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Motor and sensory deficits after spinal cord injury (SCI) result in functional reorganization of the sensorimotor network. While several task-evoked functional magnetic resonance imaging (fMRI) studies demonstrated functional alteration of the sensorimotor network in SCI, there has been no study of the possible alteration of resting-state functional connectivity using resting-state fMRI. The aim of this study was to investigate the changes of brain functional connectivity in the sensorimotor cortex of patients with SCI. We evaluated the functional connectivity scores between brain areas within the sensorimotor network in 18 patients with SCI and 18 controls. Our findings demonstrated that, compared with control subjects, patients with SCI showed increased functional connectivity between primary motor cortex and other motor areas, such as the supplementary motor area and basal ganglia. However, decreased functional connectivity between primary somatosensory cortex and secondary somatosensory cortex also was found in patients with SCI, compared with controls. These findings therefore demonstrated alteration of the resting-state sensorimotor network in patients with SCI, who showed increased connectivity between motor components, and decreased connectivity between sensory components, within the sensorimotor network, suggesting that motor components within the motor network increased in functional connectivity in order to compensate for motor deficits, whereas the sensory network did not show any such increases or compensation for sensory deficits.

Introduction It is well known that lead exposure induces neurotoxic effects, which can result in dysfunction in a variety of cognitive capacities including executive function. However, few studies have used fMRI to examine the direct neural correlates of executive function in participants with past lead exposure. Therefore, this study aimed to investigate possible alterations in the neural correlates of executive function in the previously lead-exposed brain. Methods Forty-three lead-exposed and 41 healthy participants were enrolled. During the fMRI scans, participants performed two modified versions of the Wisconsin Card Sorting Task (WCST) differing in cognitive demand, and a task that established a high-level baseline condition (HLB). Results The neural activation of left dorsolateral prefrontal cortex was greater in healthy controls than in participants with lead exposure when contrasting the difficult version of the WCST with the HLB. Moreover, cortical activation was found to be inversely associated with blood lead concentration after controlling for covariates. Discussion These data suggest that lead exposure can induce functional abnormalities in distributed cortical networks related to executive function, and that lead-induced neurotoxicity may be persistent rather than transient.

Surface coating of nanoparticles with ligands is essential in magnetic resonance imaging (MRI) because of solubility in water and biocompatibility. In this study, five organic molecules were used for surface coating of ultrasmall gadolinium-oxide (Gd2O3) nanoparticles (d avg = 2.0 nm). All of the samples showed large longitudinal (r1) and transverse (r2) water proton relaxivities with r2/r1 ratios that were close to one, corresponding to ideal conditions for T1 MRI contrast agents. Finally, in-vivo T1 MR images were acquired to prove the effectiveness of the surface-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent.

The water-soluble and biocompatible D-glucuronic acid coated Eu(OH)3 nanorods (average thickness x average length = 9.0 x 118.3 nm) have been prepared in one-pot synthesis. The D-glucuronic acid coated Eu(OH)3 nanorods showed a strong fluorescence at approximately 600 nm with a narrow emission band width. A cytotoxicity test by using DU145 cells showed that D-glucuronic acid coated Eu(OH)3 nanorods are not toxic up to 100 microM, making them a promising candidate for biomedical applications such as fluorescent imaging. The minimum Eu concentration needed for a conventional confocal imaging was estimated to be approximately 0.1 mM. Therefore, D-glucuronic acid coated Eu(OH)3 nanorods can be applied to fluorescent imaging. However, a very tiny magnetization of approximately 1.2 emu/g at room temperature and at an applied field of 5 tesla was observed. As a result, very small r1 and r2 water proton relaxivities were estimated, implying that surface coated Eu(OH)3 nanorods are not sufficient for MRI contrast agents.

A great deal of research has been devoted to identifying subclinical functional brain abnormalities in manganese (Mn)-exposed welders. However, no previous study has investigated morphological brain abnormalities, such as changes in brain volume, in welders. This study evaluates morphological changes in brain volume among welders, and investigates the relationship between structural brain abnormalities and subclinical dysfunction in this population.We used voxel-based morphometry (VBM) to assess differences in gray and white matter brain volumes between 40 welders with chronic Mn exposure and 26 age-matched control subjects. Correlation analyses were used to investigate the relationship between brain volume changes and decreased performance on neurobehavioral tests.Brain volumes in the globus pallidus and cerebellar regions were significantly diminished in welders with chronic Mn exposure compared to controls (FDR-corrected P0.05). These changes in brain volume were negatively correlated with cognitive performance and grooved pegboard scores.There are measurable brain volume reductions in the globus pallidus and cerebellum of welders chronically exposed to Mn, and these volume reductions correlate with cognitive and motor neurobehavioral deficits. Our findings therefore indicate that volumetric measurement could be a useful subclinical marker among welders that show no signs of manganism.

Repetitive transcranial magnetic stimulation (rTMS) of the primary motor cortex (M1) can modulate cortical excitability and is thought to influence activity in other brain areas. In this study, we investigated the anatomical and functional effects of rTMS of M1 and the time course of after-effects from a 1-Hz subthreshold rTMS to M1. Using an “offline” functional magnetic resonance imaging (fMRI)-rTMS paradigm, neural activation was mapped during simple finger movements after 1-Hz rTMS over the left M1 in a within-subjects repeated measurement design, including rTMS and sham stimulation. A significant decrease in the blood oxygen level dependent (BOLD) signal due to right hand motor activity during a simple finger-tapping task was observed in areas remote to the stimulated motor cortex after rTMS stimulation. This decrease in BOLD signal suggests that low frequency subthreshold rTMS may be sufficiently strong to elicit inhibitory modulation of remote brain regions. In addition, the time course patterns of BOLD activity showed this inhibitory modulation was maximal approximately 20 minutes after rTMS stimulation.

Gold-coated iron oxide (Fe3O4) nanoparticles were synthesized for use as a T2 contrast agent in magnetic resonance imaging (MRI). The coated nanoparticles were spherical in shape with an average diameter of 20 nm. The gold shell was about 2 nm thick. The bonding status of the gold on the nanoparticle surfaces was checked using a Fourier transform infrared spectrometer (FTIR). The FTIR spectra confirmed the attachment of homocysteine, in the form of thiolates, to the Au shell of the Au-Fe3O4 nanoparticles. The relaxivity ratio, R2/R1, for the coated nanoparticles was 3-fold higher than that of a commercial contrast agent, Resovist, which showed the potential for their use as a T2 contrast agent with high efficacy. In animal experiments, the presence of the nanoparticles in rat liver resulted in a 71% decrease in signal intensity in T2-weighted MR images, indicating that our gold-coated iron oxide nanoparticles are suitable for use as a T2 contrast agent in MRI.

Biomedical applications of magnetic nanoparticles (MNP), including superparamagnetic nanoparticles, have expanded dramatically in recent years. Systematic and standardized cytotoxicity assessment to ensure the biosafety and biocompatibility of those applications is compulsory. We investigated whether exposure to static magnetic field (SMF) from e.g. magnetic resonance imaging (MRI) could affect the cytotoxicity of superparamagnetic iron oxide (SPIO) nanoparticles using mouse hepatocytes and ferucarbotran, a liver-selective MRI contrast agent as a model system. We show that while the SPIO satisfied the conventional cytotoxicity assessment, clinical doses combined with SMF exposure exerts synergistic adverse effects such as reduced cell viability, apoptosis, and cell cycle aberrations on hepatocytes in vitro and in vivo. Concomitant treatments with the SPIO and SMF generated SPIO aggregates, which demonstrated enhanced cellular uptake, was sufficient to induce the cytotoxicity without further SMF, emphasizing that the SPIO aggregates were the predominant source of the cytotoxicity. Interestingly, the apoptotic effect was dependent on levels of reactive oxygen species (ROS) and SPIO uptake while the reduced cell viability was independent of these factors. Moreover, long-term monitoring showed a significant increase in multinuclear giant cells in the cells concomitantly treated with the SPIO and SMF compared with the control. The results demonstrate that the SPIO produces unidentified cytotoxicity on liver in the presence of SMF and the SPIO aggregates predominantly exert the effect. Since aggregation of MNP in biological milieu in the presence of strong SMF is inevitable, a fundamentally different approach to surface fabrication is essential to increase the biocompatibility of MNP.

BACKGROUND: It is well known that lead exposure induces neurotoxic effects, which can result in a variety of neurocognitive dysfunction. Especially, occupational lead exposures in adults are associated with decreases in cognitive performance including working memory. Despite recent advances in human neuroimaging techniques, the neural correlates of lead-exposed cognitive impairment remain unclear. Therefore, this study was aimed to compare the neural activations in relation to working memory function between the lead-exposed subjects and healthy controls. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-one lead-exposed subjects and 34 healthy subjects performed an n-back memory task during MRI scan. We performed fMRI using the 1-back and 2-back memory tasks differing in cognitive demand. Functional MRI data were analyzed using within- and between-group analysis. We found that the lead-exposed subjects showed poorer working memory performance during high memory loading task than the healthy subjects. In addition, between-group analyses revealed that the lead-exposed subjects showed reduced activation in the dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, pre supplementary motor areas, and inferior parietal cortex. CONCLUSIONS/SIGNIFICANCE: Our findings suggest that functional abnormalities in the frontoparietal working memory network might contribute to impairments in maintenance and manipulation of working memory in the lead-exposed subjects.

Background Urinary tract infections (UTIs) are the most common infectious complication in kidney transplant recipients (KTRs). The aim of this study to investigate the risk factors for and causative organisms of UTI as well as to evaluate the impact these diseases on allograft function in KTRs. Methods We analyzed patients who underwent kidney transplantation (KT) between January 2000 and December 2010. Among a total of 344 KTRs, 50 (14.5%) patients experienced 106 UTI episodes during a mean follow-up of 35.9 ± 26.0 months. Twenty three patients experiencing recurrent UTI were compared with 27 nonrecurrent UTI patients and with 50 non-UTI patients matched for age, gender, and transplantation date. Results The number of patients with renal calculi, diabetes, or prior dialysis was significantly greater among the UTI group compared with control subjects. In addition, the number of patients with renal calculi was significantly higher among the recurrent compared with the nonrecurrent cohort (43.5 vs 7.4%; P = .003). The most common causative organism was Escherichia coli (64.1%), followed by Enterococcus species (20.5%). Higher rates of antibiotic resistance, especially Extended Spectrum Beta-Lactamasc (ESBL) production, were observed among the recurrent compared with the nonrecurrent group (53.1 vs 0%; P = .013). The rate of decline of estimated glomerular filtration rate was significantly faster in the UTI than the non-UTI group, whereas it did not differ between the recurrent and nonrecurrent group. Conclusions Adequate treatment of an initial UTI to prevent as recurrent infection and prolong graft longevity is especially reasonable for KTRs with renal calculi or in cases of antibiotic-resistant microorganisms.

We report the synthesis, characterization and application of highly water-soluble fluorescein-polyethyleneimine (PEI) coated gadolinium oxide (Gd2O3) nanoparticles to magnetic resonance imaging (MRI) and cell labeling (CL). The average particle diameter and average hydrodynamic diameter were estimated to be 3.92 and 7.5 nm, respectively. Fluorescein-PEI was prepared from EDC/NHS coupling method. The surface coating was characterized by the FT-IR absorption spectrum and the surface coating amount was estimated to be 22.42 wt% from a TGA analysis, corresponding to 0.65 nm−2 grafting density. The fluorescein-PEI coated gadolinium oxide nanoparticles showed r1 and r2 of 6.76 and 20.27 s−1mM−1, respectively, and a strong fluorescence at ∼527 nm. A pronounced positive contrast enhancement was clearly observed in 3 tesla T1 MR images of a rat with a liver tumor after injection of an aqueous sample solution into a rat tail vein. After treatment of DU145 cells with a sample solution, a strong fluorescence in confocal images was also observed. These two results together confirm the excellent MRI-CL dual functionality of fluorescein-PEI coated gadolinium oxide nanoparticles.

Multiple molecular imaging is a challenging subject. Water-soluble and biocompatible lactobionic acid coated ultrasmall mixed gadolinium–europium oxide nanoparticles with an average particle diameter of 1.75 nm and an average hydrodynamic diameter of 4.16 nm were synthesized and applied for T1, T2 MRI-FI in vitro and in vivo. They had r1 and r2 values of 11.9 and 38.7 s−1 mM−1, respectively, and showed clear dose-dependent contrast changes in both R1 and R2 map images. In addition, they showed both positive and negative contrast enhancements in 3 tesla T1 and T2 MR images in a mouse, respectively, and fluorescent confocal images in both DU145 cells and C. elegans (a small nematode). This study demonstrates the T1, T2 MRI-FI multi-functionality of lactobionic acid coated mixed gadolinium–europium oxide nanoparticles.

Coprecipitated ferrite nanoparticles were coated with carbon using a hydrothermal method. From transmission electron microscope pictures, we could see that the coated iron oxide nanoparticles were spherical in shape with an average diameter of 90 nm. The strong bonding of carbon on the nanoparticle surfaces was checked by noting the C = O and C = C vibrations in Fourier transform infrared spectra. The spin-lattice relaxation process [T 1] and spin-spin relaxation process [T 2] relaxivities of hydrogen protons in the aqueous solution of coated nanoparticles were determined to be 1.139 (mM·s)-1 and 1.115 (mM·s)-1, respectively. These results showed that the carbon-coated iron oxide nanoparticles are applicable as both T 1 and T 2 contrast agents in magnetic resonance imaging. PACS: 81.05.y; 76.60.Es; 61.46; 75.50.k; 87.61.