Association between Dairy Product intake and Risk of Osteoporotic Fractures in Postmenopausal Japanese Women: Secondary Analysis of 15-Year Follow-Up data from the Japanese Population-Based Osteoporosis (JPOS) Cohort Study.

OBJECTIVES: Few prospective cohort studies have evaluated the relationship between dairy product intake frequency and risk of osteoporotic fractures in Asians. This study aimed to investigate the association between habitual dairy product intake and risk of osteoporotic fractures. DESIGN: Secondary analysis of prospective cohort study. SETTING: Five municipalities of Japan. PARTICIPANTS: This study included 1,429 postmenopausal Japanese women (age ≥45 years at baseline). MEASUREMENTS: Baseline milk-intake frequency was obtained using nurse-administered questionnaires. Intakes of yogurt and cheese, and estimated calcium intake, were assessed using a validated food frequency questionnaire. Osteoporotic fracture was defined as a clinical fracture diagnosed using radiography. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. RESULTS: Over a median follow-up period of 15.1 years (interquartile range [IQR], 10.1-15.4 years; total, 18,118 person-years), 172 women sustained at least one osteoporotic fracture. The proportions of participants with milk intakes <1, 1, and ≥2 cups/d were 34.4%, 48.0%, and 17.6%, respectively. After adjustment for age, frequency of yogurt intake, frequency of cheese intake, body mass index, history of osteoporotic fractures, and frequency of natto intake, the HRs compared with that for milk intake <1 cup/d were 0.71 (95% CI: 0.51-0.98) and 0.57 (95% CI: 0.35-0.92) for 1 cup/d and ≥2 cups/d, respectively. After adjustment for bone mineral density, HR significance for milk intakes ≥2 cups/d remained significant. Yogurt and cheese intakes were not related to the risk of osteoporotic fractures. CONCLUSION: High habitual milk intake, but not a habitual yogurt or cheese intake is associated with a decreased risk of osteoporotic fractures, independent of bone mineral density, in postmenopausal Japanese women.

Study of beamlets extracted from a multi-aperture and five-stage acceleration system.

A beam optics study using the ITER-relevant high intense negative ion beams, such as 1 MeV, 200 A/m2, has been performed experimentally and analytically using a multi-aperture and five-stage accelerator. Initially, multi-beamlets generated from this accelerator were deflected in various directions due to the magnetic field and space charge repulsion between beams and showed various divergences. These had limited the pulse length and the beam energy. Compensation methods of the beamlet deflections have worked effectively and contributed to achieving the ITER requirement, the divergence angle of <7 mrad, and the deflection angle of <1 mrad for 1 MeV beam. The beam pulse has been gradually extended from 1 to 100 s and is now going to a longer pulse based on these results. One of the remaining issues is to understand and suppress peripheral components of the beam, namely, the halo, and to reduce the local heat loads observed around the aperture edge. This halo component has been successfully distinguished from the beam core by using a newly developed beam emittance measurement system for high intense beams. By combining this measured beam emittance and the beam simulation, it was clarified for the first time that the halo components are generated in an area of 1 mm width from the aperture edge.

Analysis of the cesium distribution in the JT-60SA negative ion sources for steady long-pulse operation.

To realize stable negative ion beams for 100 s required in the neutral beam injector of JT-60SA, a physical model to control cesium (Cs) distribution inside the negative ion source has been developed in order to maintain the stable negative ion production at the plasma grid (PG) surface with Cs. In this work, to quantitatively evaluate Cs coverage on the PG, a three-dimensional Cs transportation code was introduced to consider the spatial Cs distribution in the source. The spatial temperature distribution of the chamber wall was also introduced in this model. As a result, the reasonable variation of the Cs coverage for 100 s was obtained, compared to that in the initial model. Based on the modified model, the operational temperature of the chamber wall was proposed to be less than 60 °C to suppress the desorption of Cs in the chamber wall and to sustain the stable negative ion production. In addition, it was also suggested that a slightly higher wall temperature before the operation leads to a decrease in the amount of Cs stored at the chamber wall, resulting in suppression of Cs consumption in the ion source.

Achievement of high power and long pulse negative ion beam acceleration for JT-60SA NBI.

Long pulse acceleration of hydrogen negative ion beams with the power density over 70 MW/m2 and the pulse length over 100 s has been demonstrated for the first time by using a multi-aperture 3-stage accelerator. Such long pulse acceleration was achieved by integrating the design of beam optics and voltage holding capability to meet the requirements of JT-60SA. By using the newly designed accelerator for JT-60SA, voltage holding at 500 kV with beam acceleration was stably sustained even after 5 g of cesium was seeded, and heat load on each acceleration grid was reduced below the allowable level for long pulse, less than 5% of total acceleration power. As a result, 500 keV, 154 A/m2 for 118 s beam acceleration was achieved, which satisfies the requirement of the negative ion source for JT-60SA. This pulse length of such high-power density beams is longest in the world. In addition, the result contributes to the long pulse acceleration of multi-stage electrostatic accelerators, such as 1 MeV negative ion accelerator for ITER.

Analysis of the beam halo in negative ion sources by using 3D3V PIC code.

The physical mechanism of the formation of the negative ion beam halo and the heat loads of the multi-stage acceleration grids are investigated with the 3D PIC (particle in cell) simulation. The following physical mechanism of the beam halo formation is verified: The beam core and the halo consist of the negative ions extracted from the center and the periphery of the meniscus, respectively. This difference of negative ion extraction location results in a geometrical aberration. Furthermore, it is shown that the heat loads on the first acceleration grid and the second acceleration grid are quantitatively improved compared with those for the 2D PIC simulation result.

Time evolution of negative ion profile in a large cesiated negative ion source applicable to fusion reactors.

To understand the physics of the cesium (Cs) recycling in the large Cs-seeded negative ion sources relevant to ITER and JT-60SA with ion extraction area of 45-60 cm × 110-120 cm, the time evolution of the negative ion profile was precisely measured in JT-60SA where the ion extraction area is longitudinally segmented into 5. The Cs was seeded from the oven at 180 °C to the ion source. After 1 g of Cs input, surface production of the negative ions appeared only in the central segment where a Cs nozzle was located. Up to 2 g of Cs, the negative ion profile was longitudinally expanded over full ion extraction area. The measured time evolution of the negative ion profile has the similar tendency of distribution of the Cs atoms that is calculated. From the results, it is suggested that Cs atom distribution is correlated with the formation of the negative ion profile.

Development of design technique for vacuum insulation in large size multi-aperture multi-grid accelerator for nuclear fusion.

Design techniques for the vacuum insulation have been developed in order to realize a reliable voltage holding capability of multi-aperture multi-grid (MAMuG) accelerators for fusion application. In this method, the nested multi-stage configuration of the MAMuG accelerator can be uniquely designed to satisfy the target voltage within given boundary conditions. The evaluation of the voltage holding capabilities of each acceleration stages was based on the previous experimental results about the area effect and the multi-aperture effect. Since the multi-grid effect was found to be the extension of the area effect by the total facing area this time, the total voltage holding capability of the multi-stage can be estimated from that per single stage by assuming the stage with the highest electric field, the total facing area, and the total apertures. By applying these consideration, the analysis on the 3-stage MAMuG accelerator for JT-60SA agreed well with the past gap-scan experiments with an accuracy of less than 10% variation, which demonstrated the high reliability to design MAMuG accelerators and also multi-stage high voltage bushings.

Development of the negative ion beams relevant to ITER and JT-60SA at Japan Atomic Energy Agency.

In order to realize negative ion sources and accelerators to be applicable to International Thermonuclear Experimental Reactor and JT-60 Super Advanced, a large cesium (Cs)-seeded negative ion source and a multi-aperture and multi-stage electric acceleration have been developed at Japan Atomic Energy Agency (JAEA). Long pulse production and acceleration of the negative ion beams have been independently carried out. The long pulse production of the high current beams has achieved 100 s at the beam current of 15 A by modifying the JT-60 negative ion source. The pulse duration time is increased three times longer than that before the modification. As for the acceleration, a pulse duration time has been also extended two orders of magnitudes from 0.4 s to 60 s. The developments of the negative ion source and acceleration at JAEA are well in progress towards the realization of the negative ion sources and accelerators for fusion applications.

Tumor necrosis factor-alpha gene promoter methylation in Japanese adults with chronic periodontitis and rheumatoid arthritis.

BACKGROUND AND OBJECTIVE: Over-expression of tumor necrosis factor-alpha (TNF-α) plays a pathological role in chronic periodontitis (CP) and rheumatoid arthritis (RA), which might be regulated by the epigenetic mechanism. The aim of the present study was to evaluate whether there is a unique methylation profile of the TNF-α gene promoter in blood cells of individuals with CP and RA. MATERIAL AND METHODS: The study participants consisted of 30 Japanese adults with RA (RA group), 30 race-matched adults with CP only (CP group) and 30 race-matched healthy controls (H group). Genomic DNA isolated from peripheral blood was modified by sodium bisulfite and analyzed, by direct sequencing, to investigate DNA methylation of the TNF-α gene promoter region. The level of TNF-α produced in mononuclear cells stimulated with Porphyromonas gingivalis lipopolysaccharide was determined using ELISA. RESULTS: Twelve cytosine-guanine dinucleotide (CpG) motifs were identified in the TNF-α promoter fragment from -343 to +57 bp. The CP group showed a significantly higher methylation rate and frequency at -72 bp than the H group (p < 0.01). The RA group exhibited significantly higher methylation rates at seven CpG motifs (-302, -163, -119, -72, -49, -38 and +10 bp), and significantly higher methylation frequencies at six CpG motifs (-163, -119, -72, -49, -38 and +10 bp), than the H group (p < 0.01 for all comparisons). The levels of TNF-α produced were significantly different between individuals with and without methylation at -163 bp (p = 0.03). CONCLUSION: These results suggest that the hypermethylated status of CpG motifs in the TNF-α gene promoter in blood cells may be unique to Japanese adults with CP and RA.

Roles of extracellular Ca(2+) in the occurrence of full-type hyperactivation in boar ejaculated spermatozoa pre-incubated to induce the cAMP-triggered events.

There are species differences in the regulatory system for sperm capacitation and subsequent hyperactivation between livestock and laboratory animals. In livestock spermatozoa, it is poorly understood when and how extracellular Ca(2+) is necessary for hyperactivation, although it has been demonstrated that the [Ca(2+) ]i increase is indispensable to occurrence of hyperactivation. In this study, we examined necessity of extracellular Ca(2+) for the initiation and maintenance of hyperactivation and then sought possible target molecule of Ca(2+) that was involved in hyperactivation of boar spermatozoa. Boar ejaculated spermatozoa were pre-incubated with a cell-permeable cyclic adenosine monophosphate (cAMP) analog 'cBiMPS' and without CaCl2 to induce the cAMP-triggered events including capacitation-associated changes. Subsequently, they were incubated with CaCl2 to induce hyperactivation and then used for motility assessment. Many of the spermatozoa after the incubation exhibited full-type hyperactivation which was characterized by high-amplitude and extremely asymmetrical beating of whole middle piece and principal piece. The initiation of full-type hyperactivation required the millimolar concentration of CaCl2 in the medium. However, CaCl2 of the medium was less necessary for maintenance than initiation of full-type hyperactivation, as hyperactivated spermatozoa were barely affected by the incubation with the Ca(2+) -chelating reagent. On the other hand, the pre-treatment with the inhibitor for Ca(2+) -dependent protease 'calpain 1 and 2' clearly suppressed the occurrence of CaCl2 -induced hyperactivation without influences on the percentages of motile spermatozoa. Western blotting and indirect immunofluorescence showed distribution of calpain 2 in the middle and principal pieces in which full-type hyperactivated spermatozoa exhibited extremely asymmetrical beating. On the basis of these results, we conclude that the millimolar concentration of extracellular Ca(2+) is necessary for the initiation, but not for the maintenance of full-type hyperactivation in boar spermatozoa that beforehand undergo the cAMP-triggered events including capacitation-associated changes. Moreover, we suggest possible involvement of calpain 2 in the intracellular Ca(2+) signal transduction leading to full-type hyperactivation.

Long-pulse beam acceleration of MeV-class H(-) ion beams for ITER NB accelerator.

In order to realize neutral beam systems in International Thermonuclear Experimental Reactor whose target is to produce a 1 MeV, 200 A/m(2) during 3600 s D(-) ion beam, the electrostatic five-stages negative ion accelerator so-called "MeV accelerator" has been developed at Japan Atomic Energy Agency. To extend pulse length, heat load of the acceleration grids was reduced by controlling the ion beam trajectory. Namely, the beam deflection due to the residual magnetic field of filter magnet was suppressed with the newly developed extractor with a 0.5 mm off-set aperture displacement. The new extractor improved the deflection angle from 6 mrad to 1 mrad, resulting in the reduction of direct interception of negative ions from 23% to 15% of the total acceleration power, respectively. As a result, the pulse length of 130 A/m(2), 881 keV H(-) ion beam has been successfully extended from a previous value of 0.4 s to 8.7 s. This is the first long pulse negative ion beam acceleration over 100 MW/m(2).

100 s extraction of negative ion beams by using actively temperature-controlled plasma grid.

Long pulse beam extraction with a current density of 120 A/m(2) for 100 s has been achieved with a newly developed plasma grid (PG) for the JT-60SA negative ion source which is designed to produce high power and long pulse beams with a negative ion current of 130 A/m(2) (22 A) and a pulse length of 100 s. The PG temperature is regulated by fluorinated fluids in order to keep the high PG temperature for the cesium-seeded negative ion production. The time constant for temperature controllability of the PG was measured to be below 10 s, which was mainly determined by the heat transfer coefficient of the fluorinated fluid. The measured decay time of the negative ion current extracted from the actively temperature-controlled PG was 430 s which was sufficient for the JT-60SA requirement, and much longer than that by inertial-cooling PG of 60 s. Obtained results of the long pulse capability are utilized to design the full size PG for the JT-60SA negative ion source.

Development of negative ion extractor in the high-power and long-pulse negative ion source for fusion application.

High power and long-pulse negative ion extractor, which is composed of the plasma grid (PG) and the extraction grid (EXG), is newly developed toward the neutral beam injector for heating and current drive of future fusion machines such as ITER, JT-60 Super Advanced and DEMO reactor. The PG is designed to enhance surface production of negative ions efficiently by applying the chamfered aperture. The efficiency of the negative ion production for the discharge power increased by a factor of 1.3 against that of the conventional PG. The EXG is also designed with the thermal analysis to upgrade the cooling capability for the long pulse operation of >1000 s required in ITER. Though the magnetic field for electron suppression is reduced to 0.75 of that in the conventional EXG due to this upgrade, it was experimentally confirmed that the extracted electron current can be suppressed to the allowable level for the long pulse operation. These results show that newly developed extractor has the high potential for the long pulse extraction of the negative ions.

Aggravation of inflammatory bowel diseases by oral streptococci.

OBJECTIVES: Streptococcus mutans can aggravate colitis in mice. We evaluated the virulence of colitis using type strains as well as blood isolates of several oral streptococcal species. MATERIALS AND METHODS: We investigated the susceptibility of blood isolates of several oral streptococci to phagocytosis, adhesion to and invasion of hepatic cells and interferon-γ secretion. A mouse model of dextran sodium sulphate-induced colitis was used to evaluate bacterial aggravation of colitis. In addition, interferon-γ antibody was administered to mice with prominent aggravation of colitis. RESULTS: In vitro analyses showed that Streptococcus sanguinis ATCC 10556 was a possible virulent strain among type strains of several oral streptococci, and that analysis of blood isolates of S. sanguinis TW289 revealed a potential virulent strain. Intravenous administration of ATCC 10556 and TW289 caused prominent aggravation of dextran sodium sulphate-induced colitis, and histopathological examinations showed that interferon-γ secretion due to infection of hepatic cells caused colitis aggravation. Administration of interferon-γ antibody suppressed TW289-induced colitis. CONCLUSION: These results suggest that some virulent oral streptococcal strains are associated with the aggravation of colitis induced by enhanced secretion of interferon-γ when they invade the bloodstream.

Resolution of clinical symptoms after reopening of an occluded inferior petrosal sinus in a patient with a cavernous sinus dural arteriovenous fistula. A case report.

We describe a rare case with a cavernous sinus (CS) dural arteriovenous fistula (DAVF) in which the clinical symptoms disappeared after the patient underwent reopening of an occluded inferior petrosal sinus (IPS). A 66-year-old woman presented with increased intraocular pressure, chemosis, and proptosis on the left side. Angiography demonstrated a left CS DAVF supplied by the dural branches of bilateral internal carotid arteries. The shunt flow was directed to the superior and inferior ophthalmic veins, while the bilateral IPSs were not opacified. Accordingly, a transvenous embolization of the fistula was attempted. Although the microcatheter was navigated to the cavernous sinus through the occluded left IPS, obliteration of the fistula was unsuccessful because of the failure of superselective catheterization at the fistulous point. However, the final image demonstrated the development of an antegrade shunt flow through the left IPS to the internal jugular vein and disappearance of the retrograde reflux to the superior and inferior ophthalmic veins. The patient's clinical symptoms immediately resolved after the operation, and the symptoms have not recurred during a one-year follow-up period. Inappropriate transvenous embolization of CS DAVFs can result in vascular complications arising from the unintentional redistribution of shunt flow. The present case illustrates that the disappearance of retrograde shunt flow to the ophthalmic veins after reopening of the occluded IPS may be sufficient if a superselective approach fails or is anticipated to result only in an incomplete embolization of the fistulous point.

Presence of store-operated Ca2+ entry in C57BL/6J mouse ventricular myocytes and its suppression by sevoflurane.

BACKGROUND: Store-operated Ca(2+) entry (SOCE) has been implicated in various pathological conditions of the heart including ischaemia/reperfusion and ventricular hypertrophy. This study investigated the effects of sevoflurane on SOCE. METHODS: Fluorescence imaging was performed on fluo-3- and mag-fluo-4-loaded mouse ventricular myocytes to measure the cytosolic and intraluminal sarcoplasmic reticulum (SR) Ca(2+) levels, respectively, using a confocal laser scanning microscope. Whole-cell membrane currents were recorded using the patch-clamp technique. Ventricular myocytes were exposed to thapsigargin and angiotensin II to deplete SR Ca(2+) stores and thereby activate SOCE. RESULTS: The combined application of thapsigargin and angiotensin II to the Ca(2+)-free medium evoked a significant decrease in the SR Ca(2+) levels, which was followed by the elevation of cytosolic Ca(2+) and the development of cellular hypercontracture upon subsequent addition of extracellular Ca(2+). This cytosolic Ca(2+) elevation was inhibited by 2-aminoethoxydiphenyl borate but not by verapamil and KB-R7943, which indicates that SOCE was present in mouse ventricular myocytes. Sevoflurane concentration-dependently inhibited the SOCE-mediated Ca(2+) overload (IC(50) of 137 µM, which corresponds to 0.96%) with a significant reduction occurring at concentrations of ≥2%. Patch-clamp experiments revealed that the SOCE current was also concentration-dependently blocked by sevoflurane (IC(50) of 144 µM, which corresponds to 1.0%). CONCLUSIONS: Sevoflurane at concentrations of ≥2% significantly inhibits the SOCE activity and prevents the resultant cellular Ca(2+) overload that leads to hypercontracture in ventricular myocytes. This inhibitory action may be involved in the cardioprotective effect of sevoflurane against Ca(2+) overload-mediated injury.

Vacuum insulation of the high energy negative ion source for fusion application.

Vacuum insulation on a large size negative ion accelerator with multiple extraction apertures and acceleration grids for fusion application was experimentally examined and designed. In the experiment, vacuum insulation characteristics were investigated in the JT-60 negative ion source with >1000 apertures on the grid with the surface area of ∼2 m(2). The sustainable voltages varied with a square root of the gap lengths between the grids, and decreased with number of the apertures and with the surface area of the grids. Based on the obtained results, the JT-60SA (super advanced) negative ion source is designed to produce 22 A, 500 keV D(-) ion beams for 100 s.

Voltage holding study of 1 MeV accelerator for ITER neutral beam injector.

Voltage holding test on MeV accelerator indicated that sustainable voltage was a half of that of ideal quasi-Rogowski electrode. It was suggested that the emission of the clumps is enhanced by a local electric field concentration, which leads to discharge initiation at lower voltage. To reduce the electric field concentration in the MeV accelerator, gaps between the grid supports were expanded and curvature radii at the support corners were increased. After the modifications, the accelerator succeeded in sustaining -1 MV in vacuum without beam acceleration. However, the beam energy was still limited at a level of 900 keV with a beam current density of 150 A∕m(2) (346 mA) where the 3 × 5 apertures were used. Measurement of the beam profile revealed that deflection of the H(-) ions was large and a part of the H(-) ions was intercepted at the acceleration grid. This causes high heat load on the grids and the breakdowns during beam acceleration. To suppress the direct interception, new grid system was designed with proper aperture displacement based on a 3D beam trajectory analysis. As the result, the beam deflection was compensated and the voltage holding during the beam acceleration was improved. Beam parameter of the MeV accelerator was increased to 980 keV, 185 A∕m(2) (427 mA), which is close to the requirement of ITER accelerator (1 MeV, 200 A∕m(2)).