[Evaluation of AEC Consistency in Digital X-ray Imaging Systems].

The Japan Network for Research and Information on Medical Exposures (J-RIME) established the diagnostic reference level (DRL) and is advancing optimization of radiation protection. We believe that the difference in the imaging dose between facilities may be due to the fact that automatic exposure control (AEC) adjustment is not unified among manufacturers. The consistency of AEC is specified in JIS 4751-2-54, but it is not applicable to digital X-ray imaging systems because it is for optical density of analog X-ray imaging systems. This article evaluates the consistency of AEC in digital X-ray imaging systems. The AEC consistency was compared with the AEC-estimated dose from the air kerma (KAEC) using the phosphor-based imaging plate placed at the back of the AEC detector. We measured the AEC tube voltage and subject thickness characteristics (tracking) of four types of digital X-ray imaging systems at three facilities. In the test of tube voltage characteristics, the average KAEC values at all tube voltages were 2.37±0.04 µGy for A system, 7.30±1.44 µGy for B system, 3.53±0.13 µGy for C system, and 5.70±0.18 µGy for D system. The relative errors were +2.6 to -1.8% for A system, +25.3 to -22.6% for B system, +5.2 to -1.4% for C system, and +2.5 to -4.4% for D system. In the subject thickness characteristics test, the average KAEC values for all Al thicknesses were 2.34±0.02 µGy for A system, 5.95±0.23 µGy for B system, 4.25±1.12 µGy for C system, and 5.03±1.27 µGy for D system. The relative errors were +1.0 to -0.9% for A system, +4.1 to -5.0% for B system, +40.5 to -28.1% for C system, and +19.7 to -42.9% for D system.

One-pot analysis of enantiomeric excess of free amino acids by electrospray ionization mass spectrometry.

An electrospray ionization mass spectrometric method for the simultaneous analysis of the enantiomeric excess of free amino acids, without chromatographic separation, was demonstrated using a quasi-racemic mixture of deuterium-labelled and unlabelled chiral copper(ii) complexes. This convenient method enables the simultaneous high-sensitivity determination of the enantiomeric excess of 12 amino acids.

Enantioselectivity-Evaluation of Chiral Copper(II) Complexes Coordinated by Novel Chiral Tetradentate Ligands for Free Amino Acids by Mass Spectrometry Coupled With the Isotopically Labeled Enantiomer Method.

A series of copper(II) complexes with chiral tetradentate ligands, N,N'-ethylene- bis(S-amino acid methyl amide or methyl ester) prepared from S-alanine, S-phenylalanine, S-valine or S-proline, was generated in methanol. The copper complexes provided three component complexes in the presence of a free chiral amino acid. The enantioselectivity for the amino acid was evaluated by electrospray ionization-mass spectrometry coupled with the deuterium-labeled enantiomer method and these copper complexes were found to exhibit high enantioselectivity for free amino acids having bulky side chains. This result suggests that steric interaction between the tetradentate ligand and free amino acid was a major factor in chiral recognition. The copper complex with a chiral tetradentate ligand prepared from S-proline showed opposite enantioselectivity to copper complexes consisting of tetradentate ligands prepared from other S-amino acids. The conformational difference of the tetradentate ligand in the copper complex was found to be significant for enantioselectivity.

Mass spectrometric detection of enantioselectivity in three-component complexation, copper(ii)-chiral tetradentate ligand-free amino acid in solution.

By using electrospray ionization mass spectrometry coupled with the use of deuterium-labelled quasienantiomers, enantioselective coordination of a free amino acid as the second ligand of a copper(ii) complex with a novel chiral tetradentate ligand was evaluated quantitatively in a short measurement time.

[Report Based on Fiscal 2015 Diagnostic X-ray Equipment Questionnaire Survey].

We have conducted a questionnaire survey every 5 years from 1974 to grasp the existing status of X-ray equipment. This time, we will report on the results of the fiscal 2015 diagnostic X-ray equipment questionnaire survey. Compared to the previous survey on X-ray equipment, there has been a progress in the introduction of inverter type X-ray generators and image receptor systems in digital systems. We think that this transition will be occurred when the X-ray equipment are updated. In addition, there has been an increase in digital breast tomosynthesis (DBT) and the use of tungsten anodes in the X-ray tubes of mammography apparatuses. X-ray equipment management was performed in many facilities. It seems that the importance of quality control of X-ray equipment is being realized. Constancy tests corresponding to digital systems were conducted at each facility. Maintenance by manufacturers has also increased. This is considered to be because the equipment management of digital systems has become difficult. We believe that it is necessary to continue the survey on the status of diagnostic X-ray equipment.

Kinetically controlled Ag+-coordinated chiral supramolecular polymerization accompanying a helical inversion.

We report kinetically controlled chiral supramolecular polymerization based on ligand-metal complex with a 3 : 2 (L : Ag+) stoichiometry accompanying a helical inversion in water. A new family of bipyridine-based ligands (d-L1, l-L1, d-L2, and d-L3) possessing hydrazine and d- or l-alanine moieties at the alkyl chain groups has been designed and synthesized. Interestingly, upon addition of AgNO3 (0.5-1.3 equiv.) to the d-L1 solution, it generated the aggregate I composed of the d-L1AgNO3 complex (d-L1 : Ag+ = 1 : 1) as the kinetic product with a spherical structure. Then, aggregate I (nanoparticle) was transformed into the aggregate II (supramolecular polymer) based on the (d-L1)3Ag2(NO3)2 complex as the thermodynamic product with a fiber structure, which led to the helical inversion from the left-handed (M-type) to the right-handed (P-type) helicity accompanying CD amplification. In contrast, the spherical aggregate I (nanoparticle) composed of the d-L1AgNO3 complex with the left-handed (M-type) helicity formed in the presence of 2.0 equiv. of AgNO3 and was not additionally changed, which indicated that it was the thermodynamic product. The chiral supramolecular polymer based on (d-L1)3Ag2(NO3)2 was produced via a nucleation-elongation mechanism with a cooperative pathway. In thermodynamic study, the standard ΔG° and ΔH e values for the aggregates I and II were calculated using the van't Hoff plot. The enhanced ΔG° value of the aggregate II compared to that of the formation of aggregate I confirms that aggregate II was thermodynamically more stable. In the kinetic study, the influence of concentration of AgNO3 confirmed the initial formation of the aggregate I (nanoparticle), which then evolved to the aggregate II (supramolecular polymer). Thus, the concentration of the (d-L1)3Ag2(NO3)2 complex in the initial state plays a critical role in generating aggregate II (supramolecular polymer). In particular, NO3 - acts as a critical linker and accelerator in the transformation from the aggregate I to the aggregate II. This is the first example of a system for a kinetically controlled chiral supramolecular polymer that is formed via multiple steps with coordination structural change.

[Effect of Interspaces of Anti-scatter Grid on the Image Improvement Factor].

The standard general purpose of anti-scatter girds: JIS Z 4910: 2015 (IEC 60627: 2013) has been revised, with the new addition of an image improvement factor (Q) to the physical characteristic. Using aluminum (Al) and fiber-interspaced anti-scatter grids; we studied the meaning of Q by calculating each of the physical characteristics and assessing the image. The experimental method was based on JIS Z 4910: 2015. The two anti-scatter grids had a grid ratio of 12: 1 and a strip frequency of 40 cm-1. Assessment items consisted of grid exposure factor (B), grid selectivity (Σ), contrast improvement ratio (K), and Q. In addition, the contrast to noise ratio (CNR) and contrast-detail curve (CD-curve) were determined from the contrast-detail phantom image, and the inverse image quality figure (IQF) was then calculated from the CD-curve. Compared to the Al-interspaced anti-scatter grid, the fiber-interspaced anti-scatter grid had B at 0.87, Σ at 0.95, K at 0.99, and Q at 1.14. In the assessment of the contrast-detail phantom image, the fiber-interspaced anti-scatter grid had an IQF of 1.02 times and a CNR of approximately 1.24 times when compared to the Al interspaced anti-scatter grid. The fiber-interspaced anti-scatter grid was superior with respect to the B and Q of the physical characteristics and to the CNR of image quality assessment.

Effects and Mechanisms of Tastants on the Gustatory-Salivary Reflex in Human Minor Salivary Glands.

The effects and mechanisms of tastes on labial minor salivary gland (LMSG) secretion were investigated in 59 healthy individuals. Stimulation with each of the five basic tastes (i.e., sweet, salty, sour, bitter, and umami) onto the tongue induced LMSG secretion in a dose-dependent manner. Umami and sour tastes evoked greater secretion than did the other tastes. A synergistic effect of umami on LMSG secretion was recognized: a much greater increase in secretion was observed by a mixed solution of monosodium glutamate and inosine 5'-monophosphate than by each separate stimulation. Blood flow (BF) in the nearby labial mucosa also increased following stimulation by each taste except bitter. The BF change and LMSG secretion in each participant showed a significant positive correlation with all tastes, including bitter. Administration of cevimeline hydrochloride hydrate to the labial mucosa evoked a significant increase in both LMSG secretion and BF, while adrenaline, atropine, and pirenzepine decreased LMSG secretion and BF. The change in LMSG secretion and BF induced by each autonomic agent was significantly correlated in each participant. These results indicate that basic tastes can induce the gustatory-salivary reflex in human LMSGs and that parasympathetic regulation is involved in this mechanism.

High rate of improvement in serum matrix metalloproteinase-3 levels at 4 weeks predicts remission at 52 weeks in RA patients treated with adalimumab.

OBJECTIVE: This study aimed to determine whether serum matrix metalloproteinase-3 (MMP-3) levels can predict remission in rheumatoid arthritis (RA) patients treated with adalimumab (ADA). METHODS: Subjects were 114 RA patients continuously treated with ADA for 52 weeks. Predictive factors at baseline and 4 weeks after initiation of ADA therapy for the achievement of remission (28-point count Disease Activity Score-CRP (DAS28-CRP) < 2.3) at 52 weeks were evaluated by multivariate logistic regression analysis. RESULTS: DAS28-CRP at 4 weeks (odds ratio (OR) 0.614, 95% confidence interval (CI) 0.382-0.988) and improvement in serum MMP-3 levels at 4 weeks (OR 1.057, 95% CI 1.002-1.032) were independent predictors of remission at 52 weeks. The best cut-off level of DAS28-CRP and improvement in serum MMP-3 levels at 4 weeks for predicting remission at 52 weeks was 3.73 (sensitivity: 90%, specificity: 50%, area under the receiver operating characteristic curve (AUC): 62%) and 39.93% (sensitivity: 47%, specificity: 83%, AUC: 64%), respectively. CONCLUSION: Our findings suggest that a high rate of improvement in serum MMP-3 levels at 4 weeks after initiation of ADA therapy can predict remission at 52 weeks in RA patients.

Luminescence sensing of weakly-hydrated anions in aqueous solution by self-assembled europium(iii) complexes.

Self-assembled europium(iii) complexes produced dispersed nanoparticles with diameters of about 4-8 nm, which exhibited long-lived luminescence in a 20 wt% EtOH-H2O solution. The complexes could sense weakly hydrated anions, such as perchlorate, by a change in luminescence intensity using an anion displacement method.

Longterm Retention Rate and Risk Factors for Adalimumab Discontinuation Due To Efficacy and Safety in Japanese Patients with Rheumatoid Arthritis: An Observational Cohort Study.

OBJECTIVE: To evaluate the rates of retention and discontinuation of adalimumab (ADA) due to efficacy and safety in Japanese patients with rheumatoid arthritis (RA). METHODS: All patients with RA (n = 476) who were treated with ADA in the Tsurumai Biologics Communication Registry were enrolled. RESULTS: The retention rate of ADA was 46% at 5 years. When focusing on insufficient efficacy, previous biologics use and high baseline disease activity were significant risk factors for up to 1 year. Methotrexate (MTX) use was a significantly low risk factor after 1 year of treatment. CONCLUSION: Concomitant MTX contributes to the longterm efficacy of ADA therapy.

Improved safety of biologic therapy for rheumatoid arthritis over the 8-year period since implementation in Japan: long-term results from a multicenter observational cohort study.

This study aimed to compare the long-term safety of biologics by initiation year of treatment in patients with rheumatoid arthritis (RA) in Japan. RA patients who started their first biologics including infliximab, etanercept, adalimumab, and tocilizumab between 2003 and 2008 were identified in the Tsurumai Biologics Communication Registry (TBCR), multicenter observational cohort, and followed for 2 years or until discontinuation of the drugs. We identified baseline predictors for adverse events (AEs) resulting in discontinuation of the first TNFI using Cox proportional hazards regression analysis. A total of 874 cases (1,340 person-years) were observed. During the observation period, 96 AEs (4.7 events/100 person-years) occurred. From 2003 to 2008, there were significant changes in disease duration, Steinbrocker stage, and disease activity in those aged ≤64 years with no increase of incidence of AEs, whereas those aged >64 years had no significant changes in these variables. In the later initiation year of treatment with biologics, the fewer AEs were observed (log-rank, p = 0.017, 2008 vs. 2003-2005). Multivariate analysis showed that the initiation year significantly impacted the incidence of AEs 6 months into the observation period [initiation at 2008 (vs. 2003-2005): OR: 0.30, 95 % CI: (0.14-0.68)] after adjusting for variables at baseline. The decrease of AEs in the later initiation year was evident in those aged >64 years. The safety of biologic therapy improved over the course of the 8 years from its implementation in Japan.

Redox-Triggered Helicity Inversion in Chiral Cobalt Complexes in Combination with H(+) and NO3(-) Stimuli.

Three chiral ligands with variable denticity, H2L2-H2L4, conjugated by N,N'-ethylenebis[N-methyl-(S)-alanine] and an ortho-heterosubstituted aromatic amine, were newly synthesized as analogues of previously reported H2L1. Four contracted-Λoxo cobalt(III) complexes [Co(L)](+) with left-handed helical structure of Λ4Δ2 configuration were prepared by one-electron oxidation of the corresponding contracted-Λred cobalt(II) complexes [Co(L)], which were generated from chiral ligands and Co(ClO4)2·6H2O or Co(CF3SO3)2·5.2H2O in the presence of an organic base. Although the prepared cobalt(III) complexes were very inert and kinetically stable against protonation and NO3(-) complexation, cobalt(III) reduction in the presence of CF3SO3H and/or Bu4NNO3 allowed immediate changing of their three-dimensional structures from the contracted-Λoxo form to the extended-Λ [Co(H2L)Y2](n+) (Y = solvent and/or anion, n = 0-2) form with left-handed helicity or to the extended-Δ [Co(H2L)(NO3)](+) form with right-handed helicity via N- to O-amide coordination switching. Both extended forms were contracted to the original Λoxo form by oxidation of the cobalt(II) center in the presence of an organic base. Thus, redox reactions triggered dynamic helicity inversion of the chiral cobalt complexes, via multiple molecular motions consisting of relaxation/compression, extension/contraction, and helicity inversion motions in combination with deprotonation/protonation of amide linkages and NO3(-) anion complexation.

Predictive factors for achieving low disease activity at 52 weeks after switching from tumor necrosis factor inhibitors to abatacept: results from a multicenter observational cohort study of Japanese patients.

This study aimed to identify predictive factors for achieving low disease activity (LDA) in rheumatoid arthritis (RA) patients switching from tumor necrosis factor inhibitors (TNFis) to abatacept (ABT). Patients who were registered in the multicenter observational Tsurumai Biologics Communication Registry (TBCR) were enrolled in this study. Predictive factors for LDA achievement at each time point were determined by univariate and multivariate logistic regression analyses. The cutoffs of 28-point count Disease Activity Score (DAS28)-C-reactive protein (CRP) and ΔDAS28-CRP from baseline up to 24 weeks for LDA achievement at 52 weeks were explored using receiver operating characteristic (ROC) curves. Of 2771 RA patients registered until 2013, 76 with moderate or high disease activity were selected. Twenty-six percent of the patients achieved LDA. Multivariate analysis confirmed that DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks were independent factors for LDA achievement at 52 weeks [odds ratio (OR) 0.26, 95% confident interval (CI) (0.12-0.56), OR 0.25, 95% CI (0.11-0.57), respectively]. The best cutoff values of DAS28-CRP at 12 weeks and ΔDAS28-CRP from baseline to 12 weeks for LDA at 52 weeks were 3.9 (sensitivity 0.85, specificity 0.78) and -0.97 (sensitivity 0.70, specificity 0.70), respectively. Seventy-one percent of patients who achieved both of these cutoff values at 12 weeks achieved LDA at 52 weeks. Our findings suggest that the clinical course up to 12 weeks is important for predicting long-term outcomes when switching from TNFis to ABT.

Concomitant methotrexate and tacrolimus augment the clinical response to abatacept in patients with rheumatoid arthritis with a prior history of biological DMARD use.

This observational retrospective study examined whether abatacept efficacy could be augmented with concomitant methotrexate (MTX) or tacrolimus (TAC) in patients with rheumatoid arthritis (RA) who experienced failure with prior biological disease-modifying antirheumatic drugs (DMARDs) and in whom favorable therapeutic efficacy is difficult to achieve. All patients with a prior biological DMARD history who were treated with abatacept for 52 weeks and registered in a Japanese multicentre registry were included. Clinical efficacy and safety of abatacept according to the concomitant drug used, i.e., none (ABT-mono), MTX (ABT-MTX), and TAC (ABT-TAC), were compared. A greater mean percent change of DAS28-ESR was observed in the ABT-TAC group compared with the ABT-mono group at weeks 12 (-20.5 vs. -5.4 %, p = 0.035) and 24 (-25.0 vs. -11.0 %, p = 0.036). ABT-MTX and ABT-TAC groups had a significantly higher proportion of patients who achieved low disease activity (LDA) within 52 weeks compared with the respective baselines, while no significant change was observed in the ABT-mono group. A higher proportion of patients in the ABT-TAC group achieved EULAR moderate response compared with the ABT-mono group at week 52 (66.7 vs. 35.0 %, p = 0.025). Multivariate logistic regression analysis revealed that concomitant TAC use was independently associated with the achievement of LDA and EULAR response at 52 weeks, while concomitant MTX use was not. Concomitant TAC use may offer a suitable option for RA patients treated with abatacept after prior biological DMARD failure, likely because both abatacept and TAC affect T cell activation.

[Report based on fiscal 2010 diagnostic X-ray equipment questionnaire survey (conditions of radiography)].

This is the eighth investigation which has been carried out every 5 years since 1974 for the purpose of grasping the trend of X-ray devices and the radiographic condition. We gathered it up mainly on a radiographic condition, in this report. As for the chest radiography and double contrast gastrography, introduction of the flat panel detector (FPD) advanced in comparison with the last survey. Ratio of the imaging system at chest radiography was 65% for computed radiography (CR), 33% for FPD, 1% for screen/film (S/F), and 1% for others. The radiographic condition of FPD was current time product less than CR. Ratio of the imaging system at gastrography was 3% for CR, 48% for FPD, 34% for image intensifier-digital radiography (I.I.-DR), and 15% for S/F. The tube voltage and the exposure time were similar to the last survey time, but the tube current became lower. Through this survey, the change of the radiographic condition was seen in the radiography part where introduction of the FPD advanced. We think the continuous survey is necessary in future.

Longterm efficacy and safety of abatacept in patients with rheumatoid arthritis treated in routine clinical practice: effect of concomitant methotrexate after 24 weeks.

OBJECTIVE: Our study aimed to evaluate the longterm efficacy and safety of abatacept (ABA), and to explore factors that increase its longterm efficacy in patients with rheumatoid arthritis (RA) treated in routine clinical practice. METHODS: There were 231 participants with RA treated with ABA who were prospectively registered in a Japanese multicenter registry. They were followed up for at least 52 weeks. RESULTS: Mean age of the patients was 64.3 years, mean disease duration was 12.1 years, mean 28-joint Disease Activity Score (DAS28)-C-reactive protein was 4.49, and 48.5% of patients were concomitantly treated with methotrexate (MTX). Overall retention rate of ABA was 77.1% at 52 weeks; 14.8% of patients discontinued because of inadequate response and 3.5% because of adverse events. The proportion of patients achieving DAS28-defined low disease activity (LDA) significantly increased from baseline to 52 weeks (7.3% to 43.8%, p < 0.01); 40.9% of patients who did not achieve LDA at 24 weeks had more than 1 categorical improvement in DAS28-defined disease activity at 52 weeks. Multivariate logistic regression revealed concomitant MTX use to be an independent predictor of the categorical improvement in DAS28-defined disease activity from 24 to 52 weeks (adjusted OR 3.124, p = 0.010). CONCLUSION: In routine clinical practice, ABA demonstrated satisfactory clinical efficacy and safety in patients with established RA for 52 weeks. The clinical efficacy of ABA increased with time even after 24 weeks, and this was strongly influenced by concomitant MTX use. Our study provides valuable real-world findings on the longterm management of RA with ABA.

Comparison of efficacy and safety of tacrolimus and methotrexate in combination with abatacept in patients with rheumatoid arthritis; a retrospective observational study in the TBC Registry.

OBJECTIVES: Tacrolimus (TAC) and abatacept (ABT) inhibit T-cells via different mechanisms and, in combination, may be effective against rheumatoid arthritis. However, they may also disrupt normal immune functions. We compared the efficacy and safety of ABT administered to patients in combination with TAC, methotrexate (MTX), or other drugs. METHODS: This was a retrospective multicenter study conducted to compare the efficacy and safety of ABT in 211 patients: the drug was administered together with TAC (ABT+ TAC group; 22 patients), MTX (ABT+ MTX group; 102 patients), or patients treated without concomitant MTX or TAC (ABT mono group; 87 patients). The disease activity, treatment continuation rate, and reason for discontinuation of treatment were investigated. RESULTS: The retention rate at Week 24 was similar in the three groups. There were no cases of discontinuation related to the appearance of adverse events in the ABT+ TAC group. At Week 24, according to the European League Against Rheumatism response criteria, the "good" response rates were 33.3%, 13.4%, and 13.4% in the ABT+ TAC, ABT+ MTX, and ABT mono groups, respectively. Statistically significant decreases in various disease activity scores/indices were observed in all the groups as early as Week 4. CONCLUSIONS: Although the sample size was small, the results of this retrospective study suggest that the ABT+ TAC combination therapy has at least comparable safety and efficacy to those of the ABT+ MTX combination, and that it can thus be a useful option for patients who cannot take MTX.