Search

Nickel-substituted manganese spinel LiNi0.5Mn1.5O4 (LNMO) is a promising 5 V class positive electrode material for lithium-ion batteries. As micronsized LNMO particles show high rate capability in its two-phase coexistence regions, the phase transition mechanism is of great interest in understanding the electrode behavior at high rates. Here, the phase transition dynamics of LixNi0.5Mn1.5O4 is elucidated on high rate charging-discharging using operando time-resolved X-ray diffraction (TR-XRD). The TR-XRD results indicate the existence of intermediate states, in addition to the thermodynamically stable phases, and it is shown that the origin of such intermediate states is ascribed to the solid-solution domains at the phase transition front, as supported by the analysis using transmission electron microscopy coupled with electron energy-loss spectroscopy. The phase transition pathways dependent on the reaction rate are shown, together with possible explanation for this unique transition behavior. [ABSTRACT FROM AUTHOR]

The cytotoxicity of the monofunctional alkylator, temozolomide (TMZ), is known to be mediated by mismatch repair (MMR) triggered by O6-alkylguanine. By contrast, the cytotoxicity of bifunctional alkylators, including carmustine (BCNU) and melphalan (MEL), depends on interstrand crosslinks formed through O6-alkylguanine, which is repaired by nucleotide excision repair and recombination. O6-alkylguanine is removed by O6-methylguanine-DNA methyltransferase (MGMT). The aim of the present study was to evaluate the cytotoxicity of TMZ, BCNU and MEL in two different leukemic cell lines (HL-60 and MOLT-4) in the context of DNA repair. The transcript levels of MGMT, ERCC1, hMLH1 and hMSH2 were determined using reverse transcription-quantitative polymerase chain reaction. In addition, the proliferation was measured using the trypan blue exclusion assay. Drug sensitivity was found to vary between the two cell lines. Treatment of the cells with TMZ, BCNU or MEL in combination with O6-benzylguanine, an MGMT inhibitor, was demonstrated to sensitize the two cell lines to these agents. However, the extent of sensitization was not found to be correlated with the expression levels of MGMT transcripts. Furthermore, the drug sensitivity was also not associated with the transcript levels of ERCC1, hMLH1 and hMSH2. Thus, leukemic cells were sensitized to alkylating agents by the inhibition of MGMT. [ABSTRACT FROM AUTHOR]

A novel spectro-electochemical cell for X-ray absorption spectroscopy in the tender X-ray region (TX-XAS) was designed and fabricated to investigate the electrochemical behavior of common battery materials with liquid electrolytes under in situ/operando conditions. The cell has several unique features, such as high X-ray transmittance, high signal to noise ratio, and high vacuum tightness. These features enable us quick and reliable XAS measurements. Operando P K-edge XAS measurements of an olivine-type LiFePO4 composite positive electrode were carried out to clarify its phosphorus environment during the electrochemical charging process. Results of spectral analysis show that there is no significant change in the oxidation state of phosphorus and in the coordination of the phosphate anions in the charging process, but a closer look of the consecutive XAS spectra suggests the shrinkage of the PO4 cage during the charging process, and the structural changes in a biphasic manner. These results demonstrate the usefulness of the cell for in situ/operando TX-XAS observations of light elements in practical batteries. [ABSTRACT FROM AUTHOR]

Idiopathic normal pressure hydrocephalus (iNPH) is a condition resulting from impaired cerebrospinal fluid (CSF) absorption and excretion characterized by a triad of symptoms comprising dementia, gait disturbance (impaired trunk balance), and urinary incontinence. CSF biomarkers not only assist in diagnosis but are also important for analyzing the pathology and understanding appropriate treatment indications. As the neuropathological findings characteristic of iNPH have yet to be defined, there remains no method to diagnose iNPH with 100% sensitivity and specificity. Neurotoxic proteins are assumed to be involved in the neurological symptoms of iNPH, particularly the appearance of cognitive impairment. The symptoms of iNPH can be reversed by improving CSF turnover through shunting. However, early diagnosis is essential as once neurodegeneration has progressed, pathological changes become irreversible and symptom improvement is minimal, even after shunting. Combining a variety of diagnostic methods may lead to a more definitive diagnosis and accurate prediction of the prognosis following shunt treatment. Identifying comorbidities in iNPH using CSF biomarkers does not contraindicate shunting-based intervention, but does limit the improvement in symptoms it yields, and provides vital information for predicting post-treatment prognosis. [ABSTRACT FROM AUTHOR]

Medulloblastoma is a highly malignant brain tumor that predominately affects children and requires multimodal treatment, including chemotherapy with alkylating agents. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme that plays an important role in tumor resistance to alkylating agents. Recent studies demonstrated that MGMT promoter methylation suppresses the expression of MGMT and is associated with favorable outcomes of malignant glioma patients. However, the MGMT methylation status and its prognostic impact on medulloblastoma have not been fully elucidated to date. The objective of the present study was to investigate the association between MGMT status and clinical outcomes of pediatric medulloblastoma patients. The records of 15 patients with medulloblastoma treated at our institution were reviewed, and the methylation status of 18 CpG sites in the MGMT promoter region was determined using bisulfite sequencing analysis. A larger number of methylated CpG sites was identified in 9 patients with complete remission (median, 5 sites; range, 2-9 sites) compared with that in 6 patients with relapse (median, 2 sites, range, 1-4 sites; P=0.041). These results suggest that a higher number of methylated CpG sites in the MGMT promoter region are associated with a favorable outcome of medulloblastoma. [ABSTRACT FROM AUTHOR]

NR4A3/NOR1 belongs to the NR4A subfamily of the nuclear hormone receptor superfamily, which is activated in a ligandindependent manner. To examine the role of NR4A3 in gene expression of dendritic cells (DCs), we introduced NR4A3 small interfering RNA (siRNA) into bone marrow--derived DCs and determined the expression levels of mRNA and proteins of cytokines, cell surface molecules, NF-κB signaling--related proteins, and transcription factors. The expression level of NR4A3 was markedly upregulated by TLR-mediated stimulation in DCs. NR4A3 knockdown significantly suppressed LPS, CpG, or poly(I:C)-mediated upregulation of CD80, CD86, IL-10, IL-6, and IL-12. Proliferation and IL-2 production levels of T cells cocultured with NR4A3 knocked-down DCs were significantly lower than that of T cells cocultured with control DCs. Furthermore, the expression of IKKb, IRF4, and IRF8 was significantly decreased in NR4A3 siRNA-introduced bone marrow--derived DCs. The knockdown experiments using siRNAs for IKKβ, IRF4, and/or IRF8 indicated that LPS-induced upregulation of IL-10 and IL-6 was reduced in IKKβ knocked-down cells, and that the upregulation of IL-12 was suppressed by the knockdown of IRF4 and IRF8. Taken together, these results indicate that NR4A3 is involved in TLR-mediated activation and gene expression of DCs. [ABSTRACT FROM AUTHOR]

Background: In patients with craniosynostosis, intracranial pressure (ICP) has been reported to increase even in the absence of overt symptoms. The early and non-invasive detection of intracranial hypertension is important for reducing the risk of abnormal brain development in pediatric patients. Purpose: To assess whether the apparent diffusion coefficient (ADC) of white matter during the cardiac cycle (ΔADC) would change after surgery to relieve ICP in children with craniosynostosis. Material and Methods: This prospective study included ten patients diagnosed with craniosynostosis and four normal controls. All ten patients underwent magnetic resonance (MR) examinations before and after surgical treatment. Singleshot diffusion MR imaging (MRI) triggered by an electrocardiogram was performed, with regions of interest (ROIs) placed on frontal white matter and basal ganglia. Results: In all ten patients, ΔADC values after surgery were higher than those before surgery. This difference was statistically significant (Wilcoxon signed-rank test, P¼0.005). Conclusion: The change in ΔADC in the frontal white matter before and after surgery in patients with craniosynostosis indicates that it might reflect the change in ICP. Measurements of ΔADC could be a promising tool for non-invasive monitoring of ICP. [ABSTRACT FROM AUTHOR]

A unique charge/discharge mechanism of amorphous TiS4 is reported. Amorphous transition metal polysulfide electrodes exhibit anomalous charge/discharge performance and should have a unique charge/discharge mechanism: neither the typical intercalation/deintercalation mechanism nor the conversion-type one, but a mixture of the two. Analyzing the mechanism of such electrodes has been a challenge because fewer tools are available to examine the "amorphous" structure. It is revealed that the electrode undergoes two distinct structural changes: (i) the deformation and formation of S-S disulfide bonds and (ii) changes in the coordination number of titanium. These structural changes proceed continuously and concertedly for Li insertion/extraction. The results of this study provide a novel and unique model of amorphous electrode materials with significantly larger capacities. [ABSTRACT FROM AUTHOR]

LiFePO4 is a well-known electrode material that is capable of high-rate charging and discharging despite a strong phase-separation tendency of the lithium-rich and poor end-member phases. X-ray diffraction measurements (XRD) with high time-resolution are conducted under battery operation conditions to reveal the phase-transition mechanism of LiFePO4 that leads to the high rate capability. We here propose a hidden two-step phase transition of LiFePO4 via a metastable phase. The existence of the metastable phase, not just a member of a transient solid solution, is evidenced by the operando XRD measurements. Our two-step phase-transition model explains the behavior of LiFePO4 under the battery operation conditions. It also explains asymmetric behavior during the charging and discharging at high rates and low temperatures, as well as apparent single-step two-phase reaction between the end members at low rates at room temperature. This model also suggests underlying, rate-dependent electrochemical processes that result from a competing disproportion reaction of the metastable phase. [ABSTRACT FROM AUTHOR]

Background: Patients presenting with the classical idiopathic normal pressure hydrocephalus (iNPH) triad often show additional parkinsonian spectrum signs. Accurate differential diagnosis strongly influences the long-term outcome of cerebrospinal fluid (CSF) shunting.Objective: The aim of this study was to find potential CSF microRNA (miRNA) biomarkers for NPH mimics with parkinsonian syndromes that can reliably distinguish them from iNPH patients.Methods: Two cohorts of 81 patients (cohort 1, n = 55; cohort 2, n = 26) with possible iNPH who were treated in two centers between January 2011 and May 2014 were studied. In both cohorts, CSF samples were obtained from patients clinically diagnosed with iNPH (n = 21 and n = 10, respectively), possible iNPH with parkinsonian spectrum (PS) (n = 18, n = 10, respectively), possible iNPH with Alzheimer's disease (AD) (n = 16), and non-affected elderly individuals (NC) (n = 6). A three-step qRT-PCR analysis of the CSF samples was performed to detect miRNAs that were differentially expressed in the groups.Results: The expression of hsa-miR-4274 in CSF was decreased in both cohorts of PS group patients (cohort 1: p < 0.0001, cohort 2: p < 0.0001), and was able to distinguish PS from iNPH with high accuracy (area under the curve = 0.908). The CSF concentration of hsa-miR-4274 also correlated with the specific binding ratio of ioflupane (123I) dopamine transporter scan (r = -0.494, p = 0.044). By contrast, the level of hsa-miR-4274 was significantly increased in the PS group after CSF diversion.Conclusion: Levels of CSF hsa-miR-4274 can differentiate PS from patients with iNPH, AD, and NC. This may be clinically useful for diagnostic purposes and predicting shunt treatment responses. [ABSTRACT FROM AUTHOR]

Two transferrin (Tf) glycan-isoforms were previously found in cerebrospinal fluid (CSF); one appears to be derived from serum (Tf-2) and the other from choroid plexus, a CSF-producing tissue (Tf-1). To analyse metabolic differences associated with the two isoforms, their ratio (Tf-2/Tf-1) was defined as the Tf index. Here we report that Tf indices of patients with tauopathies including Alzheimer's disease (2.29 + 0.64) were similar to those of neurological controls (2.07 + 0.87) (P = 0.147). In contrast, Tf indices with Parkinson's disease (PD, 3.38 ± 1.87) and multiple system atrophy (MSA, 3.15 ± 1.72) were higher than those of the controls (2.07 ± 0.87), the P-values being 5 0.001 and 0.024, respectively. Tf indices of PD and MSA did not appear to be normally distributed. Indeed, detrended normal Quantile--Quantile plot analysis revealed the presence of an independent subgroup showing higher Tf indices in PD and MSA. The subgroup of PD showed higher levels of CSF α-synuclein (38.3 ± 17.8ng/ml) than the rest (25.3 ± 11.3ng/ml, P = 0.012). These results suggest that PD (and MSA) includes two subgroups, which show different metabolism of CSF transferrin and α-synuclein. [ABSTRACT FROM AUTHOR]

Li2MnO3, an electrode material for Li ion batteries, belongs to the C2/m space group and is known to have a cubic-close-packed (ABC...) layered structure, in which the transition-metal layer is supposed to have an ordered atomic arrangement with Li atoms at the 2b site and Mn atoms at the 4g site. However, recently, it has been reported that this compound usually does not exhibit such an ideal structure and instead contains a large number of structural defects, not only stacking faults but also mixing of Li and Mn atoms between the 2b and 4g sites. To elucidate the effect of such structural defects on the electrochemical behavior, we examined the crystal structure of Li2MnO3 synthesized at various temperatures by simultaneously analyzing the stacking faults and cation mixing using FAULTS, a Rietveld code. Our examination showed that the crystals consist of both disordered and ordered domains; the disordered domains contain a large number of stacking faults along the c axis and have considerable Li/Mn atomic mixing within the transition-metal layer, whereas the ordered domains have almost no defects. At low synthesis temperatures, the disordered domains are dominant. However, the ordered domains increase at the expense of the disordered domains above 770 °C and become dominant at higher temperatures. It is also found that the degree of cation mixing in the disordered domains remains almost constant irrespective of synthesis temperature. The crystalline defects such as stacking faults or Li/Mn cation mixing are expected to promote the formation of smooth Li percolation paths. The decreasing of the disordered domains leads to dramatically decreased capacity. This indicates that the observed capacities of Li2MnO3 can be determined by the relative amounts of the ordered/disordered domains in the structure. [ABSTRACT FROM AUTHOR]

Background and purpose We report the results of endosaccular coil embolization of asymptomatic unruptured intracranial aneurysms (UIAs) in elderly patients (≥65 years). Materials There were 375 elderly patients with 400 asymptomatic UIAs. Patients were divided into two groups: group A included patients aged 65-74 years and group B patients aged ≥75 years. Results Endovascular procedures were completed in 97.8% of patients. Immediate anatomical outcomes showed complete occlusion in 53.7%, residual neck in 18.9%, and residual aneurysm in 27.4%. Anatomical follow-ups (mean 36.3±28.1 months) were unchanged in 55.7%, improved in 22.6%, minor recurrence in 11.5%, and major recurrence in 10.2%. Procedure related complications occurred in 31 patients (8.3%). 15 patients had ischemic and 10 hemorrhagic complications. Retreatments were performed in 16 patients (4.3%). Among 366 patients technically completed, 363 (99.2%) showed a favorable clinical outcome (modified Rankin Scale (mRS) score <1) at 30 days. The remaining three patients showed a worsening of mRS >0 at 30 days. The latest clinical follow-up outcomes showed: mRS score 0 in 362 patients; mRS score 1 in one; mRS score 3 in one; mRS score 4 in one; and mRS score 5 in one patient. Permanent morbidity and mortality rates were 1.1% and 0%, respectively. There were no statistically significant differences in gender, comorbidities, aneurysm size, neck width, dome-to-neck ratio, immediate anatomical outcomes, anatomical follow-up outcomes, or procedure related complications between the groups. Conclusions Endosaccular coil embolization is safe and feasible for elderly patients with asymptomatic UIAs. Old age itself should not be a contraindication. [ABSTRACT FROM AUTHOR]

To improve the performance of rechargeable lithium-ion batteries, a microscopic understanding of the electrochemical reaction at the cathode is necessary. The spatial distribution of the electrode redox reaction for the LiFePO4 cathode was analyzed by X-ray absorption fine structure (XAFS) imaging. Chemical state maps of the planar cathode electrode obtained by the in situ XAFS imaging revealed the inhomogeneity of the chemical state of Fe during the charge/discharge process. The chemical state maps for the reverse charge/discharge process demonstrated the reversibility of the inhomogeneous distribution. The in-plane radial progress of the reaction distribution strongly suggests that the inhomogeneous electrode reaction is caused by the difference in electrical conductivity; the charging and discharging reactions proceed through reaction channels with low electrical resistance in the cathode. [ABSTRACT FROM AUTHOR]

Intracranial aneurysms are extremely rare in infants, and to our knowledge only seven infants treated for ruptured spontaneous dissecting aneurysms have been reported. Good outcomes have been achieved with endovascular treatment of infantile aneurysm. We the endovascular treatment of a one-month-old girl for ruptured dissecting aneurysm located in the anterior communicating artery, and the unique radiological changes that were observed during the perioperative and follow-up periods. These changes suggest that blood coagulation and fibrinolytic response play a part in the repair and healing processes of dissecting aneurysms. Careful neuroradiological surveys are needed for pediatric dissecting aneurysms treated endovascularly. [ABSTRACT FROM AUTHOR]

Adrenomedullin was originally isolated from pheochromocytoma cells and reduces insulin resistance by decreasing oxidative stress. White matter lesions induced by aging and hyperglycemia play a crucial role in cognitive impairment in poststroke patients. Here, we examine whether adrenomedullin deficiency and aging exacerbate ischemic white matter injury after prolonged cerebral hypoperfusion. Adrenomedullin heterozygous, wild-type young/aged mice were subjected to prolonged hypoperfusion. Prolonged cerebral hypoperfusion followed by immunohistochemical analysis was used to evaluate white matter injury. After prolonged hypoperfusion, whitematter damage progressed in a time-dependent manner in AM+/- group compared with the wild-type group. The number of oligodendrocyte progenitor cells gradually increased after prolonged hypoperfusion, whereas oligodendrocytes decreased following a transient increase, but the ratio of increase was mild in the AM+/- group (P < 0.05). Oxidative stress was detected in oligodendrocytes, with a larger increase in the AM+/- group (P < 0.05).Aged mice showed the same tendency, but white matter damage was worse, especially in the aged AM+/- group. Our results demonstrated that white matter injury was increased in adrenomedullin deficiency, which induced oxidative stress. White matter injury was more exacerbated because of hyperglycemia in aged AM+/- group. Adrenomedullin may be an important target in the control of ischemic white matter injury. [ABSTRACT FROM AUTHOR]

Background Internal carotid artery (ICA) bifurcation aneurysms are uncommon. Therefore, there have been only a few endovascular series on ICA bifurcation aneurysms published to date. The purpose of this study is to report the safety and efficacy of endovascular therapy for ICA bifurcation aneurysms. Methods There were 25 ICA bifurcation aneurysms (unruptured n=23, ruptured n=2) in 25 patients in this study. There were 14 women, with a mean age of 60.9±10.1 years. All patients underwent endosaccular coil embolization. Results Aneurysm size and neck size ranged from 2.5 to 10.0 mm (mean 5.4±1.5) and from 1.5 to 4.0 mm (mean 2.7±0.8), respectively. Regarding the clinical outcomes of the 23 patients with unruptured aneurysms, 22 patients had no change in their preprocedural modified Rankin Scale (mRS) score. The other patient died of ventilator associated aspiration pneumonia. Two patients with ruptured aneurysms each had scores of mRS 0. Overall morbidity and death rates were 0% and 4%, respectively. 15 aneurysms were treated with a simple technique. The 10 remaining aneurysms required adjunctive techniques: balloon assisted (n=9) and double catheter (n=1). The immediate anatomical outcomes were complete occlusion (n=19 (76.0%)), residual neck (n=4 (16.0%)) and residual aneurysm (n=2 (8.0%)). The overall follow-up of anatomical outcomes were unchanged (n=14 (63.7%)), improved (n=5 (22.7%)) and recurrence (n=3 (13.6%)). No patient suffered from aneurysmal subarachnoid hemorrhage after endovascular therapy. Thromboembolic events without clinical modification occurred in two patients. Conclusions Endovascular therapy of ICA bifurcation aneurysms is safe and effective, with a low risk of recanalization and re-treatment. [ABSTRACT FROM AUTHOR]

TiO2–B nanowires were prepared by hydrothermal reaction, and the nanosized effect on lithium-ion insertion was investigated by using X-ray absorption spectroscopy (XAS). On the basis of the results of O K-edge X-ray absorption near-edge structure (XANES) of TiO2–B with various particle sizes, it was suggested that the surface of TiO2–B has local and electronic structures being different from the bulk, and the band energy of surface of TiO2–B was lower than that of the bulk. The band vended structure, which is called the space charge layer (SCL), makes lithium-ion insertion in TiO2–B smooth because the local structure of the SCL is maintained during the lithium-ion insertion, which is shown by Ti K-edge extended X-ray absorption fine structure (EXAFS) spectroscopy. It is suggested that control of the SCL, that is the nanosized effect, is a new design concept for achieving higher rate capability. [ABSTRACT FROM AUTHOR]