Serum immunoglobulin G antibody titer to Fusobacterium nucleatum is associated with unfavorable outcome after stroke.

Stroke can be a cause of death, while in non-fatal cases it is a common cause of various disabilities resulting from associated brain damage. However, whether a specific periodontal pathogen is associated with increased risk of unfavorable outcome after stroke remains unknown. We examined risk factors for unfavorable outcome following stroke occurrence, including serum antibody titers to periodontal pathogens. The enrolled cohort included 534 patients who had experienced an acute stroke, who were divided into favorable (n = 337) and unfavorable (n = 197) outcome groups according to modified ranking scale (mRS) score determined at 3 months after onset (favorable = score 0 or 1; unfavorable = score 2-6). The associations of risk factors with unfavorable outcome, including serum titers of IgG antibodies to 16 periodontal pathogens, were examined. Logistic regression analysis showed that the initial National Institutes of Health stroke scale score [odds ratio (OR) = 1·24, 95% confidence interval (CI) = 1·18-1·31, P < 0·001] and C-reactive protein (OR = 1·29, 95% CI = 1·10-1·51, P = 0·002) were independently associated with unfavorable outcome after stroke. Following adjustment with those, detection of the antibody for Fusobacterium nucleatum ATCC 10953 in serum remained an independent predictor of unfavorable outcome (OR = 3·12, 95% CI = 1·55-6·29, P = 0·002). Determination of the antibody titer to F. nucleatum ATCC 10953 in serum may be useful as a predictor of unfavorable outcome after stroke.

The glucagon-like peptide-1 receptor agonist liraglutide improves hypoxia-induced pulmonary hypertension in mice partly via normalization of reduced ET(B) receptor expression.

The glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide is an incretin hormone mimetic used in the treatment of diabetes. However, the effects of liraglutide on pulmonary hypertension (PH) and pulmonary endothelin (ET) system are unknown. Eight-week-old C57BL6/J mice were injected liraglutide or vehicle for 5 weeks. One week after injection, the mice were exposed to either room air (normoxia) or chronic hypoxia (10 % O(2)) for 4 weeks. The right ventricular systolic pressure (RVSP) was significantly higher in hypoxia + vehicle group than in normoxia + vehicle group. ET-1 mRNA expression in the lungs was comparable among all the groups. ET(B) mRNA and protein expression in the lungs was significantly lower in hypoxia + vehicle group than in normoxia + vehicle group. The above changes were normalized by liraglutide treatment. The expression of phospho-eNOS and phospho-AMPK proteins in the lungs was significantly higher in hypoxia + liraglutide group than in normoxia + vehicle group. We demonstrated for the first time that liraglutide effectively improved RVSP and RV hypertrophy in hypoxia-induced PH mice by activating eNOS through normalization of impaired ET(B) pathway and augmentation of AMPK pathway. Therefore, GLP-1R agonists can be promising therapeutic agents for PH.

Observation of the flexoelectricity of a SrTiO3 single crystal by x-ray absorption and emission spectroscopies.

Flexoelectricity, defined as the spontaneous electric polarization in a dielectric material induced by a strain gradient, is investigated from the microscopic viewpoint by x-ray spectroscopy. A single crystal SrTiO3 sample was used as a test system in order to reveal the appearance of the electric dipole moment by simple bending of the crystal. The spectral change characteristic of ferroelectric transition in SrTiO3 was not observed in the Ti K-edge absorption spectra. Instead, the gradual decrease (increase) of the post-edge feature (pre-edge structure) by bending was qualitatively explained using theoretical calculations that assumed the presence of oxygen vacancies and a slight crystal distortion. This assumption is also supported by the broadening of a tiny charge-transfer peak in the Ti Kß resonant emission spectra. Therefore, it was revealed that the flexoelectric effect in SrTiO3 is easily drowned out through local imperfection induced by crystal deformations and cracks.

Larva migrans syndrome caused by Toxocara and Ascaris roundworm infections in Japanese patients.

Larva migrans syndrome (LMS) caused by Toxocara and Ascaris roundworms is generally believed to be more common in children, while a report from Japan suggests that it is more common in adults. We conducted a large-scale retrospective study to confirm these findings and to clarify what caused the difference between Japan and other countries, to reveal overlooked aspects of this disease. The clinical information of 911 cases which we diagnosed as Toxocara or Ascaris LMS during 2001 and 2015 was analysed. Information used included age, sex, address (city or county), chief complaint, present history, dietary history, overseas travelling history, medical imaging findings and laboratory data (white blood cell count, peripheral blood eosinophil number and total IgE). The sex ratio of the disease was 2.37 (male/female = 641/270). The number of patients not younger than 20 years old were 97.8 and 95.1 % among males and females, respectively. Major disease types were visceral, ocular, neural and asymptomatic. The visceral type was more prevalent in older patients, while younger patients were more vulnerable to ocular symptoms. More than two-thirds of the patients whose dietary habits were recorded had a history of ingesting raw or undercooked animal meat. LMS caused by Toxocara or Ascaris is primarily a disease of adult males in Japan, who probably acquired infections by eating raw or undercooked animal meat/liver. Healthcare specialists should draw public attention to the risk of raw or undercooked animal meat in Europe as well.

The identification of raft-derived tau-associated vesicles that are incorporated into immature tangles and paired helical filaments.

AIMS: Neurofibrillary tangles (NFTs), a cardinal pathological feature of neurodegenerative disorders, such as Alzheimer's disease (AD) are primarily composed of hyper-phosphorylated tau protein. Recently, several other molecules, including flotillin-1, phosphatidylinositol-4,5-bisphosphate [PtdIns(4,5)P2] and cyclin-dependent kinase 5 (CDK5), have also been revealed as constituents of NFTs. Flotillin-1 and PtdIns(4,5)P2 are considered markers of raft microdomains, whereas CDK5 is a tau kinase. Therefore, we hypothesized that NFTs have a relationship with raft domains and the tau phosphorylation that occurs within NFTs. METHODS: We investigated six cases of AD, six cases of other neurodegenerative diseases with NFTs and three control cases. We analysed the PtdIns(4,5)P2-immunopositive material in detail, using super-resolution microscopy and electron microscopy to elucidate its pattern of expression. We also investigated the spatial relationship between the PtdIns(4,5)P2-immunopositive material and tau kinases through double immunofluorescence analysis. RESULTS: Pretangles contained either paired helical filaments (PHFs) or PtdIns(4,5)P2-immunopositive small vesicles (approximately 1 µm in diameter) with nearly identical topology to granulovacuolar degeneration (GVD) bodies. Various combinations of these vesicles and GVD bodies, the latter of which are pathological hallmarks observed within the neurons of AD patients, were found concurrently in neurons. These vesicles and GVD bodies were both immunopositive not only for PtdIns(4,5)P2, but also for several tau kinases such as glycogen synthase kinase-3ß and spleen tyrosine kinase. CONCLUSIONS: These observations suggest that clusters of raft-derived vesicles that resemble GVD bodies are substructures of pretangles other than PHFs. These tau kinase-bearing vesicles are likely involved in the modification of tau protein and in NFT formation.

Efficacy of stabilisation splint therapy combined with non-splint multimodal therapy for treating RDC/TMD axis I patients: a randomised controlled trial.

Stabilisation splint therapy has long been thought to be effective for the management of temporomandibular disorders (TMD). However, the superiority of stabilisation splint therapy compared to other TMD treatments remains controversial. The aim of this study was to determine the efficacy of stabilisation splint therapy combined with non-splint multimodal therapy for TMD. A total of 181 TMD participants were randomly allocated to a non-splint multimodal therapy (NS) group (n = 85) or a non-splint multimodal therapy plus stabilisation splint (NS+S) group (n = 96). Non-splint multimodal therapy included self-exercise of the jaw, cognitive-behavioural therapy, self-management education and additional jaw manipulation. Three outcome measurements were used to assess treatment efficacy: mouth-opening limitation, oro-facial pain and temporomandibular joint sounds. A two-factor repeated-measures analysis of variance (anova) was used to evaluate the efficacy of the two treatment modalities (NS vs. NS+S), and Scheffe's multiple comparison test was used to compare the treatment periods. Subgroup analyses were performed to disclose the splint effects for each TMD diagnostic group. All three parameters significantly decreased over time in both groups. However, there were no significant differences between the two treatment groups in the total comparison or subgroup analyses; an exception was the group with degenerative joint disease. No significant difference between the NS and NS+S treatment approaches was revealed in this study. Therefore, we conclude that the additional effects of stabilisation splint are not supported for patients with TMD during the application of multimodal therapy.

Differential serodiagnostics of Toxocara canis and Toxocara cati--is it possible?

One of the most common zoonotic helminth infections is caused by species in the genus Toxocara, particularly Toxocara canis and T. cati (Syn. T. mystax). However, their relative contribution to toxocarosis in humans remains largely unknown because causative larvae are seldom recovered and uncertainties regarding the validity of existing serological assays. In this study, we used sera from a pig model experimentally infected with T. canis and T. cati to evaluate whether a Western blot could discriminate between the two species. No proteins were observed that could be used as a diagnostic tool. In addition, a heterogenic protein pattern between individual hosts was found, which was most pronounced in the T. cati-infected pigs. There is therefore an urgent need to optimize and validate current methods or develop new species-specific serological methods in order to implement appropriate control measures.

Structural, magnetic and electronic state characterization of L1 0-type ordered FeNi alloy extracted from a natural meteorite.

To understand the hard magnetism of L10-type ordered FeNi alloy, we extracted the L10-FeNi phase from a natural meteorite, and evaluated its fundamental solid-state properties: sample composition, magnetic hysteresis, crystal structure and electronic structure. We executed multidirectional analyses using scanning electron microscopy with an electron probe micro-analyzer (SEM-EPMA), a superconducting quantum interference device (SQUID), x-ray diffraction (XRD) and magnetic circular dichroism (MCD). As a result, we found that the composition was Fe: 50.47 ± 1.98 at.%, Ni: 49.60 ± 1.49 at.%, and an obvious superlattice peak is confirmed. The estimated degree of order was 0.608, with lattice constants a = b = 3.582 Å and c = 3.607 Å. The obtained coercivity was more than 500 Oe. MCD analysis using the K absorption edge suggests that the magnetic anisotropy could originate from the orbital magnetic moment of 3d electrons in Fe; this result is consistent with that in a previous report obtained with synthetic L10-FeNi.

Sonographic and clinical features of collateral vessels at the splenic hilum in cirrhosis.

AIM: To examine the sonographic features of shunt vessels derived from the splenic vein at splenic hilum (SS), and explore the relationship between the SS pattern and clinical presentations. MATERIALS AND METHODS: This prospective study in cirrhotic patients consisted of study I (n = 15), which compared the anatomical features of SS at ultrasonography versus angiography, and study II (n = 233), which examined the incidence/haemodynamics of SS and SS-related presentations. RESULTS: Study I showed that SS1 (running toward the upper pole of the spleen) corresponded to short gastric veins, and SS2 (running toward the lower pole of the spleen) corresponded to splenorenal/retroperitoneal shunts. In study II, SS were detected in 47.6% of patients (111/233), SS1 in 77.5% (86/111), SS2 in 17.1% (19/111), and SS3 (both SS1 and SS2) in 5.4% (6/111). The incidence of gastric cardia varices was significantly higher in patients with SS2 (6/19) than in those with SS1 (8/86, p = 0.0097), whereas the incidence of gastric fundal varices was significantly higher in patients with SS1 (44/86) than in those with SS2 (1/19, p = 0.00025) or SS3 (0/6, p = 0.015). There was no difference in the incidence of oesophageal varices among the three SS groups. The Child-Pugh score and grade of ascites was significantly worse in patients with SS3 than in those with SS1 (p < 0.0001, p = 0.0009). Hepatic encephalopathy grade was significantly worse in patients with SS2 (p = 0.0047) or SS3 (p < 0.0001) compared to SS1. CONCLUSION: The SS pattern facilitates estimation of the possible manifestations, indicating the direction of clinical management of cirrhosis patients. Potential poor liver function is noted in patients with SS3.

NOD2 mRNA expression and NFkappaB activation in dogs with lymphocytic plasmacytic colitis.

BACKGROUND: Nucleotide Oligomerization Domain Two (NOD2) is suggested to be an intracellular pathogen-associated molecular pattern recognition molecule. NOD2, plays a key role against bacteria by triggering a host defense response through activation of the transcription factor NFkappaB and subsequent proinflammatory cytokine production. NOD2 recently was reported to be overproduced in inflamed colonic mucosa in Crohn's disease, and to be accompanied by a significant increase in NFkappaB activity. However, few studies to date have investigated intercellular signaling molecules in dogs with lymphocytic plasmacytic colitis (LPC). HYPOTHESIS: NOD2 mRNA expression and NFkappaB activation are increased in mucosal biopsies of LPC dogs as compared with control dogs. ANIMALS: Five healthy dogs and 19 dogs with LPC. METHODS: Descending colon biopsies were obtained endoscopically. Expression of NOD2 mRNA was evaluated by semiquantitative RT-PCR in the colonic mucosa. NFkappaB binding activity was assessed by electrophoretic mobility shift assay. RESULTS: NOD2 mRNA expression was approximately 63% greater in LPC dogs than in healthy controls (P = .019). NFkappaB binding activity was approximately 45% higher in the inflamed colonic mucosa of the LPC dogs, as compared with healthy controls (P = .011). No correlations were observed among NOD2 mRNA expression levels, NFkappaB binding activity, and CIBDAI in LPC dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: NOD2 mRNA and NFkappaB activity were significantly higher in the inflamed colon of dogs with LPC, as compared with healthy controls. Our data suggest that NOD2 and NFkappaB play an important role in the pathogenesis of LPC.

SU-E-T-497: Study of Restricted Mass Stopping Power Ratio in Small Electron Tube Fields.

PURPOSE: Electron tubes with small radii are useful to treat narrow regions which cannot accommodate normal electron applicators. In small electron fields, it is not trivial to estimate restricted mass stopping power ratio (MSR), which is needed to evaluate dose from ion chamber measurement. We studied MSRs in small electron tube fields using the Monte Carlo simulation. METHODS: Electron tubes with radii, 3 and 2.5 cm, were used in this study. Nominal electron energies were 6 and 9 MeV. There were two types of tubes. One has a normal cut but the other has a 45-degree cut. For the normal cut tube, percent depth dose (PDD) in water was evaluated along the center of axis (CAX) of a beam. For the 45-degree cut tube, PDD was evaluated along the vertical line from the intersection of the CAX and the phantom surface with 45-degree gantry angle. The MSRs and mean electron energies were calculated using the Monte Carlo simulation. RESULTS: We found good agreement between the measured and calculated PDDs. The changes of mean energies from those in the 10×10 cm2 field at the depth of maximum dose (dmax) were very small for the normal cut electron tubes. For the 45-degree cut tubes, the changes of mean energies at dmax were less than 1 MeV. The MSRs in the normal cut tube fields were almost the same as those in the 10×10 cm2 field at the corresponding depths. The MSRs for the 45-degree cut tubes deviated from those in the 10×10 cm2 by about 1% (1.5 % at most). CONCLUSIONS: We evaluated the mean energies and MSRs in small electron tube fields. The deviations of them from the values in the 10×10 cm2 were small. The maximum difference of MSR was 1.5% in 45-degree cut tube fields. This work was supported by KAKENHI (23791449), Japan Society for the Promotion of Science, and Cancer Professional Training Plan, The Ministry of Education, Culture, Sports, Science and Technology, Japan.

Contrast-enhanced ultrasound for characterisation of hepatic lesions appearing non-hypervascular on CT in chronic liver diseases.

OBJECTIVES: The purpose of this prospective study was to elucidate the efficacy of using contrast-enhanced ultrasound to characterise focal hepatic lesions appearing non-hypervascular on contrast-enhanced CT in chronic liver diseases. METHODS: The study population included 22 patients with cirrhosis or chronic hepatitis, who between them had 27 focal hepatic lesions smaller than 20 mm (mean 13.9 ± 3.4) that appeared non-hypervascular on contrast-enhanced CT. Contrast-enhanced ultrasound with perflubutane microbubble agent (Sonazoid, 0.0075 ml kg(-1)) was performed prior to ultrasound-guided needle biopsy, and intensity analysis was done for hepatic lesions in the early phase (-60 s) and late phase (600 s post injection). RESULTS: All seven early-phase hyperenhanced lesions were hepatocellular carcinoma (HCC). 20 lesions iso- or hypoenhanced during the early phase consisted of 11 regenerative nodules (RNs) and 9 HCCs. HCC was more frequent in early-phase hyperenhanced lesions than in iso- or hypoenhanced lesions (p=0.0108). Both late-phase hypoenhanced lesions were HCCs, whereas 25 late-phase isoenhanced lesions consisted of 11 RNs and 14 HCCs. The enhancement patterns of the 11 RNs included isoenhanced appearance in both the early and late phases in 8 lesions, and early-phase hypoenhancement combined with late-phase isoenhancement in the remaining 3. Both of these enhancement patterns (i.e. either iso-iso or hypo-iso) were found in 9 malignant lesions, 9 (75%) of the 12 well-differentiated HCCs. CONCLUSION: Hypervascularity on contrast-enhanced ultrasound with Sonazoid strongly suggested HCC regardless of non-hypervascularity on CT, and late-phase hypoenhancement was another possible finding of HCC. However, characterisation of hepatic lesions with other enhancement patterns was difficult using our technique.

Non-invasive portography: a microbubble-induced three-dimensional sonogram for discriminating idiopathic portal hypertension from cirrhosis.

OBJECTIVES: The aim of this prospective study was to elucidate the efficacy of contrast-enhanced three-dimensional (3D) ultrasound with Sonazoid(®) (GF Healthcare, Oslo, Norway) as a non-invasive tool to discriminate idiopathic portal hypertension (IPH) from cirrhosis by demonstration of portal vein structure. METHODS: There were 16 patients: 11 with biopsy-proven cirrhosis and 5 with biopsy-proven IPH. Intrahepatic right portal vein images were taken by 3D ultrasound from 1 min after the injection of Sonazoid (0.0075 ml kg(-1)). Portal vein appearances were compared between 3D ultrasound and percutaneous transhepatic portography (PTP) by four independent reviewers. Sensitivity, specificity and area under the receiver operating characteristic curve (Az) of the images were used for the diagnosis of cirrhosis/IPH, and interimaging, inter-reviewer and interoperator agreement were examined. RESULTS: Sensitivity, specificity and Az of PTP for the diagnosis of cirrhosis/IPH were 63.6%/100%, 100% and 0.9 (0.71-1.0) by Reviewer I and 90.9%/100%, 100% and 1.0 by Reviewer III, respectively. Similarly, sensitivity, specificity and Az of 3D ultrasound for diagnosis of cirrhosis/IPH were 54.5%/80%, 100% and 0.96 (0.84-1.0) by Reviewer II and 72.7%/80%, 100% and 0.97 (0.9-1.0) by Reviewer IV, respectively. Diagnostic agreement between PTP and 3D ultrasound was good between Reviewers I and II (κ=0.793) and good between Reviewers III and IV (κ=0.732). Inter-reviewer agreement was good between Reviewers I and III for PTP diagnosis (κ=0.735), and good between Reviewers II and IV for 3D ultrasound diagnosis (κ=0.792). Interoperator agreement of diagnostic results was good (κ=0.740). CONCLUSION: Non-invasive visualisation of intrahepatic portal vein structure by contrast-enhanced 3D ultrasound with Sonazoid may have the potential to discriminate IPH from cirrhosis.

Usefulness of MRA-DWI mismatch in neuroendovascular therapy for acute cerebral infarction.

BACKGROUND: This study evaluated the usefulness of MR angiography (MRA)-diffusion-weighted imaging (DWI) mismatch in neuroendovascular therapy over 3 h after onset of acute cerebral infarction. METHODS: The subjects were 14 cases (age, 73 ± 8.4 years) who had an anterior circulation deficit on DWI/MRA on arrival and underwent neuroendovascular therapy over 3 h after onset. MRA-DWI mismatch (MDM) (+) was defined as 'major artery lesion (+) and diffusion-weighted image-Alberta Stroke Program Early CT Score (DWI-ASPECTS) ≥6'; MDM (-) was defined as 'major artery lesion (+) and DWI-ASPECTS <6'. RESULTS: Reperfusion was achieved in nine of 14 patients (64%) undergoing neuroendovascular therapy. Within the reperfusion group, in the five MDM (+) patients and the four MDM (-) patients, the outcome was a favorable clinical response in the MDM (+) group. The modified Rankin Scale (mRS) scores after 90 days were 0-2 in 3 (60%) and 3-6 in 2 (40%) of the MDM (+) group patients and 0-2 in 0 (0%) and 3-6 in 4 (100%) of the MDM (-) group patients. In the MDM (+) group, a good outcome was achieved. However, the number of cases was small, so this was not a significant difference. Within the non-reperfusion group, in the three MDM (+) patients and the two MDM (-) patients, the mRS scores after 90 days were 0-2 in 1 (33%) and 3-6 in 2 (67%) of the MDM (+) group patients and 0-2 in 0 (0%) and 3-6 in 2 (100%) of the MDM (-) group patients. In both groups, the outcome was poor. CONCLUSIONS: With neuroendovascular therapy, a good outcome with reperfusion was achieved in the MDM (+) group compared to the MDM (-) group. This suggests that the presence or absence of MDM may be useful in determining prognosis after reperfusion.

Molecular cloning, in vitro expression and functional characterization of canine ADAMTS13.

A disintegrin and metalloproteinase with thrombospondin type 1 motifs, number 13 (ADAMTS13) is a plasma zinc metalloprotease also known as von Willebrand factor (VWF)-cleaving protease. Deficiency of ADAMTS13 activity is known to cause thrombotic thrombocytopenic purpura (TTP) in humans. We isolated the canine ADAMTS13 cDNA, which encodes 1502 amino acids, and expressed the recombinant protein to evaluate VWF-cleaving ability. Although the propeptide domain was longer and the TSP1 repeat domain was shorter than those in other species, the overall structures were similar to human and mouse ADAMTS13. Recombinant canine ADAMTS13 cleaved the 250-kDa VWF monomer into two fragments of 150 kDa and 120 kDa. Furthermore, high molecular weight VWF multimers were abolished based on the activity of ADAMTS13. These results could facilitate research into hemostatic disorders such as TTP in dogs.