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1.
J Infect Chemother ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38959995

RESUMEN

BACKGROUND: Vaccination is the primary method of preventing influenza infection and complications in young children. We evaluated the efficacy and safety of a single dose of MEDI3250 (intranasal, quadrivalent, live attenuated influenza vaccine) in healthy Japanese children during the 2016/17 influenza season. METHODS: In this multicenter, randomized, double-blind, phase 3 study (jRCT2080223345), participants aged 2-18 years received MEDI3250 or placebo (2:1), stratified by age (2-6 years, 7-18 years). The primary and secondary endpoints were the incidence of confirmed symptomatic onset of influenza caused by a circulating wild-type strain or by a vaccine-matched strain, respectively. Safety outcomes included the incidence of adverse events (AEs) and vaccine-related AEs. RESULTS: Overall, 910 participants received MEDI3250 (n = 608) or placebo (n = 302). For the primary endpoint (regardless of the influenza subtype), the incidence of influenza onset was 25.5 % (MEDI3250) and 35.9 % (placebo); relative risk reduction, 28.8 % (95 % confidence interval, 12.5 %-42.0 %). For the secondary endpoint (vaccine-matched strain), the incidence was 10.9 % (MEDI3250) and 17.2 % (placebo); relative risk reduction, 36.6 % (95 % confidence interval, 6.5 %-56.8 %). Solicited AEs occurred in 67.6 % (MEDI3250) and 63.6 % (placebo). Most events were mild; nasal discharge was most common (59.2 % [MEDI3250] and 52.6 % [placebo]). Unsolicited AEs occurred in 36.0 % (MEDI3250) and 33.1 % (placebo). The most common unsolicited vaccine-related AE was diarrhea (2.3 %, both groups). CONCLUSIONS: MEDI3250 had a greater preventive effect against influenza onset in Japanese children than placebo; no new safety signals were observed relative to previous clinical and post-marketing studies of MEDI3250.

2.
Neuroimage ; 281: 120377, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37714391

RESUMEN

The Human Connectome Project (HCP)-style surface-based brain MRI analysis is a powerful technique that allows precise mapping of the cerebral cortex. However, the strength of its surface-based analysis has not yet been tested in the older population that often presents with white matter hyperintensities (WMHs) on T2-weighted (T2w) MRI (hypointensities on T1w MRI). We investigated T1-weighted (T1w) and T2w structural MRI in 43 healthy middle-aged to old participants. Juxtacortical WMHs were often misclassified by the default HCP pipeline as parts of the gray matter in T1w MRI, leading to incorrect estimation of the cortical surfaces and cortical metrics. To revert the adverse effects of juxtacortical WMHs, we incorporated the Brain Intensity AbNormality Classification Algorithm into the HCP pipeline (proposed pipeline). Blinded radiologists performed stereological quality control (QC) and found a decrease in the estimation errors in the proposed pipeline. The superior performance of the proposed pipeline was confirmed using an originally-developed automated surface QC based on a large database. Here we showed the detrimental effects of juxtacortical WMHs for estimating cortical surfaces and related metrics and proposed a possible solution for this problem. The present knowledge and methodology should help researchers identify adequate cortical surface biomarkers for aging and age-related neuropsychiatric disorders.


Asunto(s)
Encefalopatías , Leucoaraiosis , Sustancia Blanca , Persona de Mediana Edad , Humanos , Sustancia Blanca/diagnóstico por imagen , Envejecimiento , Imagen por Resonancia Magnética/métodos , Corteza Cerebral/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen
3.
N Engl J Med ; 383(18): 1735-1745, 2020 10 29.
Artículo en Inglés | MEDLINE | ID: mdl-32865374

RESUMEN

BACKGROUND: Implementation of appropriate oral anticoagulant treatment for the prevention of stroke in very elderly patients with atrial fibrillation is challenging because of concerns regarding bleeding. METHODS: We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled, event-driven trial to compare a once-daily 15-mg dose of edoxaban with placebo in elderly Japanese patients (≥80 years of age) with nonvalvular atrial fibrillation who were not considered to be appropriate candidates for oral anticoagulant therapy at doses approved for stroke prevention. The primary efficacy end point was the composite of stroke or systemic embolism, and the primary safety end point was major bleeding according to the definition of the International Society on Thrombosis and Haemostasis. RESULTS: A total of 984 patients were randomly assigned in a 1:1 ratio to receive a daily dose of 15 mg of edoxaban (492 patients) or placebo (492 patients). A total of 681 patients completed the trial, and 303 discontinued (158 withdrew, 135 died, and 10 had other reasons); the numbers of patients who discontinued the trial were similar in the two groups. The annualized rate of stroke or systemic embolism was 2.3% in the edoxaban group and 6.7% in the placebo group (hazard ratio, 0.34; 95% confidence interval [CI], 0.19 to 0.61; P<0.001), and the annualized rate of major bleeding was 3.3% in the edoxaban group and 1.8% in the placebo group (hazard ratio, 1.87; 95% CI, 0.90 to 3.89; P = 0.09). There were substantially more events of gastrointestinal bleeding in the edoxaban group than in the placebo group. There was no substantial between-group difference in death from any cause (9.9% in the edoxaban group and 10.2% in the placebo group; hazard ratio, 0.97; 95% CI, 0.69 to 1.36). CONCLUSIONS: In very elderly Japanese patients with nonvalvular atrial fibrillation who were not appropriate candidates for standard doses of oral anticoagulants, a once-daily 15-mg dose of edoxaban was superior to placebo in preventing stroke or systemic embolism and did not result in a significantly higher incidence of major bleeding than placebo. (Funded by Daiichi Sankyo; ELDERCARE-AF ClinicalTrials.gov number, NCT02801669.).


Asunto(s)
Fibrilación Atrial/tratamiento farmacológico , Embolia/prevención & control , Inhibidores del Factor Xa/administración & dosificación , Piridinas/administración & dosificación , Accidente Cerebrovascular/prevención & control , Tiazoles/administración & dosificación , Anciano de 80 o más Años , Fibrilación Atrial/complicaciones , Fibrilación Atrial/mortalidad , Método Doble Ciego , Embolia/etiología , Inhibidores del Factor Xa/efectos adversos , Femenino , Estudios de Seguimiento , Hemorragia/inducido químicamente , Humanos , Incidencia , Masculino , Pacientes Desistentes del Tratamiento/estadística & datos numéricos , Piridinas/efectos adversos , Accidente Cerebrovascular/etiología , Tiazoles/efectos adversos
4.
Langmuir ; 39(16): 5911-5916, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37052535

RESUMEN

The controlled production of nanowindows in graphene layers is desirable for the development of ultrathin membranes. Herein, we propose a single-atom catalytic oxidation method for introducing nanowindows into the graphene layers of single-walled carbon nanotubes (SWCNTs). Using liquid-phase adsorption, copper(II) 2,3,9,10,16,17,23,24-octakis(octyloxy)-29H,31H-phthalocyanine (CuPc) was adsorbed on SWCNT bundles at a surface coverage of 0.9. Subsequently, narrow nanowindows with a number density of 0.13 nm-2 were produced by oxidation above 550 K, which is higher than the decomposition temperature of bulk CuPc. In particular, oxidation of the CuPc-adsorbed SWCNTs at 623 K increased the surface area from 280 to 1690 m2 g-1 owing to the efficient production of nanowindows. The nanowindow size was estimated to be similar to the molecular size of N2 based on the pronounced low-pressure adsorption hysteresis in the N2 adsorption isotherm. In addition, the enthalpy change for the nanowindow-formation equilibrium decreased by 4 kJ mol-1 when CuPc was present, further evidencing the catalytic effect of the Cu atoms supplied by the adsorbed CuPc molecules.

5.
Nature ; 548(7669): 592-596, 2017 08 30.
Artículo en Inglés | MEDLINE | ID: mdl-28858313

RESUMEN

Induced pluripotent stem cells (iPS cells) are a promising source for a cell-based therapy to treat Parkinson's disease (PD), in which midbrain dopaminergic neurons progressively degenerate. However, long-term analysis of human iPS cell-derived dopaminergic neurons in primate PD models has never been performed to our knowledge. Here we show that human iPS cell-derived dopaminergic progenitor cells survived and functioned as midbrain dopaminergic neurons in a primate model of PD (Macaca fascicularis) treated with the neurotoxin MPTP. Score-based and video-recording analyses revealed an increase in spontaneous movement of the monkeys after transplantation. Histological studies showed that the mature dopaminergic neurons extended dense neurites into the host striatum; this effect was consistent regardless of whether the cells were derived from patients with PD or from healthy individuals. Cells sorted by the floor plate marker CORIN did not form any tumours in the brains for at least two years. Finally, magnetic resonance imaging and positron emission tomography were used to monitor the survival, expansion and function of the grafted cells as well as the immune response in the host brain. Thus, this preclinical study using a primate model indicates that human iPS cell-derived dopaminergic progenitors are clinically applicable for the treatment of patients with PD.


Asunto(s)
Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/citología , Neuronas Dopaminérgicas/trasplante , Células Madre Pluripotentes Inducidas/citología , Enfermedad de Parkinson/patología , Enfermedad de Parkinson/terapia , Medicina Regenerativa/métodos , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina , Adulto , Anciano , Anciano de 80 o más Años , Animales , Proliferación Celular , Supervivencia Celular , Neuronas Dopaminérgicas/inmunología , Humanos , Macaca fascicularis , Imagen por Resonancia Magnética , Masculino , Mesencéfalo/citología , Movimiento , Neostriado/citología , Neuritas , Enfermedad de Parkinson/etiología , Enfermedad de Parkinson/fisiopatología , Tomografía de Emisión de Positrones , Serina Endopeptidasas/análisis , Serina Endopeptidasas/metabolismo
6.
Neuroimage ; 258: 119360, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35697132

RESUMEN

T1-weighted divided by T2-weighted (T1w/T2w) myelin maps were initially developed for neuroanatomical analyses such as identifying cortical areas, but they are increasingly used in statistical comparisons across individuals and groups with other variables of interest. Existing T1w/T2w myelin maps contain radiofrequency transmit field (B1+) biases, which may be correlated with these variables of interest, leading to potentially spurious results. Here we propose two empirical methods for correcting these transmit field biases using either explicit measures of the transmit field or alternatively a 'pseudo-transmit' approach that is highly correlated with the transmit field at 3T. We find that the resulting corrected T1w/T2w myelin maps are both better neuroanatomical measures (e.g., for use in cross-species comparisons), and more appropriate for statistical comparisons of relative T1w/T2w differences across individuals and groups (e.g., sex, age, or body-mass-index) within a consistently acquired study at 3T. We recommend that investigators who use the T1w/T2w approach for mapping cortical myelin use these B1+ transmit field corrected myelin maps going forward.


Asunto(s)
Imagen por Resonancia Magnética , Vaina de Mielina , Sesgo , Humanos , Imagen por Resonancia Magnética/métodos
7.
Neuroimage ; 250: 118965, 2022 04 15.
Artículo en Inglés | MEDLINE | ID: mdl-35122965

RESUMEN

Localising accurate brain regions needs careful evaluation in each experimental species due to their individual variability. However, the function and connectivity of brain areas is commonly studied using a single-subject cranial landmark-based stereotactic atlas in animal neuroscience. Here, we address this issue in a small primate, the common marmoset, which is increasingly widely used in systems neuroscience. We developed a non-invasive multi-modal neuroimaging-based targeting pipeline, which accounts for intersubject anatomical variability in cranial and cortical landmarks in marmosets. This methodology allowed creation of multi-modal templates (MarmosetRIKEN20) including head CT and brain MR images, embedded in coordinate systems of anterior and posterior commissures (AC-PC) and CIFTI grayordinates. We found that the horizontal plane of the stereotactic coordinate was significantly rotated in pitch relative to the AC-PC coordinate system (10 degrees, frontal downwards), and had a significant bias and uncertainty due to positioning procedures. We also found that many common cranial and brain landmarks (e.g., bregma, intraparietal sulcus) vary in location across subjects and are substantial relative to average marmoset cortical area dimensions. Combining the neuroimaging-based targeting pipeline with robot-guided surgery enabled proof-of-concept targeting of deep brain structures with an accuracy of 0.2 mm. Altogether, our findings demonstrate substantial intersubject variability in marmoset brain and cranial landmarks, implying that subject-specific neuroimaging-based localization is needed for precision targeting in marmosets. The population-based templates and atlases in grayordinates, created for the first time in marmoset monkeys, should help bridging between macroscale and microscale analyses.


Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/anatomía & histología , Callithrix/anatomía & histología , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodos , Puntos Anatómicos de Referencia , Animales , Encéfalo/cirugía , Callithrix/cirugía , Diseño de Equipo , Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética/instrumentación , Reproducibilidad de los Resultados , Cirugía Asistida por Computador , Tomografía Computarizada por Rayos X/instrumentación
8.
Am Heart J ; 250: 66-75, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35568194

RESUMEN

BACKGROUND: B-type natriuretic peptide (BNP) is a risk factor for stroke and cardiac death in patients with atrial fibrillation. We hypothesized the prognostic outcomes of very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment would vary according to BNP stratification. METHODS: In this subanalysis of the ELDERCARE-AF trial, patients were stratified by BNP levels at enrollment, and clinical outcomes compared among BNP subgroups. Hazard ratios were adjusted for age, atrial fibrillation type, body mass index, creatine clearance, congestive heart failure, and D-dimer. BNP levels were measured using chemiluminescence enzyme immunoassays. RESULTS: In total, 984 patients (average age: 86.6 years) not considered eligible for oral anticoagulant therapy at approved doses for stroke prevention were included. The BNP levels at enrollment were <200 (low), 200 to <400 (moderate), and ≥400 (high) pg/mL in 428, 300, and 256 patients, respectively. The number (%) of patients with stroke or systemic embolism (SSE) was 7 (1.2%), 24 (5.9%), and 28 (8.6%) in the low, moderate, and high BNP subgroups, respectively (adjusted hazard ratio 3.82, P = .0025 for low vs moderate BNP and 4.76, P = .0007 for low vs high BNP). There was no significant difference in major bleeding incidence between the BNP subgroups. Edoxaban 15 mg was associated with a consistent reduction in SSE vs placebo in all BNP subgroups. CONCLUSIONS: Stratification by BNP level was associated with the incidence of SSE for very elderly non-valvular atrial fibrillation patients ineligible for standard anticoagulation treatment, and the effect of edoxaban 15 mg was consistent across BNP levels.


Asunto(s)
Fibrilación Atrial , Embolia , Accidente Cerebrovascular , Anciano , Anciano de 80 o más Años , Anticoagulantes/uso terapéutico , Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Embolia/prevención & control , Humanos , Péptido Natriurético Encefálico , Pronóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/prevención & control
9.
Langmuir ; 38(50): 15880-15886, 2022 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-36469405

RESUMEN

Nanoscale pores in graphene oxide (GO) control various important functions. The nanoporosity of GO is sensitive to low-temperature heating. Therefore, it is important to carefully process GO and GO-based materials to achieve superior functions. Optimum pretreatment conditions, such as the pre-evacuation temperature and time, are important during gas adsorption in GO to obtain accurate pore structure information. This study demonstrated that the pre-evacuation temperature and time for gas adsorption in GO must be approximately 333-353 K and 4 h, respectively, to avoid the irreversible alteration of nanoporosity. In situ temperature-dependent Fourier-transform infrared spectra and thermogravimetric analysis-mass spectrometry suggested significant structural changes in GO above the pre-evacuation temperature (353 K) through the desorption of "physically adsorbed water" and decomposition of unstable surface functional groups. The nanoporosity of GO significantly changed above the aforementioned pre-evacuation temperature and time. Thus, standard pretreatment is indispensable for understanding the intrinsic interface properties of GO.

10.
Proc Natl Acad Sci U S A ; 116(52): 26173-26180, 2019 Dec 26.
Artículo en Inglés | MEDLINE | ID: mdl-31871175

RESUMEN

Advances in neuroimaging and neuroanatomy have yielded major insights concerning fundamental principles of cortical organization and evolution, thus speaking to how well different species serve as models for human brain function in health and disease. Here, we focus on cortical folding, parcellation, and connectivity in mice, marmosets, macaques, and humans. Cortical folding patterns vary dramatically across species, and individual variability in cortical folding increases with cortical surface area. Such issues are best analyzed using surface-based approaches that respect the topology of the cortical sheet. Many aspects of cortical organization can be revealed using 1 type of information (modality) at a time, such as maps of cortical myelin content. However, accurate delineation of the entire mosaic of cortical areas requires a multimodal approach using information about function, architecture, connectivity, and topographic organization. Comparisons across the 4 aforementioned species reveal dramatic differences in the total number and arrangement of cortical areas, particularly between rodents and primates. Hemispheric variability and bilateral asymmetry are most pronounced in humans, which we evaluated using a high-quality multimodal parcellation of hundreds of individuals. Asymmetries include modest differences in areal size but not in areal identity. Analyses of cortical connectivity using anatomical tracers reveal highly distributed connectivity and a wide range of connection weights in monkeys and mice; indirect measures using functional MRI suggest a similar pattern in humans. Altogether, a multifaceted but integrated approach to exploring cortical organization in primate and nonprimate species provides complementary advantages and perspectives.

11.
Neuroimage ; 245: 118693, 2021 12 15.
Artículo en Inglés | MEDLINE | ID: mdl-34732327

RESUMEN

Social interaction is thought to provide a selection pressure for human intelligence, yet little is known about its neurobiological basis and evolution throughout the primate lineage. Recent advances in neuroimaging have enabled whole brain investigation of brain structure, function, and connectivity in humans and non-human primates (NHPs), leading to a nascent field of comparative connectomics. However, linking social behavior to brain organization across the primates remains challenging. Here, we review the current understanding of the macroscale neural mechanisms of social behaviors from the viewpoint of system neuroscience. We first demonstrate an association between the number of cortical neurons and the size of social groups across primates, suggesting a link between neural information-processing capacity and social capabilities. Moreover, by capitalizing on recent advances in species-harmonized functional MRI, we demonstrate that portions of the mirror neuron system and default-mode networks, which are thought to be important for representation of the other's actions and sense of self, respectively, exhibit similarities in functional organization in macaque monkeys and humans, suggesting possible homologies. With respect to these two networks, we describe recent developments in the neurobiology of social perception, joint attention, personality and social complexity. Together, the Human Connectome Project (HCP)-style comparative neuroimaging, hyperscanning, behavioral, and other multi-modal investigations are expected to yield important insights into the evolutionary foundations of human social behavior.


Asunto(s)
Conectoma/métodos , Neuroimagen/métodos , Conducta Social , Animales , Imagen por Resonancia Magnética , Primates
12.
Neuroimage ; 229: 117726, 2021 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-33484849

RESUMEN

Multi-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, 'ground truth' validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how "functional connectivity" from fMRI and "tractographic connectivity" from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior.


Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador/métodos , Internacionalidad , Neuroanatomía/métodos , Neuroimagen/métodos , Animales , Callithrix , Conectoma/métodos , Conectoma/tendencias , Humanos , Procesamiento de Imagen Asistido por Computador/tendencias , Macaca mulatta , Neuroanatomía/tendencias , Neuroimagen/tendencias , Primates , Especificidad de la Especie
13.
Neuroimage ; 236: 118082, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-33882349

RESUMEN

Recent methodological advances in MRI have enabled substantial growth in neuroimaging studies of non-human primates (NHPs), while open data-sharing through the PRIME-DE initiative has increased the availability of NHP MRI data and the need for robust multi-subject multi-center analyses. Streamlined acquisition and analysis protocols would accelerate and improve these efforts. However, consensus on minimal standards for data acquisition protocols and analysis pipelines for NHP imaging remains to be established, particularly for multi-center studies. Here, we draw parallels between NHP and human neuroimaging and provide minimal guidelines for harmonizing and standardizing data acquisition. We advocate robust translation of widely used open-access toolkits that are well established for analyzing human data. We also encourage the use of validated, automated pre-processing tools for analyzing NHP data sets. These guidelines aim to refine methodological and analytical strategies for small and large-scale NHP neuroimaging data. This will improve reproducibility of results, and accelerate the convergence between NHP and human neuroimaging strategies which will ultimately benefit fundamental and translational brain science.


Asunto(s)
Encéfalo , Imagen por Resonancia Magnética/normas , Neuroimagen/normas , Animales , Encéfalo/anatomía & histología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiología , Imagen Eco-Planar/métodos , Imagen Eco-Planar/normas , Neuroimagen Funcional/métodos , Neuroimagen Funcional/normas , Macaca mulatta , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Reproducibilidad de los Resultados
14.
J Chem Phys ; 154(4): 044503, 2021 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-33514077

RESUMEN

We estimated the residual entropy of Ice Ih by the recently developed simulation protocol, namely, the combination of the replica-exchange Wang-Landau algorithm and multicanonical replica-exchange method. We employed a model with the nearest neighbor interactions on the three-dimensional hexagonal lattice, which satisfied the ice rules in the ground state. The results showed that our estimate of the residual entropy is in accordance with various previous results. In this article, we not only give our latest estimate of the residual entropy of Ice Ih but also discuss the importance of the uniformity of a random number generator in Monte Carlo simulations.

15.
J Neurosci ; 39(43): 8484-8496, 2019 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-31582526

RESUMEN

Neuromotor systems have the capacity for functional recovery following local damage. The literature suggests a possible role for the premotor cortex and cerebellum in motor recovery. However, the specific changes to interactions between these areas following damage remain unclear. Here, we demonstrate potential rewiring of connections from the ipsilesional ventral premotor cortex (ip-PMv) to cerebellar structures in a nonhuman primate model of primary motor cortex (M1) lesion and motor recovery. Cerebellar connections arising from the ip-PMv were investigated by comparing biotinylated dextran amine (BDA) between two groups of male Macaca mulatta: M1-lesion/motor recovery group and intact group. There were more BDA-labeled boutons and axons in all ipsilesional deep cerebellar nuclei (fastigial, interposed, and dentate) in the M1-lesion/recovery group than in the intact group. The difference was evident in the ipsilesional fastigial nucleus (ip-FN), and particularly observed in its middle, a putative somatosensory region of the ip-FN, which was characterized by absent or little expression of aldolase C. Some of the altered projections from the ip-PMv to ip-FN neurons were confirmed as functional because the synaptic markers, synaptophysin and vesicular glutamate transporter 1, were colocalized with BDA-labeled boutons. These results suggest that the adult primate brain after motor lesions can reorganize large-scale networks to enable motor recovery by enhancing sensorimotor coupling and motor commands via rewired fronto-cerebellar connections.SIGNIFICANCE STATEMENT Damaging the motor cortex causes motor deficits, which can be recovered over time. Such motor recovery may result from functional compensation in remaining neuromotor areas, including the ventral premotor cortex. We investigated compensatory changes in neural axonal outputs from ventral premotor to deep cerebellar nuclei in a monkey model of primary motor cortical lesion and motor recovery. The results showed an increase in premotor projections and synaptic formations in deep cerebellar nuclei, especially the sensorimotor region of the fastigial nucleus. Our results provide the first evidence that large-scale reorganization of fronto-cerebellar circuits may underlie functional recovery after motor cortical lesions.


Asunto(s)
Cerebelo/fisiopatología , Ácido Iboténico/toxicidad , Corteza Motora/fisiopatología , Red Nerviosa/fisiopatología , Plasticidad Neuronal/fisiología , Recuperación de la Función/fisiología , Animales , Cerebelo/efectos de los fármacos , Macaca mulatta , Corteza Motora/efectos de los fármacos , Red Nerviosa/efectos de los fármacos
16.
Neuroimage ; 215: 116800, 2020 07 15.
Artículo en Inglés | MEDLINE | ID: mdl-32276072

RESUMEN

Macaque monkeys are an important animal model where invasive investigations can lead to a better understanding of the cortical organization of primates including humans. However, the tools and methods for noninvasive image acquisition (e.g. MRI RF coils and pulse sequence protocols) and image data preprocessing have lagged behind those developed for humans. To resolve the structural and functional characteristics of the smaller macaque brain, high spatial, temporal, and angular resolutions combined with high signal-to-noise ratio are required to ensure good image quality. To address these challenges, we developed a macaque 24-channel receive coil for 3-T MRI with parallel imaging capabilities. This coil enables adaptation of the Human Connectome Project (HCP) image acquisition protocols to the in-vivo macaque brain. In addition, we adapted HCP preprocessing methods to the macaque brain, including spatial minimal preprocessing of structural, functional MRI (fMRI), and diffusion MRI (dMRI). The coil provides the necessary high signal-to-noise ratio and high efficiency in data acquisition, allowing four- and five-fold accelerations for dMRI and fMRI. Automated FreeSurfer segmentation of cortex, reconstruction of cortical surface, removal of artefacts and nuisance signals in fMRI, and distortion correction of dMRI all performed well, and the overall quality of basic neurobiological measures was comparable with those for the HCP. Analyses of functional connectivity in fMRI revealed high sensitivity as compared with those from publicly shared datasets. Tractography-based connectivity estimates correlated with tracer connectivity similarly to that achieved using ex-vivo dMRI. The resulting HCP-style in vivo macaque MRI data show considerable promise for analyzing cortical architecture and functional and structural connectivity using advanced methods that have previously only been available in studies of the human brain.


Asunto(s)
Encéfalo/anatomía & histología , Encéfalo/fisiología , Conectoma/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Animales , Encéfalo/diagnóstico por imagen , Macaca fascicularis , Macaca fuscata , Macaca mulatta , Vías Nerviosas/anatomía & histología , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiología
17.
Nanotechnology ; 31(7): 075704, 2020 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-31645029

RESUMEN

Unique properties and potential applications of 2D materials draw much attention for mass production of thin-layer 2D materials. Ball milling exfoliation of 2D materials has been rarely used, in spite of a promising dry phase production method, because of the superficial information in the mechanism and the effect of the operating parameters on the yield, size and thickness. Here, we investigate systematically the ball milling operating parameters in the exfoliation of bulk MoS2 in the presence of sodium cholate (SC) as an exfoliant. The yield and dimensions of the exfoliated MoS2 nanosheet were monitored by changing the parameters such as the weight ratio of bulk MoS2 and SC (SC/MoS2), the filling ratio in the volume of milling ball and container (φ), milling ball size (d B), milling revolution speed (n R ), and initial mass of bulk MoS2 ([Formula: see text]). The yield of exfoliation is found to be 95% at the optimum ball milling conditions (SC/MoS2 = 0.75, φ = 50%, [Formula: see text] = 0.20 g). In addition, yield and size of the exfoliated MoS2 were controlled by the conditions of the ball milling. As for the evaluation of the exfoliated MoS2, we developed a novel method by use of the XRD profile to determine the size and thickness of the ball-milled MoS2 powder with less than 30% difference from those determined by the well-known absorption method. Finally, the size and thickness of the MoS2 nanosheets prepared by ball milling exfoliation were correlated with their electrocatalytic and photoelectrocatalytic activities.

18.
Neuroradiology ; 62(4): 483-494, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31883043

RESUMEN

PURPOSE: The reproducibility of neurite orientation dispersion and density imaging (NODDI) metrics in the human brain has not been explored across different magnetic resonance (MR) scanners from different vendors. This study aimed to evaluate the scan-rescan and inter-vendor reproducibility of NODDI metrics in white and gray matter of healthy subjects using two 3-T MR scanners from two vendors. METHODS: Ten healthy subjects (7 males; mean age 30 ± 7 years, range 23-37 years) were included in the study. Whole-brain diffusion-weighted imaging was performed with b-values of 1000 and 2000 s/mm2 using two 3-T MR scanners from two different vendors. Automatic extraction of the region of interest was performed to obtain NODDI metrics for whole and localized areas of white and gray matter. The coefficient of variation (CoV) and intraclass correlation coefficient (ICC) were calculated to assess the scan-rescan and inter-vendor reproducibilities of NODDI metrics. RESULTS: The scan-rescan and inter-vendor reproducibility of NODDI metrics (intracellular volume fraction and orientation dispersion index) were comparable with those of diffusion tensor imaging (DTI) metrics. However, the inter-vendor reproducibilities of NODDI (CoV = 2.3-14%) were lower than the scan-rescan reproducibility (CoV: scanner A = 0.8-3.8%; scanner B = 0.8-2.6%). Compared with the finding of DTI metrics, the reproducibility of NODDI metrics was lower in white matter and higher in gray matter. CONCLUSION: The lower inter-vendor reproducibility of NODDI in some brain regions indicates that data acquired from different MRI scanners should be carefully interpreted.


Asunto(s)
Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética , Neuritas , Adulto , Femenino , Humanos , Masculino , Valores de Referencia , Reproducibilidad de los Resultados , Adulto Joven
19.
J UOEH ; 42(4): 339-346, 2020.
Artículo en Japonés | MEDLINE | ID: mdl-33268612

RESUMEN

The results of a survey of radiation workers suggest that they are worried about the effects of radiation exposure on health, and approximately 30% of Fukushima Daiichi Nuclear Power Plant (FDNPP) workers have anxiety. This questionnaire survey reveals that the higher the frequency of radiation education, the higher the knowledge of radiation the workers will have, and that the higher the level of knowledge, the lower the anxiety. To reduce anxiety, it is important to increase knowledge about radiation through radiation education. However, even those workers who had radiation education several times still had anxiety. According to the Ordinance on the Prevention of Ionizing Radiation Hazards, the time spent on education about the effects of radiation on the human body is only about 30 minutes. This education is not enough to reduce anxiety. FDNPP workers needed more effective education to increase their knowledge and to reduce their anxiety.


Asunto(s)
Ansiedad , Accidente Nuclear de Fukushima , Educación en Salud , Conocimiento , Plantas de Energía Nuclear , Salud Laboral , Exposición a la Radiación/efectos adversos , Exposición a la Radiación/prevención & control , Encuestas y Cuestionarios , Lugar de Trabajo/psicología , Adolescente , Adulto , Factores de Edad , Anciano , Ansiedad/prevención & control , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Factores de Tiempo , Adulto Joven
20.
Bipolar Disord ; 21(6): 539-546, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30430712

RESUMEN

OBJECTIVES: Five affective temperaments are regarded as potential precursors of bipolar disorder. These are depressive, cyclothymic, hyperthymic, irritable, and anxious temperaments. However, the neural substrates underlying these temperaments have not been identified. The aim of this study was to determine whether these temperaments are associated with specific neural substrates related to the brain white matter integrity in healthy participants. METHODS: We conducted a cross-sectional neuroimaging study of 71 healthy participants (38 males and 33 females) with affective temperaments. All participants screened for past and present psychiatric disorders. The scores of the five affective temperaments were measured by the temperament scale of Memphis, Pisa, Paris, and San Diego-autoquestionnaire. We analyzed the association between the fractional anisotropy (FA) and mean diffusivity (MD) of the brain white matter and these affective temperaments using tract-based spatial statistics (TBSS). RESULTS: The cyclothymic temperament score had a significant positive association with the FA and a significant negative association with the MD in the white matter in the right frontal part of brain. The hyperthymic temperament score was negatively associated with the MD in a wide area of the brain white matter. The anxious temperament score was positively associated with the FA in the bilateral frontal, temporal, and parietal regions of the brain white matter. The depressive and irritable temperament scores were not associated with either the FA or the MD. CONCLUSION: The present findings suggest that cyclothymic, hyperthymic, and anxious temperaments are associated with brain white matter integrity in healthy participants.


Asunto(s)
Temperamento/fisiología , Sustancia Blanca/anatomía & histología , Sustancia Blanca/diagnóstico por imagen , Adulto , Ansiedad/psicología , Trastorno Bipolar/psicología , Encéfalo , Estudios Transversales , Femenino , Voluntarios Sanos , Humanos , Genio Irritable , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios
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