Topology and Sequence-Dependent Micellization and Phase Separation of Pluronic L35, L64, 10R5, and 17R4: Effects of Cyclization and the Chain Ends.

The topology effects of cyclization on thermal phase transition behaviors were investigated for a series of amphiphilic Pluronic copolymers of both hydrophilic-hydrophobic-hydrophilic and hydrophobic-hydrophilic-hydrophobic block sequences. The dye solubilization measurements revealed the lowered critical micelle temperatures (TCMT) along with the decreased micellization enthalpy (ΔHmic) and entropy (ΔSmic) for the cyclized species. Furthermore, the transmittance and dynamic light scattering (DLS) measurements indicated a block sequence-dependent effect on the clouding phenomena, where a profound decrease in cloud point (Tc) was only found for the copolymers with a hydrophilic-hydrophobic-hydrophilic block sequence. Thus, the effect of cyclization on these critical temperatures was manifested differently depending on its block sequence. Finally, a comparison of the linear hydroxy-terminated, methoxy-terminated, and cyclized species indicated the effect of cyclization to be unique from a simple elimination of the terminal hydrophilic moieties.

Ketogenic Diet for a Young Adult Patient With Chronic-Phase Febrile Infection-Related Epilepsy Syndrome.

Febrile infection-related epilepsy syndrome (FIRES) is a rare disease, whereby refractory status epilepticus (a severe epileptic syndrome) occurs in previously healthy individuals following a febrile illness. Here, we report a patient with FIRES who received ketogenic diet (KD) therapy initiated in the chronic phase. A 21-year-old man presented with status epilepticus, following fever and headache. In the acute phase, his seizures were refractory to conventional antiepileptic drugs and were suppressed only by intravenous anesthetics. In the chronic phase, he showed frequent seizures with concurrent severe cognitive decline. Twenty-seven months after onset, the patient was started on KD. Consequently, his seizure frequency rapidly reduced while his cognitive function slowly improved, albeit incompletely. Recently, KD has been shown to both reduce seizures and improve cognitive prognoses in children with FIRES. Although early KD may help in both seizure control and cognitive prognosis, it is likely that KD can be applied to adult patients with chronic FIRES.

Cyclization of PEG and Pluronic Surfactants and the Effects of the Topology on Their Interfacial Activity.

A series of cyclic surfactants were synthesized from a poly(ethylene glycol) (PEG) homopolymer and Pluronic surfactants L35, L64, P123, F68, 10R5, and 17R4, and their interfacial activity depending on the topology, chain ends, and block sequence was investigated. The cyclization was performed in a single step through etherification of the PEG homopolymer and the hydrophilic-hydrophobic-hydrophilic (ABA type) poly(ethylene glycol)-poly(propylene glycol)-poly(ethylene glycol) (PEG-PPG-PEG), while the hydrophobic-hydrophilic-hydrophobic (BAB type) PPG-PEG-PPG was cyclized via acetalization. The cyclized surfactants were rigorously characterized by nuclear magnetic resonance spectroscopy and size exclusion chromatography. Cyclization of the surfactants induced a significant decrease in the hydrodynamic volume, which was more pronounced than that of the PEG homopolymer. Surface tension (γ) measurements indicated that the interfacial activity of the cyclized surfactants is stronger than their corresponding linear precursors, due to the increase in the surfactant density at the air-water interface as a consequence of the decreased molecular occupational area (A) upon cyclization. In the case of the PEG homopolymer, A considerably decreased from 410 Å2 for the linear PEG prepolymer to 100 Å2 for the cyclized PEG product. While the effects of chain-end groups were found to be limited to surfactants of relatively small molecular weights, the influence of cyclization depended strongly on the hydrophilic/hydrophobic ratio; the higher the PEG composition the surfactants had, the larger the decrease in γ and A; in other words, stronger enhancement in the interfacial activity was observed.

Anti-N-Methyl-D-Aspartate Receptor Encephalitis with Decrease in Blood Flow in Cerebellum.

In anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, progressive cerebellar atrophy potentially leads to severe sequelae. We encountered a patient with anti-NMDAR antibody encephalitis who showed a decrease of blood flow in the cerebellum. A 15-year-old girl presented with consciousness disturbance. Influenza encephalopathy was suspected, and she was treated with glucocorticoid pulse therapy, high-dose intravenous immunoglobulins, and plasma exchange sequentially. She subsequently underwent left oophorectomy due to the presence of anti-NMDAR antibodies and a left ovarian teratoma. In spite of the surgery, her neuropsychiatric symptoms persisted, and she recovered slowly after the introduction of oral methotrexate (MTX). Sequential cerebral blood flow monitoring with single-photon emission computed tomography showed marked cerebellar hypoperfusion. Although mild impairments including working memory and verbal fluency persisted, she eventually returned to high school 3 years after onset. Profound cerebellar hypoperfusion including lobules VI and VII may be the reason for her working memory impairment and speaking problems. Oral MTX may be a promising alternative treatment for some refractory cases of anti-NMDAR encephalitis.

Enhanced dispersion stability of gold nanoparticles by the physisorption of cyclic poly(ethylene glycol).

Nano-sized metal particles are attracting much interest in industrial and biomedical applications due to the recent progress and development of nanotechnology, and the surface-modifications by appropriate polymers are key techniques to stably express their characteristics. Herein, we applied cyclic poly(ethylene glycol) (c-PEG), having no chemical inhomogeneity, to provide a polymer topology-dependent stabilization for the surface-modification of gold nanoparticles (AuNPs) through physisorption. By simply mixing c-PEG, but not linear counterparts, enables AuNPs to maintain dispersibility through freezing, lyophilization, or heating. Surprisingly, c-PEG endowed AuNPs with even better dispersion stability than thiolated PEG (HS-PEG-OMe). The stronger affinity of c-PEG was confirmed by DLS, ζ-potential, and FT-IR. Furthermore, the c-PEG system exhibited prolonged blood circulation and enhanced tumor accumulation in mice. Our data suggests that c-PEG induces physisorption on AuNPs, supplying sufficient stability toward bio-medical applications, and would be an alternative approach to the gold-sulfur chemisorption.

Proximal gait adaptations in individuals with knee osteoarthritis: A systematic review and meta-analysis.

Clarifying proximal gait adaptations as a strategy to reduce knee joint loading and pain for individuals with knee osteoarthritis (OA) contributes to understanding the pathogenesis of multi-articular OA changes and musculoskeletal pain in other joints. We aimed to determine whether biomechanical alterations in knee OA patients during level walking is increased upper trunk lean in the frontal and sagittal planes, and subsequent alteration in external hip adduction moment (EHAM) and external hip flexion moment (EHFM). A literature search was conducted in PubMed, PEDro, CINAHL, and Cochrane CENTRAL through May 2018. Where possible, data were combined into a meta-analysis; pooled standardized mean differences (SMD) of between knee OA patients and healthy adults were calculated using a random-effect model. In total, 32 articles (2037 participants, mean age, 63.0 years) met inclusion criteria. Individuals with knee OA had significantly increased lateral trunk lean toward the ipsilateral limb (pooled SMD: 1.18; 95% CI: 0.59, 1.77) along with significantly decreased EHAM. These subjects also displayed a non-significantly increased trunk/pelvic flexion angle and EHFM. The GRADE approach judged all measures as "very low." These results may indicate that biomechanical alterations accompanying knee OA are associated with increased lateral trunk lean and ensuing alterations in EHAM. Biomechanical alterations in the sagittal plane were not evident. Biomechanical adaptations might have negative sequelae, such as secondary hip abductor muscle weakness and low back pain. Thus, investigations of negative sequelae due to proximal gait adaptations are warranted.

The development of diffuse panbronchiolitis during the treatment with long-term, low-dose clarithromycin for chronic sinusitis.

Diffuse panbronchiolitis (DPB) is a progressive inflammatory airway disease characterized by a chronic cough, copious sputum expectation, dyspnea, and chronic sinusitis. Owing to the long-term treatment of low-dose macrolides, the prognosis has been remarkably improved. However, in some cases, patients are refractory to macrolides, and the subsequent treatment strategies are controversial. We herein present a patient with the onset of DPB during treatment with long-term, low-dose clarithromycin (CAM) for chronic sinusitis who was successfully treated by switching to long-term treatment with normal-dose CAM. We should recognize that DPB may develop in patients with chronic sinusitis despite treatment with a long-term, low-dose macrolide. We also propose that increasing the dose of macrolide may be a useful strategy for treating refractory patients.

Combined effects of electric toothbrushing and dentifrice on artificial stain removal: An in vitro study.

BACKGROUND: This in vitro study aimed to clarify the combined effect of electric toothbrushing and dentifrice on the removal of artificial stain. MATERIAL AND METHODS: Twenty-five bovine incisors were cut at the cervix and the crown was embedded in auto-cured acrylic resin. Specimens were abraded using #240 SiC paper to obtain a flat enamel surface, and 20 specimens were treated with 10% citric acid / 3% ferric chloride solution followed by 1% tannic acid solution to produce surface staining. They were divided into four groups: 1) brushing with an electric toothbrush and whitening dentifrice (group S+B); 2) brushing with an electric toothbrush and fluoride dentifrice (group S+C); 3) brushing with an electric toothbrush and no dentifrice (group S); and 4) no brushing (control group). The remaining five specimens were used as a baseline. Color values (L*, a*, and b* were measured before brushing (0 min), and at 1 min, 5 min, 10 min, and 20 min using a microscopic area spectrophotometer. The color change (ΔE) was calculated by subtracting the baseline values from the final color values obtained at each time point. The data were statistically analyzed using two-way repeated-measures analysis of variance and Tukey's honest significant difference test as a post hoc test (p<0.05). RESULTS: The L* values of groups S+B and S+C increased over time (p<0.05), but no significant differences were observed in group S and the control group at any of the time points (p>0.05). Groups S+B and S+C demonstrated greater ΔE values than group S. CONCLUSIONS: The combination of electric toothbrushing and dentifrice removed the artificial stain more effectively than brushing without dentifrice. However, the stain removal was limited. The two dentifrices evaluated in this study exhibited similar stain removal effects. Key words:Color change, stain removal, dentifrice, electric toothbrush, whitening effect.

Elevated Serum Anti-GM-CSF Antibodies before the Onset of Autoimmune Pulmonary Alveolar Proteinosis in a Patient with Sarcoidosis and Systemic Sclerosis.

Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of periodic acid-schiff stain-positive lipoproteinaceous materials in the alveolar space due to impaired surfactant clearance by alveolar macrophage. Autoimmune PAP is the most common form of PAP, but rarely accompanies collagen disease or sarcoidosis. We report here a rare case of autoimmune PAP preceded by systemic sclerosis and sarcoidosis. A 64-year-old woman was admitted to our hospital for blurred vision, muscle weakness of extremities, Raynaud's phenomenon, and exertional dyspnea. We diagnosed her as having systemic sclerosis complicated with sarcoidosis. Chest computed tomography (CT) and transbronchial lung biopsy showed the findings of pulmonary fibrosis without PAP. We treated her with corticosteroid and intravenous cyclophosphamide therapy, followed by tacrolimus therapy. Thereafter, her symptoms improved except for exertional dyspnea, and she began to complain of productive cough thirteen months after corticosteroid and immunosuppressant therapy. On the second admission, a chest CT scan detected the emergence of crazy-paving pattern in bilateral upper lobes. Bronchoalveolar lavage (BAL) fluid with milky appearance and a lung biopsy specimen revealed acellular periodic acid-schiff stain-positive bodies. The serum titer of anti-granulocyte macrophage colony stimulating factor (GM-CSF) antibodies was elevated on first admission and remained high on second admission. We thus diagnosed her as having autoimmune PAP. Reducing the dose of immunosuppressive agents and repeating the segmental BAL resulted in the improvement of her symptoms and radiological findings. Immunosuppressant therapy may trigger the onset of autoimmune PAP in a subset of patients with systemic sclerosis and/or sarcoidosis.

[Confirming the Utility of RAISUS Antifungal Susceptibility Testing by New-Software].

Clinical and Laboratory Standards Institute (CLSI) methods for susceptibility tests of yeast are used in Japan. On the other hand, the methods have some disadvantage; 1) reading at 24 and 48 h, 2) using unclear scale, approximately 50% inhibition, to determine MICs, 3) calculating trailing growth and paradoxical effects. These makes it difficult to test the susuceptibility for yeasts. Old software of RAISUS, Ver. 6.0 series, resolved problem 1) and 2) but did not resolve problem 3). Recently, new software of RAISUS, Ver. 7.0 series, resolved problem 3). We confirmed that using the new software made it clear whether all these issue were settled or not. Eighty-four Candida isolated from Aichi Medical University was used in this study. We compared the MICs obtained by using RAISUS antifungal susceptibility testing of yeasts RSMY1, RSMY1, with those obtained by using ASTY. The concordance rates (±four-fold of MICs) between the MICs obtained by using ASTY and RSMY1 with the new software were more than 90%, except for miconazole (MCZ). The rate of MCZ was low, but MICs obtained by using CLSI methods and Yeast-like Fungus DP 'EIKEN' methods, E-DP, showed equivalent MICs of RSMY1 using the new software. The frequency of skip effects on RSMY1 using the new software markedly decreased relative to RSMY1 using the old software. In case of showing trailing growth, the new software of RAISUS made it possible to choice the correct MICs and to put up the sign of trailing growth on the result screen. New software of RAISUS enhances its usability and the accuracy of MICs. Using automatic instrument to determine MICs is useful to obtain objective results easily.

Measurement of Reduced Gingival Melanosis after Smoking Cessation: A Novel Analysis of Gingival Pigmentation Using Clinical Oral Photographs.

BACKGROUND: Due to moisture and the anatomical complexity of the oral mucosa, it is difficult to measure the extent of gingival melanosis in an optical manner. Therefore, we developed a new quantitative method using clinical oral photographs and compared the extent of gingival melanosis before and after smoking cessation. METHODS: A new analysis method, which we named the gingival melanosis record (GMR), is a quantitative analysis method using clinical oral photographs. We obtained 659 clinical photographs from 263 patients from 16 general dental offices in Japan. Standardized measuring sites were automatically spotted on the screen, and the presence of gingival melanosis was determined at the measuring sites. We assessed the validity of the GMR with the previously reported Hedin's classification using Spearman's rank correlation and intraclass correlation coefficients. RESULTS: The GMR showed a significant association with Hedin's classification (p < 0.01, correlation coefficient = 0.94). The GMR also showed excellent reproducibility of the substantial repeated agreement intraclass correlation coefficients (ICC) (1,1) and ICC (2,1), p > 0.61). The longitudinal loss of gingival melanosis was confirmed by a change in the GMR among patients who successfully achieved smoking cessation for a mean of 4.5 years. CONCLUSION: The GMR is an effective method to assess gingival melanosis. The loss of gingival melanosis after smoking cessation can be objectively confirmed with the use of the GMR.

Toxicological assessment of enzyme-treated asparagus extract in rat acute and subchronic oral toxicity studies and genotoxicity tests.

The safety of enzyme-treated asparagus extract (ETAS) developed as a novel anti-stress functional material was assessed in acute and subchronic studies and genotoxicity assays. In the acute oral dose toxicity study, all rats survived during the test period and ETAS did not influence clinical appearance, body weight gain and necropsy findings at a dosage of 2000mg/kg body weight. Thus, the 50% lethal dose (LD50) of ETAS was determined to be greater than 2000mg/kg. The 90-day subchronic study (500, 1000 and 2000mg/kg body weight, delivered by gavage) in rats reported no significant adverse effects in food consumption, body weight, mortality, urinalysis, hematology, biochemistry, necropsy, organ weight and histopathology. In the micronucleus test of mice, the incidence of micronuclei in ETAS-administered groups (500, 1000 and 2000mg/kg/day, injected twice) was equivalent to that of the negative control group, while the positive control group receiving mitomycin C showed a high incidence. The potential of ETAS to induce gene mutation was tested using four Salmonella typhimurium strains and Escherichia coli WP2uvrA. The test sample was not mutagenic to the test strains. These results support the safety of ETAS as food and dietary supplement.

Isolation, structural elucidation, and biological evaluation of a 5-hydroxymethyl-2-furfural derivative, asfural, from enzyme-treated asparagus extract.

A novel 5-hydroxymethyl-2-furfural (HMF; 1) derivative, which is named asfural (compound 2), was isolated from enzyme-treated asparagus extract (ETAS) along with HMF (1) as a heat shock protein 70 (HSP70) inducible compound. The structure of compound 2 was elucidated on the basis of its spectroscopic data from HREIMS and NMR, whereas the absolute configuration was determined using chiral HPLC analysis, compared to two synthesized compounds, (S)- and (R)-asfural. As a result, compound 2 derived from ETAS was assigned as (S)-(2-formylfuran-5-yl)methyl 5-oxopyrrolidine-2-carboxylate. When compound 2, synthesized (S)- and (R)-asfural, and HMF (1) were evaluated in terms of HSP70 mRNA expression-enhancing activity in HL-60 cells, compound 2 and (S)-asfural significantly increased the expression level in a concentration-dependent manner. HMF (1) also showed significant activity at 0.25 mg/mL.

Inverse correlations between serum ADAMTS13 levels and systolic blood pressure, pulse pressure, and serum C-reactive protein levels observed at a general health examination in a Japanese population: a cross-sectional study.

BACKGROUND: Although a defect in ADAMTS13 activity is known to cause platelet thrombosis resulting in thrombotic thrombocytopenic purpura (TTP), recent evidence has revealed that low plasma ADAMTS13 concentrations may increase the risk of ischemic vascular diseases. Furthermore, reduced plasma ADAMTS13 activity has been reported in acute systemic inflammation or sepsis. These findings prompted us to examine whether ADAMTS13 may play a role in more diverse diseases, not limited to TTP. METHODS: A cross-sectional study was conducted to examine ADAMTS13 concentrations in blood samples from 432 subjects who had undergone a general health examination. RESULTS: Serum ADAMTS 13 concentrations were lower in men than in women and in older age, as previously reported. Of note, the serum ADAMTS13 concentration was significantly and inversely correlated with the systolic blood pressure, pulse pressure, and serum C reactive protein concentration in both men and women and with the serum γ-glutamyltransferase concentration in men only. In 88 subjects, who underwent a carotid artery evaluation, serum ADAMTS13 concentrations were significantly lower in the subjects with a thicker carotid intima-media. CONCLUSIONS: ADAMTS13 may play a role in not only TTP, but also inflammation, oxidative stress, and atherosclerosis. The potentially diverse clinical significance of ADAMTS13 should be prospectively elucidated in a larger cohort.

Treatment with linezolid in a neonate with meningitis caused by methicillin-resistant Staphylococcus epidermidis.

UNLABELLED: Recent findings have focused on the possible role of linezolid (LZD) as a suitable candidate for the treatment of central nervous system infections. LZD treatment for meningitis has been sporadically reported in adults, but there are no reports in neonates or infants. We report a case of meningitis caused by methicillin-resistant Staphylococcus epidermidis (MRSE) in a neonatal girl. The patient had intraventricular hemorrhage on postnatal day 1 and was treated with ventricular drainage. Twenty-two days after drainage, the patient developed a fever and seizure. Although ampicillin and ceftriaxone were given empirically for meningitis, an increased cell count and protein were observed in cerebrospinal fluid (CSF). Vancomycin (VCM) was administered intravenously because MRSE was detected from CSF 2 days after the administration of ampicillin and ceftriaxone. However, intravenous administration of VCM did not show any effect. Subsequent treatment of LZD successfully reduced the cell count and protein in CSF. CONCLUSION: LZD may be a treatment option for neonates and infants for drain-associated meningitis caused by MRSE.

Overexpression of endogenous TIMP-2 increases the proliferation of BeWo choriocarcinoma cells through the MAPK-signaling pathway.

Choriocarcinoma is a highly malignant form of trophoblastic tumor that is characterized by malignant placental tumors and rapid cell growth. In vivo and in vitro studies have demonstrated that tissue inhibitor of metalloproteinase 2 (TIMP-2) is present in choriocarcinoma. However, the role of TIMP-2 in cell proliferation in choriocarcinoma has not been investigated. Exogenous TIMP-2 is known to promote cell proliferation. During growth, cells are subjected to varied concentrations of TIMP-2, which depend on the amount of TIMP-2 produced by the cells themselves. Thus, the effect of gradually increasing endogenous TIMP-2 on the proliferation of choriocarcinoma cells needs to be examined. Proliferation of BeWo human choriocarcinoma cells was stimulated by transient transfection of a plasmid expressing TIMP-2. Overexpression of endogenous TIMP-2 also activated ERK1/2 and JNK1/2 of the MAPK-signaling pathway. Furthermore, inhibition of these proteins resulted in suppression of the cell proliferation-stimulating effect of TIMP-2. These results suggest that TIMP-2 plays an important role in tumor growth in the case of BeWo cells. Moreover, proliferation of BeWo cells due to TIMP-2 expression can be used as a model for fast-growing choriocarcinomas, and TIMP-2 could be used as a novel tumor marker of choriocarcinoma.

Microbicidal effect of weak acid hypochlorous solution on various microorganisms.

We investigated the microbicidal effect of weak acid hypochlorous solutions of pH 5.0 - 6.0, produced by mixing NaClO and HCl in water, against various bacteria, fungi, and virus in vitro. The weak acid hypochlorous solution had excellent microbicidal effect against a broad microbicidal spectrum of standard strains and clinical isolates in a short time. The microbicidal effects of hypochlorous solutions did not depend on the available chlorine concentration but on the HClO concentration. These results show that the weak acid hypochlorous solution has practical applicability in such places as hospitals and establishments related to the food industry.

Prediction of hepatocellular carcinoma development by plasma ADAMTS13 in chronic hepatitis B and C.

BACKGROUND: Chronic liver injury evokes a wound healing response, promoting fibrosis and finally hepatocellular carcinoma (HCC), in which hepatic stellate cells play an important role. Although a blood marker of hepatic stellate cells is not known, those cells importantly contribute to the regulation of plasma a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS13) activity, a defect of which causes thrombotic thrombocytopenic purpura. METHODS: Plasma ADAMTS13 was evaluated in chronic hepatitis B or C patients with or without HCC. RESULTS: Plasma ADAMTS13 activity significantly correlated with serum aspartate aminotransferase and alanine aminotransferase, liver stiffness value, and aspartate aminotransferase-to-platelet ratio index, irrespective of the presence of HCC, suggesting that it may reflect hepatocellular damage and subsequent wound healing and fibrosis as a result of hepatic stellate cell action. During the three-year follow-up period for patients without HCC, it developed in 10 among 81 patients. Plasma ADAMTS13 activity was significantly higher in patients with HCC development than in those without and was a significant risk for HCC development by univariate and multivariate analyses. Furthermore, during the one-year follow-up period for patients with HCC treated with radiofrequency ablation, HCC recurred in 55 among 107 patients. Plasma ADAMTS13 activity or antigen level was significantly higher in patients with HCC recurrence than in those without and was retained as a significant risk for HCC recurrence by multivariate analysis. CONCLUSIONS: Higher plasma ADAMTS13 activity and antigen level was a risk of HCC development in chronic liver disease. IMPACT: Plasma ADAMTS13 as a potential marker of hepatic stellate cells may be useful in the prediction of hepatocarcinogenesis.