Lesional activation of Tc 17 cells in Behçet disease and psoriasis supports HLA class I-mediated autoimmune responses.

BACKGROUND: Behçet disease (BD) presents with lymphocytic and neutrophilic vasculitis of unknown aetiology. HLA-B*51, the endoplasmic reticulum aminopeptidase 1 (ERAP1), and interleukin 23 receptor (IL23R)/IL12R are genetic risk factors. IL-23 regulates IL-17A, which controls the recruitment and activation of neutrophils. OBJECTIVES: To determine pathological changes in BD skin lesions related to the complex genetic predisposition. METHODS: We characterized the expression of IL-17A and IL-23A in various cell types by immunohistological double staining of sections from papulopustular skin lesions of acute attacks of BD and psoriasis vulgaris lesions, another HLA-class I-associated T-cell-mediated autoimmune disease in which excessive T-cell-derived IL-17A production promotes neutrophil activation. RESULTS: We found that in BD lesions, as in psoriasis, actively expanding CD8+ T cells were the predominant source of IL-17A. IL-17A+ CD8+ T (Tc 17) cells outnumbered infiltrating IL-17A+ CD4+ T cells. Unlike the epidermal localization of CD8+ T cells in psoriasis, Tc 17 cells in BD lesions mainly infiltrated the perivascular tissue and the blood vessel walls of dermis and subcutaneous tissue. They co-localised with a marked IL-23A expression by CD11c+ dendritic cells and CD68+ macrophages. IL-17A expression was associated with extensive recruitment of neutrophils around blood vessels that formed neutrophil extracellular traps (NETs). CONCLUSIONS: In BD, the genetic predisposition may mediate antigen-specific activation and differentiation of a Tc 17 response, possibly targeting endothelial (auto)antigens. Neutrophils recruited by IL-17A in this process may enhance tissue damage by extensive NET formation (NETosis). Thus, the IL-23/IL-17 axis presumably controls neutrophilic inflammation in BD vasculitis in the context of a predominant antigen-specific CD8+ T-cell response.

Addition of Amide Proton Transfer Imaging to FDG-PET/CT Improves Diagnostic Accuracy in Glioma Grading: A Preliminary Study Using the Continuous Net Reclassification Analysis.

BACKGROUND AND PURPOSE: Amide proton transfer imaging has been successfully applied to brain tumors, however, the relationships between amide proton transfer and other quantitative imaging values have yet to be investigated. The aim was to examine the additive value of amide proton transfer imaging alongside [18F] FDG-PET and DWI for preoperative grading of gliomas. MATERIALS AND METHODS: Forty-nine patients with newly diagnosed gliomas were included in this retrospective study. All patients had undergone MR imaging, including DWI and amide proton transfer imaging on 3T scanners, and [18F] FDG-PET. Logistic regression analyses were conducted to examine the relationship between each imaging parameter and the presence of high-grade (grade III and/or IV) glioma. These parameters included the tumor-to-normal ratio of FDG uptake, minimum ADC, mean amide proton transfer value, and their combinations. In each model, the overall discriminative power for the detection of high-grade glioma was assessed with receiver operating characteristic curve analysis. Additive information from minimum ADC and mean amide proton transfer was also evaluated by continuous net reclassification improvement. P < .05 was considered significant. RESULTS: Tumor-to-normal ratio, minimum ADC, and mean amide proton transfer demonstrated comparable diagnostic accuracy in differentiating high-grade from low-grade gliomas. When mean amide proton transfer was combined with the tumor-to-normal ratio, the continuous net reclassification improvement was 0.64 (95% CI, 0.036-1.24; P = .04) for diagnosing high-grade glioma and 0.95 (95% CI, 0.39-1.52; P = .001) for diagnosing glioblastoma. When minimum ADC was combined with the tumor-to-normal ratio, the continuous net reclassification improvement was 0.43 (95% CI, -0.17-1.04; P = .16) for diagnosing high-grade glioma, and 1.36 (95% CI, 0.79-1.92; P < .001) for diagnosing glioblastoma. CONCLUSIONS: Addition of amide proton transfer imaging to FDG-PET/CT may improve the ability to differentiate high-grade from low-grade gliomas.

Temperature dependence of the single photon emission from interface-fluctuation GaN quantum dots.

The temperature dependent single photon emission statistics of interface-fluctuation GaN quantum dots are reported. Quantum light emission is confirmed at temperatures up to ~77 K, by which point the background emission degrades the emission purity and results in a measured g(2) (0) in excess of 0.5. A discussion on the extent of the background contamination is also given through comparison to extensive data taken under various ambient and experimental conditions, revealing that the quantum dots themselves are emitting single photons with high purity.

The IL15 +96522 A>T functional polymorphism is related to the differentiation of Th17 cells and the severity of Hashimoto's disease.

To clarify the association between the genetic producibility of IL-15, a pro-inflammatory cytokine, and the pathogenesis of autoimmune thyroid diseases (AITDs), we genotyped +96522 A>T and +82889 A>G polymorphisms in the IL15 gene using 127 patients with Hashimoto's disease (HD), including 55 patients with severe HD and 48 patients with mild HD; 130 patients with Graves' disease (GD), including 52 patients with intractable GD and 44 patients with GD in remission; and 79 healthy volunteers. Both the IL15 +96522 A allele and AA genotype were more frequent in patients with severe HD than in those with mild HD. The serum levels of IL-15 were higher in individuals with the IL15 +96522 AA genotype than in those with the T allele, and they were also higher in patients with severe HD than in those with mild HD. On the other hand, the mRNA levels of IL-15 were not significantly different among individuals with each genotype of both SNPs. After incubation with recombinant human IL-15, the proportions of Th17 cells in CD4+ cells were increased, and those of Treg cells in CD4+ cells were maintained. Our study indicates that the IL15 +96522A/C polymorphism correlates with the severity of HD, most likely by increasing Th17 cells.

Reduction in chlorhexidine efficacy against multi-drug-resistant Acinetobacter baumannii international clone II.

BACKGROUND: Nosocomial infections caused by Acinetobacter baumannii international clone II (IC II) can cause severe clinical outcomes. AIM: Differential evaluation of bactericidal efficacy of chlorhexidine gluconate (CHX) and benzethonium chloride (BZT) disinfectants against IC II and non-IC II isolates. METHODS: Minimum inhibitory concentrations (MICs) of CHX and BZT were determined for 137 A. baumannii IC II, 99 non-IC II and 69 non-baumannii isolates, further classified according to MIC values into disinfectant-reduced susceptible (DRS) and disinfectant-susceptible (DS) groups. Time-kill curves and minimum bactericidal concentrations (MBCs) were evaluated for representative isolates in each group. RESULTS: CHX and BZT MIC90s for IC II isolates were 100 and 175mg/L, respectively, but those for non-IC II and non-baumannii isolates were <100mg/L. Nevertheless, time-kill curves indicated that CHX and BZT reduced live bacterial cell number by 5 log10 for IC II and non-IC II isolates within 30s when used at 1000mg/L, comparable to practical use concentrations. CHX MBC at 30s was 1000mg/L for IC II and non-IC II isolates, and was not influenced by addition of 3% bovine serum albumin (BSA); BZT MBC at 30s was 100mg/L without BSA and increased up to 500mg/L upon addition of BSA. No significant differences in BSA were found between DRS and DS isolates. CONCLUSION: CHX and BZT were effective against Acinetobacter spp. including IC II at a concentration of 1000mg/L and exposure for at least 30s, but their concentrations should be considered carefully to ensure sufficient effects in both clinical and healthcare settings.

High prevalence of fosfomycin resistance gene fosA3 in bla CTX-M-harbouring Escherichia coli from urine in a Chinese tertiary hospital during 2010-2014.

Fosfomycin has become a therapeutic option in urinary tract infections. We identified 57 fosfomycin-resistant Escherichia coli from 465 urine-derived extended-spectrum ß-lactamase (ESBL)-producing isolates from a Chinese hospital during 2010-2014. Of the 57 fosfomycin-resistant isolates, 51 (89·5%) carried fosA3, and one carried fosA1. Divergent pulsed-field gel electrophoresis profiles and multi-locus sequence typing results revealed high clonal diversity in the fosA3-positive isolates. Conjugation experiments showed that the fosA3 genes from 50 isolates were transferable, with IncFII or IncI1 being the most prevalent types of plasmids. The high prevalence of fosA3 was closely associated with that of bla CTX-M. Horizontal transfer, rather than clonal expansion, might play a central role in dissemination. Such strains may constitute an important reservoir of fosA3 and bla CTX-M, which may well be readily disseminated to other potential human pathogens. Since most ESBL-producing E. coli have acquired resistance to fluoroquinolones worldwide, further spread of fosA3 in such E. coli isolates should be monitored closely.

Long-term outcome of 6-month maintenance chemotherapy for acute lymphoblastic leukemia in children.

In the treatment of childhood acute lymphoblastic leukemia (ALL), excess shortening of maintenance therapy resulted in high relapse rate, as shown by our previous trial, TCCSG L92-13, in which maintenance therapy was terminated at 1 year from initiation of treatment. In this study, we aimed to confirm the long-term outcome of L92-13, and to identify who can or cannot be cured by shorter duration of maintenance therapy. To obtain sentinel cytogenetics information that had been missed before, we performed genetic analysis with genomic microarray and target intron-capture sequencing from diagnostic bone marrow smear. Disease-free survival (DFS) at 10 years from the end of therapy was 66.0±2.8%. Females (n=138) had better DFS (74.6±3.7%) than males (n=142, 57.5±4.2%, P=0.002). Patients with TCF3-PBX1 (n=11) and ETV6-RUNX1 (n=16) had excellent DFS (90.9±8.7% and 93.8±6.1%, respectively), whereas high hyperdiploidy (n=23) was the most unfavorable subgroup, with 56.6±10.3% of DFS. Short duration of therapy can cure more than half of pediatric ALL, especially females, TCF3-PBX1 and ETV6-RUNX1. Our retrospective observations suggest a gender/karyotype inhomogeneity on the impact of brief therapy.

High current DC negative ion source for cyclotron.

A filament driven multi-cusp negative ion source has been developed for proton cyclotrons in medical applications. In Cs-free operation, continuous H(-) beam of 10 mA and D(-) beam of 3.3 mA were obtained stably at an arc-discharge power of 3 kW and 2.4 kW, respectively. In Cs-seeded operation, H(-) beam current reached 22 mA at a lower arc power of 2.6 kW with less co-extracted electron current. The optimum gas flow rate, which gives the highest H(-) current, was 15 sccm in the Cs-free operation, while it decreased to 4 sccm in the Cs-seeded operation. The relationship between H(-) production and the design/operating parameters has been also investigated by a numerical study with KEIO-MARC code, which gives a reasonable explanation to the experimental results of the H(-) current dependence on the arc power.

Performance evaluation of the small-animal PET scanner ClairvivoPET using NEMA NU 4-2008 Standards.

The aim of this study was to evaluate the performance of ClairvivoPET using NEMA NU4 standards. The ClairvivoPET incorporates a LYSO dual depth-of-interaction detector system with 151 mm axial field of view (FOV). Spatial resolution, sensitivity, counting rate capabilities, and image quality were evaluated using NEMA NU4-2008 standards. Normal mouse imaging was also performed for 10 min after intravenous injection of (18)F(-)-NaF. Data were compared with 19 other preclinical PET scanners. Spatial resolution measured using full width at half maximum on FBP-ramp reconstructed images was 2.16 mm at radial offset 5 mm of the axial centre FOV. The maximum absolute sensitivity for a point source at the FOV centre was 8.72%. Peak noise equivalent counting rate (NECR) was 415 kcps at 14.6 MBq ml(-1). The uniformity with the image-quality phantom was 4.62%. Spillover ratios in the images of air and water filled chambers were 0.19 and 0.06, respectively. Our results were comparable with the 19 other preclinical PET scanners based on NEMA NU4 standards, with excellent sensitivity because of the large FOV. The ClairvivoPET with iterative reconstruction algorithm also provided sufficient visualization of the mouse spine. The high sensitivity and resolution of the ClairvivoPET scanner provided high quality images for preclinical studies.

Differentiation between primary central nervous system lymphoma and glioblastoma: a comparative study of parameters derived from dynamic susceptibility contrast-enhanced perfusion-weighted MRI.

AIM: To evaluate the diagnostic performance of parameters derived from dynamic susceptibility contrast-enhanced perfusion-weighted magnetic resonance imaging, including first-pass slope ratio (FSR), which is potentially easier to derive than the other proposed parameters in this study, for differentiating primary central nervous system lymphoma (PCNSL) from glioblastoma. MATERIALS AND METHODS: Twenty-eight patients (10 PCNSLs and 18 glioblastomas) were analysed. Six perfusion parameters - corrected cerebral blood volume ratio (cCBVR), uncorrected CBV ratio (uCBVR), FSR, leakage coefficient (K2), percentage of signal-intensity recovery measured at the end of the first-pass (PSRend), and PSR measured using mean signal-intensity after the first-pass (PSRmean) - were derived from enhancing areas selected semi-automatically. Comparisons of cCBVR and uCBVR and of PSRend and PSRmean were conducted. The differences between PCNSL and glioblastoma were compared for the six parameters, and their diagnostic performance was evaluated by receiver operating characteristic curve analysis. RESULTS: For both tumours, cCBVR was significantly higher than uCBVR, and PSRend was significantly lower than PSRmean. PCNSL demonstrated lower cCBVR, uCBVR and FSR, and higher K2, PSRend and PSRmean compared with glioblastoma (p=0.0044 or less). On receiver operating characteristic curve analysis, the areas under the curve were 0.822 for cCBVR, 0.944 for uCBVR, 0.917 for FSR, 0.917 for K2, 0.933 for PSRend, and 0.894 for PSRmean. No significant difference was observed among the parameters, except cCBVR, which was significantly inferior to uCBVR. CONCLUSIONS: PCNSL can be differentiated from glioblastoma with high diagnostic value using any of the parameters, except cCBVR. FSR demonstrates high differential performance comparable to the other parameters.

Ultralow mode-volume photonic crystal nanobeam cavities for high-efficiency coupling to individual carbon nanotube emitters.

The unique emission properties of single-walled carbon nanotubes are attractive for achieving increased functionality in integrated photonics. In addition to being room-temperature telecom-band emitters that can be directly grown on silicon, they are ideal for coupling to nanoscale photonic structures. Here we report on high-efficiency coupling of individual air-suspended carbon nanotubes to silicon photonic crystal nanobeam cavities. Photoluminescence images of dielectric- and air-mode cavities reflect their distinctly different mode profiles and show that fields in the air are important for coupling. We find that the air-mode cavities couple more efficiently, and estimated spontaneous emission coupling factors reach a value as high as 0.85. Our results demonstrate advantages of ultralow mode-volumes in air-mode cavities for coupling to low-dimensional nanoscale emitters.

Development of a high current H(-) ion source for cyclotrons.

A multi-cusp DC H(-) ion source has been designed and fabricated for medical applications of cyclotrons. Optimization of the ion source is in progress, such as the improvement of the filament configuration, magnetic filter strength, extraction electrode's shape, configuration of electron suppression magnets, and plasma electrode material. A small quantity of Cs has been introduced into the ion source to enhance the negative ion beam current. The ion source produced 16 mA of DC H(-) ion beam with the Cs-seeded operation at a low arc discharge power of 2.8 kW.

One-stop shop for 3-dimensional anatomy of hepatic vasculature and bile duct with special reference to biliary image reconstruction.

BACKGROUND/AIMS: Three-dimensional CT has become an essential tool for successful hepatic surgery. Up to now, efforts have been made to simultaneously visualize hepatic vasculature and bile ducts. Herein, we introduce a new one-stop shop approach to hepatic 3D-anatomy, using a standard enhanced MDCT alone. METHODOLOGY: A 3D-reconstruction of hepatic vasculature was made using data from contrast enhanced MDCT and SYNAPSE VINCENT software. We identified bile ducts from axial 2D image, and then reconstructed the 3D image. Both hepatic vasculature and bile duct images were integrated into a single image and it was compared with the 3D image, utilized with MRCP or DIC-CT. RESULTS: The first branches of both the right and left hepatic ducts were hand-traced and visualized for all 100 cases. The second branches of these ducts were visualized in 69 cases, and only the right second branch was recognized in 52 cases. Anomalous variations of bile ducts, such as posterior branch joining into common hepatic duct, were recognized in 12 cases. These biliary tract variations were all confirmed by MRCP or DIC-CT. CONCLUSIONS: Our new one-stop shop approach using the 3D imaging technique might contribute to successful hepatectomy as well as reduce medical costs and radiation exposure by omission of MRCP and DIC-CT.

Measurement of an exciton Rabi rotation in a single GaN/Al(x)Ga(1-x)N nanowire-quantum dot using photoluminescence spectroscopy: evidence for coherent control.

Experimental observation of excited state exciton Rabi rotation in a single GaN quantum dot is presented. The dot is embedded in a site-controlled GaN/AlGaN nanowire. Damped oscillation is observed in the power-dependent spectra of the quantum-dot ground state upon resonant pumping of an excited state that had been identified by photoluminescence excitation spectroscopy. A discussion on the origins of the damping is given.

Giant optical rotation in a three-dimensional semiconductor chiral photonic crystal.

Optical rotation is experimentally demonstrated in a semiconductor-based three-dimensional chiral photonic crystal (PhC) at a telecommunication wavelength. We design a rotationally-stacked woodpile PhC structure, where neighboring layers are rotated by 45° and four layers construct a single helical unit. The mirror-asymmetric PhC made from GaAs with sub-micron periodicity is fabricated by a micro-manipulation technique. The linearly polarized light incident on the structure undergoes optical rotation during transmission. The obtained results show good agreement with numerical simulations. The measurement demonstrates the largest optical rotation angle as large as ∼ 23° at 1.3 µm wavelength for a single helical unit.

Association of polymorphisms in DNMT1, DNMT3A, DNMT3B, MTHFR and MTRR genes with global DNA methylation levels and prognosis of autoimmune thyroid disease.

To clarify the association between factors regulating DNA methylation and the prognosis of autoimmune thyroid diseases (AITDs), we genotyped single nucleotide polymorphisms in genes encoding DNA methyltransferase 1 (DNMT1), DNMT3A, DNMT3B, methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR), which are enzymes essential for DNA methylation. Subjects for this study included 125 patients with Hashimoto's disease (HD), including 48 patients with severe HD and 49 patients with mild HD; 176 patients with Graves' disease (GD), including 79 patients with intractable GD and 47 patients with GD in remission; and 83 healthy volunteers (control subjects). The DNMT1+32204GG genotype was more frequent in patients with intractable GD than in patients with GD in remission. Genomic DNA showed significantly lower levels of global methylation in individuals with the DNMT1+32204GG genotype than in those with the AA genotype. The MTRR+66AA genotype was observed to be more frequent in patients with severe HD than in those with mild HD. The DNMT1+14395A/G, DNMT3B-579G/T, MTHFR+677C/T and +1298A/C polymorphisms were not correlated with the development or prognosis of AITD. Our study indicates that the DNMT1+32204GG genotype correlates with DNA hypomethylation and with the intractability of GD, and that the MTRR+66AA genotype may correlate with the severity of HD.

Genotypes and infection sites in an outbreak of multidrug-resistant Pseudomonas aeruginosa.

An outbreak of multidrug-resistant (MDR) Pseudomonas aeruginosa occurred in an acute care hospital in Japan, which lasted for more than three years. During January 2006 to June 2009, 59 hospitalised patients with MDR P. aeruginosa were mainly detected by urine culture in the first half, whereas isolation from respiratory tract samples became dominant in the latter half of the outbreak. Non-duplicate MDR P. aeruginosa isolates were available from 51 patients and all isolates were positive for bla(VIM-2). Pulsed-field gel electrophoresis (PFGE) analysis categorised the isolates into three major clusters; types A, B and C with eight, 19 and 21 isolates, respectively. The outbreak started with patients harbouring PFGE type A strains, followed by type B, and type C strains. Multivariate analysis demonstrated that patients with PFGE type C strains were more likely to be detected by respiratory tract samples (odds ratio: 11.87; 95% confidence interval: 1.21-116.86). Improved aseptic urethral catheter care controlled PFGE type A and type B strains and improvement in respiratory care procedures finally contained the transmission of PFGE type C strains.