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1.
ACS Chem Neurosci ; 14(24): 4383-4394, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38050970

RESUMO

Parkinson's disease (PD) is characterized by extrapyramidal motor disturbances and nonmotor cognitive impairments which impact activities of daily living. Although the etiology of PD is still obscure, autopsy reports suggest that oxidative stress (OS) is one of the important factors in the pathophysiology of PD. In the current study, we have investigated the impact of OS in PD by measuring the antioxidant glutathione (GSH) levels from the substantia nigra (SN), left hippocampus (LH) and neurotransmitter γ-amino butyric acid (GABA) levels from SN region. Concomitant quantitative susceptibility mapping (QSM) from SN and LH was also acquired from thirty-eight PD patients and 30 age-matched healthy controls (HC). Glutathione levels in the SN region decreased significantly and susceptibility increased significantly in PD compared to HC. Nonsignificant depletion of GABA was observed in the SN region. GSH levels in the LH region were depleted significantly, but LH susceptibility did not alter in the PD cohort compared to HC. Neuropsychological and physical assessment demonstrated significant impairment of cognitive functioning in PD patients compared to HC. GSH depletion was negatively correlated to motor function performance. Multivariate receiver operating characteristic (ROC) curve analysis on the combined effect of GSH, GABA, and susceptibility in the SN region yielded an improved diagnostic accuracy of 86.1% compared to individual diagnostic accuracy based on GSH (65.8%), GABA (57.5%), and susceptibility (69.6%). This is the first comprehensive report in PD demonstrating significant GSH depletion as well as concomitant iron enhancement in the SN region.


Assuntos
Doença de Parkinson , Humanos , Atividades Cotidianas , Imageamento por Ressonância Magnética/métodos , Substância Negra , Glutationa , Espectroscopia de Ressonância Magnética , Ácido gama-Aminobutírico
2.
Sci Rep ; 13(1): 8091, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208434

RESUMO

The geographical location of any region, as well as large-scale environmental changes caused by a variety of factors, invite a wide range of disasters. Floods, droughts, earthquakes, cyclones, landslides, tornadoes, and cloudbursts are all common natural disasters that destroy property and kill people. On average, 0.1% of the total deaths globally in the past decade have been due to natural disasters. The National Disaster Management Authority (NDMA), a branch of the Ministry of Home Affairs, plays an important role in disaster management in India by taking responsibility for risk mitigation, response, and recovery from all natural and man-made disasters. This article presents an ontology-based disaster management framework based on the NDMA's responsibility matrix. This ontological base framework is named as Disaster Management Ontology (DMO). It aids in task distribution among necessary authorities at various stages of a disaster, as well as a knowledge-driven decision support system for financial assistance to victims. In the proposed DMO, ontology has been used to integrate knowledge as well as a working platform for reasoners, and the Decision Support System (DSS) ruleset is written in Semantic Web Rule Language (SWRL), which is based on the First Order Logic (FOL) concept. In addition, OntoGraph, a class view of taxonomy, is used to make taxonomy more interactive for users.

3.
Brain Commun ; 4(5): fcac215, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072647

RESUMO

Oxidative stress has been implicated in Alzheimer's disease, and it is potentially driven by the depletion of primary antioxidant, glutathione, as well as elevation of the pro-oxidant, iron. Present study evaluates glutathione level by magnetic resonance spectroscopy, iron deposition by quantitative susceptibility mapping in left hippocampus, as well as the neuropsychological scores of healthy old participants (N = 25), mild cognitive impairment (N = 16) and Alzheimer's disease patients (N = 31). Glutathione was found to be significantly depleted in mild cognitive impaired (P < 0.05) and Alzheimer's disease patients (P < 0.001) as compared with healthy old participants. A significant higher level of iron was observed in left hippocampus region for Alzheimer's disease patients as compared with healthy old (P < 0.05) and mild cognitive impairment (P < 0.05). Multivariate receiver-operating curve analysis for combined glutathione and iron in left hippocampus region provided diagnostic accuracy of 82.1%, with 81.8% sensitivity and 82.4% specificity for diagnosing Alzheimer's disease patients from healthy old participants. We conclude that tandem glutathione and iron provides novel avenue to investigate further research in Alzheimer's disease.

4.
J Alzheimers Dis ; 88(1): 1-6, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35527551

RESUMO

Oxidative stress (OS) is a critical factor in the pathogenesis of Alzheimer's disease (AD). Elevated OS in AD lowers the level of glutathione (GSH), a brain antioxidant. Currently, GSH is under examination in the clinical population for understanding its association with oxidative load in AD research. Significant depletion in hippocampal GSH, as observed using in vivo magnetic resonance spectroscopy (MRS), reportedly correlates with cognitive impairment in AD. Alterations in cellular-energy metabolism and increased hippocampal pH have also been reported in AD. Hence, this combined molecular interplay between hippocampal GSH and pH must be studied longitudinally for advancing AD research. Herein, we propose a schematic model depicting the molecular events in AD pathogenesis and provide a possible link between OS, GSH depletion, and pH alterations in the hippocampus. The model would further potentiate the need for in vivo longitudinal studies to confirm the interlinked mechanism between OS, hippocampal GSH depletion, and pH increment in an AD patient brain.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/patologia , Disfunção Cognitiva/metabolismo , Glutationa/metabolismo , Hipocampo/patologia , Humanos , Concentração de Íons de Hidrogênio
5.
NMR Biomed ; 35(7): e4702, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35078266

RESUMO

Edited MRS sequences are widely used for studying γ-aminobutyric acid (GABA) in the human brain. Several algorithms are available for modelling these data, deriving metabolite concentration estimates through peak fitting or a linear combination of basis spectra. The present study compares seven such algorithms, using data obtained in a large multisite study. GABA-edited (GABA+, TE = 68 ms MEGA-PRESS) data from 222 subjects at 20 sites were processed via a standardised pipeline, before modelling with FSL-MRS, Gannet, AMARES, QUEST, LCModel, Osprey and Tarquin, using standardised vendor-specific basis sets (for GE, Philips and Siemens) where appropriate. After referencing metabolite estimates (to water or creatine), systematic differences in scale were observed between datasets acquired on different vendors' hardware, presenting across algorithms. Scale differences across algorithms were also observed. Using the correlation between metabolite estimates and voxel tissue fraction as a benchmark, most algorithms were found to be similarly effective in detecting differences in GABA+. An interclass correlation across all algorithms showed single-rater consistency for GABA+ estimates of around 0.38, indicating moderate agreement. Upon inclusion of a basis set component explicitly modelling the macromolecule signal underlying the observed 3.0 ppm GABA peaks, single-rater consistency improved to 0.44. Correlation between discrete pairs of algorithms varied, and was concerningly weak in some cases. Our findings highlight the need for consensus on appropriate modelling parameters across different algorithms, and for detailed reporting of the parameters adopted in individual studies to ensure reproducibility and meaningful comparison of outcomes between different studies.


Assuntos
Algoritmos , Ácido gama-Aminobutírico , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Humanos , Espectroscopia de Ressonância Magnética/métodos , Espectroscopia de Prótons por Ressonância Magnética , Reprodutibilidade dos Testes , Ácido gama-Aminobutírico/metabolismo
6.
Neuroradiology ; 64(2): 217-232, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34654960

RESUMO

J-difference-edited spectroscopy is a valuable approach for the detection of low-concentration metabolites with magnetic resonance spectroscopy (MRS). Currently, few edited MRS studies are performed in neonates due to suboptimal signal-to-noise ratio, relatively long acquisition times, and vulnerability to motion artifacts. Nonetheless, the technique presents an exciting opportunity in pediatric imaging research to study rapid maturational changes of neurotransmitter systems and other metabolic systems in early postnatal life. Studying these metabolic processes is vital to understanding the widespread and rapid structural and functional changes that occur in the first years of life. The overarching goal of this review is to provide an introduction to edited MRS for neonates, including the current state-of-the-art in editing methods and editable metabolites, as well as to review the current literature applying edited MRS to the neonatal brain. Existing challenges and future opportunities, including the lack of age-specific reference data, are also discussed.


Assuntos
Encéfalo , Ácido gama-Aminobutírico , Artefatos , Encéfalo/diagnóstico por imagem , Criança , Humanos , Recém-Nascido , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética
7.
J Alzheimers Dis ; 84(3): 1139-1152, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34633325

RESUMO

BACKGROUND: Oxidative stress plays a major role in Alzheimer's disease (AD) pathogenesis, and thus, antioxidant glutathione (GSH) has been actively investigated in mitigating the oxidative load. Significant hippocampal GSH depletion has been correlated with cognitive impairment in AD. Furthermore, postmortem studies indicated alterations in cellular-energy metabolism and hippocampal pH change toward alkalinity in AD. OBJECTIVE: Concurrent analysis of hippocampal GSH and pH interplay in vivo on the same individual is quite unclear and hence requires investigation to understand the pathological events in AD. METHODS: Total 39 healthy old (HO), 22 mild cognitive impairment (MCI), and 37 AD patients were recruited for hippocampal GSH using 1H-MRS MEGA-PRESS and pH using 2D 31P-MRSI with dual tuned (1H/31P) transmit/receive volume head coil on 3T-Philips scanner. All MRS data processing using KALPANA package and statistical analysis were performed MedCalc, respectively and NINS-STAT package. RESULTS: Significant GSH depletion in the left and right hippocampus (LH and RH) among MCI and AD study groups as compared to HO was observed, whereas pH increased significantly in the LH region between HO and AD. Hippocampal GSH level negatively correlated with pH in both patient groups. The ROC analysis on the combined effect of GSH and pH in both hippocampal regions give accuracy for MCI (LH: 78.27%; RH: 86.96%) and AD (LH: 88%; RH: 78.26%) groups differentiating from HO. CONCLUSION: Outcomes from this study provide further insights to metabolic alterations in terms of concurrent assessment of hippocampal GSH and pH levels in AD pathogenesis, aiding in early diagnosis of MCI and AD.


Assuntos
Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Glutationa/metabolismo , Hipocampo/metabolismo , Concentração de Íons de Hidrogênio , Idoso , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Estresse Oxidativo/fisiologia , Espectroscopia de Prótons por Ressonância Magnética
8.
Lancet Glob Health ; 9(9): e1273-e1285, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34358491

RESUMO

BACKGROUND: Although therapeutic hypothermia reduces death or disability after neonatal encephalopathy in high-income countries, its safety and efficacy in low-income and middle-income countries is unclear. We aimed to examine whether therapeutic hypothermia alongside optimal supportive intensive care reduces death or moderate or severe disability after neonatal encephalopathy in south Asia. METHODS: We did a multicountry open-label, randomised controlled trial in seven tertiary neonatal intensive care units in India, Sri Lanka, and Bangladesh. We enrolled infants born at or after 36 weeks of gestation with moderate or severe neonatal encephalopathy and a need for continued resuscitation at 5 min of age or an Apgar score of less than 6 at 5 min of age (for babies born in a hospital), or both, or an absence of crying by 5 min of age (for babies born at home). Using a web-based randomisation system, we allocated infants into a group receiving whole body hypothermia (33·5°C) for 72 h using a servo-controlled cooling device, or to usual care (control group), within 6 h of birth. All recruiting sites had facilities for invasive ventilation, cardiovascular support, and access to 3 Tesla MRI scanners and spectroscopy. Masking of the intervention was not possible, but those involved in the magnetic resonance biomarker analysis and neurodevelopmental outcome assessments were masked to the allocation. The primary outcome was a combined endpoint of death or moderate or severe disability at 18-22 months, assessed by the Bayley Scales of Infant and Toddler Development (third edition) and a detailed neurological examination. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02387385. FINDINGS: We screened 2296 infants between Aug 15, 2015, and Feb 15, 2019, of whom 576 infants were eligible for inclusion. After exclusions, we recruited 408 eligible infants and we assigned 202 to the hypothermia group and 206 to the control group. Primary outcome data were available for 195 (97%) of the 202 infants in the hypothermia group and 199 (97%) of the 206 control group infants. 98 (50%) infants in the hypothermia group and 94 (47%) infants in the control group died or had a moderate or severe disability (risk ratio 1·06; 95% CI 0·87-1·30; p=0·55). 84 infants (42%) in the hypothermia group and 63 (31%; p=0·022) infants in the control group died, of whom 72 (36%) and 49 (24%; p=0·0087) died during neonatal hospitalisation. Five serious adverse events were reported: three in the hypothermia group (one hospital readmission relating to pneumonia, one septic arthritis, and one suspected venous thrombosis), and two in the control group (one related to desaturations during MRI and other because of endotracheal tube displacement during transport for MRI). No adverse events were considered causally related to the study intervention. INTERPRETATION: Therapeutic hypothermia did not reduce the combined outcome of death or disability at 18 months after neonatal encephalopathy in low-income and middle-income countries, but significantly increased death alone. Therapeutic hypothermia should not be offered as treatment for neonatal encephalopathy in low-income and middle-income countries, even when tertiary neonatal intensive care facilities are available. FUNDING: National Institute for Health Research, Garfield Weston Foundation, and Bill & Melinda Gates Foundation. TRANSLATIONS: For the Hindi, Malayalam, Telugu, Kannada, Singhalese, Tamil, Marathi and Bangla translations of the abstract see Supplementary Materials section.


Assuntos
Encefalopatias/terapia , Hipotermia Induzida , Bangladesh/epidemiologia , Encefalopatias/mortalidade , Países em Desenvolvimento , Feminino , Humanos , Índia/epidemiologia , Recém-Nascido , Terapia Intensiva Neonatal , Masculino , Índice de Gravidade de Doença , Sri Lanka/epidemiologia , Resultado do Tratamento
9.
J Alzheimers Dis ; 83(1): 305-317, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34308905

RESUMO

BACKGROUND: In vivo neuroimaging modalities such as magnetic resonance imaging (MRI), functional MRI (fMRI), magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), and quantitative susceptibility mapping (QSM) are useful techniques to understand brain anatomical structure, functional activity, source localization, neurochemical profiles, and tissue susceptibility respectively. Integrating unique and distinct information from these neuroimaging modalities will further help to enhance the understanding of complex neurological diseases. OBJECTIVE: To develop a processing scheme for multimodal data integration in a seamless manner on healthy young population, thus establishing a generalized framework for various clinical conditions (e.g., Alzheimer's disease). METHODS: A multimodal data integration scheme has been developed to integrate the outcomes from multiple neuroimaging data (fMRI, MEG, MRS, and QSM) spatially. Furthermore, the entire scheme has been incorporated into a user-friendly toolbox- "PRATEEK". RESULTS: The proposed methodology and toolbox has been tested for viability among fourteen healthy young participants. The data-integration scheme was tested for bilateral occipital cortices as the regions of interest and can also be extended to other anatomical regions. Overlap percentage from each combination of two modalities (fMRI-MRS, MEG-MRS, fMRI-QSM, and fMRI-MEG) has been computed and also been qualitatively assessed for combinations of the three (MEG-MRS-QSM) and four (fMRI-MEG-MRS-QSM) modalities. CONCLUSION: This user-friendly toolbox minimizes the need of an expertise in handling different neuroimaging tools for processing and analyzing multimodal data. The proposed scheme will be beneficial for clinical studies where geometric information plays a crucial role for advance brain research.


Assuntos
Pesquisa Biomédica , Encéfalo , Imagem Multimodal , Neuroimagem , Adulto , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Masculino
10.
Front Neuroinform ; 14: 571039, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33214792

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting millions of people worldwide. The etiology of AD is not known, and intense research involving multimodal neuroimaging data (e.g., MRI, functional MRI, PET etc.) is extensively used to identify the causal molecular process for AD. In this context, various imaging-based databases accessible to researchers globally, are useful for an independent analysis. Apart from MRI-based brain imaging data, the neurochemical data using magnetic resonance spectroscopy (MRS) provide early molecular processes before the structural or functional changes are manifested. The existing imaging-based databases in AD lack the integration of MRS modality and, thus, limits the availability of neurochemical information to the AD research community. This perspective is an initiative to bring attention to the development of the neuroimaging database, "ANSH," that includes brain glutathione (GSH), gamma aminobutyric acid (GABA) levels, and other neurochemicals along with MRI-based information for AD, mild cognitive impairment (MCI), and healthy subjects. ANSH is supported by a JAVA-based workflow environment and python providing a simple, dynamic, and distributed platform with data security. The platform consists of two-tiered architecture for data collection and management further supporting quality control, report generation for analyzed data, and data backup with a dedicated storage system. The ANSH database aims to present a single neuroimaging data platform incorporating diverse data types from healthy control and patient groups to provide better insights pertaining to disease progression. This data management platform provides flexible data sharing across users with continuous project monitoring. The development of ANSH platform will facilitate collaborative research and multi-site data sharing across the globe.

11.
J Alzheimers Dis ; 75(2): 397-402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32200359

RESUMO

Magnetic resonance spectroscopy (MRS) plays a substantial role in the non-invasive detection of brain neurochemicals, antioxidants, and neurotransmitters. Quantitative monitoring of these neurochemicals and neurotransmitters in the brain has a profound application for the understanding of brain disorders. Significant progress in the MR scanner as well as MR pulse sequence development to detect in vivo neurochemicals has been accomplished. The processing of MR signal from these low abundant neurochemicals/neurotransmitters should be very robust and sensitive in order to provide distinctive observations of disease-related neurochemical alterations and their absolute quantitation to aid in early clinical diagnosis. We highlight the diversity in currently available MRS processing tools, and recently introduced, KALPANA, a promising package integrating the end-to-end processing as well as robust quantitation of neurochemicals in a user-friendly approach through a graphical user interface. This further necessitates the futuristic need for advanced MRS processing pipeline and the respective readout that can help in early diagnosis and prognosis of diseases in the clinical environment.


Assuntos
Encefalopatias/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Processamento de Sinais Assistido por Computador , Diagnóstico Precoce , Humanos
12.
Magn Reson Imaging ; 70: 5-21, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31917995

RESUMO

Differences in brain morphology across population groups necessitate creation of population-specific Magnetic Resonance Imaging (MRI) brain templates for interpretation of neuroimaging data. Variations in the neuroanatomy in a genetically heterogeneous population make the development of a population-specific brain template for the Indian subcontinent imperative. A dataset of high-resolution 3D T1, T2-weighted, and FLAIR images acquired from a group of 113 volunteers (M/F - 56/57, mean age-28.96 ±â€¯7.80 years) are used to construct T1, T2-weighted, and FLAIR templates, collectively referred to as Indian Brain Template, "BRAHMA". A processing pipeline is developed and implemented in a MATLAB based toolbox for template construction and generation of tissue probability maps and segmentation atlases, with additional labels for deep brain regions such as the Substantia Nigra generated from the T2-weighted and FLAIR templates. The use of BRAHMA template for analysis of structural and functional neuroimaging data obtained from Indian participants, provides improved accuracy with statistically significant results over that obtained using the ICBM-152 (International Consortium for Brain Mapping) template. Our results indicate that segmentations generated on structural images are closer in volume to those obtained from registration to the BRAHMA template than to the ICBM-152. Furthermore, functional MRI data obtained for Working Memory and Finger Tapping paradigms processed using the BRAHMA template show a significantly higher percentage of the activation area than ICBM-152 in relevant brain regions, i.e. the left middle frontal gyrus, and the left and right precentral gyri, respectively. The availability of different image contrasts, tissue maps, and segmentation atlases makes the BRAHMA template a comprehensive tool for multi-modal image analysis in laboratory and clinical settings.


Assuntos
Mapeamento Encefálico , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Adulto , Algoritmos , Povo Asiático , Encéfalo/patologia , Meios de Contraste , Feminino , Humanos , Imageamento Tridimensional , Índia/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo , Probabilidade , Software , Substância Negra/diagnóstico por imagem , Adulto Jovem
13.
Hum Brain Mapp ; 41(1): 194-217, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31584232

RESUMO

Oxidative stress (OS) plays an important role in Alzheimer's disease (AD) and glutathione (GSH) mitigates this effect by maintaining redox-imbalance and free-radical neutralization. Quantified brain GSH concentration provides distinct information about OS among age-matched normal control (NC), mild cognitive impairment (MCI) and AD patients. We report alterations of in vivo GSH conformers, along with the choline, creatine, and N-acetylaspartate levels in the cingulate cortex (CC) containing anterior (ACC) and posterior (PCC) regions of 64 (27 NC, 19 MCI, and 18 AD) participants using MEscher-GArwood-Point-RESolved spectroscopy sequence. Result indicated, tissue corrected GSH depletion in PCC among MCI (p = .001) and AD (p = .028) and in ACC among MCI (p = .194) and AD (p = .025) as compared to NC. Effects of the group, region, and group × region on GSH with age and gender as covariates were analyzed using a generalized linear model with Bonferroni correction for multiple comparisons. A significant effect of group with GSH depletion in AD and MCI was observed as compared to NC. Receiver operator characteristic (ROC) analysis of GSH level in CC differentiated between MCI and NC groups with an accuracy of 82.8% and 73.5% between AD and NC groups. Multivariate ROC analysis for the combined effect of the GSH alteration in both ACC and PCC regions provided improved diagnostic accuracy of 86.6% for NC to MCI conversion and 76.4% for NC to AD conversion. We conclude that only closed GSH conformer depletion in the ACC and PCC regions is critical and constitute a potential biomarker for AD.


Assuntos
Doença de Alzheimer/metabolismo , Disfunção Cognitiva/metabolismo , Glutationa/metabolismo , Giro do Cíngulo/metabolismo , Espectroscopia de Ressonância Magnética , Estresse Oxidativo/fisiologia , Idoso , Doença de Alzheimer/diagnóstico por imagem , Biomarcadores/metabolismo , Disfunção Cognitiva/diagnóstico por imagem , Estudos Transversais , Feminino , Giro do Cíngulo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade
14.
J Alzheimers Dis ; 68(2): 531-535, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30776003

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting millions of people worldwide. The actual cause of AD is still unknown. Oxidative stress is believed to be important player in AD pathology. Glutathione (GSH) is a major antioxidant, and it is already known that GSH is depleted significantly in the hippocampal regions in mild cognitive impairment (MCI) and AD patients compared to healthy old subjects. Hence there is a serious discussion to improve the brain GSH level by supplementation. This editorial highlights the need for GSH supplementation for the cognitive enhancement in MCI and AD.


Assuntos
Doença de Alzheimer/metabolismo , Encéfalo/metabolismo , Disfunção Cognitiva/metabolismo , Suplementos Nutricionais , Glutationa/administração & dosagem , Glutationa/metabolismo , Doença de Alzheimer/dietoterapia , Disfunção Cognitiva/dietoterapia , Humanos , Estresse Oxidativo/fisiologia
15.
Front Neurol ; 10: 9, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30800093

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting millions of people worldwide. Progressive and relentless efforts are being made for therapeutic development by way of advancing understanding of non-invasive imaging modalities for the causal molecular process of AD. We present a Hadoop-based big data framework integrating non-invasive magnetic resonance imaging (MRI), MR spectroscopy (MRS) as well as neuropsychological test outcomes to identify early diagnostic biomarkers of AD. This big data framework for AD incorporates the three "V"s (volume, variety, velocity) with advanced data mining, machine learning, and statistical modeling algorithms. A large volume of longitudinal information from non-invasive imaging modalities with colligated parametric variety and speed for both data acquisition and processing as velocity complete the fundamental requirements of this big data framework for early AD diagnosis. Brain structural, neurochemical, and behavioral features are extracted from MRI, MRS, and neuropsychological scores, respectively. Subsequently, feature selection and ensemble-based classification are proposed and their outputs are fused based on the combination rule for final accurate classification and validation from clinicians. A multi-modality-based decision framework (BHARAT) for classification of early AD will be immensely helpful.

16.
J Alzheimers Dis ; 66(2): 517-532, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30198874

RESUMO

Molecular dynamics simulation and in vitro nuclear magnetic resonance (NMR) studies on glutathione (GSH) indicated existence of closed and extended conformations. The present work in a multi-center research setting reports in-depth analysis of GSH conformers in vivo using a common magnetic resonance spectroscopy (MRS) protocol and signal processing scheme. MEGA-PRESS pulse sequence was applied on healthy subjects using 3T Philips MRI scanner (India) and 3T GE MRI scanner (Norway) using the same experimental parameters (echo time, repetition time, and selective 180° refocusing ON-pulse at 4.40 ppm and 4.56 ppm). All MRS data were processed at one site National Brain Research Center (NBRC) using in-house MRS processing toolbox (KALPANA) for consistency. We have found that both the closed and extended GSH conformations are present in human brain and the relative proportion of individual conformer peak depends on the specific selection of refocusing ON-pulse position in MEGA-PRESS pulse sequence. It is important to emphasize that in vivo experiments with different refocusing and inversion pulse positions, echo time, and voxel size, clearly evidence the presence of both the GSH conformations. The GSH conformer peak positions for the closed GSH (Cys-Hß) peak at ∼2.80 ppm and extended GSH (Cys-Hß) peak at ∼2.95 ppm remain consistent irrespective of the selective refocusing OFF-pulse positions. This is the first in vivo study where both extended and closed GSH conformers are detected using the MEGA-PRESS sequence employing the parameters derived from the high resolution in vitro NMR studies on GSH.


Assuntos
Encéfalo/metabolismo , Glutationa/química , Glutationa/metabolismo , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Encéfalo/diagnóstico por imagem , Feminino , Voluntários Saudáveis , Humanos , Processamento de Imagem Assistida por Computador , Técnicas In Vitro , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Conformação Proteica , Trítio/metabolismo
18.
J Alzheimers Dis ; 63(3): 935-939, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29630555

RESUMO

Alzheimer's disease (AD) is a devastating neurodegenerative disorder affecting millions of people worldwide. Laboratory research and longitudinal clinical studies have helped to reveal various information about the disease but the exact causal process is not known yet. Patterns from alteration of neurochemicals (e.g., glutathione depletion, etc.), hippocampal atrophy, and brain effective connectivity loss as well as associated behavioral changes have generated important characteristic features. These imaging-based readouts and neuropsychological outcomes along with supervised clinical review are critical for developing a comprehensive artificial intelligence strategy for early predictive AD diagnosis and therapeutic development.


Assuntos
Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Encéfalo/metabolismo , Encéfalo/patologia , Deficiências da Aprendizagem/etiologia , Transtornos Mentais/etiologia , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
19.
J Oral Maxillofac Pathol ; 22(3): 442, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30651697

RESUMO

CONTEXT: Early detection of oral cancer is of paramount importance in determining the prognosis of oral cancer. Literature suggests that several diagnostic modalities have been proposed to aid a clinician in early detection of oral cancer without much conclusive evidence. AIMS: The present study aims to compare toluidine blue and chemiluminescence screening methods in early detection of carcinoma in North Indian population and also to evaluate these methods with histopathological diagnosis. METHODS: In this prospective study, 42 patients with clinically visible premalignant lesions were included. Demographic data were collected, and suspicious lesions were examined by chemiluminescence light (Vizilite) and followed by local application of toluidine blue (Mashberg's recommendation). Findings were recorded for each lesion under standard incandescent light as positive or negative. Biopsy and histopathological analysis of the tissues were performed. STATISTICAL ANALYSIS: Sensitivity, specificity and positive and negative predictive values for the chemiluminescence technique and toluidine blue were calculated for diagnostic tests. RESULTS AND CONCLUSIONS: In the present study, toluidine blue test was found to be moderately sensitive (63.33%) whereas chemiluminescence test (Vizilite) was found to be highly sensitive (90%); however, the test has limited specificity (50%). Thus, the study concluded that both toluidine blue and Vizilite can be used as an adjunct to simple, conventional visual examination and in screening procedure for oral potentially malignant disorders.

20.
J Alzheimers Dis ; 59(2): 537-541, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28527221

RESUMO

Glutathione (GSH) is a major antioxidant in humans that is involved in the detoxification of reactive radicals and peroxides. The molecular structural conformations of GSH depend on the surrounding micro-environment, and it has been experimentally evaluated using NMR and Raman spectroscopic techniques as well as by molecular dynamics simulation studies. The converging report indicates that GSH exists mainly in two major conformations, i.e., "extended" and "folded". The NMR-derived information on the GSH conformers is essential to obtain optimal acquisition parameters in in vivo MRS experiments targeted for GSH detection. To further investigate the implications of GSH conformers in in vivo MRS studies and their relative proportions in healthy and pathological conditions, a multi-center clinical research study is necessary with a common protocol for GSH detection and quantification.


Assuntos
Encéfalo/metabolismo , Glutationa/química , Espectroscopia de Ressonância Magnética , Animais , Humanos , Modelos Químicos , Conformação Proteica
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