[Time-sparing screening method for mild cognitive impairment and early Alzheimer's disease: Self- and family reports using the TMIG index of competence].

AIM: To verify the clinical utility of instrumental activities of daily life evaluated using the Tokyo Metropolitan Institute of Gerontology index of competence (TMIG-IC) as a screening tool for patients with early-phase cognitive impairment, including mild cognitive impairment (MCI) and early Alzheimer's disease (AD). METHODS: We recruited healthy subjects from our community-based cohort and consecutive subjects with MCI and AD from our clinic. The TMIG-IC was investigated in all participants and their family members. The total and subscale scores were compared among all groups. We then statistically determined the accuracy of the differentiation of MCI and AD. RESULTS: We registered 187 normal controls (NC), 39 participants with MCI, 50 AD patients with functional assessment staging (FAST) 4, and 19 AD patients with ≥5 FAST. The family-report score was significantly lower in MCI patients than in others, followed by AD patients. The total score was able to differentiate MCI and AD with a sensitivity of 85.7% and a specificity of 90.9% (area under the curve [AUC]=0.913). Differentiation of MCI alone had a low accuracy (AUC=0.787). However, the AUC was 0.847 when only the items with inconsistent responses between self and family reports were used as indices. CONCLUSIONS: The TMIG-IC is a useful tool for evaluating the severity of AD, including early AD. These findings suggest that family-report scores can differentiate MCI and AD from cognitive normal aging with a sufficient degree of accuracy. It was also suggested that inconsistencies between self and family reports were higher when differentiating MCI than the self- and family-reports.

[Study of encoding and storage in memorization among patients with Alzheimer's disease].

AIM: Memorization comprises three stages: encoding, storage, and retrieval. Using neuropsychological tests, we investigated the stage at which encoding and storage are retained in Alzheimer's disease (AD) patients with progressive memory disorder. METHODS: The target patients were an amnestic mild cognitive impairment (MCI) group (21 cases) and FAST 4 (37 cases), 5 (10 cases), and 6 (4 cases) AD groups. The neuropsychological tests performed were the Rivermead behavioral memory test and Wechsler memory scale-revised. These were carried out in the MCI group as well as in each AD stage group. We investigated the delayed recall (free recall and cued recall) based on the disease stage and raw score of the sub-items in delayed recognition. RESULTS: The MCI group had 48% (median 0 point) correct respondents (providing ≥1 correct answer) for free recall, whereas FAST 4 and 5 groups had ≤14% correct respondents. In the verbal paired associates II evaluated in cued recall, the MCI group had 90% correct respondents, and the FAST 4, 5, and 6 groups had rates of 51%, 60%, and 50%, respectively. For the pictures and photos in the delayed recognition tasks, there were no significant differences in the percentage of correct respondents between the MCI group (100%) and the FAST 4 and 5 groups (70%-90%). CONCLUSIONS: Given that retrieval is impossible if encoding and storage are impaired, we inferred that the encoding and retrieval abilities were retained even in moderately advanced AD.

Endovascular treatment for secondary basilar occlusion caused by spontaneous thrombus migration from the vertebral artery: Two case reports.

Thrombus migration is a well-known clinical condition that occurs before mechanical thrombectomy and after intravenous thrombolysis in patients with anterior circulation strokes. Although thrombus migration from the vertebral artery (VA) can result in life-threatening basilar artery (BA) occlusion, its occurrence in the posterior circulation has rarely been discussed. Two patients with secondary BA occlusion caused by spontaneous thrombus migration from the VA are presented. A 60-year-old man with a left cerebellar infarction secondary to ipsilateral VA occlusion was admitted to our hospital 8 hours after onset, with a National Institute of Health Stroke Scale (NIHSS) score of 4. The patient became comatose 3.5 hours after arrival owing to subsequent BA occlusion. He was successfully treated with mechanical thrombectomy. A 74-year-old man with right cerebellar infarction secondary to ipsilateral VA occlusion was admitted to our hospital 26 hours after onset, with an NIHSS score of 3. He became comatose 1 hour after arrival owing to BA occlusion and was treated with thrombectomy, followed by internal and external decompression. Despite the mild symptoms of VA occlusion and consequently delayed admission to the hospital, stroke physicians should be aware that spontaneous thrombus migration from the VA to the BA can result in a life-threatening presentation.

Visible-light-induced superhydrophilicity of crystallized WO3 thin films fabricated by using a newly isolated W6+ complex salt of citric acid.

Transparent tungsten trioxide thin films, which demonstrated visible-light (Vis-light)-induced superhydrophilicity, with thicknesses of 100-120 nm, adhesion strengths greater than 49 MPa, bandgap energies of 2.8-2.9 eV, and haze values of 0.4-0.5%, were fabricated using a solution-based process on quartz glass substrates. The precursor solution was prepared by dissolving a W6+ complex salt isolated from a reacted solution of tungstic acid, citric acid, and dibutylamine in H2O, in ethanol. By heating the spin-coated films in air for 30 min at temperatures higher than 500 °C, crystallized WO3 thin films were obtained. The O/W atomic ratio was evaluated to be 2.90, based on the peak area analysis of X-ray photoelectron spectroscopy spectra of the thin-film surfaces, indicating the co-presence of W5+ ions. The water contact angle on film surfaces, which was approximately 25° prior to light irradiation, decreased to less than 10° upon irradiation with 0.06 mW cm-2 Vis-light for only 20 min at 20-25 °C and a relative humidity (RH) of 40-50%. By comparing the contact angle changes at RH values of 20-25%, it was revealed that the interaction between ambient water molecules and the partially O-deficient WO3 thin films plays an important role in achieving photoinduced superhydrophilicity.

Ischemic Stroke Due to Spontaneous Dissection of the Brachiocephalic to the Common Carotid Artery with a Fatal Course after Expansion to the Ascending Aorta.

Spontaneous dissection of the brachiocephalic artery is rare, and there is insufficient evidence for optimal treatment. We herein report a case of ischemic stroke due to spontaneous dissection of the brachiocephalic to the right common carotid artery. The patient was treated medically but died suddenly 18 days after the onset because of aortic dissection. Although almost all reported cases of spontaneous dissection of the brachiocephalic artery have had good outcomes with medical management, it is important to note that sudden development of aortic dissection might occur, even without initial findings suggestive of this condition.

Tandem Lesions of the Vertebrobasilar System Treated by Thrombectomy and Vertebral Artery Stenting: A Case Report.

Objective: There are few reports on endovascular treatment of tandem lesions in the posterior circulation and no consensus on treatment strategies has been reached. We report a case of tandem lesions of basilar artery occlusion and vertebral artery stenosis treated by thrombectomy and vertebral artery stenting. Case Presentation: We present the case of a 73-year-old man who developed consciousness disorder and tetraplegia. Head and neck CTA revealed tandem left vertebral artery stenosis and basilar artery occlusion. The patient was treated using a reverse technique, which involves performing thrombectomy first and then vertebral artery stenting, along with Carotid Guardwire PS. Postoperative impairment of consciousness and improvement of tetraplegia were achieved. Conclusion: The reverse technique combined with Carotid Guardwire PS may be a useful treatment strategy for tandem lesions in the posterior circulation.

Facile Fabrication of Single-Walled Carbon Nanotube/Anatase Composite Thin Film on Quartz Glass Substrate for Translucent Conductive Photoelectrode.

A single-walled carbon nanotube/anatase (SWCNT/anatase) composite thin film with a transmittance of over 70% in the visible-light region was fabricated on a quartz glass substrate by heat treating a precursor film at 500 °C in air. The precursor film was formed by spin coating a mixed solution of the titania molecular precursor and well-dispersed SWCNTs (0.075 mass%) in ethanol. The anatase crystals and Ti3+ ions in the composite thin films were determined by X-ray diffraction and X-ray photoelectron spectroscopy, respectively. The effect of the heating process on the SWCNTs was analyzed using Raman spectroscopy. The composite film showed an even surface with a scratch resistance of 4H pencil hardness, as observed using field-emission scanning electron microscopy and atomic force microscopy. The electrical resistivity and optical bandgap energy of the composite thin film with a thickness of 100 nm were 6.6 × 10-2 Ω cm and 3.4 eV, respectively, when the SWCNT content in the composite thin film was 2.9 mass%. An anodic photocurrent density of 4.2 µA cm-2 was observed under ultraviolet light irradiation (16 mW cm-2 at 365 nm) onto the composite thin film, thus showing excellent properties as a photoelectrode without conductive substrates.

Deep-Ultraviolet Transparent Conductive MWCNT/SiO2 Composite Thin Film Fabricated by UV Irradiation at Ambient Temperature onto Spin-Coated Molecular Precursor Film.

Deep-ultraviolet (DUV) light-transparent conductive composite thin films, consisting of dispersed multiwalled carbon nanotubes (MWCNTs) and SiO2 matrix composites, were fabricated on a quartz glass substrate. Transparent and well-adhered amorphous thin films, with a thickness of 220 nm, were obtained by weak ultraviolet (UV) irradiation (4 mW cm-2 at 254 nm) for more than 6 h at 20-40 °C onto the precursor films, which were obtained by spin coating with a mixed solution of MWCNT in water and Si(IV) complex in ethanol. The electrical resistivity of MWCNT/SiO2 composite thin film is 0.7 Ω·cm, and transmittance in the wavelength region from DUV to visible light is higher than 80%. The MWCNT/SiO2 composite thin film showed scratch resistance at pencil hardness of 8H. Importantly, the resistivity of the MWCNT/SiO2 composite thin film was maintained at the original level even after heat treatment at 500 °C for 1 h. It was observed that the heat treatment of the composite thin film improved durability against both aqueous solutions involving a strong acid (HCl) and a strong base (NaOH).

Fabrication of Transparent and Conductive SWCNT/SiO2 Composite Thin-Film by Photo-Irradiation of Molecular Precursor Films.

A single-walled carbon nanotube (SWCNT)-silica composite thin film on a quartz glass was formed by ultraviolet irradiation (20-40 °C) onto a spin-coated precursor film. With 7.4 mass% SWCNTs, the electrical resistivity reached 7.7 × 10-3 Ω·cm after UV-irradiation. The transmittance was >80% at 178-2600 nm, and 79%-73% at 220-352 nm. Heat treatment increased the transparency and pencil hardness, without affecting the low electrical resistivity. Raman spectroscopy and microscopic analyses revealed the excellent film morphology with good SWCNT dispersal. The low refractive index (1.49) and haze value (<1.5%) are invaluable for transparent windows for novel optoelectronic devices.

In situ gellable oxidized citrus pectin for localized delivery of anticancer drugs and prevention of homotypic cancer cell aggregation.

The aim of this study was to develop in situ gellable hydrogels composed of periodate oxidized citrus pectin (OP) for localized anticancer drug delivery and evaluate the potential of OP to inhibit cancer metastasis. Doxorubicin (Dox) was coupled to OP by imine bonds. Adipic dihydrazide (ADH) was used for cross-linking of the Dox-OP conjugates. The Dox-OP conjugate solution gelled within 2 min after addition of ADH. The release rate of Dox from the hydrogels was controllable by an additive amount of ADH. The released Dox retained anticancer activity. OP was shown to have a potency to prevent homotypic cancer cell aggregation compared to unmodified citrus pectin, strongly suggesting that OP released from hydrogels in vivo will inhibit cancer metastasis. These results indicate that OP hydrogels have the potential to prevent progression of primary cancer by the released Dox and generation of metastatic cancer by the released OP.

In vivo evaluation of composites of PLGA and apatite with two different levels of crystallinity.

The cortical bone response towards poly(lactide-co-glycolide) (70/30) (PLGA) (70/30)/apatite complex scaffolds with different levels of crystallinity was investigated. Apatite with different levels of crystallinity, Ca-deficient hydroxyapatite (CDHA), which has a low crystallinity, and a mixture of carbonated hydroxyapatite (CHA) and CDHA, which has a higher crystallinity, were prepared from an aqueous mixture of Ca-EDTA complex, H(2)O(2), H(3)PO(4), and NH(4)OH. Two porous PLGA(70/30)/apatite composite scaffolds, composite scaffold A (containing low crystallinity CDHA) and composite scaffold B (containing the higher crystallinity CHA/CDHA mixture), were prepared. Afterwards, pure porous PLGA and the two composite scaffolds were implanted into the cortical bone of rabbit tibiae for 12 weeks. High-resolution microfocus X-ray computed tomography and histological examinations revealed a better bone response for composite scaffold A compared with PLGA and composite scaffold B. For composite scaffold A, the original bone defect was almost filled with new bone. Quantitative analysis revealed that composite scaffold A produced a significantly greater amount of new bone. The present study demonstrated that the level of apatite crystallinity influences bone response. A PLGA/apatite porous composite with a low level of apatite crystallinity shows promise as a bone substitute or scaffold material for bone tissue engineering.

Molecular precursor method for thin carbonate-containing apatite coating on dental implants.

The molecular precursor method is an easy and simple method for coating thin carbonate-containing apatite (CA) films onto titanium surfaces. A molecular precursor solution containing ethanol, calcium-EDTA complex, and phosphate salt was dropped onto a titanium surface and then heated at 600°C for 2 h. An adherent thin CA coating was achieved. Animal implantation experiments showed that CA-coated implants had significantly higher bone-to-implant values than non-coated implants (p<0.05). The molecular precursor method was also used to coat three-dimensional titanium webs (TWs). Thin CA films could be coated inside the center area, as well as the surface of the TW, with excellent bone formation inside the CA-coated TW. Furthermore, the molecular precursor method was used to coat partially stabilized zirconia with CA. Better bone response was observed for CA-coated zirconia. From this, it is concluded that the molecular precursor method is useful for producing thin CA coatings on implant materials.

Photo-Induced Super-hydrophilic Thin Films on Quartz Glass by UV Irradiation of Precursor Films Involving a Ti(IV) Complex at Room Temperature.

Photo-induced super-hydrophilic thin films were fabricated on a quartz glass substrate by ultraviolet (UV) irradiation of a molecular precursor film at room temperature. A molecular precursor film exhibiting high solubility to both ethanol and water was obtained by spin-coating a solution involving a Ti(IV) complex; this complex was prepared by the reaction of Ti(IV) alkoxide with butylammonium hydrogen oxalate and hydrogen peroxide in ethanol. Transparent and well-adhered amorphous thin films of 160⁻170 nm thickness were obtained by weak UV irradiation (4 mW·cm-2 at 254 nm) of the precursor films for over 4 h at room temperature. The resultant thin films exhibiting low refractive indices of 1.78⁻1.79 were mechanically robust and water-insoluble. The chemical components of the thin films were examined by means of Fourier transform-infrared (FT-IR) and X-ray photoelectron spectroscopy (XPS) spectra, focusing on the presence of the original ligands. The super-hydrophilic properties (evaluated based on the water contact angles on the surfaces) of the thin films after being kept in a dark condition overnight emerged when the aforementioned UV-light irradiation was performed for 10 min. It was additionally clarified that the super-hydrophilicity can be photo-induced repeatedly by UV irradiation for 10 min (indicated by a contact angle smaller than 4°) even after the hydrophilic level of the thin films had once been lowered by being in a dark condition for 4 h.

An Anatomical Variation in the Cervical Carotid Artery of a Young Stroke Patient.

The cervical carotid artery has been reported to show anatomical variations. We report the case of a young stroke patient with a small right-parietal-lobe infarction whose cervical carotid artery showed anatomical variation. The right internal carotid artery (ICA) originated at the C2 level of the external carotid artery with protrusion at the right carotid bifurcation. The vessel wall of the protrusion showed a high signal intensity on T1-weighted magnetic resonance carotid plaque imaging. The protrusion, considered a remnant of the ICA, possibly caused the stroke due to the formation of thrombi as a result of changes in blood flow and viscosity.

Detecting lenticulostriate artery lesions in patients with acute ischemic stroke using high-resolution MRA at 7 T.

BACKGROUND: Recent advances in high-resolution (HR) magnetic resonance angiography (MRA) using ultrahigh-field systems enable direct visualization of the lenticulostriate arteries (LSAs), which had been hardly achieved by conventional MRA. Hence, by using HR-MRA at 7 T, we attempted to assess occlusive changes in the LSAs in patients with LSA territorial infarcts. METHODS: We prospectively examined 34 consecutive patients with acute ischemic stroke in the LSA territory using a 7 T scanner. We measured the lengths of the relevant LSAs on HR-MRA and the diameters/volume of the infarcts and compared these between the patients with/without occlusive changes in the LSAs. RESULTS: On HR-MRA, occlusion of the LSAs was observed in 19 (59%) of 32 patients who were eligible for the analyses. The curved/straight lengths of the LSAs in the patients with LSA occlusion (23.1-31.1/17.8-24.3 mm) were significantly shorter than in those without apparent LSA occlusion (25.8-39.5/24.0-30.4 mm) ( P = 0.027/0.003). The anteroposterior/superoinferior diameters of the infarcts were significantly larger in the occluded-LSA group (14.5-21.4/14.9-22.2 mm) than in the intact-LSA group (10.9-16.8/10.8-16.2 mm) ( P = 0.041/0.011). In addition, the curved lengths of the relevant LSAs showed significant correlations with the superoinferior diameters of the infarcts ( r = 0.38, P = 0.034). CONCLUSION: Occlusive changes in the LSAs were frequently found in patients with acute ischemic stroke within the LSA territory when using HR-MRA at 7 T and were substantially related to superoinferior extension of the infarcts.

Involvement of an autocrine stromal cell derived factor-1/CXCR4 system on the distant metastasis of human oral squamous cell carcinoma.

We have previously shown that a stromal cell-derived factor-1 (SDF-1; CXCL12)/CXCR4 system is involved in the establishment of lymph node metastasis, but not in that of distant metastasis, in oral squamous cell carcinoma (SCC). In this study, we investigated the role of the autocrine SDF-1/CXCR4 system, with a focus on distant metastasis in oral SCC cells. The immunohistochemical staining of SDF-1 and CXCR4 using primary oral SCCs and metastatic lymph nodes showed a significantly higher number of SDF-1-positive cases among the metastatic lymph nodes than among the primary oral SCCs, which was associated with a poor survival rate among those of the former group. The forced expression of SDF-1 in B88 cells, which exhibit functional CXCR4 and lymph node metastatic potential (i.e., the autocrine SDF-1/CXCR4 system), conferred enhanced cell motility and anchorage-independent growth potential onto the cells. Orthotopic inoculation of the transfectant into nude mice was associated with an increase in the number of metastatic lymph nodes and more aggressive metastatic foci in the lymph nodes. Furthermore, the SDF-1 transfectant (i.e., the autocrine SDF-1/CXCR4 system) exhibited dramatic metastasis to the lung after i.v. inoculation, whereas the mock transfectant (i.e., the paracrine SDF-1/CXCR4 system) did not. Under the present conditions, AMD3100, a CXCR4 antagonist, significantly inhibited the lung metastasis of the SDF-1 transfectant, ameliorated body weight loss, and improved the survival rate of tumor-bearing nude mice. These results suggested that, in cases of oral SCC, the paracrine SDF-1/CXCR4 system potentiates lymph node metastasis, but distant metastasis might require the autocrine SDF-1/CXCR4 system.

S-1 inhibits tumorigenicity and angiogenesis of human oral squamous cell carcinoma cells by suppressing expression of phosphorylated Akt, vascular endothelial growth factor and fibroblast growth factor-2.

It has been reported that S-1 can exert antitumor effects on various human cancers including oral squamous cell carcinoma (OSCC). However, little is known about the detailed mechanisms of the antitumor activity of S-1. In the present study, we determined whether S-1 could suppress the angiogenesis and growth of human OSCC cells in vitro and in vivo. The S-1 component (5-FU plus CDHP) significantly suppressed the growth and migration of OSCC cells and BAEC, which inhibited tubule formation in HUVECs in vitro. Also, S-1 inhibited the nuclear factor-kappaB (NF-kappaB) activity in human OSCC cells in vitro. Moreover, S-1 inhibited the expression of survival signal, phosphorylated Akt (p-Akt), and of two major proangiogenic molecules, vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2), in cells implanted into the subcutaneous tissue of nude mice. The decreased expression of p-Akt, VEGF and FGF-2 correlated with decreased tumorigenicity and decreased vascularization of lesions in vivo. These findings suggest that S-1 can suppress the angiogenesis and growth of OSCC cells by inhibiting the expression of p-Akt, VEGF and FGF-2 involved in the blockade of Akt/NF-kappaB pathway.

Characterization and Bone Response of Carbonate-Containing Apatite-Coated Titanium Implants Using an Aqueous Spray Coating.

We performed thin carbonate-containing apatite (CA) coating on titanium (Ti) by an aqueous spray coating (ASC) method that consisted of a Ca-CO3-PO4 complex. Two different CA coatings were produced by two different spray amounts and were heat-treated after spraying. We evaluated three-dimensional structures, adhesiveness to Ti, and durability of the CA film. In addition, we performed immersion experiments in simulated body fluid (SBF), and bone responses were evaluated after implantation into a femoral bone defect in rats. The bonding ability of ASC-coated implant into the bone was examined by push-in tests. Unique network structures with small particles were identified on CA coatings. Although heat treatment produced no significant difference in surface morphology, scratch tests revealed that heat treatment improved the adhesion of CA coatings to Ti. Crystal formation progressed on CA-coated specimens, and the sample placement direction influenced crystal formation and growth in SBF immersion. Animal implantation experiments revealed significantly greater bone-to-implant contact ratio and bone mass in both cortical and bone marrow, respectively, four weeks after implantation. Push-in tests suggested that the bonding of the CA coating to Ti is clinically acceptable. Therefore, we conclude that CA coating to Ti by the ASC method would be possible for clinical applications, including dentistry.

Epithelial-mesenchymal transition induced by the stromal cell-derived factor-1/CXCR4 system in oral squamous cell carcinoma cells.

Epithelial-mesenchymal transition (EMT) refers to critical events occasionally observed during tumor progression, including invasion and metastasis, by which cancer cells acquire a fibroblast-like phenotype. Since the stromal cell-derived factor-1 (SDF-1)/CXCR4 system can facilitate lymph node metastasis in oral squamous cell carcinoma (SCC), we have explored the possibility that this system might be involved in EMT. Oral SCC cells, B88 and HNt, which have functional CXCR4 and lymph node metastatic potential, were found to lose their epithelial cell morphology due to SDF-1. In this context, the downregulation of epithelial markers, cytokeratin, E-cadherin and beta-catenin, and the upregulation of mesenchymal marker, vimentin and snail were detected. Furthermore, upregulation of vimentin by treatment with SDF-1 was impaired by phosphatidylinositol 3 kinase (PI3K) inhibitor Wortmannin, but not by mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor U0126. In the type I collagen embedding culture, SDF-1-treated B88 cells formed protruding extensions, but the effect was impaired by treatment with Wortmannin. These results suggested that EMT induced by the SDF-1/CXCR4 system might be involved in the lymph node metastasis of oral SCCs via activation of PI3K-Akt/PKB pathway.

Immunosuppressive diacetylenes, ceramides and cerebrosides from Hydrocotyle leucocephala.

Three C-17 diacetylenic compounds (1-3), one monoterpenoid (4), seven ceramides (leucoceramides A-G, 5a-g), six cerebrosides (leucocerebrosides A-F, 6a-f) and nine known compounds were isolated from the methanolic extract of Hydrocotyle leucocephala. Their structures were established by spectroscopic methods. The isolated compounds 1-3, 5a-g, 6a-f and 7 were shown to be active in the lipopolysaccharide (LPS) induced cytokine production assay for IL-10, IL-12, and TNF-alpha.