treatment, and the lack of early detection methods. The pathology of this disease causes the formation of protein deposits in the brain of patients called plaque amyloid. Generally, the diagnosis of this disease is done by performing tests such as a cerebrospinal fluid, CT scan, MRI, and spinal cord fluid testing, or mental testing tests and eye tracing tests. In this paper, we tried to use the Medial Temporal Atrophy (MTA) method and the Leave One Out (LOO) cycle to extract the statistical properties of the three Fz, Pz, and Cz channels of ERP signals for early diagnosis of this disease. In the process of CT scan images, the accuracy of the results is 81% for the healthy person and 88% for the severe patient. After the process of ERP signaling, the accuracy of the results for a healthy person in the delta band in the Cz channel is 81% and in the alpha band the Pz channel is 90%. In the results obtained from the signal processing, the results of the severe patient in the delta band of the Cz channel were 89% and in the alpha band Pz channel 92%.Keywords: Alzheimer's disease, image and signal processing, LOO cycle, medial temporal atrophy
Procedia PDF Downloads 1931182 A Survey and Theory of the Effects of Various Hamlet Videos on Viewers’ Brains
Authors: Mark Pizzato
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How do ideas, images, and emotions in stage-plays and videos affect us? Do they evoke a greater awareness (or cognitive reappraisal of emotions) through possible shifts between left-cortical, right-cortical, and subcortical networks? To address these questions, this presentation summarizes the research of various neuroscientists, especially Bernard Baars and others involved in Global Workspace Theory, Matthew Lieberman in social neuroscience, Iain McGilchrist on left and right cortical functions, and Jaak Panksepp on the subcortical circuits of primal emotions. Through such research, this presentation offers an ‘inner theatre’ model of the brain, regarding major hubs of neural networks and our animal ancestry. It also considers recent experiments, by Mario Beauregard, on the cognitive reappraisal of sad, erotic, and aversive film clips. Finally, it applies the inner-theatre model and related research to survey results of theatre students who read and then watched the ‘To be or not to be’ speech in 8 different video versions (from stage and screen productions) of William Shakespeare’s Hamlet. Findings show that students become aware of left-cortical, right-cortical, and subcortical brain functions—and shifts between them—through staging and movie-making choices in each of the different videos.Keywords: cognitive reappraisal, Hamlet, neuroscience, Shakespeare, theatre
Procedia PDF Downloads 3051181 Rehabilitation Team after Brain Damages as Complex System Integrating Consciousness
Authors: Olga Maksakova
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A work with unconscious patients after acute brain damages besides special knowledge and practical skills of all the participants requires a very specific organization. A lot of said about team approach in neurorehabilitation, usually as for outpatient mode. Rehabilitologists deal with fixed patient problems or deficits (motion, speech, cognitive or emotional disorder). Team-building means superficial paradigm of management psychology. Linear mode of teamwork fits casual relationships there. Cases with deep altered states of consciousness (vegetative states, coma, and confusion) require non-linear mode of teamwork: recovery of consciousness might not be the goal due to phenomenon uncertainty. Rehabilitation team as Semi-open Complex System includes the patient as a part. Patient's response pattern becomes formed not only with brain deficits but questions-stimuli, context, and inquiring person. Teamwork is sourcing of phenomenology knowledge of patient's processes as Third-person approach is replaced with Second- and after First-person approaches. Here is a chance for real-time change. Patient’s contacts with his own body and outward things create a basement for restoration of consciousness. The most important condition is systematic feedbacks to any minimal movement or vegetative signal of the patient. Up to now, recovery work with the most severe contingent is carried out in the mode of passive physical interventions, while an effective rehabilitation team should include specially trained psychologists and psychotherapists. It is they who are able to create a network of feedbacks with the patient and inter-professional ones building up the team. Characteristics of ‘Team-Patient’ system (TPS) are energy, entropy, and complexity. Impairment of consciousness as the absence of linear contact appears together with a loss of essential functions (low energy), vegetative-visceral fits (excessive energy and low order), motor agitation (excessive energy and excessive order), etc. Techniques of teamwork are different in these cases for resulting optimization of the system condition. Directed regulation of the system complexity is one of the recovery tools. Different signs of awareness appear as a result of system self-organization. Joint meetings are an important part of teamwork. Regular or event-related discussions form the language of inter-professional communication, as well as the patient's shared mental model. Analysis of complex communication process in TPS may be useful for creation of the general theory of consciousness.Keywords: rehabilitation team, urgent rehabilitation, severe brain damage, consciousness disorders, complex system theory
Procedia PDF Downloads 1411180 Neuroprotective Effect of Chrysin on Thioacetamide-Induced Hepatic Encephalopathy in Rats: Role of Oxidative Stress and TLR-4/NF-κB Pathway
Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam
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This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway
Procedia PDF Downloads 1561179 An Analysis of the Temporal Aspects of Visual Attention Processing Using Rapid Series Visual Processing (RSVP) Data
Authors: Shreya Borthakur, Aastha Vartak
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This Electroencephalogram (EEG) project on Rapid Visual Serial Processing (RSVP) paradigm explores the temporal dynamics of visual attention processing in response to rapidly presented visual stimuli. The study builds upon previous research that used real-world images in RSVP tasks to understand the emergence of object representations in the human brain. The objectives of the research include investigating the differences in accuracy and reaction times between 5 Hz and 20 Hz presentation rates, as well as examining the prominent brain waves, particularly alpha and beta waves, associated with the attention task. The pre-processing and data analysis involves filtering EEG data, creating epochs for target stimuli, and conducting statistical tests using MATLAB, EEGLAB, Chronux toolboxes, and R. The results support the hypotheses, revealing higher accuracy at a slower presentation rate, faster reaction times for less complex targets, and the involvement of alpha and beta waves in attention and cognitive processing. This research sheds light on how short-term memory and cognitive control affect visual processing and could have practical implications in fields like education.Keywords: RSVP, attention, visual processing, attentional blink, EEG
Procedia PDF Downloads 641178 Mapping Iron Content in the Brain with Magnetic Resonance Imaging and Machine Learning
Authors: Gabrielle Robertson, Matthew Downs, Joseph Dagher
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Iron deposition in the brain has been linked with a host of neurological disorders such as Alzheimer’s, Parkinson’s, and Multiple Sclerosis. While some treatment options exist, there are no objective measurement tools that allow for the monitoring of iron levels in the brain in vivo. An emerging Magnetic Resonance Imaging (MRI) method has been recently proposed to deduce iron concentration through quantitative measurement of magnetic susceptibility. This is a multi-step process that involves repeated modeling of physical processes via approximate numerical solutions. For example, the last two steps of this Quantitative Susceptibility Mapping (QSM) method involve I) mapping magnetic field into magnetic susceptibility and II) mapping magnetic susceptibility into iron concentration. Process I involves solving an ill-posed inverse problem by using regularization via injection of prior belief. The end result from Process II highly depends on the model used to describe the molecular content of each voxel (type of iron, water fraction, etc.) Due to these factors, the accuracy and repeatability of QSM have been an active area of research in the MRI and medical imaging community. This work aims to estimate iron concentration in the brain via a single step. A synthetic numerical model of the human head was created by automatically and manually segmenting the human head on a high-resolution grid (640x640x640, 0.4mm³) yielding detailed structures such as microvasculature and subcortical regions as well as bone, soft tissue, Cerebral Spinal Fluid, sinuses, arteries, and eyes. Each segmented region was then assigned tissue properties such as relaxation rates, proton density, electromagnetic tissue properties and iron concentration. These tissue property values were randomly selected from a Probability Distribution Function derived from a thorough literature review. In addition to having unique tissue property values, different synthetic head realizations also possess unique structural geometry created by morphing the boundary regions of different areas within normal physical constraints. This model of the human brain is then used to create synthetic MRI measurements. This is repeated thousands of times, for different head shapes, volume, tissue properties and noise realizations. Collectively, this constitutes a training-set that is similar to in vivo data, but larger than datasets available from clinical measurements. This 3D convolutional U-Net neural network architecture was used to train data-driven Deep Learning models to solve for iron concentrations from raw MRI measurements. The performance was then tested on both synthetic data not used in training as well as real in vivo data. Results showed that the model trained on synthetic MRI measurements is able to directly learn iron concentrations in areas of interest more effectively than other existing QSM reconstruction methods. For comparison, models trained on random geometric shapes (as proposed in the Deep QSM method) are less effective than models trained on realistic synthetic head models. Such an accurate method for the quantitative measurement of iron deposits in the brain would be of important value in clinical studies aiming to understand the role of iron in neurological disease.Keywords: magnetic resonance imaging, MRI, iron deposition, machine learning, quantitative susceptibility mapping
Procedia PDF Downloads 1271177 Computer-Integrated Surgery of the Human Brain, New Possibilities
Authors: Ugo Galvanetto, Pirto G. Pavan, Mirco Zaccariotto
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The discipline of Computer-integrated surgery (CIS) will provide equipment able to improve the efficiency of healthcare systems and, which is more important, clinical results. Surgeons and machines will cooperate in new ways that will extend surgeons’ ability to train, plan and carry out surgery. Patient specific CIS of the brain requires several steps: 1 - Fast generation of brain models. Based on image recognition of MR images and equipped with artificial intelligence, image recognition techniques should differentiate among all brain tissues and segment them. After that, automatic mesh generation should create the mathematical model of the brain in which the various tissues (white matter, grey matter, cerebrospinal fluid …) are clearly located in the correct positions. 2 – Reliable and fast simulation of the surgical process. Computational mechanics will be the crucial aspect of the entire procedure. New algorithms will be used to simulate the mechanical behaviour of cutting through cerebral tissues. 3 – Real time provision of visual and haptic feedback A sophisticated human-machine interface based on ergonomics and psychology will provide the feedback to the surgeon. The present work will address in particular point 2. Modelling the cutting of soft tissue in a structure as complex as the human brain is an extremely challenging problem in computational mechanics. The finite element method (FEM), that accurately represents complex geometries and accounts for material and geometrical nonlinearities, is the most used computational tool to simulate the mechanical response of soft tissues. However, the main drawback of FEM lies in the mechanics theory on which it is based, classical continuum Mechanics, which assumes matter is a continuum with no discontinuity. FEM must resort to complex tools such as pre-defined cohesive zones, external phase-field variables, and demanding remeshing techniques to include discontinuities. However, all approaches to equip FEM computational methods with the capability to describe material separation, such as interface elements with cohesive zone models, X-FEM, element erosion, phase-field, have some drawbacks that make them unsuitable for surgery simulation. Interface elements require a-priori knowledge of crack paths. The use of XFEM in 3D is cumbersome. Element erosion does not conserve mass. The Phase Field approach adopts a diffusive crack model instead of describing true tissue separation typical of surgical procedures. Modelling discontinuities, so difficult when using computational approaches based on classical continuum Mechanics, is instead easy for novel computational methods based on Peridynamics (PD). PD is a non-local theory of mechanics formulated with no use of spatial derivatives. Its governing equations are valid at points or surfaces of discontinuity, and it is, therefore especially suited to describe crack propagation and fragmentation problems. Moreover, PD does not require any criterium to decide the direction of crack propagation or the conditions for crack branching or coalescence; in the PD-based computational methods, cracks develop spontaneously in the way which is the most convenient from an energy point of view. Therefore, in PD computational methods, crack propagation in 3D is as easy as it is in 2D, with a remarkable advantage with respect to all other computational techniques.Keywords: computational mechanics, peridynamics, finite element, biomechanics
Procedia PDF Downloads 701176 Neuroblastoma in Children and the Potential Involvement of Viruses in Its Pathogenesis
Authors: Ugo Rovigatti
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Neuroblastoma (NBL) has epitomized for at least 40 years our understanding of cancer cellular and molecular biology and its potential applications to novel therapeutic strategies. This includes the discovery of the very first oncogene aberrations and tumorigenesis suppression by differentiation in the 80s; the potential role of suppressor genes in the 90s; the relevance of immunotherapy in the millennium first, and the discovery of additional mutations by NGS technology in the millennium second decade. Similar discoveries were achieved in the majority of human cancers, and similar therapeutic interventions were obtained subsequently to NBL discoveries. Unfortunately, targeted therapies suggested by specific mutations (such as MYCN amplification –MNA- present in ¼ or 1/5 of cases) have not elicited therapeutic successes in aggressive NBL, where the prognosis is still dismal. The reasons appear to be linked to Tumor Heterogeneity, which is particularly evident in NBL but also a clear hallmark of aggressive human cancers generally. The new avenue of cancer immunotherapy (CIT) provided new hopes for cancer patients, but we still ignore the cellular or molecular targets. CIT is emblematic of high-risk disease (HR-NBL) since the mentioned GD2 passive immunotherapy is still providing better survival. We recently critically reviewed and evaluated the literature depicting the genomic landscapes of HR-NBL, coming to the qualified conclusion that among hundreds of affected genes, potential targets, or chromosomal sites, none correlated with anti-GD2 sensitivity. A better explanation is provided by the Micro-Foci inducing Virus (MFV) model, which predicts that neuroblasts infection with the MFV, an RNA virus isolated from a cancer-cluster (space-time association) of HR-NBL cases, elicits the appearance of MNA and additional genomic aberrations with mechanisms resembling chromothripsis. Neuroblasts infected with low titers of MFV amplified MYCN up to 100 folds and became highly transformed and malignant, thus causing neuroblastoma in young rat pups of strains SD and Fisher-344 and larger tumor masses in nu/nu mice. An association was discovered with GD2 since this glycosphingolipid is also the receptor for the family of MFV virus (dsRNA viruses). It is concluded that a dsRNA virus, MFV, appears to provide better explicatory mechanisms for the genesis of i) specific genomic aberrations such as MNA; ii) extensive tumor heterogeneity and chromothripsis; iii) the effects of passive immunotherapy with anti-GD2 monoclonals and that this and similar models should be further investigated in both pediatric and adult cancers.Keywords: neuroblastoma, MYCN, amplification, viruses, GD2
Procedia PDF Downloads 981175 Sphingosomes: Potential Anti-Cancer Vectors for the Delivery of Doxorubicin
Authors: Brajesh Tiwari, Yuvraj Dangi, Abhishek Jain, Ashok Jain
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The purpose of the investigation was to evaluate the potential of sphingosomes as nanoscale drug delivery units for site-specific delivery of anti-cancer agents. Doxorubicin Hydrochloride (DOX) was selected as a model anti-cancer agent. Sphingosomes were prepared and loaded with DOX and optimized for size and drug loading. The formulations were characterized by Malvern zeta-seizer and Transmission Electron Microscopy (TEM) studies. Sphingosomal formulations were further evaluated for in-vitro drug release study under various pH profiles. The in-vitro drug release study showed an initial rapid release of the drug followed by a slow controlled release. In vivo studies of optimized formulations and free drug were performed on albino rats for comparison of drug plasma concentration. The in- vivo study revealed that the prepared system enabled DOX to have had enhanced circulation time, longer half-life and lower elimination rate kinetics as compared to free drug. Further, it can be interpreted that the formulation would selectively enter highly porous mass of tumor cells and at the same time spare normal tissues. To summarize, the use of sphingosomes as carriers of anti-cancer drugs may prove to be a fascinating approach that would selectively localize in the tumor mass, increasing the therapeutic margin of safety while reducing the side effects associated with anti-cancer agents.Keywords: sphingosomes, anti-cancer, doxorubicin, formulation
Procedia PDF Downloads 2931174 Tumour-Associated Tissue Eosinophilia as a Prognosticator in Oral Squamous Cell Carcinoma
Authors: Karen Boaz, C. R. Charan
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Background: The infiltration of tumour stroma by eosinophils, Tumor-Associated Tissue Eosinophilia (TATE), is known to modulate the progression of Oral Squamous Cell Carcinoma (OSCC). Eosinophils have direct tumoricidal activity by release of cytotoxic proteins and indirectly they enhance permeability into tumor cells enabling penetration of tumoricidal cytokines. Also, eosinophils may promote tumor angiogenesis by production of several angiogenic factors. Identification of eosinophils in the inflammatory stroma has been proven to be an important prognosticator in cancers of mouth, oesophagus, larynx, pharynx, breast, lung, and intestine. Therefore, the study aimed to correlate TATE with clinical and histopathological variables, and blood eosinophil count to assess the role of TATE as a prognosticator in Oral Squamous Cell Carcinoma (OSCC). Methods: Seventy two biopsy-proven cases of OSCC formed the study cohort. Blood eosinophil counts and TNM stage were obtained from the medical records. Tissue sections (5µm thick) were stained with Haematoxylin and Eosin. The eosinophils were quantified at invasive tumour front (ITF) in 10HPF (40x magnification) with an ocular grid. Bryne’s grading of ITF was also performed. A subset of thirty cases was also assessed for association of TATE with recurrence, involvement of lymph nodes and surgical margins. Results: 1) No statistically significant correlation was found between TATE and TNM stage, blood eosinophil counts and most parameters of Bryne’s grading system. 2) Statistically significant relation of intense degree of TATE was associated with the absence of distant metastasis, increased lympho-plasmacytic response and increased survival (diseasefree and overall) of OSCC patients. 3) In the subset of 30 cases, tissue eosinophil counts were higher in cases with lymph node involvement, decreased survival, without margin involvement and in cases that did not recur. Conclusion: While the role of eosinophils in mediating immune responses seems ambiguous as eosinophils support cell-mediated tumour immunity in early stages while inhibiting the same in advanced stages, TATE may be used as a surrogate marker for determination of prognosis in oral squamous cell carcinoma.Keywords: tumour-associated tissue eosinophilia, oral squamous cell carcinoma, prognosticator, tumoral immunity
Procedia PDF Downloads 2431173 Relevance of Dosing Time for Everolimus Toxicity in Respect to the Circadian P-Glycoprotein Expression in Mdr1a::Luc Mice
Authors: Narin Ozturk, Xiao-Mei Li, Sylvie Giachetti, Francis Levi, Alper Okyar
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P-glycoprotein (P-gp, MDR1, ABCB1) is a transmembrane protein acting as an ATP-dependent efflux pump and functions as a biological barrier by extruding drugs and xenobiotics out of cells in healthy tissues especially in intestines, liver and brain as well as in tumor cells. The circadian timing system controls a variety of biological functions in mammals including xenobiotic metabolism and detoxification, proliferation and cell cycle events, and may affect pharmacokinetics, toxicity and efficacy of drugs. Selective mTOR (mammalian target of rapamycin) inhibitor everolimus is an immunosuppressant and anticancer drug that is active against many cancers, and its pharmacokinetics depend on P-gp. The aim of this study was to investigate the dosing time-dependent toxicity of everolimus with respect to the intestinal P-gp expression rhythms in mdr1a::Luc mice using Real Time-Biolumicorder (RT-BIO) System. Mdr1a::Luc male mice were synchronized with 12 h of Light and 12 h of Dark (LD12:12, with Zeitgeber Time 0 – ZT0 – corresponding Light onset). After 1-week baseline recordings, everolimus (5 mg/kg/day x 14 days) was administered orally at ZT1-resting period- and ZT13-activity period- to mdr1a::Luc mice singly housed in an innovative monitoring device, Real Time-Biolumicorder units which let us monitor real-time and long-term gene expression in freely moving mice. D-luciferin (1.5 mg/mL) was dissolved in drinking water. Mouse intestinal mdr1a::Luc oscillation profile reflecting P-gp gene expression and locomotor activity pattern were recorded every minute with the photomultiplier tube and infrared sensor respectively. General behavior and clinical signs were monitored, and body weight was measured every day as an index of toxicity. Drug-induced body weight change was expressed relative to body weight on the initial treatment day. Statistical significance of differences between groups was validated with ANOVA. Circadian rhythms were validated with Cosinor Analysis. Everolimus toxicity changed as a function of drug timing, which was least following dosing at ZT13, near the onset of the activity span in male mice. Mean body weight loss was nearly twice as large in mice treated with 5 mg/kg everolimus at ZT1 as compared to ZT13 (8.9% vs. 5.4%; ANOVA, p < 0.001). Based on the body weight loss and clinical signs upon everolimus treatment, tolerability for the drug was best following dosing at ZT13. Both rest-activity and mdr1a::Luc expression displayed stable 24-h periodic rhythms before everolimus and in both vehicle-treated controls. Real-time bioluminescence pattern of mdr1a revealed a circadian rhythm with a 24-h period with an acrophase at ZT16 (Cosinor, p < 0.001). Mdr1a expression remained rhythmic in everolimus-treated mice, whereas down-regulation was observed in P-gp expression in 2 of 4 mice. The study identified the circadian pattern of intestinal P-gp expression with an unprecedented precision. The circadian timing depending on the P-gp expression rhythms may play a crucial role in the tolerability/toxicity of everolimus. The circadian changes in mdr1a genes deserve further studies regarding their relevance for in vitro and in vivo chronotolerance of mdr1a-transported anticancer drugs. Chronotherapy with P-gp-effluxed anticancer drugs could then be applied according to their rhythmic patterns in host and tumor to jointly maximize treatment efficacy and minimize toxicity.Keywords: circadian rhythm, chronotoxicity, everolimus, mdr1a::Luc mice, p-glycoprotein
Procedia PDF Downloads 3391172 Rathke’s Cleft Cyst Presenting as Unilateral Visual Field Defect
Authors: Ritesh Verma, Manisha Rathi, Chand Singh Dhull, Sumit Sachdeva, Jitender Phogat
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A Rathke's cleft cyst is a benign growth found on the pituitary gland in the brain, specifically a fluid-filled cyst in the posterior portion of the anterior pituitary gland. It occurs when the Rathke's pouch does not develop properly and ranges in size from 2 to 40mm in diameter. A 38-year-old male presented to the outpatient department with loss of vision in the inferior quadrant of the left eye since 15 days. Visual acuity was 6/6 in the right eye and 6/9 in the left eye. Visual field analysis by HFA-24-2 revealed an inferior field defect extending to the supero-temporal quadrant in the left eye. MRI brain and orbit was advised to the patient and it revealed a well defined cystic pituitary adenoma indenting left optic nerve near optic chiasm consistent with the diagnosis of Rathke’s cleft cyst (RCC). The patient was referred to neurosurgery department for further management. Symptoms vary greatly between individuals having RCCs. RCCs can be non-functioning, functioning, or both. Besides headaches, neurocognitive deficits are almost always present but have a high rate of immediate reversal if the cyst is properly treated or drained.Keywords: pituitary tumors, rathke’s cleft cyst, visual field defects, vision loss
Procedia PDF Downloads 1931171 In vitro and in vivo Assessment of Cholinesterase Inhibitory Activity of the Bark Extracts of Pterocarpus santalinus L. for the Treatment of Alzheimer’s Disease
Authors: K. Biswas, U. H. Armin, S. M. J. Prodhan, J. A. Prithul, S. Sarker, F. Afrin
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Alzheimer’s disease (AD) (a progressive neurodegenerative disorder) is mostly predominant cause of dementia in the elderly. Prolonging the function of acetylcholine by inhibiting both acetylcholinesterase and butyrylcholinesterase is most effective treatment therapy of AD. Traditionally Pterocarpus santalinus L. is widely known for its medicinal use. In this study, in vitro acetylcholinesterase inhibitory activity was investigated and methanolic extract of the plant showed significant activity. To confirm this activity (in vivo), learning and memory enhancing effects were tested in mice. For the test, memory impairment was induced by scopolamine (cholinergic muscarinic receptor antagonist). Anti-amnesic effect of the extract was investigated by the passive avoidance task in mice. The study also includes brain acetylcholinesterase activity. Results proved that scopolamine induced cognitive dysfunction was significantly decreased by administration of the extract solution, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that bark extract of Pterocarpus santalinus can be better option for further studies on AD via their acetylcholinesterase inhibitory actions.Keywords: Pterocarpus santalinus, cholinesterase inhibitor, passive avoidance, Alzheimer’s disease
Procedia PDF Downloads 2381170 Relevance Of Cognitive Rehabilitation Amongst Children Having Chronic Illnesses – A Theoretical Analysis
Authors: Pulari C. Milu Maria Anto
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Background: Cognitive Rehabilitation/Retraining has been variously used in the research literature to represent non-pharmacological interventions that target the cognitive impairments with the goal of ameliorating cognitive function and functional behaviors to optimize the quality of life. Along with adult’s cognitive impairments, the need to address acquired cognitive impairments (due to any chronic illnesses like CHD - congenital heart diseases or ALL - Acute Lymphoblastic Leukemia) among child populations is inevitable. Also, it has to be emphasized as same we consider the cognitive impairments seen in the children having neurodevelopmental disorders. Methods: All published brain image studies (Hermann, B. et al,2002, Khalil, A. et al., 2004, Follin, C. et al, 2016, etc.) and studies emphasizing cognitive impairments in attention, memory, and/or executive function and behavioral aspects (Henkin, Y. et al,2007, Bellinger, D. C., & Newburger, J. W. (2010), Cheung, Y. T., et al,2016, that could be identified were reviewed. Based on a systematic review of the literature from (2000 -2021) different brain imaging studies, increased risk of neuropsychological and psychosocial impairments are briefly described. Clinical and research gap in the area is discussed. Results:30 papers, both Indian studies and foreign publications (Sage journals, Delhi psychiatry journal, Wiley Online Library, APA PsyNet, Springer, Elsevier, Developmental medicine, and child neurology), were identified. Conclusions: In India, a very limited number of brain imaging studies and neuropsychological studies have done by indicating the cognitive deficits of a child having or undergone chronic illness. None of the studies have emphasized the relevance nor the need of implementingCR among such children, even though its high time to address but still not established yet. The review of the current evidence is to bring out an insight among rehabilitation professionals in establishing a child specific CR and to publish new findings regarding the implementation of CR among such children. Also, this study will be an awareness on considering cognitive aspects of a child having acquired cognitive deficit (due to chronic illness), especially during their critical developmental period.Keywords: cognitive rehabilitation, neuropsychological impairments, congenital heart diseases, acute lymphoblastic leukemia, epilepsy, and neuroplasticity
Procedia PDF Downloads 1721169 Computational Analysis and Daily Application of the Key Neurotransmitters Involved in Happiness: Dopamine, Oxytocin, Serotonin, and Endorphins
Authors: Hee Soo Kim, Ha Young Kyung
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Happiness and pleasure are a result of dopamine, oxytocin, serotonin, and endorphin levels in the body. In order to increase the four neurochemical levels, it is important to associate daily activities with its corresponding neurochemical releases. This includes setting goals, maintaining social relationships, laughing frequently, and exercising regularly. The likelihood of experiencing happiness increases when all four neurochemicals are released at the optimal level. The achievement of happiness is important because it increases healthiness, productivity, and the ability to overcome adversity. To process emotions, electrical brain waves, brain structure, and neurochemicals must be analyzed. This research uses Chemcraft and Avogadro to determine the theoretical and chemical properties of the four neurochemical molecules. Each neurochemical molecule’s thermodynamic stability is calculated to observe the efficiency of the molecules. The study found that among dopamine, oxytocin, serotonin, alpha-, beta-, and gamma-endorphin, beta-endorphin has the lowest optimized energy of 388.510 kJ/mol. Beta-endorphin, a neurotransmitter involved in mitigating pain and stress, is the most thermodynamically stable and efficient molecule that is involved in the process of happiness. Through examining such properties of happiness neurotransmitters, the science of happiness is better understood.Keywords: happiness, neurotransmitters, positive psychology, dopamine, oxytocin, serotonin, endorphins
Procedia PDF Downloads 1501168 Neuroprotective Effect of Vildagliptin against Cerebral Ischemia in Rats
Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam
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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin
Procedia PDF Downloads 1511167 Association of Brain Derived Neurotrophic Factor with Iron as well as Vitamin D, Folate and Cobalamin in Pediatric Metabolic Syndrome
Authors: Mustafa M. Donma, Orkide Donma
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The impact of metabolic syndrome (MetS) on cognition and functions of the brain is being investigated. Iron deficiency and deficiencies of B9 (folate) as well as B12 (cobalamin) vitamins are best-known nutritional anemias. They are associated with cognitive disorders and learning difficulties. The antidepressant effects of vitamin D are known and the deficiency state affects mental functions negatively. The aim of this study is to investigate possible correlations of MetS with serum brain-derived neurotrophic factor (BDNF), iron, folate, cobalamin and vitamin D in pediatric patients. 30 children, whose age- and sex-dependent body mass index (BMI) percentiles vary between 85 and 15, 60 morbid obese children with above 99th percentiles constituted the study population. Anthropometric measurements were taken. BMI values were calculated. Age- and sex-dependent BMI percentile values were obtained using the appropriate tables prepared by the World Health Organization (WHO). Obesity classification was performed according to WHO criteria. Those with MetS were evaluated according to MetS criteria. Serum BDNF was determined by enzyme-linked immunosorbent assay. Serum folate was analyzed by an immunoassay analyzer. Serum cobalamin concentrations were measured using electrochemiluminescence immunoassay. Vitamin D status was determined by the measurement of 25-hydroxycholecalciferol [25-hydroxy vitamin D3, 25(OH)D] using high performance liquid chromatography. Statistical evaluations were performed using SPSS for Windows, version 16. The p values less than 0.05 were accepted as statistically significant. Although statistically insignificant, lower folate and cobalamin values were found in MO children compared to those observed for children with normal BMI. For iron and BDNF values, no alterations were detected among the groups. Significantly decreased vitamin D concentrations were noted in MO children with MetS in comparison with those in children with normal BMI (p ≤ 0.05). The positive correlation observed between iron and BDNF in normal-BMI group was not found in two MO groups. In THE MetS group, the partial correlation among iron, BDNF, folate, cobalamin, vitamin D controlling for waist circumference and BMI was r = -0.501; p ≤ 0.05. None was calculated in MO and normal BMI groups. In conclusion, vitamin D should also be considered during the assessment of pediatric MetS. Waist circumference and BMI should collectively be evaluated during the evaluation of MetS in children. Within this context, BDNF appears to be a key biochemical parameter during the examination of obesity degree in terms of mental functions, cognition and learning capacity. The association observed between iron and BDNF in children with normal BMI was not detected in MO groups possibly due to development of inflammation and other obesity-related pathologies. It was suggested that this finding may contribute to mental function impairments commonly observed among obese children.Keywords: brain-derived neurotrophic factor, iron, vitamin B9, vitamin B12, vitamin D
Procedia PDF Downloads 1141166 Criteria for Assessing Prostate Structure after Proton Radiotherapy for Prostate Cancer
Authors: Kuplevatsky V., Kuplevatskay, Cherkashin M., Berezina N.
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After 6 months, a violation of the differentiation of the structure of the gland due to edema in 100%. 20% retained signs of a tumor according to DWI/ADC data. By 12 months, the reduction in the size of the gland is 100%. In all cases, no diffusion restriction was observed. The study after 18 months showed no significant changes in all (100%) patients. In the study, 24 months after treatment, the size of the gland was stable in all cases (+/- up to 5%). Diffuse decrease in T2VI signals from peripheral zones, without signs of diffusion restriction in 100%. After 30 months, signs of recovery of adenomatous changes in the transient zone were revealed in 85%. After 36 and 42 months, the restoration of organ differentiation was observed in 93% of patients. In 4 patients, by the 48th month, signs of biochemical relapse were clinically noted. According to the MRI data, signs of a local relapse were revealed. After 48 months, there were signs of restoration of organ differentiation, which allowed the use of PI-RADS criteria. The study after 54 months showed no changes compared to the control. 60 months after treatment, 97% of patients showed a restoration of differentiation of the gland structure, which allows evaluating the organ according to PI-RADS criteria Conclusions: The beginning of restoration of the structure of the prostate gland began 24 months after proton radiation therapy, the PI-RADS criteria can be fully applied after 48 months of treatment. Control studies every 6 months without clinical signs of relapse are not advisable. Local control of the prostate tumor after proton radiation therapy was achieved in 95% of patients during the entire follow-up period ( 60 months).Keywords: proton therapy, prostate cancer, MRI imaging, PI-RADS
Procedia PDF Downloads 981165 Multi-Scale Modelling of the Cerebral Lymphatic System and Its Failure
Authors: Alexandra K. Diem, Giles Richardson, Roxana O. Carare, Neil W. Bressloff
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Alzheimer's disease (AD) is the most common form of dementia and although it has been researched for over 100 years, there is still no cure or preventive medication. Its onset and progression is closely related to the accumulation of the neuronal metabolite Aβ. This raises the question of how metabolites and waste products are eliminated from the brain as the brain does not have a traditional lymphatic system. In recent years the rapid uptake of Aβ into cerebral artery walls and its clearance along those arteries towards the lymph nodes in the neck has been suggested and confirmed in mice studies, which has led to the hypothesis that interstitial fluid (ISF), in the basement membranes in the walls of cerebral arteries, provides the pathways for the lymphatic drainage of Aβ. This mechanism, however, requires a net reverse flow of ISF inside the blood vessel wall compared to the blood flow and the driving forces for such a mechanism remain unknown. While possible driving mechanisms have been studied using mathematical models in the past, a mechanism for net reverse flow has not been discovered yet. Here, we aim to address the question of the driving force of this reverse lymphatic drainage of Aβ (also called perivascular drainage) by using multi-scale numerical and analytical modelling. The numerical simulation software COMSOL Multiphysics 4.4 is used to develop a fluid-structure interaction model of a cerebral artery, which models blood flow and displacements in the artery wall due to blood pressure changes. An analytical model of a layer of basement membrane inside the wall governs the flow of ISF and, therefore, solute drainage based on the pressure changes and wall displacements obtained from the cerebral artery model. The findings suggest that an active role in facilitating a reverse flow is played by the components of the basement membrane and that stiffening of the artery wall during age is a major risk factor for the impairment of brain lymphatics. Additionally, our model supports the hypothesis of a close association between cerebrovascular diseases and the failure of perivascular drainage.Keywords: Alzheimer's disease, artery wall mechanics, cerebral blood flow, cerebral lymphatics
Procedia PDF Downloads 5211164 Extensive Cerebral Venous Thrombosis after Resection of Third Ventricle Colloid Cyst
Authors: Naim Izet Kajtazi
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Context: The third ventricle colloid cyst (CC) is a benign growth usually located in the third ventricle and can cause various neurological symptoms, including sudden death. Modern surgical interventions may still result in a wide range of complications and cerebral venous thrombosis (CVT) is among them. Process: A 38-year-old female with an existing diagnosis of diabetes mellitus (DM) and hypothyroidism and a six-month history of headaches, blurred vision, and vomiting presented to our clinic three days after the headaches became excessively severe. Neurological examination on admission revealed bilateral papilledema without any associated focal neurological deficits. Brain computed tomography (CT) and magnetic resonance imaging (MRI) confirmed the presence of a third ventricle colloid cyst and associated non-communicating hydrocephalus involving the lateral ventricles. As a result, the patient underwent emergency bilateral external ventricular drainage (EVD) insertion followed by a third ventricular CC excision under neuronavigation through a right frontal craniotomy. Twelve days post-operatively, the patient developed further headaches, followed by a generalized tonic-clonic seizure that led to no postictal neurological deficits. Nonetheless, computed tomography venography of the brain revealed extensive thrombosis of the superior sagittal sinus, inferior sagittal sinus, right sigmoid sinus, and right internal jugular vein. A newly diagnosed CVT was treated with intravenous heparin. The patient was discharged with warfarin, which was discontinued after 12 months. Ten years after her illness, she remained stable and free from any neurological deficits but still suffered from mild chronic headaches. Outcome: Ten years after her illness, she remained stable and free from any neurological deficits but still suffered from mild chronic headaches. Relevance: A preoperative venous study should be performed in all cases to gain a better understanding of the venous anatomy. We advocate meticulous microsurgical techniques to protect the venous system surrounding the foramen of Monro and reduce the amount of retraction during surgery.Keywords: CVT, seizures, third ventricle colloid cyst, MRI of brain
Procedia PDF Downloads 611163 A Theragnostic Approach for Alzheimer’s Disease Focused on Phosphorylated Tau
Authors: Tomás Sobrino, Lara García-Varela, Marta Aramburu-Núñez, Mónica Castro, Noemí Gómez-Lado, Mariña Rodríguez-Arrizabalaga, Antía Custodia, Juan Manuel Pías-Peleteiro, José Manuel Aldrey, Daniel Romaus-Sanjurjo, Ángeles Almeida, Pablo Aguiar, Alberto Ouro
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Introduction: Alzheimer’s disease (AD) and other tauopathies are primary causes of dementia, causing progressive cognitive deterioration that entails serious repercussions for the patients' performance of daily tasks. Currently, there is no effective approach for the early diagnosis and treatment of AD and tauopathies. This study suggests a theragnostic approach based on the importance of phosphorylated tau protein (p-Tau) in the early pathophysiological processes of AD. We have developed a novel theragnostic monoclonal antibody (mAb) to provide both diagnostic and therapeutic effects. Methods/Results: We have developed a p-Tau mAb, which was doped with deferoxamine for radiolabeling with Zirconium-89 (89Zr) for PET imaging, as well as fluorescence dies for immunofluorescence assays. The p-Tau mAb was evaluated in vitro for toxicity by MTT assay, LDH activity, propidium iodide/Annexin V assay, caspase-3, and mitochondrial membrane potential (MMP) assay in both mouse endothelial cell line (bEnd.3) and cortical primary neurons cell cultures. Importantly, non-toxic effects (up to concentrations of p-Tau mAb greater than 100 ug/mL) were detected. In vivo experiments in the tauopathy model mice (PS19) show that the 89Zr-pTau-mAb and 89Zr-Fragments-pTau-mAb are stable in circulation for up to 10 days without toxic effects. However, only less than 0.2% reached the brain, so further strategies have to be designed for crossing the Brain-Blood-Barrier (BBB). Moreover, an intraparenchymal treatment strategy was carried out. The PS19 mice were operated to implement osmotic pumps (Alzet 1004) at two different times, at 4 and 7 months, to stimulate the controlled release for one month each of the B6 antibody or the IgG1 control antibody. We demonstrated that B6-treated mice maintained their motor and memory abilities significantly compared with IgG1 treatment. In addition, we observed a significant reduction in p-Tau deposits in the brain. Conclusions /Discussion: A theragnostic pTau-mAb was developed. Moreover, we demonstrated that our p-Tau mAb recognizes very-early pathology forms of p-Tau by non-invasive techniques, such as PET. In addition, p-Tau mAb has non-toxic effects, both in vitro and in vivo. Although the p-Tau mAb is stable in circulation, only 0.2% achieve the brain. However, direct intraventricular treatment significantly reduces cognitive impairment in Alzheimer's animal models, as well as the accumulation of toxic p-Tau species.Keywords: alzheimer's disease, theragnosis, tau, PET, immunotherapy, tauopathies
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