Search results for: Brain Float-16
Commenced in January 2007
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Paper Count: 1121

Search results for: Brain Float-16

911 Brain-Computer Interfaces That Use Electroencephalography

Authors: Arda Ozkurt, Ozlem Bozkurt

Abstract:

Brain-computer interfaces (BCIs) are devices that output commands by interpreting the data collected from the brain. Electroencephalography (EEG) is a non-invasive method to measure the brain's electrical activity. Since it was invented by Hans Berger in 1929, it has led to many neurological discoveries and has become one of the essential components of non-invasive measuring methods. Despite the fact that it has a low spatial resolution -meaning it is able to detect when a group of neurons fires at the same time-, it is a non-invasive method, making it easy to use without possessing any risks. In EEG, electrodes are placed on the scalp, and the voltage difference between a minimum of two electrodes is recorded, which is then used to accomplish the intended task. The recordings of EEGs include, but are not limited to, the currents along dendrites from synapses to the soma, the action potentials along the axons connecting neurons, and the currents through the synaptic clefts connecting axons with dendrites. However, there are some sources of noise that may affect the reliability of the EEG signals as it is a non-invasive method. For instance, the noise from the EEG equipment, the leads, and the signals coming from the subject -such as the activity of the heart or muscle movements- affect the signals detected by the electrodes of the EEG. However, new techniques have been developed to differentiate between those signals and the intended ones. Furthermore, an EEG device is not enough to analyze the data from the brain to be used by the BCI implication. Because the EEG signal is very complex, to analyze it, artificial intelligence algorithms are required. These algorithms convert complex data into meaningful and useful information for neuroscientists to use the data to design BCI devices. Even though for neurological diseases which require highly precise data, invasive BCIs are needed; non-invasive BCIs - such as EEGs - are used in many cases to help disabled people's lives or even to ease people's lives by helping them with basic tasks. For example, EEG is used to detect before a seizure occurs in epilepsy patients, which can then prevent the seizure with the help of a BCI device. Overall, EEG is a commonly used non-invasive BCI technique that has helped develop BCIs and will continue to be used to detect data to ease people's lives as more BCI techniques will be developed in the future.

Keywords: BCI, EEG, non-invasive, spatial resolution

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910 Field Prognostic Factors on Discharge Prediction of Traumatic Brain Injuries

Authors: Mohammad Javad Behzadnia, Amir Bahador Boroumand

Abstract:

Introduction: Limited facility situations require allocating the most available resources for most casualties. Accordingly, Traumatic Brain Injury (TBI) is the one that may need to transport the patient as soon as possible. In a mass casualty event, deciding when the facilities are restricted is hard. The Extended Glasgow Outcome Score (GOSE) has been introduced to assess the global outcome after brain injuries. Therefore, we aimed to evaluate the prognostic factors associated with GOSE. Materials and Methods: In a multicenter cross-sectional study conducted on 144 patients with TBI admitted to trauma emergency centers. All the patients with isolated TBI who were mentally and physically healthy before the trauma entered the study. The patient’s information was evaluated, including demographic characteristics, duration of hospital stays, mechanical ventilation on admission laboratory measurements, and on-admission vital signs. We recorded the patients’ TBI-related symptoms and brain computed tomography (CT) scan findings. Results: GOSE assessments showed an increasing trend by the comparison of on-discharge (7.47 ± 1.30), within a month (7.51 ± 1.30), and within three months (7.58 ± 1.21) evaluations (P < 0.001). On discharge, GOSE was positively correlated with Glasgow Coma Scale (GCS) (r = 0.729, P < 0.001) and motor GCS (r = 0.812, P < 0.001), and inversely with age (r = −0.261, P = 0.002), hospitalization period (r = −0.678, P < 0.001), pulse rate (r = −0.256, P = 0.002) and white blood cell (WBC). Among imaging signs and trauma-related symptoms in univariate analysis, intracranial hemorrhage (ICH), interventricular hemorrhage (IVH) (P = 0.006), subarachnoid hemorrhage (SAH) (P = 0.06; marginally at P < 0.1), subdural hemorrhage (SDH) (P = 0.032), and epidural hemorrhage (EDH) (P = 0.037) were significantly associated with GOSE at discharge in multivariable analysis. Conclusion: Our study showed some predictive factors that could help to decide which casualty should transport earlier to a trauma center. According to the current study findings, GCS, pulse rate, WBC, and among imaging signs and trauma-related symptoms, ICH, IVH, SAH, SDH, and EDH are significant independent predictors of GOSE at discharge in TBI patients.

Keywords: field, Glasgow outcome score, prediction, traumatic brain injury.

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909 Comparing the Detection of Autism Spectrum Disorder within Males and Females Using Machine Learning Techniques

Authors: Joseph Wolff, Jeffrey Eilbott

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Autism Spectrum Disorders (ASD) are a spectrum of social disorders characterized by deficits in social communication, verbal ability, and interaction that can vary in severity. In recent years, researchers have used magnetic resonance imaging (MRI) to help detect how neural patterns in individuals with ASD differ from those of neurotypical (NT) controls for classification purposes. This study analyzed the classification of ASD within males and females using functional MRI data. Functional connectivity (FC) correlations among brain regions were used as feature inputs for machine learning algorithms. Analysis was performed on 558 cases from the Autism Brain Imaging Data Exchange (ABIDE) I dataset. When trained specifically on females, the algorithm underperformed in classifying the ASD subset of our testing population. Although the subject size was relatively smaller in the female group, the manual matching of both male and female training groups helps explain the algorithm’s bias, indicating the altered sex abnormalities in functional brain networks compared to typically developing peers. These results highlight the importance of taking sex into account when considering how generalizations of findings on males with ASD apply to females.

Keywords: autism spectrum disorder, machine learning, neuroimaging, sex differences

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908 Impact of Interventions on Brain Functional Connectivity in Young Male Basketball Players: A Comparative Study

Authors: Mohammad Khazaei, Reza Rostami, Hassan Gharayagh Zandi, Ruhollah Basatnia, Mahboubeh Ghayour Najafabadi

Abstract:

Introduction: This study delves into the influence of diverse interventions on brain functional connectivity among young male basketball players. Given the significance of understanding how interventions affect cognitive functions in athletes, particularly in the context of basketball, this research contributes to the growing body of knowledge in sports neuroscience. Methods: Three distinct groups were selected for comprehensive investigation: the Motivational Interview Group, Placebo Consumption Group, and Ritalin Consumption Group. The study involved assessing brain functional connectivity using various frequency bands (Delta, Theta, Alpha, Beta1, Beta2, Gamma, and Total Band) before and after the interventions. The participants were subjected to specific interventions corresponding to their assigned groups. Results: The findings revealed substantial differences in brain functional connectivity across the studied groups. The Motivational Interview Group exhibited optimal outcomes in PLI (Total Band) connectivity. The Placebo Consumption Group demonstrated a marked impact on PLV (Alpha) connectivity, and the Ritalin Consumption Group experienced a considerable enhancement in imCoh (Total Band) connectivity. Discussion: The observed variations in brain functional connectivity underscore the nuanced effects of different interventions on young male basketball players. The enhanced connectivity in specific frequency bands suggests potential cognitive and performance improvements. Notably, the Motivational Interview and Placebo Consumption groups displayed unique patterns, emphasizing the multifaceted nature of interventions. These findings contribute to the understanding of tailored interventions for optimizing cognitive functions in young male basketball players. Conclusion: This study provides valuable insights into the intricate relationship between interventions and brain functional connectivity in young male basketball players. Further research with expanded sample sizes and more sophisticated statistical analyses is recommended to corroborate and expand upon these initial findings. The implications of this study extend to the broader field of sports neuroscience, aiding in the development of targeted interventions for athletes in various disciplines.

Keywords: electroencephalography, Ritalin, Placebo effect, motivational interview

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907 The Effects of Transcranial Direct Current Stimulation on Brain Oxygenation and Pleasure during Exercise

Authors: Alexandre H. Okano, Pedro M. D. Agrícola, Daniel G. Da S. Machado, Luiz I. Do N. Neto, Luiz F. Farias Junior, Paulo H. D. Nascimento, Rickson C. Mesquita, John F. Araujo, Eduardo B. Fontes, Hassan M. Elsangedy, Shinsuke Shimojo, Li M. Li

Abstract:

The prefrontal cortex is involved in the reward system and the insular cortex integrates the afferent inputs arriving from the body’ systems and turns into feelings. Therefore, modulating neuronal activity in these regions may change individuals’ perception in a given situation such as exercise. We tested whether transcranial direct current stimulation (tDCS) change cerebral oxygenation and pleasure during exercise. Fourteen volunteer healthy adult men were assessed into five different sessions. First, subjects underwent to a maximum incremental test on a cycle ergometer. Then, subjects were randomly assigned to a transcranial direct current stimulation (2mA for 15 min) intervention in a cross over design in four different conditions: anode and cathode electrodes on T3 and Fp2 targeting the insular cortex, and Fpz and F4 targeting prefrontal cortex, respectively; and their respective sham. These sessions were followed by 30 min of moderate intensity exercise. Brain oxygenation was measured in prefrontal cortex with a near infrared spectroscopy. Perceived exertion and pleasure were also measured during exercise. The asymmetry in prefrontal cortex oxygenation before the stimulation decreased only when it was applied over this region which did not occur after insular cortex or sham stimulation. Furthermore, pleasure was maintained during exercise only after prefrontal cortex stimulation (P > 0.7), while there was a decrease throughout exercise (P < 0.03) during the other conditions. We conclude that tDCS over the prefrontal cortex changes brain oxygenation in ventromedial prefrontal cortex and maintains perceived pleasure during exercise. Therefore, this technique might be used to enhance effective responses related to exercise.

Keywords: affect, brain stimulation, dopamine neuromodulation, pleasure, reward, transcranial direct current stimulation

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906 Postmortem Analysis of Lidocaine in Women Died of Criminal Abortion

Authors: Mohammed A. Arishy, Sultan M. Alharbi, Mohammed A. Hakami, Farid M. Abualsail, Mohammad A. Attafi, Riyadh M. Tobaiqi, Hussain M. Alsalem, Ibraheem M. Attafi

Abstract:

Lidocaine is the most common local anesthetics used for para cervical block to reduce pain associated with surgical abortion. A 25-year-old pregnant woman who. She died before reaching hospital, and she was undergoing criminal abortion during the first trimester. In post-mortem investigations and autopsy shows no clear finding; therefore, toxic substances must be suspected and searched for routinely toxicology analysis. In this case report, the postmortem concentration of lidocaine was detected blood, brain, liver, kidney, and stomach. For lidocaine identification and quantification, sample was extracted using solid phase extraction and analyzed by GC-MS (Shimadzu, Japan). Initial screening and confirmatory analysis results showed that only lidocaine was detected in all collected samples, and no other toxic substances or alcohol were detected. The concentrations of lidocaine in samples were 19, 17, 14, 7, and 3 ug/m in the brain, blood, kidney, liver, and stomach, respectively. Lidocaine blood concentration (17 ug/ml) was toxic level and may result in death. Among the tissues, brain showed the highest level of lidocaine, followed by the kidney, liver, and stomach.

Keywords: forensic toxicology, GC-MS, lidocaine, postmortem

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905 Data Collection Techniques for Robotics to Identify the Facial Expressions of Traumatic Brain Injured Patients

Authors: Chaudhary Muhammad Aqdus Ilyas, Matthias Rehm, Kamal Nasrollahi, Thomas B. Moeslund

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This paper presents the investigation of data collection procedures, associated with robots when placed with traumatic brain injured (TBI) patients for rehabilitation purposes through facial expression and mood analysis. Rehabilitation after TBI is very crucial due to nature of injury and variation in recovery time. It is advantageous to analyze these emotional signals in a contactless manner, due to the non-supportive behavior of patients, limited muscle movements and increase in negative emotional expressions. This work aims at the development of framework where robots can recognize TBI emotions through facial expressions to perform rehabilitation tasks by physical, cognitive or interactive activities. The result of these studies shows that with customized data collection strategies, proposed framework identify facial and emotional expressions more accurately that can be utilized in enhancing recovery treatment and social interaction in robotic context.

Keywords: computer vision, convolution neural network- long short term memory network (CNN-LSTM), facial expression and mood recognition, multimodal (RGB-thermal) analysis, rehabilitation, robots, traumatic brain injured patients

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904 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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903 A Nutrient Formulation Affects Brain Myelination in Infants: An Investigative Randomized Controlled Trial

Authors: N. Schneider, M. Bruchhage, M. Hartweg, G. Mutungi, J. O Regan, S. Deoni

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Observational neuroimaging studies suggest differences between breast-fed and formula-fed infants in developmental myelination, a key brain process for learning and cognitive development. However, the possible effects of a nutrient formulation on myelin development in healthy term infants in an intervention study have not been investigated. Objective was, therefore, to investigate the efficacy of a nutrient formulation with higher levels of myelin-relevant nutrients as compared to a control formulation with lower levels of the same nutrients on brain myelination and cognitive development in the first 6 months of life. The study is an ongoing randomized, controlled, double-blind, two-center, parallel-group clinical trial with a nonrandomized, non-blinded arm of exclusively breastfed infants. The current findings result from a staged statistical analysis at 6 months; the recruitment and intervention period has been completed for all participants. Follow-up visits at 12, 18 and 24 months are still ongoing. N= 81 enrolled full term, neurotypical infants of both sexes were randomized into either the investigational (N= 42) or the control group (N= 39), and N= 108 children in the breast-fed arm served as a natural reference group. The effect of a blend of docosahexaenoic acid, arachidonic acid, iron, vitamin B12, folic acid as well as sphingomyelin from a uniquely proceed whey protein concentrate enriched in alpha-lactalbumin and phospholipids in an infant nutrition product matrix was investigated. The main outcomes for the staged statistical analyses at 6 months included brain myelination measures derived from MRI. Additional outcomes were brain volume, cognitive development and safety. The full analyses set at 6 months comprised N= 66 infants. Higher levels of myelin-relevant nutrients compared to lower levels resulted in significant differences in myelin structure, volume, and rate of myelination as early as 3 and 6 months of life. The cross-sectional change of means between groups for whole-brain myelin volume was 8.4% for investigational versus control formulation (3.5% versus the breastfeeding reference) group at 3 months and increased to 36.4% for investigational versus control formulation (14.1% versus breastfeeding reference) at 6 months. No statistically significant differences were detected for early cognition scores. Safety findings were largely similar across groups. This is the first pediatric nutritional neuroimaging study demonstrating the efficacy of a myelin nutrient blend on developmental myelination in well-nourished term infants. Myelination is a critical process in learning and development. The effects were demonstrated across the brain, particularly in temporal and parietal regions, known to be functionally involved in sensory, motor and language skills. These first results add to the field of nutritional neuroscience by demonstrating early life nutrition benefits for brain architecture which may be foundational for later cognitive and behavioral outcomes. ClinicalTrials.gov Identifier: NCT03111927 (Infant Nutrition and Brain Development - Full-Text View - ClinicalTrials.gov).

Keywords: brain development, infant nutrition, MRI, myelination

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902 Depressive-Like Behavior in a Murine Model of Colorectal Cancer Associated with Altered Cytokine Levels in Stress-Related Brain Regions

Authors: D. O. Miranda, L. R. Azevedo, J. F. C. Cordeiro, A. H. Dos Santos, S. F. Lisboa, F. S. Guimarães, G. S. Bisson

Abstract:

Background: The Colorectal cancer (CRC) is one of the most common cancers and the fourth leading cause of cancer death in the world. The prevalence of psychiatric-disorders among CRC patients, mainly depression, is high, resulting in impaired quality of life and side effects of primary treatment. High levels of proinflammatory cytokines at tumor microenvironment is a feature of CRC and the literature suggests that those mediators could contribute to the development of psychiatric disorders. Nevertheless, the ability of tumor-associated biological processes to affect the central nervous system (CNS) has only recently been explored in the context of symptoms of depression and is still not well understood. Therefore, the aim of the present study was to test the hypothesis that depressive-like behavior in an experimental model of CCR induced by N-methyl-N-nitro-N-nitrosoguanidine (MNNG) was correlated to proinflammatory profile in the periphery and in the brain. Methods: Colorectal carcinogenesis was induced in adult C57BL/6 mice (n=12) by administration of MNNG (5mg/kg, 0.1ml/intrarectal instillation) 2 times a week, for 2 week. Control group (n=12) received saline (0.1ml/intrarectal instillation). Eight weeks after beginning of MNNG administration animals were submitted to the forced swim test (FST) and the sucrose preference test for evaluation, respectively, of depressive- and anhedonia-like behaviors. After behavioral evaluation, the colon was collected and brain regions dissected (cortex-C, striatum-ST and hippocampus-HIP) for posterior evaluation of cytokine levels (IL-1β, IL-10, IL-17, and CX3CL1) by ELISA. Results: MNNG induced depressive-like behavior, represented by increased immobility time in the FST (Student t test, p < 0.05) and lower sucrose preference (Student t test, p < 0.05). Moreover, there were increased levels of IL-1β, IL-17 and CX3CL1 in the colonic tissue (Student t test, p < 0.05) and in the brain (IL-1 β in the ST and HIP, Student t test, p < 0.05; IL-17 and CX3CL1 in the C and HIP, p < 0.05). IL-10 levels, in contrast, were decreased in both the colon (p < 0.05) and the brain (C and HIP, p < 0.05). Conclusions: The results obtained in the present work support the notion that tumor growth induces neuroinflammation in stress-related brain regions and depressive-like behavior, which could be related to the high incidence of depression in colorectal carcinogenesis. This work have important clinical and research implications, taken into account that cytokine levels may be a marker promissory for the developing depression in CRC patients. New therapeutic strategies to assist in alleviating mental suffering in cancer patients might result from a better understanding of the role of cytokines in the pathophysiology of depression in these subjects.

Keywords: cytokines, brain, depression, colorectal cancer

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901 Replicating Brain’s Resting State Functional Connectivity Network Using a Multi-Factor Hub-Based Model

Authors: B. L. Ho, L. Shi, D. F. Wang, V. C. T. Mok

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The brain’s functional connectivity while temporally non-stationary does express consistency at a macro spatial level. The study of stable resting state connectivity patterns hence provides opportunities for identification of diseases if such stability is severely perturbed. A mathematical model replicating the brain’s spatial connections will be useful for understanding brain’s representative geometry and complements the empirical model where it falls short. Empirical computations tend to involve large matrices and become infeasible with fine parcellation. However, the proposed analytical model has no such computational problems. To improve replicability, 92 subject data are obtained from two open sources. The proposed methodology, inspired by financial theory, uses multivariate regression to find relationships of every cortical region of interest (ROI) with some pre-identified hubs. These hubs acted as representatives for the entire cortical surface. A variance-covariance framework of all ROIs is then built based on these relationships to link up all the ROIs. The result is a high level of match between model and empirical correlations in the range of 0.59 to 0.66 after adjusting for sample size; an increase of almost forty percent. More significantly, the model framework provides an intuitive way to delineate between systemic drivers and idiosyncratic noise while reducing dimensions by more than 30 folds, hence, providing a way to conduct attribution analysis. Due to its analytical nature and simple structure, the model is useful as a standalone toolkit for network dependency analysis or as a module for other mathematical models.

Keywords: functional magnetic resonance imaging, multivariate regression, network hubs, resting state functional connectivity

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900 Predictive Value of Coagulopathy in Patients with Isolated Blunt Traumatic Brain Injury: A Cohort of Pakistani Population

Authors: Muhammad Waqas, Shahan Waheed, Mohsin Qadeer, Ehsan Bari, Salman Ahmed, Iqra Patoli

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Objective: To determine the value of aPTT, platelets and INR as the predictor of unfavorable outcomes in patients with blunt isolated traumatic brain injury. Methods: This was an observational cohort study conducted in a tertiary care facility from 1st January 2008 to 31st December 2012. All the patients with isolated traumatic brain injury presenting within 24 hours of injury were included in the study. Coagulation parameters at presentation were recorded and Glasgow Outcome Scale calculated on last follow up. Outcomes were dichotomized into favorable and unfavorable outcomes. Relationship of coagulopathy with GOS and unfavorable outcomes was calculated using Spearman`s correlation and area under curve ROC analysis. Results: 121 patients were included in the study. The incidence of coagulopathy was found to be 6 %. aPTT was found to a significantly associated with unfavorable outcomes with an AUC = 0.702 (95%CI = 0.602-0.802). Predictive value of platelets and INR was not found to be significant. Conclusion: Incidence of coagulopathy was found to be low in current population compared to data from the West. aPTT was found to be a good predictor of unfavorable outcomes compared with other parameters of coagulation.

Keywords: aPTT, coagulopathy, unfavorable outcomes, parameters

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899 Antioxidant Effects of Withania Somnifera (Ashwagandha) on Brain

Authors: Manju Lata Sharma

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Damage to cells caused by free radicals is believed to play a central role in the ageing process and in disease progression. Withania somnifera is widely used in ayurvedic medicine, and it is one of the ingredients in many formulations to increase energy, improve overall health and longevity and prevent disease. Withania somnifera possesses antioxidative properties. The antioxdant activity of Withania somnifera consisting of an equimolar concentration of active principles of sitoindoside VII-X and withaferin A. The antioxidant effect of Withania somnifera extract was investigated on lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity in mice. Aim: To study the antioxidant activity of an extract of Withania somnifera leaf against a mice model of chronic stress. Healthy swiss albino mice (3-4 months old) selected from an inbred colony were divided in to 6 groups. Biochemical estimation revealed that stress induced a significant change in SOD, LPO, CAT AND GPX. These stress induced perturbations were attenuated Withania somnifera (50 and 100 mg/kg BW). Result: Withania somnifera tended to normalize the augmented SOD and LPO activities and enhanced the activities of CAT and GPX. The result indicates that treatment with an alcoholic extract of Withania somnifera produced a significant decrease in LPO ,and an increase in both SOD and CAT in brain mice. This indicates that Withania somnifera extract possesses free radical scavenging activity .

Keywords: Withania somnifera, antioxidant, lipid peroxidation, brain

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898 EEG and DC-Potential Level Сhanges in the Elderly

Authors: Irina Deputat, Anatoly Gribanov, Yuliya Dzhos, Alexandra Nekhoroshkova, Tatyana Yemelianova, Irina Bolshevidtseva, Irina Deryabina, Yana Kereush, Larisa Startseva, Tatyana Bagretsova, Irina Ikonnikova

Abstract:

In the modern world the number of elderly people increases. Preservation of functionality of an organism in the elderly becomes very important now. During aging the higher cortical functions such as feelings, perception, attention, memory, and ideation are gradual decrease. It is expressed in the rate of information processing reduction, volume of random access memory loss, ability to training and storing of new information decrease. Perspective directions in studying of aging neurophysiological parameters are brain imaging: computer electroencephalography, neuroenergy mapping of a brain, and also methods of studying of a neurodynamic brain processes. Research aim – to study features of a brain aging in elderly people by electroencephalogram (EEG) and the DC-potential level. We examined 130 people aged 55 - 74 years that did not have psychiatric disorders and chronic states in a decompensation stage. EEG was recorded with a 128-channel GES-300 system (USA). EEG recordings are collected while the participant sits at rest with their eyes closed for 3 minutes. For a quantitative assessment of EEG we used the spectral analysis. The range was analyzed on delta (0,5–3,5 Hz), a theta - (3,5–7,0 Hz), an alpha 1-(7,0–11,0 Hz) an alpha 2-(11–13,0 Hz), beta1-(13–16,5 Hz) and beta2-(16,5–20 Hz) ranges. In each frequency range spectral power was estimated. The 12-channel hardware-software diagnostic ‘Neuroenergometr-KM’ complex was applied for registration, processing and the analysis of a brain constant potentials level. The DC-potential level registered in monopolar leads. It is revealed that the EEG of elderly people differ in higher rates of spectral power in the range delta (р < 0,01) and a theta - (р < 0,05) rhythms, especially in frontal areas in aging. By results of the comparative analysis it is noted that elderly people 60-64 aged differ in higher values of spectral power alfa-2 range in the left frontal and central areas (р < 0,05) and also higher values beta-1 range in frontal and parieto-occipital areas (р < 0,05). Study of a brain constant potential level distribution revealed increase of total energy consumption on the main areas of a brain. In frontal leads we registered the lowest values of constant potential level. Perhaps it indicates decrease in an energy metabolism in this area and difficulties of executive functions. The comparative analysis of a potential difference on the main assignments testifies to unevenness of a lateralization of a brain functions at elderly people. The results of a potential difference between right and left hemispheres testify to prevalence of the left hemisphere activity. Thus, higher rates of functional activity of a cerebral cortex are peculiar to people of early advanced age (60-64 years) that points to higher reserve opportunities of central nervous system. By 70 years there are age changes of a cerebral power exchange and level of electrogenesis of a brain which reflect deterioration of a condition of homeostatic mechanisms of self-control and the program of processing of the perceptual data current flow.

Keywords: brain, DC-potential level, EEG, elderly people

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897 The Effect of Excess Sulphur on Najdi Sheep

Authors: Fatima Al-Humaid

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This research work was done to investigate the cause of paralysis in Najdi lambs born in certain farms where the drinking water and diet contained high concentrations of sulphur. The drinking water in these farms was obtained from deep bore wells drilled in the farm. The lambs developed paralysis of the hind limbs at the age of 4-6 weeks and their condition deteriorated continuously until they finally died. The appetite and suckling ability remained good throughout the course of the disease but when the lambs were completely unable to move and reach for the udder, feed and water they died. Postmortem examination of the brain of paralyzed lambs showed that it was liquefied. When the brain was examined histologically, a liquefactive necrosis was seen in the form of cavities in the nervous tissue. Similar histologic picture was seen in the spinal cord of the affected lambs. Analysis for the mineral content of the fodder showed that the concentration of sulphur was 21.6 3.4 g/kg DM which is considered very high for the nutrition of sheep. Analysis for the concentration of copper and selenium in the feed showed that the concentrations of both were normal. This excluded diseases such as swayback which is caused by copper deficiency and white muscle disease, which caused by selenium deficiency. Both of these two last diseases are characterized by paralysis of lambs.

Keywords: brain histology, sulphur poisoning, Najdi sheep, veterinary medicine

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896 Integration of an Augmented Reality System for the Visualization of the HRMAS NMR Analysis of Brain Biopsy Specimens Using the Brainlab Cranial Navigation System

Authors: Abdelkrim Belhaoua, Jean-Pierre Radoux, Mariana Kuras, Vincent Récamier, Martial Piotto, Karim Elbayed, François Proust, Izzie Namer

Abstract:

This paper proposes an augmented reality system dedicated to neurosurgery in order to assist the surgeon during an operation. This work is part of the ExtempoRMN project (Funded by Bpifrance) which aims at analyzing during a surgical operation the metabolic content of tumoral brain biopsy specimens by HRMAS NMR. Patients affected with a brain tumor (gliomas) frequently need to undergo an operation in order to remove the tumoral mass. During the operation, the neurosurgeon removes biopsy specimens using image-guided surgery. The biopsy specimens removed are then sent for HRMAS NMR analysis in order to obtain a better diagnosis and prognosis. Image-guided refers to the use of MRI images and a computer to precisely locate and target a lesion (abnormal tissue) within the brain. This is performed using preoperative MRI images and the BrainLab neuro-navigation system. With the patient MRI images loaded on the Brainlab Cranial neuro-navigation system in the operating theater, surgeons can better identify their approach before making an incision. The Brainlab neuro-navigation tool tracks in real time the position of the instruments and displays their position on the patient MRI data. The results of the biopsy analysis by 1H HRMAS NMR are then sent back to the operating theater and superimposed on the 3D localization system directly on the MRI images. The method we have developed to communicate between the HRMAS NMR analysis software and Brainlab makes use of a combination of C++, VTK and the Insight Toolkit using OpenIGTLink protocol.

Keywords: neuro-navigation, augmented reality, biopsy, BrainLab, HR-MAS NMR

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895 Protective Effect of Herniarin on Ionizing Radiation-Induced Impairments in Brain

Authors: Sophio Kalmakhelidze, Eka Shekiladze, Tamar Sanikidze, Mikheil Gogebashvili, Nazi Ivanishvili

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Radiation-induced various degrees of brain injury and cognitive impairment have been described after cranial radiotherapy of brain tumors. High doses of ionizing radiation have a severe impact on the central nervous system, resulting in morphological and behavioral impairments. Structures of the limbic system are especially sensitive to radiation exposure. Hence, compounds or drugs that can reduce radiation-induced impairments can be used as promising antioxidants or radioprotectors. In our study Mice whole-body irradiation with 137Cs was performed at a dose rate of 1,1 Gy/min for a total dose of 5 Gy with a “Gamma-capsule-2”. Irradiated mice were treated with Herniarin (20 mg/kg) for five days before irradiation and the same dose was administrated after one hour of irradiation. The immediate and delayed effects of ionizing radiation, as well as, protective effect of Herniarin was evaluated during early and late post-irradiation periods. The results reveal that ionizing radiation (5 Gy) alters the structure of the hippocampus in adult mice during the late post-irradiation period resulting in the decline of memory formation and learning process. Furthermore, Simple Coumarin-Herniarin reveals a radiosensitizing effect reducing morphological and behavioral alterations.

Keywords: ionizing radiation, cognitive impairments, hippocampus, limbic system, Herniarin

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894 Effect of Oral Administration of "Gadagi" Tea on Activities of Some Antioxidant Enzymes in Rats

Authors: A. M. Gadanya, M. S. Sule

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Effect of oral administration of Gadagi tea on some antioxidant enzymes was assessed in healthy male albino rats. The rats were grouped and administered with standard doses of the 3 types of Gadagi tea i.e. Sak, Sada and Magani for a period of four weeks. Animals that were not administered with the tea constituted the control group. At the end of fourth week, the animals were sacrificed and their serum superoxide dismutase (SOD), glutathione reductase (GR) and catalase (CAT) activities were determined. The activities of the enzymes were also determined in the brain, liver, kidney and intestine homogenates of the rats. Mean SOD activity in brain of rats orally administered with “sada” was found to be significantly higher (P < 0.05) than that of the control group. Mean CAT activity in the intestine of rats orally administered with “magani” was found to be significantly higher (P < 0.05) than that of the control group and the experimental groups of Sak and Sada at standard dose level. Thus, all the “Gadagi” tea preparations studied at standard dose level could stimulate antioxidant enzymes, especially SOD in brain and CAT in intestine (by Sada) and CAT in intestine (by Magani).

Keywords: “Gadagi” tea, superoxide dismutase, catalase, glutathione reductase

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893 Multiscale Model of Blast Explosion Human Injury Biomechanics

Authors: Raj K. Gupta, X. Gary Tan, Andrzej Przekwas

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Bomb blasts from Improvised Explosive Devices (IEDs) account for vast majority of terrorist attacks worldwide. Injuries caused by IEDs result from a combination of the primary blast wave, penetrating fragments, and human body accelerations and impacts. This paper presents a multiscale computational model of coupled blast physics, whole human body biodynamics and injury biomechanics of sensitive organs. The disparity of the involved space- and time-scales is used to conduct sequential modeling of an IED explosion event, CFD simulation of blast loads on the human body and FEM modeling of body biodynamics and injury biomechanics. The paper presents simulation results for blast-induced brain injury coupling macro-scale brain biomechanics and micro-scale response of sensitive neuro-axonal structures. Validation results on animal models and physical surrogates are discussed. Results of our model can be used to 'replicate' filed blast loadings in laboratory controlled experiments using animal models and in vitro neuro-cultures.

Keywords: blast waves, improvised explosive devices, injury biomechanics, mathematical models, traumatic brain injury

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892 Newly Designed Ecological Task to Assess Cognitive Map Reading Ability: Behavioral Neuro-Anatomic Correlates of Mental Navigation

Authors: Igor Faulmann, Arnaud Saj, Roland Maurer

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Spatial cognition consists in a plethora of high level cognitive abilities: among them, the ability to learn and to navigate in large scale environments is probably one of the most complex skills. Navigation is thought to rely on the ability to read a cognitive map, defined as an allocentric representation of ones environment. Those representations are of course intimately related to the two geometrical primitives of the environment: distance and direction. Also, many recent studies point to a predominant hippocampal and para-hippocampal role in spatial cognition, as well as in the more specific cluster of navigational skills. In a previous study in humans, we used a newly validated test assessing cognitive map processing by evaluating the ability to judge relative distances and directions: the CMRT (Cognitive Map Recall Test). This study identified in topographically disorientated patients (1) behavioral differences between the evaluation of distances and of directions, and (2) distinct causality patterns assessed via VLSM (i.e., distinct cerebral lesions cause distinct response patterns depending on the modality (distance vs direction questions). Thus, we hypothesized that: (1) if the CMRT really taps into the same resources as real navigation, there would be hippocampal, parahippocampal, and parietal activation, and (2) there exists underlying neuroanatomical and functional differences between the processing of this two modalities. Aiming toward a better understanding of the neuroanatomical correlates of the CMRT in humans, and more generally toward a better understanding of how the brain processes the cognitive map, we adapted the CMRT as an fMRI procedure. 23 healthy subjects (11 women, 12 men), all living in Geneva for at least 2 years, underwent the CMRT in fMRI. Results show, for distance and direction taken together, than the most active brain regions are the parietal, frontal and cerebellar parts. Additionally, and as expected, patterns of brain activation differ when comparing the two modalities. Furthermore, distance processing seems to rely more on parietal regions (compared to other brain regions in the same modality and also to direction). It is interesting to notice that no significant activity was observed in the hippocampal or parahippocampal areas. Direction processing seems to tap more into frontal and cerebellar brain regions (compared to other brain regions in the same modality and also to distance). Significant hippocampal and parahippocampal activity has been shown only in this modality. This results demonstrated a complex interaction of structures which are compatible with response patterns observed in other navigational tasks, thus showing that the CMRT taps at least partially into the same brain resources as real navigation. Additionally, differences between the processing of distances and directions leads to the conclusion that the human brain processes each modality distinctly. Further research should focus on the dynamics of this processing, allowing a clearer understanding between the two sub-processes.

Keywords: cognitive map, navigation, fMRI, spatial cognition

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891 Combined Use of FMRI and Voxel-Based Morphometry in Assessment of Memory Impairment in Alzheimer's Disease Patients

Authors: A. V. Sokolov, S. V. Vorobyev, A. Yu. Efimtcev, V. Yu. Lobzin, I. A. Lupanov, O. A. Cherdakov, V. A. Fokin

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Alzheimer’s disease (AD) is the most common form of dementia. Different brain regions are involved to the pathological process of AD. The purpose of this study was to evaluate brain activation by visual memory task in patients with Alzheimer's disease and determine correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. To investigate the organization of memory and localize cortical areas activated by visual memory task we used functional magnetic resonance imaging and to evaluate brain atrophy of patients with Alzheimer's disease we used voxel-based morphometry. FMRI was performed on 1.5 T MR-scanner Siemens Magnetom Symphony with BOLD (Blood Oxygenation Level Dependent) technique, based on distinctions of magnetic properties of hemoglobin. For test stimuli we used series of 12 not related images for "Baseline" and 12 images with 6 presented before for "Active". Stimuli were presented 3 times with reduction of repeated images to 4 and 2. Patients with Alzheimer's disease showed less activation in hippocampal formation (HF) region and parahippocampal gyrus then healthy persons of control group (p<0.05). The study also showed reduced activation in posterior cingulate cortex (p<0.001). Voxel-based morphometry showed significant atrophy of grey matter in Alzheimer’s disease patients, especially of both temporal lobes (fusiform and parahippocampal gyri); frontal lobes (posterior cingulate and superior frontal gyri). The study showed correlation between memory impairment and atrophy of memory specific brain regions of frontal and medial temporal lobes. Thus, reduced activation in hippocampal formation and parahippocampal gyri, in posterior cingulate gyrus in patients with Alzheimer's disease correlates to significant atrophy of these regions, detected by voxel-based morphometry, and to deterioration of specific cognitive functions.

Keywords: Alzheimer’s disease, functional MRI, voxel-based morphometry

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890 Infused Mesenchymal Stem Cells Ameliorate Organs Morphology in Cerebral Malaria Infection

Authors: Reva Sharan Thakur, Mrinalini Tiwari, Jyoti das

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Cerebral malaria-associated over expression of pro-inflammatory cytokines and chemokines ultimately results in the up-regulation of adhesion molecules in the brain endothelium leading to sequestration of mature parasitized RBCs in the brain. The high-parasitic load subsequently results in increased mortality or development of neurological symptoms within a week of infection. Studies in the human and experimental cerebral malaria have implicated the breakdown of the integrity of blood-brain barrier during the lethal course of infection, cerebral dysfunction, and fatal organ pathologies that result in multi-organ failure. In the present study, using Plasmodium berghei Anka as a mouse model and in vitro conditions, we have investigated the effect of MSCs to attenuate cerebral malaria pathogenesis by diminishing the effect of inflammation altered organ morphology, reduced parasitemia, and increased survival of the mice. MSCs are also validated for their role in preventing BBB dysfunction and reducing malarial toxins. It was observed that administration of MSCs significantly reduced parasitemia and increased survival in Pb A infected mice. It was further demonstrated that MSCs play a significant role in reversing neurological complexities associated with cerebral malaria. Infusion of MSCs in infected mice decreased hemozoin deposition; oedema, and haemorrhagic lesions in vascular organs. MSCs administration also preserved the integrity of the blood-brain barrier and reduced neural inflammation. Taken together, our results demonstrate the potential of MSCs as an emerging anti-malarial candidate.

Keywords: cerebral malaria, mesenchymal stem cells, erythropoesis, cell death

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889 Cognitive Dysfunctioning and the Fronto-Limbic Network in Bipolar Disorder Patients: A Fmri Meta-Analysis

Authors: Rahele Mesbah, Nic Van Der Wee, Manja Koenders, Erik Giltay, Albert Van Hemert, Max De Leeuw

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Introduction: Patients with bipolar disorder (BD), characterized by depressive and manic episodes, often suffer from cognitive dysfunction. An up-to-date meta-analysis of functional Magnetic Resonance Imaging (fMRI) studies examining cognitive function in BD is lacking. Objective: The aim of the current fMRI meta-analysis is to investigate brain functioning of bipolar patients compared with healthy subjects within three domains of emotion processing, reward processing, and working memory. Method: Differences in brain regions activation were tested within whole-brain analysis using the activation likelihood estimation (ALE) method. Separate analyses were performed for each cognitive domain. Results: A total of 50 fMRI studies were included: 20 studies used an emotion processing (316 BD and 369 HC) task, 9 studies a reward processing task (215 BD and 213 HC), and 21 studies used a working memory task (503 BD and 445 HC). During emotion processing, BD patients hyperactivated parts of the left amygdala and hippocampus as compared to HC’s, but showed hypoactivation in the inferior frontal gyrus (IFG). Regarding reward processing, BD patients showed hyperactivation in part of the orbitofrontal cortex (OFC). During working memory, BD patients showed increased activity in the prefrontal cortex (PFC) and anterior cingulate cortex (ACC). Conclusions: This meta-analysis revealed evidence for activity disturbances in several brain areas involved in the cognitive functioning of BD patients. Furthermore, most of the found regions are part of the so-called fronto-limbic network which is hypothesized to be affected as a result of BD candidate genes' expression.

Keywords: cognitive functioning, fMRI analysis, bipolar disorder, fronto-limbic network

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888 Offering a Model for Selecting the Most Suitable Type of Thinking for Managers

Authors: H. Emari, Z. Emari

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The purpose of this paper is to design an applied framework for strategic thinking which can be applied in all managerial levels and all types of organizational environments. No special applied frame has been presented for this thinking. This paper presents a theoretical framework for the thinking type of a manager by making a historical research and studying the scientific documents about thinking of a strategist. In the new theoretical framework it has been tried to suggest the best type of thinking for a strategist after analyzing the environment of his decisions. So, in this framework, the traditional viewpoint about strategic thinking, which has considered it as a special type of right-brain thinking against other types of right-brain thinking and suggested it for a strategist, was put aside and suggests that the strategist should use a suitable type of thinking under different conditions.

Keywords: strategic thinking, systemic thinking, lateral thinking, intuitive thinking, hybrid thinking

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887 Psychological Intervention for Partners Post-Stroke: A Case Study

Authors: Natasha Yasmin Felles, Gerard Riley

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Background and Aims: Relationship breakdown is typical when one partner lives with an acquired brain injury caused by issues like a stroke. Research has found that the perception of relationship satisfaction decreases following such an injury among non-injured partners. Non-injured partners also are found to experience caregiver stress/burden as they immediately have to take the role of a caregiver along with being a partner of the injured. Research has also found that the perception of a continuous relationship, i.e. the perception of the relationship to be essentially the same as it was before the injury, also changes among those caregiving partners. However, there is a lack of available intervention strategies that can help those partners with both individual and relationship difficulties. The aim of this case study was to conduct a pilot test of an intervention aimed to explore whether it is possible to support a partner to experience greater continuity within the relationship poststroke, and what benefits such a change might have. Method: A couple, where one partner experienced an acquired brain injury poststroke were provided with Integrated Behavioural Couples Therapy for 3-months. The intervention addressed goals identified as necessary by the couple and by the formulation of their individual and relationship difficulties, alongside the goal of promoting relationship continuity. Before and after measures were taken using a battery of six questionnaires to evaluate changes in perceptions of continuity, stress, and other aspects of the relationship. Results: Both quantitative and qualitative data showed that relationship continuity was improved after the therapy, as were the measures of stress and other aspects of the relationship. The stress felt by the person with the acquired brain injury also showed some evidence of improvement. Conclusion: The study found that perceptions of relationship continuity can be improved by therapy and that improving these might have a beneficial impact on the stress felt by the carer, their satisfaction with the relationship and overall levels of conflict and closeness within the relationship. The study suggested the value of further research on enhancing perceptions of continuity in the relationship after an acquired brain injury. Currently, the findings of the study have been used to develop a pilot feasibility study to collect substantive evidence on the impact of the intervention on the couples and assess its feasibility and acceptability, which will help in further developing a specific generalized relationship continuity intervention, that will be beneficial in preventing relationship breakdown in the future.

Keywords: acquired brain injury, couples therapy, relationship continuity, stroke

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886 Site-Specific Delivery of Hybrid Upconversion Nanoparticles for Photo-Activated Multimodal Therapies of Glioblastoma

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

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In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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885 The Effectiveness of Transcranial Electrical Stimulation on Brain Wave Pattern and Blood Pressure in Patients with Generalized Anxiety Disorder

Authors: Mahtab Baghaei, Seyed Mahmoud Tabatabaei

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Aim & Background: Electrical stimulation of transcranial direct current is considered one of the treatment methods for mental disorders. The aim of this study was to evaluate the effectiveness of transcranial electrical stimulation on the delta, theta, alpha, beta and systolic and diastolic blood pressure in patients with generalized anxiety disorder. Materials and Methods: The present study was a double-blind intervention with a pre-test and post-test design on people with generalized anxiety disorder in Tabriz in 1400. In this study, 30 patients with generalized anxiety disorder were selected by purposive sampling method based on the criteria specified in DSM-5 and randomly divided into an experimental group (n = 15) and a control group (n = 15). The experimental group received two sessions of 30 minutes of electrical stimulation of transcranial direct current with an intensity of 2 mA in the area of the lateral dorsal prefrontal cortex, and the control group also received artificial stimulation. Results: The results showed that transcranial electrical stimulation reduces delta and theta waves and increases beta and alpha brain waves in the experimental group. On the other hand, this method also showed a significant decrease in systolic and diastolic blood pressure in these patients (p <0.01). Conclusion: The results show that transcranial electrical stimulation has a statistically significant effect on brain waves and blood pressure, and this non-invasive method can be used as one of the treatment methods in people with generalized anxiety disorder.

Keywords: transcranial direct current electrical stimulation, brain waves, systolic blood pressure, diastolic blood pressure

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884 3D-Printed Collagen/Chitosan Scaffolds Loaded with Exosomes Derived from Neural Stem Cells Pretreated with Insulin Growth Factor-1 for Neural Regeneration after Traumatic Brain Injury

Authors: Xiao-Yin Liu, Liang-Xue Zhou

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Traumatic brain injury (TBI), as a kind of nerve trauma caused by an external force, affects people all over the world and is a global public health problem. Although there are various clinical treatments for brain injury, including surgery, drug therapy, and rehabilitation therapy, the therapeutic effect is very limited. To improve the therapeutic effect of TBI, scaffolds combined with exosomes are a promising but challenging method for TBI repair. In this study, we examined whether a novel 3D-printed collagen/chitosan scaffold/exosomes derived from neural stem cells (NSCs) pretreated with insulin growth factor-1 (IGF-I) scaffolds (3D-CC-INExos) could be used to improve TBI repair and functional recovery after TBI. Our results showed that composite scaffolds of collagen-, chitosan- and exosomes derived from NSCs pretreated with IGF-I (INExos) could continuously release the exosomes for two weeks. In the rat TBI model, 3D-CC-INExos scaffold transplantation significantly improved motor and cognitive function after TBI, as assessed by the Morris water maze test and modified neurological severity scores. In addition, immunofluorescence staining and transmission electron microscopy showed that the recovery of damaged nerve tissue in the injured area was significantly improved by 3D-CC-INExos implantation. In conclusion, our data suggest that 3D-CC-INExos might provide a potential strategy for the treatment of TBI and lay a solid foundation for clinical translation.

Keywords: traumatic brain injury, exosomes, insulin growth factor-1, neural stem cells, collagen, chitosan, 3D printing, neural regeneration, angiogenesis, functional recovery

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883 Linking Enhanced Resting-State Brain Connectivity with the Benefit of Desirable Difficulty to Motor Learning: A Functional Magnetic Resonance Imaging Study

Authors: Chien-Ho Lin, Ho-Ching Yang, Barbara Knowlton, Shin-Leh Huang, Ming-Chang Chiang

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Practicing motor tasks arranged in an interleaved order (interleaved practice, or IP) generally leads to better learning than practicing tasks in a repetitive order (repetitive practice, or RP), an example of how desirable difficulty during practice benefits learning. Greater difficulty during practice, e.g. IP, is associated with greater brain activity measured by higher blood-oxygen-level dependent (BOLD) signal in functional magnetic resonance imaging (fMRI) in the sensorimotor areas of the brain. In this study resting-state fMRI was applied to investigate whether increase in resting-state brain connectivity immediately after practice predicts the benefit of desirable difficulty to motor learning. 26 healthy adults (11M/15F, age = 23.3±1.3 years) practiced two sets of three sequences arranged in a repetitive or an interleaved order over 2 days, followed by a retention test on Day 5 to evaluate learning. On each practice day, fMRI data were acquired in a resting state after practice. The resting-state fMRI data was decomposed using a group-level spatial independent component analysis (ICA), yielding 9 independent components (IC) matched to the precuneus network, primary visual networks (two ICs, denoted by I and II respectively), sensorimotor networks (two ICs, denoted by I and II respectively), the right and the left frontoparietal networks, occipito-temporal network, and the frontal network. A weighted resting-state functional connectivity (wRSFC) was then defined to incorporate information from within- and between-network brain connectivity. The within-network functional connectivity between a voxel and an IC was gauged by a z-score derived from the Fisher transformation of the IC map. The between-network connectivity was derived from the cross-correlation of time courses across all possible pairs of ICs, leading to a symmetric nc x nc matrix of cross-correlation coefficients, denoted by C = (pᵢⱼ). Here pᵢⱼ is the extremum of cross-correlation between ICs i and j; nc = 9 is the number of ICs. This component-wise cross-correlation matrix C was then projected to the voxel space, with the weights for each voxel set to the z-score that represents the above within-network functional connectivity. The wRSFC map incorporates the global characteristics of brain networks measured by the between-network connectivity, and the spatial information contained in the IC maps measured by the within-network connectivity. Pearson correlation analysis revealed that greater IP-minus-RP difference in wRSFC was positively correlated with the RP-minus-IP difference in the response time on Day 5, particularly in brain regions crucial for motor learning, such as the right dorsolateral prefrontal cortex (DLPFC), and the right premotor and supplementary motor cortices. This indicates that enhanced resting brain connectivity during the early phase of memory consolidation is associated with enhanced learning following interleaved practice, and as such wRSFC could be applied as a biomarker that measures the beneficial effects of desirable difficulty on motor sequence learning.

Keywords: desirable difficulty, functional magnetic resonance imaging, independent component analysis, resting-state networks

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882 Assessing P0.1 and Occlusion Pressures in Brain-Injured Patients on Pressure Support Ventilation: A Study Protocol

Authors: S. B. R. Slagmulder

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Monitoring inspiratory effort and dynamic lung stress in patients on pressure support ventilation in the ICU is important for protecting against self inflicted lung injury (P-SILI) and diaphragm dysfunction. Strategies to address the detrimental effects of respiratory drive and effort can lead to improved patient outcomes. Two non-invasive estimation methods, occlusion pressure (Pocc) and P0.1, have been proposed for achieving lung and diaphragm protective ventilation. However, their relationship and interpretation in neuro ICU patients is not well understood. P0.1 is the airway pressure measured during a 100-millisecond occlusion of the inspiratory port. It reflects the neural drive from the respiratory centers to the diaphragm and respiratory muscles, indicating the patient's respiratory drive during the initiation of each breath. Occlusion pressure, measured during a brief inspiratory pause against a closed airway, provides information about the inspiratory muscles' strength and the system's total resistance and compliance. Research Objective: Understanding the relationship between Pocc and P0.1 in brain-injured patients can provide insights into the interpretation of these values in pressure support ventilation. This knowledge can contribute to determining extubation readiness and optimizing ventilation strategies to improve patient outcomes. The central goal is to asses a study protocol for determining the relationship between Pocc and P0.1 in brain-injured patients on pressure support ventilation and their ability to predict successful extubation. Additionally, comparing these values between brain-damaged and non-brain-damaged patients may provide valuable insights. Key Areas of Inquiry: 1. How do Pocc and P0.1 values correlate within brain injury patients undergoing pressure support ventilation? 2. To what extent can Pocc and P0.1 values serve as predictive indicators for successful extubation in patients with brain injuries? 3. What differentiates the Pocc and P0.1 values between patients with brain injuries and those without? Methodology: P0.1 and occlusion pressures are standard measurements for pressure support ventilation patients, taken by attending doctors as per protocol. We utilize electronic patient records for existing data. Unpaired T-test will be conducted to compare P0.1 and Pocc values between both study groups. Associations between P0.1 and Pocc and other study variables, such as extubation, will be explored with simple regression and correlation analysis. Depending on how the data evolve, subgroup analysis will be performed for patients with and without extubation failure. Results: While it is anticipated that neuro patients may exhibit high respiratory drive, the linkage between such elevation, quantified by P0.1, and successful extubation remains unknown The analysis will focus on determining the ability of these values to predict successful extubation and their potential impact on ventilation strategies. Conclusion: Further research is pending to fully understand the potential of these indices and their impact on mechanical ventilation in different patient populations and clinical scenarios. Understanding these relationships can aid in determining extubation readiness and tailoring ventilation strategies to improve patient outcomes in this specific patient population. Additionally, it is vital to account for the influence of sedatives, neurological scores, and BMI on respiratory drive and occlusion pressures to ensure a comprehensive analysis.

Keywords: brain damage, diaphragm dysfunction, occlusion pressure, p0.1, respiratory drive

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