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Neurogastroenterology and motility is a new but advanced subspecialty within gasteroenterology that cater to difficult, persistent and refractory gut-brain symptoms. Hospital USM has the country's first and new state-of-the art motility lab that was recently launched on the 25 May 2023, and is covered in nationwide media. Another first is the Brain-Gut Clinic, established on the 16 November 2022. The clinic is a new concept that builds on unique multiple disciplines in relation to the gut-brain axis. It is hoped that there will be more awareness on the existence of neurogastroenterology and motility among doctors and community, and that more research can be forthcoming to reduce the disease burden.
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This paper extends frequency domain quantitative electroencephalography (qEEG) methods pursuing higher sensitivity to detect Brain Developmental Disorders. Prior qEEG work lacked integration of cross-spectral information omitting important functional connectivity descriptors. Lack of geographical diversity precluded accounting for site-specific variance, increasing qEEG nuisance variance. We ameliorate these weaknesses. (i) Create lifespan Riemannian multinational qEEG norms for cross-spectral tensors. These norms result from the HarMNqEEG project fostered by the Global Brain Consortium. We calculate the norms with data from 9 countries, 12 devices, and 14 studies, including 1564 subjects. Instead of raw data, only anonymized metadata and EEG cross-spectral tensors were shared. After visual and automatic quality control, developmental equations for the mean and standard deviation of qEEG traditional and Riemannian DPs were calculated using additive mixed-effects models. We demonstrate qEEG "batch effects" and provide methods to calculate harmonized z-scores. (ii) We also show that harmonized Riemannian norms produce z-scores with increased diagnostic accuracy predicting brain dysfunction produced by malnutrition in the first year of life and detecting COVID induced brain dysfunction. (iii) We offer open code and data to calculate different individual z-scores from the HarMNqEEG dataset. These results contribute to developing bias-free, low-cost neuroimaging technologies applicable in various health settings.
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Encefalopatias , COVID-19 , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Eletroencefalografia/métodos , HumanosRESUMO
Working memory (WM) encompasses crucial cognitive processes or abilities to retain and manipulate temporary information for immediate execution of complex cognitive tasks in daily functioning such as reasoning and decision-making. The WM of individuals sustaining traumatic brain injury (TBI) was commonly compromised, especially in the domain of WM. The current study investigated the brain responses of WM in a group of participants with mild-moderate TBI compared to their healthy counterparts employing functional magnetic resonance imaging. All consented participants (healthy: n = 26 and TBI: n = 15) performed two variations of the n-back WM task with four load conditions (0-, 1-, 2-, and 3-back). The respective within-group effects showed a right hemisphere-dominance activation and slower reaction in performance for the TBI group. Random-effects analysis revealed activation difference between the two groups in the right occipital lobe in the guided n-back with cues, and in the bilateral occipital lobe, superior parietal region, and cingulate cortices in the n-back without cues. The left middle frontal gyrus was implicated in the load-dependent processing of WM in both groups. Further group analysis identified that the notable activation changes in the frontal gyri and anterior cingulate cortex are according to low and high loads. Though relatively smaller in scale, this study was eminent as it clarified the neural alterations in WM in the mild-moderate TBI group compared to healthy controls. It confirmed the robustness of the phenomenon in TBI with the reproducibility of the results in a heterogeneous non-Western sample.
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Concussão Encefálica , Lesões Encefálicas Traumáticas , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Malásia , Memória de Curto Prazo/fisiologia , Reprodutibilidade dos TestesRESUMO
Approximately one in five children worldwide suffers from childhood malnutrition and its complications, including increased susceptibility to inflammation and infectious diseases. Due to improved early interventions, most of these children now survive early malnutrition, even in low-resource settings (LRS). However, many continue to exhibit neurodevelopmental deficits, including low IQ, poor school performance, and behavioral problems over their lifetimes. Most studies have relied on neuropsychological tests, school performance, and mental health and behavioral measures. Few studies, in contrast, have assessed brain structure and function, and to date, these have mainly relied on low-cost techniques, including electroencephalography (EEG) and evoked potentials (ERP). The use of more advanced methods of neuroimaging, including magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), has been limited by cost factors and lack of availability of these technologies in developing countries, where malnutrition is nearly ubiquitous. This report summarizes the current state of knowledge and evidence gaps regarding childhood malnutrition and the study of its impact on neurodevelopment. It may help to inform the development of new strategies to improve the identification, classification, and treatment of neurodevelopmental disabilities in underserved populations at the highest risk for childhood malnutrition.
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Encéfalo/diagnóstico por imagem , Desnutrição/diagnóstico por imagem , Desnutrição/epidemiologia , Transtornos do Neurodesenvolvimento/diagnóstico por imagem , Transtornos do Neurodesenvolvimento/epidemiologia , Neuroimagem/métodos , Criança , Eletroencefalografia/métodos , Eletroencefalografia/tendências , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/tendências , Desnutrição/psicologia , Transtornos do Neurodesenvolvimento/psicologia , Neuroimagem/tendências , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Espectroscopia de Luz Próxima ao Infravermelho/tendênciasRESUMO
Vascular aging is highly associated with cardiovascular morbidity and mortality. Although the senescence of vascular smooth muscle cells (VSMCs) has been well established as a major contributor to vascular aging, intracellular and exosomal microRNA (miRNA) signaling pathways in senescent VSMCs have not been fully elucidated. This study aimed to identify the differential expression of intracellular and exosomal miRNA in human VSMCs (hVSMCs) during replicative senescence. To achieve this aim, intracellular and exosomal miRNAs were isolated from hVSMCs and subsequently subjected to whole genome small RNA next-generation sequencing, bioinformatics analyses, and qPCR validation. Three significant findings were obtained. First, senescent hVSMC-derived exosomes tended to cluster together during replicative senescence and the molecular weight of the exosomal protein tumor susceptibility gene 101 (TSG-101) increased relative to the intracellular TSG-101, suggesting potential posttranslational modifications of exosomal TSG-101. Second, there was a significant decrease in both intracellular and exosomal hsa-miR-155-5p expression [n = 3, false discovery rate (FDR) < 0.05], potentially being a cell type-specific biomarker of hVSMCs during replicative senescence. Importantly, hsa-miR-155-5p was found to associate with cell-cycle arrest and elevated oxidative stress. Lastly, miRNAs from the intracellular pool, that is, hsa-miR-664a-3p, hsa-miR-664a-5p, hsa-miR-664b-3p, hsa-miR-4485-3p, hsa-miR-10527-5p, and hsa-miR-12136, and that from the exosomal pool, that is, hsa-miR-7704, were upregulated in hVSMCs during replicative senescence (n = 3, FDR < 0.05). Interestingly, these novel upregulated miRNAs were not functionally well annotated in hVSMCs to date. In conclusion, hVSMC-specific miRNA expression profiles during replicative senescence potentially provide valuable insights into the signaling pathways leading to vascular aging.NEW & NOTEWORTHY This is the first study on intracellular and exosomal miRNA profiling on human vascular smooth muscle cells during replicative senescence. Specific dysregulated sets of miRNAs were identified from human vascular smooth muscle cells. Hsa-miR-155-5p was significantly downregulated in both intracellular and exosomal hVSMCs, suggesting its crucial role in cellular senescence. Hsa-miR-155-5p might be the mediator in linking cellular senescence to vascular aging and atherosclerosis.
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Proliferação de Células , Senescência Celular , Exossomos/metabolismo , Perfilação da Expressão Gênica , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Transcriptoma , Células Cultivadas , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Complexos Endossomais de Distribuição Requeridos para Transporte/genética , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Exossomos/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , MicroRNAs/genética , Processamento de Proteína Pós-Traducional , Análise de Sequência de RNA , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Sequenciamento Completo do GenomaRESUMO
Optometrists, ophthalmologists, orthoptists, and other trained medical professionals use fundus photography to monitor the progression of certain eye conditions or diseases. Segmentation of the vessel tree is an essential process of retinal analysis. In this paper, an interactive blood vessel segmentation from retinal fundus image based on Canny edge detection is proposed. Semi-automated segmentation of specific vessels can be done by simply moving the cursor across a particular vessel. The pre-processing stage includes the green color channel extraction, applying Contrast Limited Adaptive Histogram Equalization (CLAHE), and retinal outline removal. After that, the edge detection techniques, which are based on the Canny algorithm, will be applied. The vessels will be selected interactively on the developed graphical user interface (GUI). The program will draw out the vessel edges. After that, those vessel edges will be segmented to bring focus on its details or detect the abnormal vessel. This proposed approach is useful because different edge detection parameter settings can be applied to the same image to highlight particular vessels for analysis or presentation.
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Processamento de Imagem Assistida por Computador , Vasos Retinianos , Algoritmos , Técnicas de Diagnóstico Oftalmológico , Fundo de Olho , Vasos Retinianos/diagnóstico por imagemRESUMO
BACKGROUND: The auditory and prefrontal cortex supports auditory working memory processing. Many neuroimaging studies have shown hemispheric lateralization of auditory working memory brain regions in the presence of background noise, but few studies have focused on the lateralization of these regions during stochastic resonance. PURPOSE: To investigate the effects of stochastic resonance on lateralization of auditory working memory regions, and also to examine the brain-behavior relationship during stochastic resonance. STUDY TYPE: Cross-sectional. POPULATION/SUBJECTS: Forty healthy young adults (18-24 years old). FIELD STRENGTH/SEQUENCE: 3.0T, T1 , and T2 *-weighted imaging. ASSESSMENT: The auditory working memory performance was assessed using a backward recall task. Functional magnetic resonance imaging (fMRI) was used to measure brain activity during task performance. Functional MRI data were analyzed using SPM12 and WFU PickAtlas. STATISTICAL TESTS: One-way independent analyses of variance (ANOVA) were conducted on the behavioral and functional data to examine the main effect of noise level on performance (P < 0.01) and brain activity (P < 0.0042). Hemispheric lateralization was determined by calculating the laterality index. A paired samples t-test was performed to compare brain activity between hemispheres (P < 0.05). Pearson's correlation analysis and simple linear regression (P < 0.0042) were used to examine the relationship between brain activity and behavioral performance. RESULTS: Performance was significantly enhanced during the 50 and 55 dB sound pressure level (SPL) conditions via the stochastic resonance mechanism [F(1,195) = 49.17, P < 0.001]. Activity of the right superior frontal gyrus in the 55 dB SPL condition was significantly positively correlated with performance (R2 = 0.681, P < 0.001). DATA CONCLUSION: Our findings demonstrate changes in the lateralization of auditory working memory regions during stochastic resonance and suggest that the right superior frontal gyrus may be a strategic structure involved in the enhancement of auditory working memory performance. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 4 J. Magn. Reson. Imaging 2020;51:1821-1828.
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Mapeamento Encefálico , Imageamento por Ressonância Magnética , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Estudos Transversais , Lateralidade Funcional , Humanos , Memória de Curto Prazo , Adulto JovemRESUMO
The present study examined the impact of white noise on word recall performance and brain activity in 40 healthy adolescents, split in two groups (normal and low) depending on their auditory working memory capacity (AWMC). Using functional magnetic resonance imaging, participants performed a backward recall task under four different signal-to-noise ratio (SNR) conditions: 15, 10, 5, and 0-dB SNR. Behaviorally, normal AWMC individuals scored significantly higher than low AWMC individuals across noise levels. Whole-brain analyses showed brain activation not to be statistically different between groups across noise levels. In the normal group, a significant positive relationship was found between performance and number of activated voxels in the right superior frontal gyrus. In the low group, significant positive correlations were found between performance and number of activated voxels in left superior frontal gyrus, left inferior frontal gyrus, and left anterior cingulate cortex. These findings suggest that the strategic structure involved in the enhancement of AWM performance may differ in normal and low AWMC individuals.
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Atenção/fisiologia , Percepção Auditiva/fisiologia , Mapeamento Encefálico , Giro do Cíngulo/fisiologia , Memória de Curto Prazo/fisiologia , Rememoração Mental/fisiologia , Córtex Pré-Frontal/fisiologia , Adolescente , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Ruído , Córtex Pré-Frontal/diagnóstico por imagemRESUMO
Traumatic brain injury (TBI) is one of the common injuries when the human head receives an impact due to an accident or fall and is one of the most frequently submitted insurance claims. However, it is often always misused when individuals attempt an insurance fraud claim by providing false medical conditions. Therefore, there is a need for an instant brain condition classification system. This study presents a novel classification architecture that can classify non-severe TBI patients and healthy subjects employing resting-state electroencephalogram (EEG) as the input, solving the immobility issue of the computed tomography (CT) scan and magnetic resonance imaging (MRI). The proposed architecture makes use of long short term memory (LSTM) and error-correcting output coding support vector machine (ECOC-SVM) to perform multiclass classification. The pre-processed EEG time series are supplied to the network by each time step, where important information from the previous time step will be remembered by the LSTM cell. Activations from the LSTM cell is used to train an ECOC-SVM. The temporal advantages of the EEG were amplified and able to achieve a classification accuracy of 100%. The proposed method was compared to existing works in the literature, and it is shown that the proposed method is superior in terms of classification accuracy, sensitivity, specificity, and precision.
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Lesões Encefálicas Traumáticas , Eletroencefalografia , Máquina de Vetores de Suporte , Lesões Encefálicas Traumáticas/classificação , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios XRESUMO
Background: Impairment in cognitive function is a recognized outcome of traumatic brain injury (TBI). However, the degree of impairment has variable relationship with TBI severity and time post injury. The underlying pathology is often due to diffuse axonal injury that has been found even in mild TBI. In this study, we examine the state of white matter putative connectivity in patients with non-severe TBI in the subacute phase, i.e., within 10 weeks of injury and determine its relationship with neuropsychological scores. Methods: We conducted a case-control prospective study involving 11 male adult patients with non-severe TBI and an age-matched control group of 11 adult male volunteers. Diffusion MRI scanning and neuropsychological tests were administered within 10 weeks post injury. The difference in fractional anisotropy (FA) values between the patient and control groups was examined using tract-based spatial statistics. The FA values that were significantly different between patients and controls were then correlated with neuropsychological tests in the patient group. Results: Several clusters with peak voxels of significant FA reductions (p < 0.05) in the white matter skeleton were seen in patients compared to the control group. These clusters were located in the superior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus, and cingulum, as well as white matter fibers in the area of genu of corpus callosum, anterior corona radiata, superior corona radiata, anterior thalamic radiation and part of inferior frontal gyrus. Mean global FA magnitude correlated significantly with MAVLT immediate recall scores while matrix reasoning scores correlated positively with FA values in the area of right superior fronto-occipital fasciculus and left anterior corona radiata. Conclusion: The non-severe TBI patients had abnormally reduced FA values in multiple regions compared to controls that correlated with several measures of executive function during the sub-acute phase of TBI.
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The debilitating effect of traumatic brain injury (TBI) extends years after the initial injury and hampers the recovery process and quality of life. In this study, we explore the functional reorganization of the default mode network (DMN) of those affected with non-severe TBI. Traumatic brain injury (TBI) is a wide-spectrum disease that has heterogeneous effects on its victims and impacts everyday functioning. The functional disruption of the default mode network (DMN) after TBI has been established, but its link to causal effective connectivity remains to be explored. This study investigated the differences in the DMN between healthy participants and mild and moderate TBI, in terms of functional and effective connectivity using resting-state functional magnetic resonance imaging (fMRI). Nineteen non-severe TBI (mean age 30.84 ± 14.56) and twenty-two healthy (HC; mean age 27.23 ± 6.32) participants were recruited for this study. Resting-state fMRI data were obtained at the subacute phase (mean days 40.63 ± 10.14) and analyzed for functional activation and connectivity, independent component analysis, and effective connectivity within and between the DMN. Neuropsychological tests were also performed to assess the cognitive and memory domains. Compared to the HC, the TBI group exhibited lower activation in the thalamus, as well as significant functional hypoconnectivity between DMN and LN. Within the DMN nodes, decreased activations were detected in the left inferior parietal lobule, precuneus, and right superior frontal gyrus. Altered effective connectivities were also observed in the TBI group and were linked to the diminished activation in the left parietal region and precuneus. With regard to intra-DMN connectivity within the TBI group, positive correlations were found in verbal and visual memory with the language network, while a negative correlation was found in the cognitive domain with the visual network. Our results suggested that aberrant activities and functional connectivities within the DMN and with other RSNs were accompanied by the altered effective connectivities in the TBI group. These alterations were associated with impaired cognitive and memory domains in the TBI group, in particular within the language domain. These findings may provide insight for future TBI observational and interventional research.
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BACKGROUND: Modifying brain activity using non-invasive, low intensity transcranial electrical brain stimulation (TES) has rapidly increased during the past 20â¯years. Alternating current stimulation (ACS), for example, has been shown to alter brain rhythm activities and modify neuronal functioning in the visual system. Daily application of transorbital ACS to patients with optic nerve damage induces functional connectivity reorganization, and partially restores vision. While ACS is thought to mainly modify neuronal mechanisms, e.g. changes in brain oscillations that can be detected by EEG, it is still an open question, whether and how it may alter BOLD activity. OBJECTIVE: We evaluated whether transorbital ACS modulates BOLD activity in early visual cortex using high-resolution 7 Tesla functional magnetic resonance imaging (fMRI). METHODS: In this feasibility study transorbital ACS in the alpha range and sham ACS was applied in a random block design in five healthy subjects for 20â¯min at 1â¯mA. Brain activation in the visual areas V1, V2 and V3 were measured using 7 Tesla fMRI-based retinotopic mapping at the time points before (baseline) and after stimulation. In addition, we collected data from one hemianopic stroke patient with visual cortex damage after ten daily sessions with 25-50â¯min stimulation duration. RESULTS: In healthy subjects transorbital ACS increased the activated cortical surface area, decreased the fMRI response amplitude and increased coherence in the visual cortex, which was most prominent in the full field task. In the patient, stimulation improved contrast sensitivity in the central visual field. BOLD amplitudes and coherence values were increased in most early visual areas in both hemispheres, with the most pronounced activation detected during eccentricity testing in retinotopic mapping. CONCLUSIONS: This feasibility study showed that transorbital ACS modifies BOLD activity to visual stimulation, which outlasts the duration of the AC stimulation. This is in line with earlier neurophysiological findings of increased power in EEG recordings and functional connectivity reorganization in patients with impaired vision. Accordingly, the larger BOLD response area after stimulation can be explained by more coherent activation and lower variability in the activation. Alternatively, increased neuronal activity can also be taken into account. Controlled trials are needed to systematically evaluate the potential of repetitive transorbital ACS to improve visual function after visual pathway stroke and to determine the cause-effect relationship between neural and BOLD activity changes.
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Hemianopsia , Acidente Vascular Cerebral , Mapeamento Encefálico , Estudos de Viabilidade , Voluntários Saudáveis , Humanos , Imageamento por Ressonância Magnética , Acidente Vascular Cerebral/complicaçõesRESUMO
Traumatic brain injury (TBI) is one of the injuries that can bring serious consequences if medical attention has been delayed. Commonly, analysis of computed tomography (CT) or magnetic resonance imaging (MRI) is required to determine the severity of a moderate TBI patient. However, due to the rising number of TBI patients these days, employing the CT scan or MRI scan to every potential patient is not only expensive, but also time consuming. Therefore, in this paper, we investigate the possibility of using electroencephalography (EEG) with computational intelligence as an alternative approach to detect the severity of moderate TBI patients. EEG procedure is much cheaper than CT or MRI. Although EEG does not have high spatial resolutions as compared with CT and MRI, it has high temporal resolutions. The analysis and prediction of moderate TBI from EEG using conventional computational intelligence approaches are tedious as they normally involve complex preprocessing, feature extraction, or feature selection of the signal. Thus, we propose an approach that uses convolutional neural network (CNN) to automatically classify healthy subjects and moderate TBI patients. The input to this computational intelligence system is the resting-state eye-closed EEG, without undergoing preprocessing and feature selection. The EEG dataset used includes 15 healthy volunteers and 15 moderate TBI patients, which is acquired at the Hospital Universiti Sains Malaysia, Kelantan, Malaysia. The performance of the proposed method has been compared with four other existing methods. With the average classification accuracy of 72.46%, the proposed method outperforms the other four methods. This result indicates that the proposed method has the potential to be used as a preliminary screening for moderate TBI, for selection of the patients for further diagnosis and treatment planning.
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Concussão Encefálica/diagnóstico , Eletroencefalografia , Redes Neurais de Computação , Processamento de Sinais Assistido por Computador , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Research suggests that white noise may facilitate auditory working memory performance via stochastic resonance. Stochastic resonance is quantified by plotting cognitive performance as a function of noise intensity. The plot would appear as an inverted U-curve, that is, a moderate noise is beneficial for performance whereas too low and too much noise attenuates performance. However, knowledge about the optimal signal-to-noise ratio (SNR) needed for stochastic resonance to occur in the brain, particularly in the neural network of auditory working memory, is limited and demand further investigation. In the present study, we extended previous works on the impact of white noise on auditory working memory performance by including multiple background noise levels to map out the inverted U-curve for the stochastic resonance. Using functional magnetic resonance imaging (fMRI), twenty healthy young adults performed a word-based backward recall span task under four signal-to-noise ratio conditions: 15, 10, 5, and 0-dB SNR. Group results show significant behavioral improvement and increased activation in frontal cortices, primary auditory cortices, and anterior cingulate cortex in all noise conditions, except at 0-dB SNR, which decreases activation and performance. When plotted as a function of signal-to-noise ratio, behavioral and fMRI data exhibited a noise-benefit inverted U-shaped curve. Additionally, a significant positive correlation was found between the activity of the right superior frontal gyrus (SFG) and performance in 5-dB SNR. The predicted phenomenon of SR on auditory working memory performance is confirmed. Findings from this study suggest that the optimal signal-to-noise ratio to enhance auditory working memory performance is within 10 to 5-dB SNR and that the right SFG may be a strategic structure involved in enhancement of auditory working memory performance.
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The discovery of tumour selective virus-mediated apoptosis marked the birth of an alternative cancer treatment in the form of oncolytic viruses. Even though, its oncolytic efficiency was demonstrated more than 50 years ago, safety concerns which resulted from mild to lethal side effects hampered the progress of oncolytic virus research. Since the classical oncolytic virus studies rely heavily on its natural oncolytic ability, virus manipulation was limited, thereby, restricted efforts to improve its safety. In order to circumvent such restriction, experiments involving non-human viruses such as the avian Newcastle disease virus (NDV) was conducted using cultured cells, animal models and human subjects. The corresponding reports on its significant tumour cytotoxicity along with impressive safety profile initiated immense research interest in the field of oncolytic NDV. The varying degree of oncolytic efficiency and virulency among NDV strains encouraged researchers from all around the world to experiment with their respective local NDV isolates in order to develop an oncolytic virus with desirable characteristics. Such desirable features include high tumour-killing ability, selectivity and low systemic cytotoxicity. The Malaysian field outbreak isolate, NDV strain AF2240, also currently, receives significant research attention. Apart from its high cytotoxicity against tumour cells, this strain also provided fundamental insight into NDV-mediated apoptosis mechanism which involves Bax protein recruitment as well as death receptor engagement. Studies on its ability to selectively induce apoptosis in tumour cells also resulted in a proposed p38 MAPK/NF-κB/IκBα pathway. The immunogenicity of AF2240 was also investigated through PBMC stimulation and macrophage infection. In addition, the enhanced oncolytic ability of this strain under hypoxic condition signifies its dynamic tumour tropism. This review is aimed to introduce and discuss the aforementioned details of the oncolytic AF2240 strain along with its current challenges which outlines the future research direction of this virus.
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Doença de Newcastle/genética , Vírus da Doença de Newcastle/genética , Terapia Viral Oncolítica , Vírus Oncolíticos/genética , Animais , Apoptose , Linhagem Celular Tumoral , Humanos , Leucócitos Mononucleares , Inibidor de NF-kappaB alfa , NF-kappa B/metabolismo , Doença de Newcastle/prevenção & controle , Terapia Viral Oncolítica/métodos , Proteínas Virais/genéticaRESUMO
Since the concept of working memory was introduced over 50 years ago, different schools of thought have offered different definitions for working memory based on the various cognitive domains that it encompasses. The general consensus regarding working memory supports the idea that working memory is extensively involved in goal-directed behaviors in which information must be retained and manipulated to ensure successful task execution. Before the emergence of other competing models, the concept of working memory was described by the multicomponent working memory model proposed by Baddeley and Hitch. In the present article, the authors provide an overview of several working memory-relevant studies in order to harmonize the findings of working memory from the neurosciences and psychological standpoints, especially after citing evidence from past studies of healthy, aging, diseased, and/or lesioned brains. In particular, the theoretical framework behind working memory, in which the related domains that are considered to play a part in different frameworks (such as memory's capacity limit and temporary storage) are presented and discussed. From the neuroscience perspective, it has been established that working memory activates the fronto-parietal brain regions, including the prefrontal, cingulate, and parietal cortices. Recent studies have subsequently implicated the roles of subcortical regions (such as the midbrain and cerebellum) in working memory. Aging also appears to have modulatory effects on working memory; age interactions with emotion, caffeine and hormones appear to affect working memory performances at the neurobiological level. Moreover, working memory deficits are apparent in older individuals, who are susceptible to cognitive deterioration. Another younger population with working memory impairment consists of those with mental, developmental, and/or neurological disorders such as major depressive disorder and others. A less coherent and organized neural pattern has been consistently reported in these disadvantaged groups. Working memory of patients with traumatic brain injury was similarly affected and shown to have unusual neural activity (hyper- or hypoactivation) as a general observation. Decoding the underlying neural mechanisms of working memory helps support the current theoretical understandings concerning working memory, and at the same time provides insights into rehabilitation programs that target working memory impairments from neurophysiological or psychological aspects.
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fMRI-based retinotopic mapping was used to assess systematic variations in activated cortical surface area, amplitude, and coherence across sessions. Seven healthy subjects were scanned at 7 T in three separate sessions with intervals of 51.4 ± 5.4 days (Sessions 1 and 2) and 167.9 ± 24.4 days (Sessions 2 and 3). We found a reduction between Sessions 1 and 2 for activated cortical surface area, between Sessions 1 and 3 for amplitude, and between Sessions 1 and 2/3 for coherence. The results do not support head motion as a major cause of the observed effect seen in Session 1, suggesting that cognitive effects were the underlying cause of change. The phase correlations for both eccentricity and polar angle mapping were highly correlated between sessions, demonstrating the stability of the maps. Furthermore, the sensitivity in determining inter-session changes of cortical surface area, response amplitude, and coherence were, at a 5% significance level, estimated to be 1.5, 6, and 5%, respectively. Any future longitudinal fMRI study should carefully evaluate activation across sessions to determine the eligibility of inclusion of all time points. This experimental design provides guidance in methodological issues of clinical longitudinal fMRI-studies, specifically regarding effects of subject experience.
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Cognitive and neurological dysfunctions can severely impact a patient's daily activities. In addition to medical treatment, non-invasive transcranial alternating current stimulation (tACS) has been proposed as a therapeutic technique to improve the functional state of the brain. Although during the last years tACS was applied in numerous studies to improve motor, somatosensory, visual and higher order cognitive functions, our knowledge is still limited regarding the mechanisms as to which type of ACS can affect cortical functions and altered neuronal oscillations seem to be the key mechanism. Because alternating current send pulses to the brain at predetermined frequencies, the online- and after-effects of ACS strongly depend on the stimulation parameters so that "optimal" ACS paradigms could be achieved. This is of interest not only for neuroscience research but also for clinical practice. In this study, we summarize recent findings on ACS-effects under both normal conditions and in brain diseases.
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BACKGROUND: In spite of extensive research conducted to study how human brain works, little is known about a special function of the brain that stores and manipulates information-the working memory-and how noise influences this special ability. In this study, Functional magnetic resonance imaging (fMRI) was used to investigate brain responses to arithmetic problems solved in noisy and quiet backgrounds. METHODS: Eighteen healthy young males performed simple arithmetic operations of addition and subtraction with in-quiet and in-noise backgrounds. The MATLAB-based Statistical Parametric Mapping (SPM8) was implemented on the fMRI datasets to generate and analyse the activated brain regions. RESULTS: Group results showed that addition and subtraction operations evoked extended activation in the left inferior parietal lobe, left precentral gyrus, left superior parietal lobe, left supramarginal gyrus, and left middle temporal gyrus. This supported the hypothesis that the human brain relatively activates its left hemisphere more compared with the right hemisphere when solving arithmetic problems. The insula, middle cingulate cortex, and middle frontal gyrus, however, showed more extended right hemispheric activation, potentially due to the involvement of attention, executive processes, and working memory. For addition operations, there was extensive left hemispheric activation in the superior temporal gyrus, inferior frontal gyrus, and thalamus. In contrast, subtraction tasks evoked a greater activation of similar brain structures in the right hemisphere. For both addition and subtraction operations, the total number of activated voxels was higher for in-noise than in-quiet conditions. CONCLUSION: These findings suggest that when arithmetic operations were delivered auditorily, the auditory, attention, and working memory functions were required to accomplish the executive processing of the mathematical calculation. The respective brain activation patterns appear to be modulated by the noisy background condition.