Search results for: brain tumours

Authors: Mark P. Mayala, Henry Mayala, Khuzeima Khanbhai

Abstract:

Background: Heart failure has been a rising concern in Tanzania. New drugs have been introduced, including the group of drugs called Angiotensin receptor Neprilysin Inhibitor (ARNI), but due to their high cost, angiotensin-converting enzymes inhibitors (ACEIs) and Angiotensin receptor blockers (ARBs) have been mostly used in Tanzania. However, according to our knowledge, the efficacy comparison of the two groups is yet to be studied in Tanzania. The aim of this study was to compare the efficacy of ACEIs and ARBs among patients with heart failure. Methodology: This was a hospital-based prospective cohort study done at Jakaya Kikwete Cardiac Institution (JKCI), Tanzania, from June to December 2020. Consecutive enrollment was done until fulfilling the inclusion criteria. Clinical details were measured at baseline. We assessed the relationship between ARBs and ACEIs users with N-terminal pro-brain natriuretic peptide (NT pro-BNP) levels at admission and at 1-month follow-up using a chi-square test. A Kaplan-Meier curve was used to estimate the survival time of the two groups. Results: 155 HF patients were enrolled, with a mean age of 48 years, whereby 52.3% were male, and their mean left ventricular ejection fraction (LVEF) was 37.3%. 52 (33.5%) heart failure patients were on ACEIs, 57 (36.8%) on ARBs, and 46 (29.7%) were neither using ACEIs nor ARBs. At least half of the patients did not receive a guideline-directed medical therapy (GDMT), with only 82 (52.9%) receiving a GDMT. A drop in NT pro-BNP levels was observed during admission and at 1-month follow-up on both groups, from 6389.2 pg/ml to 4000.1 pg/ml for ARB users and 5877.7 pg/ml to 1328.2 pg/ml for the ACEIs users. There was no statistical difference between the two groups when estimated by the Kaplan-Meier curve, though more deaths were observed in those who were neither on ACEIs nor ARBs, with a calculated P value of 0.01. Conclusion: This study demonstrates that ACEIs have more efficacy and overall better clinical outcome than ARBs, but this should be taken under the patient-based case, considering the side effects of ACEIs and patients’ adherence.

Keywords: angiotensin converting enzymes inhibitors, angiotensin receptor blockers, guideline direct medical therapy, N-terminal pro-brain natriuretic peptide

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Authors: Janneth Gonzalez, Andres Pinzon Velasco, Maria Angarita, Nicolas Mendoza

Abstract:

Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatory pathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, there are few studies on the neuro-protective mechanisms of tibolone, especially at the systemic (omic) level. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also use control theory to identify those reactions that control the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a change in energy source use through inhibition of folate cycle and fatty acid β-oxidation and upregulation of ketone bodies formation.We found 25 metabolic switches under PA-mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation in metabolic pathways that increase neurotoxicity and represent potential treatment targets. Finally, this study framework facilitates the understanding of metabolic regulation strategies, andit can be used for in silico exploring the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics, control theory

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Authors: Mikel Alonso López

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In the first decade of the twenty-first century, advanced imaging techniques began to be applied for neuroscience research. The Functional Magnetic Resonance Imaging (fMRI) is one of the most important and most used research techniques for the investigation of emotions, because of its ease to observe the brain areas that oxygenate when performing certain tasks. In this research, we make a review about the main research carried out on the influence of the emotions in the decision-making process that is exposed by using the fMRI.

Keywords: decision making, emotions, fMRI, consumer behaviour

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Authors: Rai Sachindra Prasad

Abstract:

Thought is physical force. This has been well recognized but hardly translated visually or otherwise in the sense of its transfer from one individual to another. In the present world of chaos and disorder with yawning gaps between right and wrong thinking individuals, if it is possible to transfer the right thoughts to replace the wrong ones it would indeed be a great achievement in the present situation of the world which is torn with violence with dangerous thoughts of individuals. Moreover, such a possibility would completely remove the barrier of language between two persons, which at times proves to be a great obstacle in realizing a desired purpose. If a proper instrumentation scheme containing appropriate transducers and electronics is designed and implemented to realize this thought ransfer phenomenon, this would prove to be extremely useful when properly used. Considering the advancements already made in recording the nerve impulses in the brain, which are electrical events of very short durations that move along the axon, it is conceivable that this may be used to good effect in implementing the scheme. In such a proposition one shoud consider the roles played by pineal body, pituitary gland and ‘association’ areas. Pioneer students of brain have thought that associations or connections between sensory input and motor output were made in these areas. It is currently believed that rather than being regions of simple sensory-motor connections, the association areas process and integrate sensory information relayed to them from the primary sensory areas of the cortex and from the thalamus, after the information has been processed, it may be sent to motor areas to be acted upon. Again, even though the role played by pineal body is not known fully to neurologists its interconnection with pituitary gland is a matter of great significance to the ‘Rishis’ and; Seers’ s described in Vedas and Puranas- the ancient Holy books of Hindus. If the pineal body is activated through meditation it would control the pituitary gland thereby the individual’s thoughts and acts. Thus, if thoughts can be picked up by special transducers, these can be connected to suitable electronics circuitry to amplify the signals. These signals in the form of electromagnetic waves can then be transmitted using modems for long distance transmission and eventually received by or passed on to a subject of interest through another set of electronics circuit and devices.

Keywords: modems, pituitary gland, pineal body, thought transfer

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Authors: Sylwia Baluta, Joanna Cabaj, Karol Malecha

Abstract:

The evolution of biosensors was driven by the need for faster and more versatile analytical methods for application in important areas including clinical, diagnostics, food analysis or environmental monitoring, with minimum sample pretreatment. Rapid and sensitive neurotransmitters detection is extremely important in modern medicine. These compounds mainly occur in the brain and central nervous system of mammals. Any changes in the neurotransmitters concentration may lead to many diseases, such as Parkinson’s or schizophrenia. Classical techniques of chemical analysis, despite many advantages, do not permit to obtain immediate results or automatization of measurements.

Keywords: adrenaline, biosensor, dopamine, laccase, tyrosinase

Procedia PDF Downloads 128

Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Emhimed Saffor

Abstract:

In this paper, the problem of edge detection in digital images is considered. Three methods of edge detection based on mathematical morphology algorithm were applied on two sets (Brain and Chest) CT images. 3x3 filter for first method, 5x5 filter for second method and 7x7 filter for third method under MATLAB programming environment. The results of the above-mentioned methods are subjectively evaluated. The results show these methods are more efficient and satiable for medical images, and they can be used for different other applications.

Keywords: CT images, Matlab, medical images, edge detection

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Authors: Nicole Scott, Emily Dwyer, Cara Patrissy, Samantha Bonventre, Lina Begdache

Abstract:

Across North America, the use and abuse of Attention Deficit Hyperactivity Disorder (ADHD) medication, cannabis, nicotine, and other psychoactive substances across college campuses have become an increasingly prevalent problem. Students frequently use these substances to aid their studying or deal with their mental health issues. However, it is still unknown what psychoactive substances are likely to be abused when college students illicitly use ADHD medication. In addition, it is not clear which psychoactive substance is associated with mental distress. Thus, the purpose of this study is to fill these gaps by assessing the use of different psychoactive substances when illicit ADHD medication is used; and how this association relates to mental stress. A total of 702 undergraduate students from different college campuses in the U.S. completed an anonymous survey distributed online. Data were self-reported on demographics, the use of ADHD medications, cannabis, nicotine, other psychoactive drugs, and mental distress, and feelings and opinions on the use of illicit study drugs were all included in the survey. Mental distress was assessed using the Kessler Psychological Distress 6 Scale. Data were analyzed in SPSS, Version 25.0, using Pearson’s Correlation Coefficient. Our results show that use of ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent), there were both statistically significant positive and negative correlations to specific psychoactive substances and their corresponding frequencies. Along the same lines, ADHD medication, cannabis use (non-frequent and very frequent), and nicotine use (non-frequent and very frequent) had statistically significant positive and negative correlations to specific mental distress experiences. As these findings are combined, a vicious loop can initiate a cycle where individuals who abuse psychoactive substances may or may not be inclined to use other psychoactive substances. This may later inhibit brain functions in those main areas of the brain stem, amygdala, and prefrontal cortex where this vicious cycle may or may not impact their mental distress. Addressing the impact of study drug abuse and its potential to be associated with further substance abuse may provide an educational framework and support proactive approaches to promote awareness among college students.

Keywords: stimulant, depressant, nicotine, ADHD medication, psychoactive substances, mental health, illicit, ecstasy, adrenochrome

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Authors: Janneth Gonzalez, Andrés Pinzon Velasco, Maria Angarita

Abstract:

Astrocytes play an important role in various processes in the brain, including pathological conditions such as neurodegenerative diseases. Recent studies have shown that the increase in saturated fatty acids such as palmitic acid (PA) triggers pro-inflammatorypathways in the brain. The use of synthetic neurosteroids such as tibolone has demonstrated neuro-protective mechanisms. However, broad studies with a systemic point of view on the neurodegenerative role of PA and the neuro-protective mechanisms of tibolone are lacking. In this study, we performed the integration of multi-omic data (transcriptome and proteome) into a human astrocyte genomic scale metabolic model to study the astrocytic response during palmitate treatment. We evaluated metabolic fluxes in three scenarios (healthy, induced inflammation by PA, and tibolone treatment under PA inflammation). We also applied a control theory approach to identify those reactions that exert more control in the astrocytic system. Our results suggest that PA generates a modulation of central and secondary metabolism, showing a switch in energy source use through inhibition of folate cycle and fatty acid β‐oxidation and upregulation of ketone bodies formation. We found 25 metabolic switches under PA‐mediated cellular regulation, 9 of which were critical only in the inflammatory scenario but not in the protective tibolone one. Within these reactions, inhibitory, total, and directional coupling profiles were key findings, playing a fundamental role in the (de)regulation of metabolic pathways that may increase neurotoxicity and represent potential treatment targets. Finally, the overall framework of our approach facilitates the understanding of complex metabolic regulation, and it can be used for in silico exploration of the mechanisms of astrocytic cell regulation, directing a more complex future experimental work in neurodegenerative diseases.

Keywords: astrocytes, data integration, palmitic acid, computational model, multi-omics

Procedia PDF Downloads 86

Authors: Lynn Louis, Bor Shin Chee, Marion McAfee, Michael Nugent

Abstract:

This article aims to develop a sustained release formulation of microspheres containing the mTOR inhibitor Everolimus (EVR) using Polyvinyl alcohol (PVA) to enhance the bioavailability of the drug and to overcome poor solubility characteristics of Everolimus. This paper builds on recent work in the manufacture of microspheres using the sessile droplet technique by freezing the polymer-drug solution by suspending the droplets into pre-cooled ethanol vials immersed in liquid nitrogen. The spheres were subjected to 6 freezing cycles and 3 freezing cycles with thawing to obtain proper geometry, prevent aggregation, and achieve physical cross-linking. The prepared microspheres were characterised for surface morphology by SEM, where a 3-D porous structure was observed. The in vitro release studies showed a 62.17% release over 12.5 days, indicating a sustained release due to good encapsulation. This result is comparatively much more than the 49.06% release achieved within 4 hours from the solvent cast Everolimus film as a control with no freeze-thaw cycles performed. The solvent cast films were made in this work for comparison. A prolonged release of Everolimus using a polymer-based drug delivery system is essential to reach optimal therapeutic concentrations in treating SEGA tumours without systemic exposure. These results suggest that the combination of PVA and Everolimus via a rheological synergism enhanced the bioavailability of the hydrophobic drug Everolimus. Physical-chemical characterisation using DSC and FTIR analysis showed compatibility of the drug with the polymer, and the stability of the drug was maintained owing to the high molecular weight of the PVA. The obtained results indicate that the developed PVA/EVR microsphere is highly suitable as a potential drug delivery system with improved bioavailability in treating Subependymal Giant cell astrocytoma (SEGA).

Keywords: drug delivery system, everolimus, freeze-thaw cycles, polyvinyl alcohol

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Authors: Sara Mosteller, Larissa K. Samuelson, Sobanawartiny Wijeakumar, John P. Spencer

Abstract:

This study was designed to examine how humans are able to teach and learn semantic information as well as cooperate in order to jointly achieve sophisticated goals. Specifically, we are measuring individual differences in how these abilities develop from foundational building blocks in early childhood. The current study adopts a paradigm for novel noun learning developed by Samuelson, Smith, Perry, and Spencer (2011) to a hyperscanning paradigm [Cui, Bryant and Reiss, 2012]. This project measures coordinated brain activity between a parent and child using simultaneous functional near infrared spectroscopy (fNIRS) in pairs of 2.5, 3.5 and 4.5-year-old children and their parents. We are also separately testing pairs of adult friends. Children and parents, or adult friends, are seated across from one another at a table. The parent (in the developmental study) then teaches their child the names of novel toys. An experimenter then tests the child by presenting the objects in pairs and asking the child to retrieve one object by name. Children are asked to choose from both pairs of familiar objects and pairs of novel objects. In order to explore individual differences in cooperation with the same participants, each dyad plays a cooperative game of Jenga, in which their joint score is based on how many blocks they can remove from the tower as a team. A preliminary analysis of the noun-learning task showed that, when presented with 6 word-object mappings, children learned an average of 3 new words (50%) and that the number of objects learned by each child ranged from 2-4. Adults initially learned all of the new words but were variable in their later retention of the mappings, which ranged from 50-100%. We are currently examining differences in cooperative behavior during the Jenga playing game, including time spent discussing each move before it is made. Ongoing analyses are examining the social dynamics that might underlie the differences between words that were successfully learned and unlearned words for each dyad, as well as the developmental differences observed in the study. Additionally, the Jenga game is being used to better understand individual and developmental differences in social coordination during a cooperative task. At a behavioral level, the analysis maps periods of joint visual attention between participants during the word learning and the Jenga game, using head-mounted eye trackers to assess each participant’s first-person viewpoint during the session. We are also analyzing the coherence in brain activity between participants during novel word-learning and Jenga playing. The first hypothesis is that visual joint attention during the session will be positively correlated with both the number of words learned and with the number of blocks moved during Jenga before the tower falls. The next hypothesis is that successful communication of new words and success in the game will each be positively correlated with synchronized brain activity between the parent and child/the adult friends in cortical regions underlying social cognition, semantic processing, and visual processing. This study probes both the neural and behavioral mechanisms of learning and cooperation in a naturalistic, interactive and developmental context.

Keywords: communication, cooperation, development, interaction, neuroscience

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Authors: Sylvia Nkiru Ogbuoji

Abstract:

This paper discussed the consequences of inadequate funding in Nigerian education system. It briefly explained the meaning of education in relation to the context and identified various ways education in Nigeria can be funded. It highlighted some of the consequences of inadequate funding education system to include: Inadequate facilitates for teaching and learning, western brain drain, unemployment, crises of poverty, low staff morale it. Finally, some recommendations were put forward, the government should improve the annual budget allocation to education, in order to achieve educational objective, also government should monitor the utilization of allocated funds to minimize embezzlement.

Keywords: consequences, corruption, education, funding

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Authors: Lev Bertovsky

Abstract:

The purpose of this study was to determine the reasons for the formation of false testimony from witnesses and make recommendations on the recognition of such cases. During the studies, which were based on the achievements of professionals in the field of psychology, as well as personal investigative practice, the stages of perception of the information were studied, as well as the process of its reclaim from the memory and transmission to the communicator upon request. Based on the principles of the human brain, kinds of conscientious witness mistakes were systematized. Proposals were formulated for the optimization of investigative actions in cases where the witnesses make an honest mistake with respect to the effects previously observed by them.

Keywords: criminology, eyewitness testimony, honest mistake, information, investigator, investigation, questioning

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Authors: Mohammad Zavid Parvez, Manoranjan Paul

Abstract:

A seizure prediction method is proposed by extracting global features using phase correlation between adjacent epochs for detecting relative changes and local features using fluctuation/deviation within an epoch for determining fine changes of different EEG signals. A classifier and a regularization technique are applied for the reduction of false alarms and improvement of the overall prediction accuracy. The experiments show that the proposed method outperforms the state-of-the-art methods and provides high prediction accuracy (i.e., 97.70%) with low false alarm using EEG signals in different brain locations from a benchmark data set.

Keywords: Epilepsy, seizure, phase correlation, fluctuation, deviation.

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Authors: Rutej R. Mehta, Michael A. Chappell

Abstract:

Introduction: Arterial spin labelling (ASL) is an increasingly popular perfusion MRI technique, in which arterial blood water is magnetically labelled in the neck before flowing into the brain, providing a non-invasive measure of cerebral blood flow (CBF). The accuracy of ASL CBF measurements, however, is hampered by dispersion effects; the distortion of the ASL labelled bolus during its transit through the vasculature. In spite of this, the current recommended implementation of ASL – the white paper (Alsop et al., MRM, 73.1 (2015): 102-116) – does not account for dispersion, which leads to the introduction of errors in CBF. Given that the transport time from the labelling region to the tissue – the arterial transit time (ATT) – depends on the region of the brain and the condition of the patient, it is likely that these errors will also vary with the ATT. In this study, various dispersion models are assessed in comparison with the white paper (WP) formula for CBF quantification, enabling the errors introduced by the WP to be quantified. Additionally, this study examines the relationship between the errors associated with the WP and the ATT – and how this is influenced by dispersion. Methods: Data were simulated using the standard model for pseudo-continuous ASL, along with various dispersion models, and then quantified using the formula in the WP. The ATT was varied from 0.5s-1.3s, and the errors associated with noise artefacts were computed in order to define the concept of significant error. The instantaneous slope of the error was also computed as an indicator of the sensitivity of the error with fluctuations in ATT. Finally, a regression analysis was performed to obtain the mean error against ATT. Results: An error of 20.9% was found to be comparable to that introduced by typical measurement noise. The WP formula was shown to introduce errors exceeding 20.9% for ATTs beyond 1.25s even when dispersion effects were ignored. Using a Gaussian dispersion model, a mean error of 16% was introduced by using the WP, and a dispersion threshold of σ=0.6 was determined, beyond which the error was found to increase considerably with ATT. The mean error ranged from 44.5% to 73.5% when other physiologically plausible dispersion models were implemented, and the instantaneous slope varied from 35 to 75 as dispersion levels were varied. Conclusion: It has been shown that the WP quantification formula holds only within an ATT window of 0.5 to 1.25s, and that this window gets narrower as dispersion occurs. Provided that the dispersion levels fall below the threshold evaluated in this study, however, the WP can measure CBF with reasonable accuracy if dispersion is correctly modelled by the Gaussian model. However, substantial errors were observed with other common models for dispersion with dispersion levels similar to those that have been observed in literature.

Keywords: arterial spin labelling, dispersion, MRI, perfusion

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Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

Abstract:

Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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Authors: Merve Colak, Gizem Donmez Yalcin

Abstract:

Glutamate has many neurological functions in the central nervous system and is found at high concentrations in the brain. Increased levels of glutamate in the neuronal space are toxic, causing neuron damage and death. This is called glutamate-induced excitotoxicity. Excitotoxicity is among the causes of many neurological diseases such as trauma, cerebral ischemia, epilepsy, Parkinson's Disease, Alzheimer's Disease. Since neuroblastoma cells are known to be excitotoxic, we propose that excitotoxicity can be studied in neuroblastoma cells. Excitotoxicity can be induced using kainic acid in neuroblastoma cells. Measuring the secretion of glutamate, excitotoxicity can be analyzed in neuroblastoma cells.

Keywords: glutamate, excitotoxicity, kainic acid, Sirt4

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Authors: Silvia D. Vaca, Benjamin J. Kuo, Joao Ricardo N. Vissoci, Catherine A. Staton, Linda W. Xu, Michael Muhumuza, Hussein Ssenyonjo, John Mukasa, Joel Kiryabwire, Henry E. Rice, Gerald A. Grant, Michael M. Haglund

Abstract:

Background: While delays to care exist in resource rich settings, greater delays are seen along the care continuum in low- and middle-income countries (LMICs) largely due to limited healthcare capacity to address the disproportional rates of traumatic brain injury (TBI) in Sub Saharan Africa (SSA). While many LMICs have government subsidized systems to offset surgical costs, the burden of securing funds by the patients for medications, supplies, and CT diagnostics poses a significant challenge to timely surgical interventions. In Kampala Uganda, the challenge of obtaining timely CT scans is twofold. First, due to a lack of a functional CT scanner at the tertiary hospital, patients need to arrange their own transportation to the nearby private facility for CT scans. Second, self-financing for the private CT scans ranges from $80 - $130, which is near the average monthly income in Kampala. These bottlenecks contribute significantly to the care continuum delays and are associated with poor TBI outcomes. Objective: The objectives of this study are to 1) describe the temporal delays through a modified three delays model that fits the context of neurosurgical interventions for TBI patients in Kampala and 2) investigate the association between delays and mortality. Methods: Prospective data were collected for 563 TBI patients presenting to a tertiary hospital in Kampala from 1 June – 30 November 2016. Four time intervals were constructed along five time points: injury, hospital arrival, neurosurgical evaluation, CT results, and definitive surgery. Time interval differences among mild, moderate and severe TBI and their association with mortality were analyzed. Results: The mortality rate of all TBI patients presenting to MNRH was 9.6%, which ranged from 4.7% for mild and moderate TBI patients receiving surgery to 81.8% for severe TBI patients who failed to receive surgery. The duration from injury to surgery varied considerably across TBI severity with the largest gap seen between mild TBI (174 hours) and severe TBI (69 hours) patients. Further analysis revealed care continuum differences for interval 3 (neurosurgical evaluation to CT result) and 4 (CT result to surgery) between severe TBI patients (7 hours for interval 3 and 24 hours for interval 4) and mild TBI patients (19 hours for interval 3, and 96 hours for interval 4). These post-arrival delays were associated with mortality for mild (p=0.05) and moderate TBI (p=0.03) patients. Conclusions: To our knowledge, this is the first analysis using a modified ‘three delays’ framework to analyze the care continuum of TBI patients in Uganda from injury to surgery. We found significant associations between delays and mortality for mild and moderate TBI patients. As it currently stands, poorer outcomes were observed for these mild and moderate TBI patients who were managed non-operatively or failed to receive surgery while surgical services were shunted to more severely ill patients. While well intentioned, high mortality rates were still observed for the severe TBI patients managed surgically. These results suggest the need for future research to optimize triage practices, understand delay contributors, and improve pre-hospital logistical referral systems.

Keywords: care continuum, global neurosurgery, Kampala Uganda, LMIC, Mulago, prospective registry, traumatic brain injury

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Authors: Thomas Ousterhout

Abstract:

In an effort to test the ability of a commercial grade EEG headset to effectively measure the N400 ERP, a replication study was conducted to see if similar results could be produced as that which used a medical grade EEG. Pictures of meaningful and meaningless hand postures were borrowed from the original author and subjects were required to perform a semantic discrimination task. The N400 was detected indicating semantic processing of the meaningfulness of the hand postures. The results corroborate those of the original author and support the use of some commercial grade EEG headsets for non-critical research applications.

Keywords: EEG, ERP, N400, semantics, congruency, gestures, emotiv

Procedia PDF Downloads 249

Authors: M. Skibinska, A. Rajewska-Rager, M. Dmitrzak-Weglarz, N. Lepczynska, P. Sibilski, P. Kapelski, J. Pawlak, J. Twarowska-Hauser

Abstract:

Introduction: Neurotrophic factors have been implicated in neuropsychiatric disorders. Brain-Derived Neurotrophic Factor (BDNF) influences neuron differentiation in development as well as synaptic plasticity and neuron survival in adulthood. BDNF is widely studied in mood disorders and has been proposed as a biomarker for depression. BDNF is synthesized as precursor protein – proBDNF. Both forms are biologically active and exert opposite effects on neurons. Aim: The aim of the study was to examine the serum levels of BDNF and proBDNF in unipolar and bipolar young patients below 24 years old during hypo/manic, depressive episodes and in remission compared to healthy control group. Methods: In a prospective 2 years follow-up study, we investigated alterations in levels of BDNF and proBDNF in 79 patients (23 males, mean age 19.08, SD 3.3 and 56 females, mean age 18.39, SD 3.28) diagnosed with mood disorders: unipolar and bipolar disorder compared with 35 healthy control subjects (7 males, mean age 20.43, SD 4.23 and 28 females, mean age 21.25, SD 2.11). Clinical characteristics including mood, comorbidity, family history, and treatment, were evaluated during control visits and clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Serum BDNF and proBDNF concentrations were determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Serum BDNF and proBDNF levels were analysed with covariates: sex, age, age > 18 and < 18 years old, family history of affective disorders, drug-free vs. medicated status. Normality of the data was tested using Shapiro-Wilk test. Levene’s test was used to calculate homogeneity of variance. Non-parametric Tests: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient were applied in analyses The statistical significance level was set at p < 0.05. Results: BDNF and proBDNF serum levels did not differ between patients at baseline and controls as well as comparing patients in acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6). Comparing BDNF and proBDNF levels between patients in euthymia and control group no differences have been found. Increased BDNF level in women compared to men at baseline (p=0.01) have been observed. BDNF level at baseline was negatively correlated with depression and mania occurence at 24 month (p=0.04). BDNF level at 12 month was negatively correlated with depression and mania occurence at 12 month (p=0.01). Correlation of BDNF level with sex have been detected (p=0.01). proBDNF levels at month 3, 6 and 12 negatively correlated with disease status (p=0.02, p=0.008, p=0.009, respectively). No other correlations of BDNF and proBDNF levels with clinical and demographical variables have been detected. Discussion: Our results did not show any differences in BDNF and proBDNF levels between depression, mania, euthymia, and controls. Imbalance in BDNF/proBDNF signalling may be involved in pathogenesis of mood disorders. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: bipolar disorder, Brain-Derived Neurotrophic Factor (BDNF), proBDNF, unipolar depression

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Authors: Khushboo Shah

Abstract:

Categorical bans on the death penalty and life-without-parole sentences for juvenile offenders in a growing number of countries have established a new era in juvenile jurisprudence. This has been brought about by integration of the growing knowledge in cognitive neuroscience and appreciation of the inherent differences between adults and adolescents over the last ten years. This evolving understanding of being a child in the criminal system can be aptly reflected through policies that incorporate the mitigating traits of youth. First, the presentation will delineate the structures in cognitive neuroscience and in particular, focus on the prefrontal cortex, the amygdala, and the basal ganglia. These key anatomical structures in the brain are linked to three mitigating adolescent traits—an underdeveloped sense of responsibility, an increased vulnerability to negative influences, and transitory personality traits—that establish why juveniles have a lessened culpability. The discussion will delve into the details depicting how an underdeveloped prefrontal cortex results in the heightened emotional angst, high-energy and risky behavior characteristic of the adolescent time period or how the amygdala, the emotional center of the brain, governs different emotional expression resulting in why teens are susceptible to negative influences. Based on this greater understanding, it is incumbent that policies adequately reflect the adolescent physiology and psychology in the criminal system. However, it is important to ensure that these views are appropriately weighted while considering the jurisprudence for the treatment of children in the law. To ensure this balance is appropriately stricken, policies must incorporate the distinctive traits of youth in sentencing and legal considerations and yet refrain from the potential fallacies of absolving a juvenile offender of guilt and culpability. Accordingly, three policies will demonstrate how these results can be achieved: (1) eliminate housing of juvenile offenders in the adult prison system, (2) mandate fitness hearings for all transfers of juveniles to adult criminal court, and (3) use the post-disposition review as a type of rehabilitation method for juvenile offenders. Ultimately, this interdisciplinary approach of science and law allows for a better understanding of adolescent psychological and social functioning and can effectuate better legal outcomes for juveniles tried as adults.

Keywords: criminal law, Juvenile Justice, interdisciplinary, neuroscience

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Authors: M. Liebherr, P. Schubert, S. Kersten, C. Dietz, L. Franz, C. T. Haas

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With a long history, dual-task has become one of the most intriguing research fields regarding human brain functioning and cognition. However, findings considering effects of task-interrelations are limited (especially, in combined motor and cognitive tasks). Therefore, we aimed at developing a measurement system in order to analyse interrelation effects of cognitive and motor tasks. On the one hand, the present study demonstrates the applicability of the measurement system and on the other hand first results regarding a systematization of different task combinations are shown. Future investigations should combine imagine technologies and this developed measurement system.

Keywords: dual-task, interference, cognition, measurement

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Authors: H. Namazi, H. T. N. Kuan

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It is known that in humans, the adaptation to a given odor occurs within a quite short span of time (typically one minute) after the odor is presented to the brain. Different models of human olfaction have been developed by scientists but none of these models consider the diffusion phenomenon in olfaction. A novel microscopic model of the human olfaction is presented in this paper. We develop this model by incorporating the transient diffusivity. In fact, the mathematical model is written based on diffusion of the odorant within the mucus layer. By the use of the model developed in this paper, it becomes possible to provide quantification of the objective strength of odor.

Keywords: diffusion, microscopic model, mucus layer, olfaction

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Authors: Jalil ur Rehman, Ramesh C, Tailor, Isa Khan, Jahanzeeb Ashraf, Muhammad Afzal, Geofferry S. Ibbott

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The purpose of this analysis is to estimate secondary cancer risks after VMAT compared to other modalities of head and neck radiotherapy (IMRT, 3DCRT). Computer tomography (CT) scans of Radiological Physics Center (RPC) head and neck phantom were acquired with CT scanner and exported via DICOM to the treatment planning system (TPS). Treatment planning was done using four arc (182-178 and 180-184, clockwise and anticlockwise) for volumetric modulated arc therapy (VMAT) , Nine fields (200, 240, 280, 320,0,40,80,120 and 160), which has been commonly used at MD Anderson Cancer Center Houston for intensity modulated radiation therapy (IMRT) and four fields for three dimensional radiation therapy (3DCRT) were used. True beam linear accelerator of 6MV photon energy was used for dose delivery, and dose calculation was done with CC convolution algorithm with prescription dose of 6.6 Gy. Primary Target Volume (PTV) coverage, mean and maximal doses, DVHs and volumes receiving more than 2 Gy and 3.8 Gy of OARs were calculated and compared. Absolute point dose and planar dose were measured with thermoluminescent dosimeters (TLDs) and GafChromic EBT2 film, respectively. Quality Assurance of VMAT and IMRT were performed by using ArcCHECK method with gamma index criteria of 3%/3mm dose difference to distance to agreement (DD/DTA). PTV coverage was found 90.80 %, 95.80 % and 95.82 % for 3DCRT, IMRT and VMAT respectively. VMAT delivered the lowest maximal doses to esophagus (2.3 Gy), brain (4.0 Gy) and thyroid (2.3 Gy) compared to all other studied techniques. In comparison, maximal doses for 3DCRT were found higher than VMAT for all studied OARs. Whereas, IMRT delivered maximal higher doses 26%, 5% and 26% for esophagus, normal brain and thyroid, respectively, compared to VMAT. It was noted that esophagus volume receiving more than 2 Gy was 3.6 % for VMAT, 23.6 % for IMRT and up to 100 % for 3DCRT. Good agreement was observed between measured doses and those calculated with TPS. The averages relative standard errors (RSE) of three deliveries within eight TLD capsule locations were, 0.9%, 0.8% and 0.6% for 3DCRT, IMRT and VMAT, respectively. The gamma analysis for all plans met the ±5%/3 mm criteria (over 90% passed) and results of QA were greater than 98%. The calculations for maximal doses and volumes of OARs suggest that the estimated risk of secondary cancer induction after VMAT is considerably lower than IMRT and 3DCRT.

Keywords: RPC, 3DCRT, IMRT, VMAT, EBT2 film, TLD

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Authors: Prateek Rastogi, Jenash Acharya

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Histopathology examination has been a boon to forensic experts all around the world since its implication in autopsy cases. Whenever a case of sudden death is encountered, forensic experts clandestinely focus on cardiovascular, respiratory, gastrointestinal or cranio-cerebral causes. After ruling out poisoning or trauma, they are left with the only option available, histopathology examination. Besides preserving thoracic and abdominal organs, brain tissues are very less frequently subjected for the analysis. Based on provisional diagnosis documented on hospital treatment record files, one hemisphere of grossly unremarkable cerebrum was confirmatively diagnosed by histopathology examination to be a case of cerebral toxoplasmosis.

Keywords: cerebral toxoplasmosis, sudden death, health information, histopathology

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Authors: Ana Bermudez de Castro Muela, Xiomara Santos Salas, Silvia Cayon Somacarrera

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The aim of this review is to explain what is the intracranial hypotension and its main causes, and also to approach to the diagnostic management in the different clinical situations, understanding radiological findings, and physiopathological substrate. An approach to the diagnostic management is presented: what are the guidelines to follow, the different tests available, and the typical findings. We review the myelo-CT and myelo-RM studies in patients with suspected CSF fistula or hypotension of unknown cause during the last 10 years in three centers. Signs of intracranial hypotension (subdural hygromas/hematomas, pachymeningeal enhancement, venous sinus engorgement, pituitary hyperemia, and lowering of the brain) that are evident in baseline CT and MRI are also sought. The intracranial hypotension is defined as a lower opening pressure of 6 cmH₂O. It is a relatively rare disorder with an annual incidence of 5 per 100.000, with a female to male ratio 2:1. The clinical features it’s an orthostatic headache, which is defined as development or aggravation of headache when patients move from a supine to an upright position and disappear or typically relieve after lay down. The etiology is a decrease in the amount of cerebrospinal fluid (CSF), usually by loss of it, either spontaneous or secondary (post-traumatic, post-surgical, systemic disease, post-lumbar puncture etc.) and rhinorrhea and/or otorrhea may exist. The pathophysiological mechanisms of hypotension and CSF hypertension are interrelated, as a situation of hypertension may lead to hypotension secondary to spontaneous CSF leakage. The diagnostic management of intracranial hypotension in our center includes, in the case of being spontaneous and without rhinorrhea and/or otorrhea and according to necessity, a range of available tests, which will be performed from less to more complex: cerebral CT, cerebral MRI and spine without contrast and CT/MRI with intrathecal contrast. If we are in a situation of intracranial hypotension with the presence of rhinorrhea/otorrhea, a sample can be obtained for the detection of b2-transferrin, which is found in the CSF physiologically, as well as sinus CT and cerebral MRI including constructive interference steady state (CISS) sequences. If necessary, cisternography studies are performed to locate the exact point of leakage. It is important to emphasize the significance of myelo-CT / MRI to establish the diagnosis and location of CSF leak, which is indispensable for therapeutic planning (whether surgical or not) in patients with more than one lesion or doubts in the baseline tests.

Keywords: cerebrospinal fluid, neuroradiology brain, magnetic resonance imaging, fistula

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Vaibhavi Birle

Abstract:

Posterior reversible encephalopathy syndrome is a rare clinic-radiological syndrome associated with acute changes in blood pressure during pregnancy. It is characterized symptomatically by headache, seizures, altered mental status, and visual blurring with radiological changes of white matter (vasogenic oedema) affecting the posterior occipital and parietal lobes of the brain. It is being increasingly recognized due to increased institutional deliveries and advances in imaging particularly magnetic resonance imaging (MRI). In spite of the increasing diagnosis the prediction of PRES and patient factors affecting susceptibility is still not clear. Hence, we conducted the retrospective study to analyse the factors associated with PRES at our tertiary centre.

Keywords: pres syndrome, eclampsia, maternal outcome, fetal outcome

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Authors: Marie-Eve Joret, Marijn Van Vliet, Flavio Camarrone, Marc M. Van Hulle

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Event-related potentials (ERPs) provide evidence that the human brain can process and understand music at a pre-attentive level. Music-specific ERPs include the Early Right Anterior Negativity (ERAN) and a late Negativity (N5). This study aims to further investigate this issue using two types of syntactic manipulations in music: mild violations, containing no out-of-key tones and strong violations, containing out-of-key tones. We will examine whether both manipulations will elicit the same ERPs.

Keywords: ERAN ERPs, Music, N5, P3, ERPs, Music, N5 component, P3 component

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Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi

Abstract:

Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.

Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation

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