Low-Frequency Spectra of Hydrated Ionic Liquids with Kosmotropic and Chaotropic Anions.

In this study, we investigated the water concentration dependence of the intermolecular vibrations of two hydrated ionic liquids (ILs), cholinium dihydrogen phosphate ([ch][dhp]) and cholinium bromide ([ch]Br), using femtosecond Raman-induced Kerr effect spectroscopy (fs-RIKES). The anions of the former and latter hydrated ILs are kosmotropic and chaotropic, respectively. We found that the spectral peak of ∼50 cm-1 shifted to the low-frequency side in hydrated [ch][dhp], indicating the weakening of its intermolecular interactions. In contrast, no change in the peak frequency of the low-frequency band at ∼50 cm-1 was observed with increasing water concentration in hydrated [ch]Br. The vibrational density of states (VDOS) spectra generated from molecular dynamics (MD) simulations were in qualitative agreement with the experimental results. Decomposition analysis of the VDOS spectra for each component revealed that the red shift of the low-frequency band in the hydrated [ch][dhp] upon water addition was essentially due to the contributions of anions and water rather than that of the cholinium cation. We also found from the low-frequency spectra of the two hydrated ILs that they differed in the concentration dependence of the 180 cm-1 band, which is assigned as a hindered translational motion of water molecules combined to form O···O stretching motions. From the relationship between the peak frequency of the low-frequency band and the bulk parameter, which is the square root of the surface tension divided by the density, we found that the peak frequency in the hydrated IL with kosmotropic [dhp]- depends on the bulk parameter, similar to the case for an aqueous solution of the typical deep eutectic solvent reline. However, the peak frequency of the hydrated IL with chaotropic Br- is constant with the bulk parameter.

Hydrated Ionic Liquids: Perspective for Bioscience.

Hydrated ionic liquid (IL) is a simple mixture of IL and water. Unique aqueous electrolyte solution can be designed by mixing IL with limited amount of water. In most hydrated ILs, there are no free water and all are strongly interacted with ions. The properties of hydrated ILs, such as polarity, viscosity, ion mobility, and hydrogen bonding ability, can therefore be controlled simply by water content. This mixture is expected to provide similar environment to that of living cell, and is desired to be effective solvents for biomolecules. In this account, we would like to survey the basic properties, recent results, and future aspects of the hydrated ILs.

Investigation of Hydration States of Ionic Liquids by Fourier Transform Infrared Absorption Spectroscopy: Relevance to Stabilization of Protein Molecules.

Among many kinds of ionic liquids, some hydrated ionic liquids (Hy ILs) have shown an exceptional capability to stabilize protein molecules and maintain their structure and functions over a long period. However, the complex IL-water interaction among these protein-stabilizing Hy ILs has yet to be elucidated clearly. In this work, we investigate the origin of the compatibility of ionic liquid with proteins from the viewpoint of hydration structure. We systematically analyzed the hydrogen-bonding state of water molecules around ionic liquid using Fourier transform infrared absorption (FT-IR) spectroscopy. We found that the native hydrogen-bonding network of water remained relatively unperturbed in the protein-stabilizing ILs. We also observed that the protein-stabilizing ILs have a strong electric field interaction with the surrounding water molecules and this water-IL interaction did not disrupt the water-water hydrogen-bonding interaction. On the other hand, protein-denaturing ILs perturb the hydrogen-bonding network of the water molecules to a greater extent. Furthermore, the protein-denaturing ILs were found to have a weak electric field effect on the water molecules. We speculate that the direct hydrogen bonding of the ILs with water molecules and the strong electric field of the ions lasting several hydration shells while maintaining the relatively unperturbed hydrogen-bonding network of the water molecules play an essential role in protein stabilization.

Electrochemical sensing of the secretion of indoxyl sulfate in a rat intestinal loop using a self-assembled monolayer-modified gold bead electrode.

Indoxyl sulfate is a uremic toxin that accumulates in the plasma after a decline in renal function that might progress to chronic kidney disease (CKD). This accumulation is associated with the onset of dialysis and exacerbation of CKD and cardiovascular diseases. In this study, we aimed to demonstrate intestinal secretion as an excretion pathway of indoxyl sulfate in the severe stage of CKD using electrochemical sensing. A self-assembled monolayer (SAM) of 2-mercaptobenzimidazole on gold beads was successfully used for the separate sensing of indoxyl sulfate, uric acid (UA), and ascorbic acid. This electrode could detect indoxyl sulfate at concentrations as low as 50 nM in the presence of UA. No indoxyl sulfate secretion was observed in the intestinal loop of healthy rats or those intravenously administered saline. However, indoxyl sulfate secretion was detected in the 5/6 nephrectomized rats that showed high serum indoxyl sulfate levels, which also occurs in patients with CKD stage 4 or 5 and the healthy rats intravenously injected with indoxyl sulfate. These results suggest that indoxyl sulfate is excreted through the intestine when serum indoxyl sulfate level is high. The results of the present study showed that the SAM-modified gold bead electrode can be used as an easy and sensitive method for evaluating indoxyl sulfate secreted in the intestine over time.

Three-year Follow-up of Progressive Chorioretinal Atrophy in Atypical Alagille Syndrome: a Case Report.

PURPOSE: To report a case of atypical Alagille syndrome (ALGS) with progressive chorioretinal atrophy. METHODS: Case report. RESULTS: A 42-year-old Japanese man presented with atypical ALGS. At the first visit, funduscopy revealed anterior circumferential chorioretinal atrophy in peripheral retina and in peripapillary region with posterior pole sparing in both eyes. Fundus autofluorescence (FAF) showed hypoautofluorescence in the peripheral and peripapillary regions, but normal findings in the macular region. After follow-up for three years, hypopigmentated area with well visualized large choroidal vessels extended to mid-peripheral region. On FAF images, hypoautofluorescence newly appeared in macular region in both eyes. Perivascular hypoautofluorescence and granular hyperautofluorescence scattering within the posterior pole were also observed. BCVA deteriorated and concentric visual field contraction worsened progressively. CONCLUSION: ALGS is known to have many ophthalmic manifestations, most of which are stable with minimal threat to vision. In the present case, chorioretinal atrophy progressed during three-year follow-up, suggesting that progression of chorioretinal atrophy with vision loss may occur over time in ALGS.

Bilateral Serous Retinal Detachment in Lymphoid Blast Crisis of Chronic Myeloid Leukemia.

We herein report a patient with Philadelphia chromosome-positive lymphoid blast crisis of chronic myeloid leukemia (CML), who presented with bilateral serous retinal detachment (SRD). A 36-year-old Asian male presented with the symptoms of decreased vision and was found to have bilateral SRD involving fovea. There was no inflammation in the anterior chamber or vitreous. Physical examination showed hepatomegaly and splenomegaly. A blood count revealed white blood cell count of 38.2 × 109/L with 51.5% blast cells. Bone marrow aspirate showed total cell count of 145 × 103/µL with 80.6% blast cells and negative neutrophil myeloperoxidase staining. Cytogenetic analysis using fluorescence in situ hybridization confirmed a 9;22 chromosomal translocation, indicating the presence of the Philadelphia chromosome. Flow cytometry analysis demonstrated expression of CD10, CD19, and positive TdT. According to morphology, immunology, cytogenetics, and molecular criteria, the patient was diagnosed as having Philadelphia chromosome-positive lymphoid blast crisis of CML. Based on the ocular findings and hematological abnormalities, the SRD was considered to be ocular involvement secondary to the blast crisis of leukemia. Two months after starting induction therapy, fundus examination and optical coherence tomography showed complete resolution of bilateral SRD and improved vision. Prompt diagnosis of the disease leads to early systemic chemotherapy and may help restore visual function and improve survival.

Impact of low luminance conditions on quality of life for the visually impaired: development of the Low Luminance Questionnaire Japanese version.

PURPOSE: This study aimed to develop a Japanese version of the Low Luminance Questionnaire (LLQ-J) and to evaluate its reliability and validity. STUDY DESIGN: Cross-sectional study. METHODS: LLQ-J was developed by standardized methods. A total of 101 patients comprising 55 with age-related macular degeneration, 25 with glaucoma, 15 with regressed proliferative diabetic retinopathy, and 6 with retinitis pigmentosa were included in this study. The patients completed the LLQ-J and Japanese version of the visual function Questionnaire-25 (VFQ-25). Using the LLQ-J data, floor and ceiling effects were computed. To examine internal consistency, some patients completed the LLQ-J a second time 2-4 weeks later and the data were analyzed for Cronbach's alpha and intra-class correlation coefficients (ICCs). Best-corrected visual acuity (BCVA) and low luminance visual acuity (LLVA) were measured, and low-luminance deficit (LLD) was calculated. Criterion validity was also tested. RESULTS: No ceiling or floor effects were present in the LLQ-J data. Cronbach's alfa was 0.88, and ICCs were higher than 0.70 for all subscales. Moderate to high correlation was observed between LLQ-J and VFQ-25 (p < 0.01), confirming concurrent validity. "General dim lighting" and "Peripheral vision" were significantly associated with LLVA in the better eye (p < 0.05). "Mobility", "General dim lighting" and "Peripheral vision" were significantly associated with LLD (p < 0.05). "Emotional distress" was significantly associated with BCVA in the worse eye (p < 0.05). No subscales were associated with BCVA of the better eye. CONCLUSIONS: The LLQ-J is a valid and reliable questionnaire for assessing QOL under low luminance conditions.

Oxygen Release and Storage Property of Fe-Al Spinel Compounds: A Three-Way Catalytic Reaction over a Supported Rh Catalyst.

We evaluated the catalytic performance of the Rh-Fe/Al2O3 catalyst during a three-way catalytic reaction and found, by chance, that a part of Fe species was dissolved into the γ-Al2O3 support and worked as an oxygen storage material, which adjusts the oxygen concentration around the catalytically active sites to a suitable level for three-way catalysis. In this study, we demonstrated that the Fe-doped γ-Al2O3 can reversibly store and release oxygen by the redox of Fe2+/Fe3+ at the tetrahedral (Td) site of the spinel structure without its structure deformation. The finding that a spinel-structured metal oxide, Fe-doped γ-Al2O3, could work as an oxygen storage material suggested a new opportunity for the development of oxygen storage materials without rare metals.

Fundus Autofluorescence after Half-Dose Photodynamic Therapy for Chronic Central Serous Chorioretinopathy.

INTRODUCTION: To evaluate the fundus autofluorescence (FAF) images 1 year after half-dose photodynamic therapy (hdPDT) for chronic central serous chorioretinopathy (CSC). METHODS: Forty-six eyes of 46 consecutive patients with chronic CSC underwent hdPDT. Short wavelength-elicited FAF images and enhanced depth imaging optical coherence tomographic (EDI-OCT) images were recorded before and at 1, 3, 6, 9, and 12 months after the hdPDT. The FAF images at 1 month were compared to those at 12 months after the hdPDT. RESULTS: The serous retinal detachment (SRD) was resolved in all eyes. The best-corrected visual acuity (BCVA) improved significantly from 0.13 ± 0.28 logarithm of minimum angle of resolution (logMAR) units before to 0.01 ± 0.17 logMAR units at 12 months after the hdPDT (p = 0.001; paired t test). The mean choroidal thickness decreased significantly from 365.4 ± 103.0 µm to 284.3 ± 92.5 µm at 12 months (p < 0.001). Abnormal FAF images were present within the irradiated area in all the eyes before the hdPDT. In 5 of 46 eyes, identifiable changes of the FAF images were observed 12 months after hdPDT. None of the eyes had the confluent hypo-FAF type during the follow-up period. Univariate analyses showed that the choroidal thickness before hdPDT correlated significantly with hypo-FAF enlargement (p = 0.005). However, multivariate analyses showed that the association was not significant (p = 0.06). CONCLUSIONS: The progression of the RPE damages occurred in approximately one-tenth of the eyes that underwent hdPDT for chronic CSC. The long-term effect of progression of hypo-FAF on visual functions remains to be determined.

Early non-convulsive seizures are associated with the development of acute encephalopathy with biphasic seizures and late reduced diffusion.

INTRODUCTION: Children with either febrile seizure or acute encephalopathy exhibit seizures and/or impaired consciousness accompanied by fever of unknown etiology (SICF). Among children with SICF, we previously reported those who have refractory status epilepticus or prolonged neurological abnormalities with normal AST levels are at a high risk for the development of acute encephalopathy with biphasic seizures and late reduced diffusion (AESD), considered to be caused by excitotoxicity. Non-convulsive seizures (NCS) are common in critically ill children and cause excitotoxic neuronal injury. The aim of this study was to elucidate the prevalence of NCS in the acute phase of children at a high risk for developing AESD and the relationship between NCS in the acute phase and neurological outcomes. METHODS: We studied 137 children with SICF at a high risk for developing AESD and who underwent continuous electroencephalogram monitoring (cEEG) upon admission to a tertiary pediatric care center at Hyogo Prefectural Kobe Children's Hospital between October 2007 and August 2018. Patient characteristics and outcomes were compared between patients with NCS and without NCS. RESULTS: Of the 137 children, NCS occurred in 30 children; the first NCS were detected in cEEG at the beginning in 63.3%, during the first hour in 90%, and within 12 h in 96.7%. Neurological sequelae were more common in NCS patients (20.0%) than in non-NCS patients (1.9%; p = 0.001). Five in 30 NCS patients (16.7%) and 3 in 107 non-NCS patients (2.8%) developed AESD (p = 0.013). CONCLUSION: The occurrence of NCS is associated with subsequent neurological sequelae, especially the development of AESD.

Improvement of Low Luminance Visual Acuity in Patients with Chronic Central Serous Chorioretinopathy after Half-Dose Verteporfin Photodynamic Therapy.

Patients with central serous chorioretinopathy (CSC) often complain of visual difficulties under low luminance conditions. In this study, we evaluated low luminance visual acuity (LLVA) after half-dose verteporfin photodynamic therapy (hdPDT) in eyes with CSC. The study included eight eyes of eight patients with chronic CSC that underwent hdPDT. The best-corrected visual acuity, LLVA and optical coherence tomography (OCT) findings were evaluated at baseline, and at 1, 3, 6, 9, and 12 months after hdPDT. LLVA was measured at six levels of background luminance. Serous retinal detachment was completely resolved in all eyes. Although the mean LLVA at 1 month did not improve significantly compared to baseline at all luminance levels, significant improvements were observed at 3, 6, 9, and 12 months (p < 0.05). In OCT images, although the ellipsoid zone was not detectable in all eyes before hdPDT, it was observed in 2 eyes at 1 month, in 7 eyes at 3 months, and in all eyes from 6 months. The LLVA and the ellipsoid zone improved similarly with postoperative time courses. In conclusion, hdPDT improves LLVA in eyes with chronic CSC. The recovery of the ellipsoid zone may play a part in improving LLVA after hdPDT.

Predicting Entropic Effects of Water Mixing with Ionic Liquids Containing Anions of Strong Hydrogen Bonding Ability: Role of the Cation.

Ionic liquids (ILs) such as choline dihydrogen phosphate exhibit an extraordinary solubilizing ability for proteins such as cytochrome C when mixed with 20 wt % water. Most widely used imidazolium-based ionic liquids coupled with dihydrogen phosphate do not exhibit the same solubilizing properties, suggesting that a multifunctional cation such as choline might play a key role in enhancing these properties of ionic liquid mixtures with water. In this theoretical work, we compare intermolecular interactions between the water molecule and ionic liquid ions in two ion-paired clusters of choline- and 1-butyl-3-methyl-imidazolium-based ionic liquids coupled with acetate, dihydrogen phosphate, and mesylate. Gibbs free energy (GFE) of solvation of water in these ionic liquids was calculated. Incorporation of a water molecule into ionic liquid clusters was accompanied by negative GFEs of solvation in both types of cations. These results were in good agreement with previously reported experimental GFEs of solvation of water in ILs. Compared to imidazolium-based clusters, strong interionic interactions of choline ionic liquids resulted in more negative GFEs due to their smaller deformation upon the addition of a water molecule, with dihydrogen phosphate and mesylate predicting the lowest GFEs of -30.1 and -43.5 kJ/mol-1, respectively. Lower GFEs of solvation of water in choline-based clusters were also accompanied with smaller entropic penalties, suggesting that water easily incorporates itself into the existing ionic network. Analysis of the intramolecular bonds within the water molecule showed that the choline hydroxyl group donates electron density to the neighboring water molecule, leading to additional polarization. The predicted infrared spectra of clusters of ionic liquids with water showed a pronounced red shift due to strongly polarized O-H bonds, in excellent agreement with the experimentally measured infrared spectra of ionic liquid mixtures with water. Increased polarization of water in choline-based ionic liquids undoubtedly creates more effective solvents for stabilizing biological molecules such as proteins.

Detailed clinical course of fatal acute encephalopathy in children.

OBJECTIVE: Although the mortality among previously healthy children with acute encephalopathy (AE) is approximately 5%, their detailed clinical course has not been clarified. The objective of the present study was to describe the detailed clinical course, in minutes, of fatal AE. METHODS: We retrospectively reviewed the medical records of five patients (from 6 months to 14 years of age) who previously had no neurological disorders and were diagnosed with brain death due to AE between 2002 and 2018 at Kobe Children's Hospital. RESULTS: The initial clinical symptoms were convulsion in three cases and impaired consciousness in two. The earliest noted brain imaging abnormality was 7.5 h after neurological symptom detection. Liver enzymes and creatinine levels increased at initial examination, and sodium elevated gradually. All patients met the criteria of systemic inflammatory response syndrome, disseminated intravascular coagulation, and shock within 14 h of symptom detection. High dose steroids and targeted temperature management were initiated 3.5-14 h after onset. Despite these therapies, patients were diagnosed with brain death from 16 h to 4 days after initial neurological symptoms. AE diagnoses were made between 4 h 29 min and 4 days after initial neurological symptoms and included hemorrhagic shock and encephalopathy syndromes, Reye-like syndrome, and acute necrotizing encephalopathy in two, two, and one patient(s), respectively. CONCLUSIONS: We revealed the time series' of clinical events (e.g. SIRS, shock, DIC, AE diagnosis, brain death, and treatments) and laboratory findings relative to initial neurological symptom in fatal AE.

Effects of charge balance and hydrophobicity of the surface of cytochrome c on the distribution behaviour in an ionic liquid/buffer biphasic system.

Factors contributing to the different distribution behaviour of cytochrome c were investigated in a biphasic tetrabutylphosphonium 2,4,6-trimethylbenzenesulfonate and potassium phosphate buffer system, which shows a lower critical solution temperature. To change charge balance and hydrophobicity of cytochrome c, surface modification with a few modifier molecules was applied. Surface charge and hydrophobicity affected the distribution behavior of chemically modified cytochrome c in the tetrabutylphosphonium 2,4,6-trimethylbenzenesulfonate and potassium phosphate buffer biphasic system. The distribution ratio into tetrabutylphosphonium 2,4,6-trimethylbenzenesulfonate decreased with decreasing isoelectric point of cytochrome c. Furthermore, cytochrome c possessing a low isoelectric point showed different distribution ratio depending on surface hydrophobicity. Taken together, these findings indicate that isoelectric point and surface hydrophobicity of cytochrome c are important factors controlling the distribution behavior in temperature sensitive biphasic systems.

Predicting the outcomes of targeted temperature management for children with seizures and/or impaired consciousness accompanied by fever without known etiology.

BACKGROUND: Seizures and/or impaired consciousness accompanied by fever without known etiology (SICF) is common in the pediatric emergency setting. No optimal strategy for the management of SICF in childhood currently exists. We previously demonstrated the effectiveness of targeted temperature management (TTM) against SICF with a high risk of morbidity; however, some patients with SICF develop neurological sequelae despite TTM, which necessitate additional neuroprotective treatment. The clinical characteristics of these severe cases have not been studied. Accordingly, the aim of this study was to identify the clinical characteristics of children with SICF who exhibit poor outcomes after TTM. METHODS: The medical records of children admitted to Kobe Children's Hospital (Kobe, Japan) between October 2002 and September 2016 were retrospectively reviewed. Patients with SICF treated using TTM were included and divided into the satisfactory and poor outcome groups. Univariate and multivariate logistic regression analyses were used to compare clinical characteristics and laboratory findings between the two groups. RESULTS: Of the 73 included children, 10 exhibited poor outcomes. Univariate logistic regression analysis revealed that acute circulatory failure before TTM initiation, the use of four or more types of anticonvulsants, methylprednisolone pulse therapy, and an aspartate aminotransferase (AST) level ≥73 IU/L were associated with poor outcomes. Multivariate logistic regression analysis identified an elevated AST level as a significant independent predictor of a poor outcome. CONCLUSIONS: An elevated AST level within 12 h of onset in children with SICF is an independent predictor of a poor outcome after TTM initiated within 24 h of onset.

Clinical time course of pediatric acute disseminated encephalomyelitis.

The detailed clinical time course in acute disseminated encephalomyelitis (ADEM) from initial symptoms, through exacerbation, to remission has not been widely reported. Hence, this study aimed to investigate the clinical time course of pediatric ADEM. This was a multicenter retrospective study based on registry data from medical chart reviews. The study included children who met the international consensus diagnostic criteria for ADEM. The patients comprised 18 boys and 6 girls, with a mean age of 5.5 ±â€¯3.3 years at onset. From onset, the time until peak neurological symptoms, time until initial improvement, and time until full recovery was 3.1 ±â€¯3.7 days, 6.0 ±â€¯4.5 days, and 26 ±â€¯34 days, respectively. Twenty-three (96%) patients were treated with high-dose methylprednisolone (mPSL) with a mean duration of 4.1 ±â€¯4.0 days from onset. The condition of 15 patients (65%) improved within 3 days of high-dose mPSL initiation, whereas, that of four patients began to improve after >5 days of high-dose mPSL initiation. Only one patient (4%) did not achieve full recovery despite treatment with high-dose mPSL, intravenous immunoglobulin, and plasma exchange. This study presents the detailed clinical time course in pediatric ADEM in Japan. Progression of neurologic deficits typically lasts a few days, with initial improvement in 1 week leading to full recovery within 1 month.

Hydrated ionic liquids enable both solubilisation and refolding of aggregated concanavalin A.

The dissolution and refolding of aggregated concanavalin A have been achieved, in hydrated ionic liquids containing a limited number of water molecules. Both ammonium and phosphonium salts were examined to find a suitable hydrophobicity of ions and water content for refolding. Recovery of sugar recognition was confirmed as a proof of refolding.

Electrochemical analysis of uric acid excretion to the intestinal lumen: Effect of serum uric acid-lowering drugs and 5/6 nephrectomy on intestinal uric acid levels.

Recently, extensive efforts have been made to understand the importance of the extra-renal uric acid (UA) excretion pathways and their contribution to UA-related diseases. However, the method typically used to measure UA concentrations in the intestinal lumen is difficult to real time and dynamic analysis. In this study, UA excretion in the rat intestinal lumen was measured in real time using an electrochemical method. A sensitive electrode to detect UA was constructed using a gold electrode modified with a mixed self-assembled monolayer. Excretion rate of UA in the intestine was calculated using time course data. A decrease in UA excretion rate was observed in the intestine after administration of serum UA-lowering drugs (benzbromarone, febuxostat, and topiroxostat). Inhibition of ATP-binding cassette transporter G2 (ABCG2) which has been reported as an important exporter of UA was suggested by administration of these drugs. On the other hand, an increase in excretion rate of UA was observed in the intestine of 5/6 nephrectomy rats. Upregulation of mRNA expression of the UA transporter organic anion transporter OAT3, which is related to the secretion at the basal membrane, suggested an enhancement of UA excretion by ABCG2, a high-capacity UA exporter. Observed urate excretion dynamics and mRNA expression of UA transporters in the intestine upon administration of serum UA-lowering drugs and 5/6 nephrectomy improve our understanding of the underlying mechanisms of intestinal UA excretion.

Ionic Liquids as Stabilization and Refolding Additives and Solvents for Proteins.

This chapter focuses on recent advances in the use of ionic liquids as additives and solvents in protein applications. The solvent properties of ionic liquids can be tuned by the appropriate selection of cation and anion. The effects of different kinds of ionic liquids on protein stability and refolding behavior have been investigated and reported. The ionic liquid properties affect the intermolecular interactions of proteins, inducing different formations and folding behavior. These effects also vary with the concentration of ionic liquids. Although many of the associated mechanisms are not completely clear, some of this behavior may be attributed to the kosmotropicity of the ions and their Hofmeister effects. Graphical Abstract.