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Background: The regenerative and adaptive capacity of skeletal muscles reduces with age, leading to severe disability and frailty in the elderly. Therefore, development of effective therapeutic interventions for muscle wasting is important both medically and socioeconomically. In the present study, we aimed to elucidate the potential contribution of fibro-adipogenic progenitors (FAPs), which are mesenchymal stem cells in skeletal muscles, to immobilization-induced muscle atrophy. Methods: Young (2–3 months), adult (12–14 months), and aged (20–22 months) mice were used for analysis. Muscle atrophy was induced by immobilizing the hind limbs with a steel wire. FAPs were isolated from the hind limbs on days 0, 3, and 14 after immobilization for transcriptome analysis. The expression of ST2 and IL-33 in FAPs was evaluated by flow cytometry and immunostaining, respectively. To examine the role of IL-33-ST2 signaling in vivo, we intraperitoneally administered recombinant IL-33 or soluble ST2 (sST2) twice a week throughout the 2-week immobilization period. After 2-week immobilization, the tibialis anterior muscles were harvested and the cross-sectional area of muscle fibers was evaluated. Results: The number of FAPs increased with the progression of muscle atrophy after immobilization in all age-groups. Transcriptome analysis of FAPs collected before and after immobilization revealed that Il33 and Il1rl1 transcripts, which encode the IL-33 receptor ST2, were transiently induced in young mice and, to a lesser extent, in aged mice. The number of FAPs positive for ST2 increased after immobilization in young mice. The number of ST2-positive FAPs also increased after immobilization in aged mice, but the difference from the baseline was not statistically significant. Immunostaining for IL-33 in the muscle sections revealed a significant increase in the number of FAPs expressing IL-33 after immobilization. Administration of recombinant IL-33 suppressed immobilization-induced muscle atrophy in aged mice but not in young mice. Conclusions: Our data reveal a previously unknown protective role of IL-33-ST2 signaling against immobilization-induced muscle atrophy in FAPs and suggest that IL-33-ST2 signaling is a potential new therapeutic target for alleviating disuse muscle atrophy, particularly in older adults. [ABSTRACT FROM AUTHOR]

Dependence of the radiative-convective equilibrium structure of the lower atmosphere of Venus on the specification of an atmospheric thermodynamic model is investigated. A series of thermodynamic models including ideal gases, van der Waals gases, and real gases are introduced by the use of the Helmholtz energy given by the EOS-CG mixture model (EOS-CG: Equation of State for Combustion Gases and Combustion Gas-like Mixtures). It is demonstrated that the radiative-convective equilibrium profile for the real gas differs significantly from that for the ideal gas with temperature-dependent specific heat by an increase of about 7 K in the surface temperature. This difference is caused by the fact that the adiabatic lapse rate evaluated with the thermodynamic model of real gas is larger than that of ideal gas, since the non-ideality of gas increases the thermal expansion coefficient, which overwhelms the increases in density and specific heat. It is confirmed that, in order to obtain better calculations of atmospheric circulations including the lower atmosphere of Venus, the ideal gas with a constant specific heat should be abandoned. The ideal gas with a temperature-dependent specific heat may not be enough. A promising method is to use the ideal gas but with the temperature-dependent specific heat such that its adiabatic lapse rate profile mimics that for the real gas. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICPIs) have revolutionized cancer therapy, although immune-related adverse events (irAEs) remain a serious issue. The clinical characteristics of colitis induced by ICPIs are very similar to inflammatory bowel disease. Recently, cluster of differentiation 8 positive (CD8+) lymphocyte infiltration into organs has been associated with the onset of irAEs. The present study compared the histological infiltration of CD8+ lymphocytes in irAE colitis with that in other colitis. Methods: Newly diagnosed and untreated patients were retrospectively enrolled. Biopsy specimens were obtained from endoscopic areas of high inflammation for immunohistochemical analysis of the number of cluster of differentiation 4 positive (CD4+) and CD8+ lymphocytes in the high-powered microscopic field with the most inflammation. Results: A total of 102 patients [12 with irAE colitis, 37 with ulcerative colitis (UC), 22 with Crohn's disease (CD), and 31 with ischemic colitis (IC)] were analyzed. In irAE colitis, CD8+ lymphocyte infiltration was significantly greater than that of CD4+ lymphocytes (p < 0.01). The amount of CD8+ lymphocyte infiltration was significantly higher in irAE colitis than in UC (p < 0.05), CD (p < 0.05), and IC (p < 0.01). The CD8+/CD4+ ratio was also significantly higher in irAE colitis (p < 0.01 versus UC, CD, and IC, respectively). The optimal cutoff CD8+/CD4+ ratio for diagnosing irAE colitis was 1.17 (sensitivity 83%, specificity 84%). The optimal cutoff number of CD8+ lymphocytes for diagnosing irAE colitis was 102 cells per high-power field (sensitivity 75%, specificity 81%). Conclusions: Greater CD8+ lymphocyte infiltration and a higher CD8+/CD4+ ratio may be simple and useful biomarkers to distinguish irAE colitis from other forms of colitis. [ABSTRACT FROM AUTHOR]

A set of line-by-line and correlated k-distribution radiation models are developed aiming for applications in simulations and examinations of Venus and Mars-Iike planetary atmospheres. Our line-by-line model is validated by comparing the results with observations and those of previous studies under conditions of Venus, and present and possible early Mars. The radiation fields calculated by our line-by-line model agree well with observed profiles and are within the acceptable range from those presented in previous studies. The results obtained by our line-by-line model are then processed to generate a series of parameters for our correlated k-distribution model. It is confirmed that the radiation fields calculated with those sets of parameters by our correlated k-distribution model sufficiently agree with those by our line-by-line model for the atmospheres with a wide range of surface pressure. By the use of our correlated k-distribution model implemented with those sets of parameters, we evaluate the radiation field for Venus and calculate radiative-convective equilibrium profiles for Venus and Mars. The obtained vertical thermal structures for Venus are qualitatively consistent with observations, and the behaviors of surface pressure and surface temperature for Mars are similar to those reported by previous studies. Those results demonstrate that our models including the procedure for generating tables of radiation parameters are applicable to examine climates of CO2 dominant atmospheres in our solar and exoplanetary systems. [ABSTRACT FROM AUTHOR]

We assessed the sequential magnetic resonance imaging changes of indirect neural decompression after minimally invasive lumbar lateral interbody fusion (LIF) combined with posterior percutaneous pedicle screw (PPS) fixation for degenerative spondylolisthesis (DS) according to the severity of preoperative lumbar spinal stenosis. A total of 43 patients (mean age, 68.7 years; 16 men and 27 women) with DS who had undergone LIF and closed reduction with PPS fixation were enrolled. The intervertebral levels were divided into the moderate stenosis (MS) group (preoperative cross-sectional area [CSA] of the thecal sac >50 mm2) and severe stenosis (SS) group (CSA ≤50 mm2). The CSA, ligamentum flavum thickness, and diameter of the thecal sac at the affected level were measured on cross-sectional magnetic resonance images at baseline, immediately postoperatively, and 2 years postoperatively. For the 31 and 29 intervertebral levels in the MS and SS groups, the mean CSA at baseline, immediately postoperatively, and 2 years postoperatively was 76.9 mm2 and 35.8 mm2, 104.3 mm2 and 81.4 mm2, and 130.9 mm2 and 105.7 mm2, respectively. The mean ligamentum flavum thicknesses at 2 years postoperatively became thinner than that immediately after surgery in both groups (P < 0.01). The mean diameter of the thecal sac at 2 years was longer than that immediately after surgery in both groups (MS group, P < 0.05; SS group, P < 0.01) The expansion ratio of the CSA at 2 years postoperatively was significantly greater in the SS group than that in the MS group (P < 0.01). Sequential enlargement of the spinal canal was obtained by the thinning of the ligamentum flavum after LIF and PPS fixation in patients with DS with both mild and severe stenosis. The effect of indirect neural decompression was equivalent even in those with severe lumbar spinal stenosis. [ABSTRACT FROM AUTHOR]

In order to make high-speed deposition of diamond effective, diamond growth rates for gas-phase microwave plasma chemical vapor deposition and in-liquid microwave plasma chemical vapor deposition are compared. A mixed gas of methane and hydrogen is used as the source gas for the gas-phase deposition, and a methanol solution of ethanol is used as the source liquid for the in-liquid deposition. The experimental system pressure is in the range of 60–150 kPa. While the growth rate of diamond increases as the pressure increases, the amount of input microwave energy per unit volume of diamond is 1 kW h/mm3 regardless of the method used. Since the in-liquid deposition method provides a superior cooling effect through the evaporation of the liquid itself, a higher electric input power can be applied to the electrodes under higher pressure environments. The growth rate of in-liquid microwave plasma chemical vapor deposition process is found to be greater than conventional gas-phase microwave plasma chemical vapor deposition process under the same pressure conditions. [ABSTRACT FROM AUTHOR]

Abstract The Kyoto University electron linac, KURRI-LINAC, has been used for executing a project to develop methodology for the integrity evaluation of nuclear fuels, named the N-DeMAIN (Development of Non-Destructive Methods Adapted for Integrity test of Next generation nuclear fuels) project in Japan. As a non-destructive method, the neutron resonance transmission analysis was adopted for the identification and the quantification of nuclide in the fuels. Furthermore, determination of temperature distribution in the fuels based on Doppler broadening was also planned as well as traditional transmission imaging. A target-moderator-reflector system (TMRS) and a beam collimator system has been redesigned to obtain the highest intensity with the use of simulation calculation. The neutron beam line is placed at an angle of 135° with respect to the electron beam line. Optimal arrangement of the target and the moderator was investigated. After then, collimator design was performed, and a collimator system to shape the neutron and γ ray beams was designed. Test experiments were performed by using this system. Here, we explain the results of design study of the TMRS and the collimator, and the test experiments. [ABSTRACT FROM AUTHOR]

Recent reports revealed that intravenous (iv) busulfan (BU) may not only reduce early nonrelapse mortality (NRM) but also improve overall survival (OS) probability in adults. Therefore, we retrospectively compared outcomes for 460 children with acute leukemia who underwent hematopoietic stem cell transplantation with either iv-BU (n = 198) or oral busulfan (oral-BU) (n = 262) myeloablative conditioning. OS at 3 years was 53.4% ± 3.7% with iv-BU and 55.1% ± 3.1% with oral-BU; the difference was not statistically significant (P = .77). OS at 3 years in 241 acute lymphoblastic leukemia and 219 acute myeloid leukemia patients was 56.4% ± 5.5% with iv-BU and 54.6% ± 4.1 with oral-BU (P = .51) and 51.0% ± 5.0% with iv-BU and 55.8% ± 4.8% with oral-BU (P = .83), respectively. Cumulative incidence of relapse at 3 years with iv-BU was similar to that with oral-BU (39.0% ± 3.6% and 36.4% ± 3.1%, respectively; P = .67). Cumulative incidence of NRM at 3 years was 16.6% ± 2.7% with iv-BU and 18.3% ± 2.5% with oral-BU (P = .51). Furthermore, multivariate analysis showed no significant survival advantage with iv-BU. In conclusion, iv-BU failed to show a significant survival advantage in children with acute leukemia. [ABSTRACT FROM AUTHOR]

Highlights: [•] We examined the circadian rhythm of performance in the novel location recognition (NLR) task using rats. [•] The performance was better during the dark period than during the light period. [•] Artificial change of melatonin level modulated the diurnal variation of performance. [ABSTRACT FROM AUTHOR]

Unlabelled: The aim of this study was to investigate changes in CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) throughout the clinical course of Kawasaki disease (KD) and correlations with response to intravenous immunoglobulin (IVIg) therapy. Participants comprised 18 patients who fulfilled the diagnostic criteria for KD and 20 healthy subjects. Expressions of CD25 and FOXP3 among all CD4(+) T cells in peripheral blood mononuclear cells were analyzed by flow cytometry before and 7 and 30 days after IVIg therapy. Before treatment, percentages of CD4(+)CD25(+)FOXP3(+) Tregs among total CD4(+) Tregs were significantly lower among KD patients (4.19 %; range, 0.16-8.11 %) than among healthy subjects (7.32 %; 4.18-13.42 %; P = 0.0001). Both percentages and absolute numbers of CD4(+)CD25(+)FOXP3(+) Tregs on day  7 after IVIg therapy were significantly increased compared with values before treatment (8.02 % (range, 0.51-12.6 %) vs. 4.19 % (range, 0.16-8.11 %), P = 0.0005; 93.25/ μL (range, 6.67-258.05) vs. 41.85/ μL (range, 0.44-160.62), P < 0.0001, respectively). Moreover, percentages and absolute numbers of CD4(+)CD25(+)FOXP3(+) Tregs before treatment were significantly lower in the IVIg-resistant group than in the IVIg-sensitive group (0.18 % (range, 0.16-3.34 %) vs. 4.52 % (range, 2.8-8.11 %), P = 0.0022; 0.68/μL (range, 0.44-53.81) vs. 51.66/μL (range, 2.88-160.62), P = 0.0098, respectively). The frequency of CD4(+)CD25(+)FOXP3(+) Tregs in four of the five IVIg-resistant patients at diagnosis was more than 3 standard deviations below that in healthy subjects. Two of these four patients displayed coronary abnormalities, and one of these two patients developed coronary aneurysm.Conclusion: Lack of CD4(+)CD25(+)FOXP3(+) Tregs before treatment may predict resistance to IVIg therapy in patients with KD. [ABSTRACT FROM AUTHOR]

Gene delivery using magnetic nanoparticles (MNPs) is known as magnetofection and is an efficient non-viral gene delivery system. γ-FeO nanoparticles (primary diameter = 29 nm) and FeO nanoparticles (primary diameter = 20-30 nm) coated with deacylated linear polyethylenimine (PEI max) were prepared and conjugated with DNA. The dependency of transfection efficiency on the weight of MNPs, viability of HeLa cells, and size of DNA/PEI max/MNP complexes was evaluated. Transfection efficiency initially increased with the weight of the complexes; however, it decreased with further increase in weight. In contrast, cell viability increased with further increase in weight. Cytotoxicity assay showed that the decline in transfection efficiency at higher weights was not attributable to cytotoxicity of DNA/PEI max/MNP complexes. The DNA/PEI max/MNP complexes aggregated because of DNA binding and pH interaction with the medium. Aggregation depending on the weight of MNPs was confirmed. The number of complexes was estimated from the size distribution. In addition, the dependency of the transfection efficiency on aggregation was assessed with respect to cellular endocytic pathways using the complexes. The complexes were internalized through clathrin-dependent endocytosis, which was a size-dependent pathway. This study reveals that decreased transfection efficiency was associated with the extent of aggregation, which was induced by high weight of MNPs. [ABSTRACT FROM AUTHOR]

Abstract: The Kyoto University Research Reactor Institute is engaged in research on an accelerator-driven system (ADS) using the fixed field alternating gradient accelerator at the Kyoto University Critical Assembly. With the aim of achieving the high-energy neutrons anticipated in the actual ADS experiments, we propose the use of a new target concept (the multi-target) in this study. The conceptual design of the multi-target is numerically carried out, and the high-energy neutrons generated by the injection of high-energy protons at the multi-target are successfully measured using a liquid organic scintillator in the experiments. The conceptual design and effectiveness of the multi-target is confirmed by the obtained neutron spectrum and neutron yield in both the experimental and calculated results. [Copyright &y& Elsevier]

Background: Radiological discrimination of histologic subtypes of small peripheral adenocarcinoma of the lung is clinically important. Although there are many articles in which CT findings were used for this purpose, there are only a few reports on the capability of FDG PET-CT findings for histologic classification of this tumor. Purpose: To investigate the correlation between visual assessment or maximum standard uptake values (SUVmax) on F18-FDG PET-CT and histology grading of small peripheral adenocarcinoma of the lung. Material and Methods: Proportions of positive PET-CT diagnoses and SUVmax were retrospectively reviewed on 96 solitary pulmonary nodules of ≤2 cm in 90 consecutive patients. Tumors were classified into four groups according to Noguchi's classification (group 1 [n = 10], atypical adenomatous hyperplasia and type A tumors; group 2 [n = 12], type B tumors; group 3 [n = 42], type C tumors; group 4 [n = 32], types D, E, and F tumors). Proportions of positive PET-CT diagnoses and mean SUVmax of lesions among four groups were compared using trend tests to examine if there is a significant linear correlation with the progression of the histology grading of tumors. Then, an optimal threshold of SUVmax was proposed to best discriminate tumors of poor (groups 3 and 4) from good (groups 1 and 2) prognosis. Results: There was a significant linear trend for both visual assessment (P < 0.01) and SUVmax (P < 0.01). A SUVmax of 0.42 showed the highest accuracy of 84% with 95% sensitivity and 50% specificity for predicting tumors of poor prognosis. A SUVmax of 2.05 showed 100% specificity with 49% sensitivity, and 60% accuracy. Positive visual diagnoses showed accuracy of 83% with 90% sensitivity and 59% specificity. Conclusion: Visual assessment and SUVmax on PET-CT correlated well with the histology grading of small peripheral adenocarcinoma of the lung. [ABSTRACT FROM AUTHOR]

We have investigated 3D profiling of the objects by a low-coherence optical interferometer using MEMS grating. This system, constructed with optical fibers and MEMS devices, is a Fourier domain interferometer, which can discriminate distance to the object by wavelength analysis of the interference spectra. A MEMS mirror gives the object 2D optical scanning, and a MEMS grating permits spectroscopy of interference spectra. The MEMS grating can tilt to dual axis with electromagnetic force induced by planar coils and a permanent magnet. One axis tilting enables near-infrared spectroscopy and another axis tilting functions as optical axis alignment in an interferometer. Fabricated MEMS grating could tilt ±3.5° (mech.)/less than ±10 mA in both directions at low frequency, which were equivalent to approximately 1400 to 1700 nm in wavelength. The interferometer, whose S/N was 50 dB and vertical standard deviation was 0.6 µm, could scan full wavelength width (1400 to 1700 nm) in 25 ms. Finally, we could realize 3D profiling which was not only surface reflection profiling of 1-µm step, but also transparent profiling of IC process layer from the wafer backside. © 2013 Wiley Periodicals, Inc. Electron Comm Jpn, 96(2): 9-15, 2013; Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/ecj.11452 [ABSTRACT FROM AUTHOR]

Abstract: Juvenile myelomonocytic leukemia (JMML) progenitor cells exhibit in vitro hypersensitivity to granulocyte-macrophage colony-stimulating factor (GM-CSF). Phospho-specific flow cytometry using anti-phosphorylated STAT5 antibody is a new method recently reported to detect GM-CSF hypersensitivity of cells. However, colony assays using methylcellulose medium to measure GM-CSF-hypersensitivity remain as the current gold standard. Interestingly, cytomegalovirus (CMV) infection in infancy often presents with a variety of clinical symptoms that mimic JMML, with CMV giving a positive result by colony assay. We wanted to determine whether aberrant STAT5 activation occurs in CMV infection by using phospho-specific flow cytometry, and to ascertain whether this method is effective at discriminating CMV infection from JMML. Peripheral blood mononuclear cells from patients with JMML and CMV infection displayed an elevated proportion of p-STAT5 cells after low-dose GM-CSF stimulation when compared with cells from normal individuals. However, we found no significant differences in the percentage of p-STAT5 positive cells from patients with CMV infection and JMML at any doses of the GM-CSF doses used. We conclude that patients with CMV infection cannot be discriminated from patients with JMML by this new diagnostic method. [Copyright &y& Elsevier]

Watanabe N, Takahashi Y, Matsumoto K, Horikoshi Y, Hama A, Muramatsu H, Yoshida N, Yagasaki H, Kudo K, Horibe K, Kato K, Kojima S. Total body irradiation and melphalan as a conditioning regimen for children with hematological malignancies undergoing transplantation with stem cells from HLA-identical related donors. Pediatr Transplantation 2011: 15: 642-649. © 2011 John Wiley & Sons A/S. Abstract: Although some studies have reported that TBI and MEL offer an effective conditioning regimen for autologous SCT in acute leukemia, little has been reported regarding outcomes of allogeneic SCT. We retrospectively evaluated outcomes for 50 pediatric patients who underwent allo-SCT conditioned with intravenous MEL (180-210 mg/m2) and fractionated TBI (12-13.2 Gy) from HLA-identical related donors. Nineteen patients were in CR1, 18 were in CR2, and 13 showed advanced-stage disease (≥CR3). Patients had received allo-SCT from HLA-identical siblings (n = 45) or phenotypically HLA-identical family donors (n = 5). Median duration of follow-up for all disease-free patients was 61 months (range, 8.8-177 months). At the time of analysis, 12 patients had died. Eleven of those died of relapse, and one died of TRM. DFS rates for all patients, patients with AML (n = 12), and patients with lymphoid malignancy (n = 38) were 61.4% and 82.1%, respectively. DFS rates for CR1, CR2, and ≥CR3 cases were 89.2%, 88.1%, and 23.1%, respectively (p < 0.05). MEL/TBI for pediatric patients with hematological malignancies was associated with lower relapse rates and no increase in toxicity, resulting in better survival. [ABSTRACT FROM AUTHOR]

Abstract: The usefulness of the measurements of the backscattering neutron and 2.22MeV capture γ-ray from hydrogen in the landmine detection method is described in this paper. When the soil moisture content is increased, the reaction rates of both the neutron scattering reaction and capture reaction are increased. However, the backscattering neutrons are more influenced than the capture γ-rays by the soil moisture before the reaction with the detector. The facts that the backscattering neutron method is useful in the dry soil case and that the capture γ-ray method is effective in well-wet soil case are confirmed by the experiments and the calculations. The landmine detection efficiency is improved in various soil moisture conditions by combining the backscattering neutron method together with the capture γ-ray method. The effectiveness of the pulse mode operation was confirmed numerically. [Copyright &y& Elsevier]

Allogeneic stem cell transplantation (SCT) is the only curative therapy for patients with refractory or relapsed acute leukemia, although the prognosis remains poor. Few reports have described outcomes of SCT in pediatric patients with refractory acute leukemia. To identify prognostic factors for these patients, we retrospectively evaluated SCT outcomes for advanced acute leukemia in 82 pediatric patients from 3 transplant units in Nagoya City between 1990 and 2008. Median age at transplantation was 8 years (range, 0.5-17 years). Transplantation was performed in the first refractory relapse for 53 patients (64.6%), in the second or subsequent relapse for 16 patients (19.5%), and during primary induction failure for 13 patients (15.9%). Only 4 patients (4.9%) underwent transplantation in the untreated first relapse, and 39 patients (47.6%) received unrelated donor progenitor cells. Of the 82 patients, 61 died (77.9%), with a median survival of 7.1 months (95% confidence interval [CI], 4.2-10.0 months). Median disease-free survival (DFS) was 4.7 months (95% CI, 2.6-6.9 months). In multivariate analysis, peripheral blood blasts, cord blood transplantation, and more than 3 courses of previous salvage chemotherapy were predictive of DFS. These results support the notion that allogeneic SCT offers only a small chance of cure for most pediatric patients with refractory or relapsed acute leukemia, and suggest that reduction of the leukemia burden and earlier optimal timing of transplantation are essential for long-term survival even in patients with refractory acute leukemia. [ABSTRACT FROM AUTHOR]

Nishio N, Takahashi Y, Ohashi H, Doisaki S, Muramatsu H, Hama A, Shimada A, Yagasaki H, Kojima S. Reduced-intensity conditioning for alternative donor hematopoietic stem cell transplantation in patients with dyskeratosis congenita. Pediatr Transplantation 2011: 15:161-166. © 2010 John Wiley & Sons A/S. DC is an inherited bone marrow failure syndrome mainly characterized by nail dystrophy, abnormal skin pigmentation, and oral leukoplakia. Bone marrow failure is the most common cause of death in patients with DC. Because previous results of HSCT with a myeloablative regimen were disappointing, we used a reduced-intensity conditioning regimen for two patients with classic DC, and one patient with cryptic DC who harbored the TERT mutation. Graft sources included two mismatched-related bone marrow (BM) donors and one unrelated BM donor. Successful engraftment was achieved with few regimen-related toxicities in all patients. They were alive 10, 66, and 72 months after transplantation, respectively. Long-term follow-up is crucial to determine the late effects of our conditioning regimen. [ABSTRACT FROM AUTHOR]

Abstract: Hippocampal long-term potentiation (LTP) is reportedly reduced in the presence of melatonin, but the cellular mechanisms of LTP inhibition by melatonin remain unclear. Since melatonin has the ability to scavenge free radicals such as nitric oxide (NO) and since NO has been suggested as an important contributor to LTP induction, in the present study we electrophysiologically examined whether melatonin inhibits hippocampal LTP by way of the NO signaling pathway. Field EPSP at Schaffer collateral – CA1 pyramidal cell synapses were recorded, and LTP was induced by tetanic stimulation (100Hz, 1s). Melatonin (100nM) reduced the degree of LTP, and l-NAME (100μM), an inhibitor of NO synthase, also reduced LTP, but simultaneous application of melatonin and l-NAME did not evoke any additional reduction of LTP in comparison with when only melatonin or only l-NAME were applied. Furthermore, the inhibition of LTP by the application of melatonin and l-NAME was disrupted by the application of an NO donor, DEA/NO (3μM). The paired-pulse facilitation ratios before and after LTP induction by tetanic stimulation were nearly identical in the absence and presence of l-NAME. These results demonstrate that the inhibition of LTP in the presence of melatonin is due to the action of melatonin on the postsynaptic NO signaling pathway. [ABSTRACT FROM AUTHOR]

Abstract: For the detection of landmines, a new γ-ray detector system, a neutron source, and control and measurement devices were developed. A prototype system has newly been developed by combining these devices. The usefulness of capture γ-ray and backscattering neutron methods is examined with real explosives in several conditions and the performance of the prototype landmine detection system is demonstrated experimentally in this study. The combination of the methods is confirmed to be sufficiently effective for application to actual landmine detection. [Copyright &y& Elsevier]

Two kinds of naphtols, 2, 7-dihydroxynaphthalene (2,7-DHN) and 2-hydroxy naphthalene (2-HN), were reacted with formaldehyde to produce dimeric naphtols. One of the products, designated as DN-a, was prepared only from 2-DHN and thus possessed tetra-functionality. Two other kinds of dimeric naphtols, DN-b and DN-c were prepared from the mixture of 2-DHN and 2-HN in different ratios providing hydroxyl functionalities of 3.0 and 2.6 for DN-b and DN-c, respectively. The epoxy resins, E-a, E-b, and E-c, were prepared by the reaction of the corresponding dimeric naphtol with epichlorohydrine. The melt viscosity of E-a was comparable with that of cresol novolac type epoxy resin (ECN), and those of E-b and E-c were sufficiently lower so as to provide better flow-ability in comparison with ECN making them potentially more useful. The cured epoxy resins in this report showed higher Tg values in comparison with that of ECN. In particular, the E-a cured resin showed a Tg of 328 °C, which is the highest Tg for epoxy resins reported so far. [ABSTRACT FROM PUBLISHER]

Purpose. Muscular co-contraction resulted in corrected elbow and shoulder joint stiffness; however, this correction neither ameliorated endpoint oscillation nor assisted in the execution of smooth two-joint arm movements. We hypothesised that the reacquisition of smooth arm movements became synonymous with the restoration of time-domain reciprocal electromyographic (EMG) activities in biarticular arm muscles. The purpose of this study was to investigate whether or not the restored reciprocal EMG activities in biarticular arm muscles reflected improved smooth motor performance in patients with stroke after 10 days of two-joint arm-movement training. Methods. Three male patients with sub-acute stroke with left-arm paralysis performed circle-drawing tasks using a haptic device system for upper limb neuromuscular rehabilitation. Results. After the training, the movement velocities and achievement periods increased with the enhancement of the reciprocal EMG activities in biarticular arm muscles, and there was less jerkness in movement after training for the same duration. Conclusions. Patients with stroke could achieve smooth motor performance with the restoration of the reciprocal EMG activities in biarticular arm muscles. Therefore, the reciprocal EMG activities in biarticular arm muscles in response to circle drawing would be an index for the progressive improvements of smooth motor functions in the upper limbs. [ABSTRACT FROM AUTHOR]

Aplastic anemia (AA) is characterized by a reduced number of hematopoietic stem cells and fatty replacement in the bone marrow. Transcriptional factor GATA-2 plays several important roles in both hematopoiesis and adipogenesis. Decreased levels of GATA-2 compromise the proliferation and survival of hematopoietic stem cells. GATA-2 suppresses adipocyte differentiation through direct inhibition of adipogenic factors, including peroxisome proliferator-activated receptor−γ (PPARγ). Previous studies have shown that expression of GATA-2 is decreased in marrow CD34-positive cells in AA. To elucidate the mechanisms of fatty marrow replacement, we evaluated the mRNA expression for GATA-2 and PPARγ in mesenchymal stem cells (MSCs) from patients with AA by quantitative real-time polymerase chain reaction. GATA-2 expression by MSCs from AA patients was significantly lower than in normal subjects. Conversely, expression of PPARγ was significantly higher in AA patients. Western blot analysis demonstrated that protein levels of GATA-2 were lower in AA patients than those in normal subjects. Moreover, incubation with interferon-γ induced downregulation of GATA-2 levels in MSCs from normal subjects. These findings indicate that fatty marrow replacement in AA patients can be explained by downregulation of GATA-2 and overexpression of PPARγ in MSCs. Decreased expression of GATA-2 might be responsible for the pathogenesis and development of the clinical features of the disease. [Copyright &y& Elsevier]

JEM-EUSO is a space science mission to explore the extreme energies and physics of the Universe. Its instrument will watch the darkside of the earth and will detect UV photons emitted from the extensive air shower caused by an ultra-high energy cosmic ray (UHECR above 1018 eV), or an extremely high energy cosmic ray (EHECR) particle (e.g. above about 1020 eV). Such a high-rigidity particle as the latter arrives almost in a straight line from its origin through the magnetic fields of our Milky Way Galaxy and is expected to allow us to trace the source location by its arrival direction. This can open the door to new astronomy with charged particles. In its 5 years of operation including the tilted mode, Extreme Universe Space Observatory an Japanese Experiment Module (JEM-EUSO) will detect at least 1000 events with E > 7 × 1019 eV with the Greisen--Zatsepin--Ku'zmin (GZK) suppression spectrum. It can determine the energy spectrum and source locations of GZK to super-GZK regions with a statistical accuracy of several percent. JEM-EUSO is planned to be deployed by H2 transfer vehicle (HTV) and will be attached to the Japanese Experiment Module/Exposure Facility (JEM/EF) of International Space Station. JAXA has selected JEM-EUSO as one of the mission candidates of the second phase utilization of JEM/EF for launch in the early-to-mid 2010 s. [ABSTRACT FROM AUTHOR]

Abstract: Recent molecular studies have revealed that the GM-CSF/RAS signaling pathway plays a central role in the pathogenesis of juvenile myelomonocytic leukemia (JMML). CFU-GM colony assay is an important test for GM-CSF hypersensitivity in patients with JMML, but requires specific skills. We established a simple and easy quantification method to test GM-CSF hypersensitivity, using a 3H-thymidine assay. With this quantification method, JMML patients with RAS mutations showed significantly higher GM-CSF sensitivity than JMML patients with PTPN11 mutations. This method will be useful not only in the diagnosis of JMML, but also to evaluate the difference of GM-CSF sensitivity among patients. [Copyright &y& Elsevier]

Transplanted donor lymphocytes infused during hematopoietic stem cell transplantation (HSCT) have been shown to cure patients with hematological malignancies. However, less is known about the effects of HSCT on metastatic solid tumors. Thus, a better understanding of the immune cells and their target antigens that mediate tumor regression is urgently needed to develop more effective HSCT approaches for solid tumors. Here we report regression of metastatic renal cell carcinoma (RCC) in patients following nonmyeloablative HSCT consistent with a graft-versus-tumor effect. We detected RCC-reactive donor-derived CD8(+) T cells in the blood of patients following nonmyeloablative HSCT. Using cDNA expression cloning, we identified a 10-mer peptide (CT-RCC-1) as a target antigen of RCC-specific CD8(+) T cells. The genes encoding this antigen were found to be derived from human endogenous retrovirus (HERV) type E and were expressed in RCC cell lines and fresh RCC tissue but not in normal kidney or other tissues. We believe this to be the first solid tumor antigen identified using allogeneic T cells from a patient undergoing HSCT. These data suggest that HERV-E is activated in RCC and that it encodes an overexpressed immunogenic antigen, therefore providing a potential target for cellular immunity. [ABSTRACT FROM AUTHOR]

Abstract: We propose and demonstrate an OCT optical probe using eccentric optics. This probe enabled both forward imaging and side imaging by dividing a circular scanning area into two semicircular scanning areas using an external motor to rotate the flexible tube. The outer diameter of the probe was 2.6mm, and its rigid portion length was 10mm. The lateral resolution was 23μm, and the eccentric radius was 1.1mm. The circumferential length in scanning was 6.9mm, and the working distance was 5mm. OCT images of 1.5mm×6.9mm (in tissue, axial × circumference), including forward image and side image, were measured with the axial resolution of 19μm in air and a frame rate of one frame per second. The epidermis, dermis, and sweat gland of in vivo human ventral finger tips were observed. [Copyright &y& Elsevier]

Abstract: The present study characterized alterations of the endometrial epidermal growth factor (EGF) and examined potential relationships between normalization of the EGF and restoration of fertility in repeat breeder cows. In Experiment 1, endometrial tissues were obtained by biopsy on Days 3, 7 and 14 of the estrous cycle from 99 fertile dairy cows and normal ranges of uterine tissue EGF concentrations were determined. Then, eight fertile cows were examined for endometrial EGF concentrations on Days 3, 7 and 14 during the three consecutive estrous cycles. All eight cows had a normal EGF profile (EGF concentrations were within the normal ranges of all 3 days) in all three estrous cycles and endometrial EGF concentrations were similar among the three estrous cycles. In Experiment 2, 61 repeat breeder cows were examined EGF profile and 43 (70.5%) cows had altered EGF profiles compared with control profiles. A typical alteration was characterized by decreased concentrations on Days 3 and 14 and accounted for 86.0% of all alterations. When repeat breeder cows with altered EGF profiles (n =17) were left untreated, abnormality persisted in 14 (82.4%) cows at the second examination and only 3 animals became pregnant within the next two estrous cycles. Among 15 cows showing a typical alteration at the first examination, 11 (73.3%) cows had the same alteration until the third examination performed after two infertile inseminations following the second examination. When repeat breeder cows with altered EGF profiles (n =26) were given one of four therapeutic treatments, cows in which the EGF profile normalized after treatment had a greater pregnancy rate than those with altered profiles (11/14 animals versus 3/12 animals pregnant; P <0.05). In conclusion, suppressed endometrial EGF concentrations on Days 3 and 14 may be common alterations and persist between estrous cycles in repeat breeder cows. Potential relationship between normalization of the endometrial EGF profile and restoration of fertility was observed. Additional study to confirm results of the treatment is, however, necessary because the present study used a limited number of animals. Nevertheless, current data suggest that normalization of the EGF profile is one of the prerequisite factors to restore fertility. [Copyright &y& Elsevier]

Allogeneic haematopoietic cell transplantation (HCT) can cure a variety of non-malignant haematological disorders. Although transplant outcomes for selected patients with severe aplastic anaemia (SAA) and paroxysmal nocturnal haemoglobinuria (PNH) have improved, older age, allo-immunisation from transfusions, prior immunosuppressive therapy and a prolonged time from diagnosis to transplantation are associated with worse outcome. Because of its potent immunosuppressive effects, we investigated a fludarabine-based non-myeloablative conditioning regimen in patients with transfusion-dependent non-malignant haematological disorders at increased risk for graft rejection with conventional transplant conditioning. Twenty-six patients with transfusion dependent/anti-thymocyte globulin (ATG)-refractory SAA, PNH or pure red cell aplasia underwent HCT from a human leucocyte antigen (HLA)-compatible relative. Transplant conditioning consisted of cyclophosphamide (120 mg/kg) and fludarabine (125 mg/m2) with or without ATG. Ciclosporine, alone or combined with mycophenolate mofetil or methotrexate, was used as graft- versus-host disease (GVHD) prophylaxis. All patients achieved durable engraftment and transfusion-independence. Twenty-four of 26 patients are alive at a median of 21 months following transplantation. Although a high cumulative incidence of acute (65% grades II–IV, 54% grades III–IV) and chronic GVHD (56%) was observed, only one patient died from transplant-related causes (cumulative incidence 7%). These data show that HCT following fludarabine-based non-myeloablative conditioning results in durable engraftment and excellent survival in SAA and PNH patients at high risk for graft rejection. [ABSTRACT FROM AUTHOR]

A new bacterial black spot disease was observed onOdontoglossum,Odontioda,Odontocidium, andVuylstekearaorchids in Japan. Typical symptoms on the leaves were dark or black spots (or both) with a yellow halo. The causal agent was identified asBurkholderia andropogonis(Smith 1911) Gillis, Van Van, Bardin, Goor, Hebbar, Willems, Segers, Kersters, Heulin and Fernandez 1995. The isolates were pathogenic on four original host orchids,Phalaenopsisorchid, and tulip; they were not pathogenic on white clover or corn after needle stab inoculation. An antibiotic bactericide (oxytetracycline/streptomycin mixture WP) was most effective for controlling the disease. [ABSTRACT FROM AUTHOR]

The objective of the present study was to determine if abnormalities in the cyclic changes of endometrial EGF concentrations can be a diagnostic tool for repeat breeder cows. First, the profile of EGF concentrations during the estrous cycle was determined using endometrial tissues obtained from 31 Holstein cows after slaughter. Cyclic cows had two peaks of EGF concentrations. Then, endometrial tissues were obtained from 12 control and 20 repeat breeder cows by biopsy on Days 3, 7, and 14 of the same estrous cycle. Endometrial EGF concentrations in biopsied samples of the controls were similar to those found in slaughterhouse materials; they were high on Days 3 and 14 (9.2 and 10.4 ng/g tissue, respectively) and low on Day 7 (3.8 ng/g tissue). Concentrations of EGF in repeat breeder cows had a different profile; they were similar on Days 3, 7, and 14 (4.4, 3.4, and 4.0 ng/g tissue, respectively). In conclusion, changes in endometrial EGF concentrations were altered in repeat breeders; these alterations may be a potential diagnostic marker for repeat breeder cows. [Copyright &y& Elsevier]

It can be exhausting, both physically and emotionally, to assist physically handicapped persons. Therefore, an assistive mobile system called AMOS (Assistive MObile robot System) has been developed to help alleviate this burden. The purpose of AMOS is to pick up and transport daily use objects, placing them in a designated indoor location semi-autonomously. AMOS consists of a self-contained mobile robot body, a user interface with a touch-panel and a computer network (Ethernet LAN, Internet). The user interacts with the mobile robot through a Web browser connected to a computer network, allowing for communication anytime, from anywhere and by anyone. This mode provides a simple way for communicating with and determining the status of the robot. Experiments were performed to verify the successful operation of AMOS. Although the system performed as designed, it would prove useful to the extend service area of the robot through communication mechanisms and the user interface. [ABSTRACT FROM AUTHOR]

We measured the temperature and frequency dispersion of the permittivity of vinylidene fluoride and trifluoroethylene (YDF/TrFE) thin films spin-coated on glass substrates with evaporated aluminium electrodes. Assuming the existence of two surface layers with different dielectric properties from the bulk material, a thickness of 2 nm was deduced for each surface layer. The temperature dependence of the frequency dispersion of the permittivity of the surface layers was obtained. Each surface layer has a dielectric relaxation which is essentially the same as the segment mode of the amorphous region of the bulk. It shows no anomaly at the temperature of the paraelectric-ferroelectric phase transition for thick samples. The surface layers appear to be amorphous. [ABSTRACT FROM AUTHOR]

A single-electron circuit can be operated as a discrete dynamical system because it changes its internal state discontinuously because of electron tunneling. To confirm this idea, we designed a sample circuit for discrete dynamical operation and confirmed by computer simulation that the circuit successfully generated a sequence of discrete-time outputs by following a return map. The concept of discrete dynamical systems will be useful in developing new functional systems that consist of quantum devices and nanostructures. [Copyright &y& Elsevier]

Background: Human colorectal neuroendocrine cell carcinoma (NEC) is a rare disease with a poor prognosis. The biological behavior of NEC remains poorly understood. Materials and Methods: We established two new NEC cell lines from a patient with rectal neuroendocrine carcinoma, NECS-P and NECS-L from the primary tumor and a liver metastasis, respectively. We investigated the biological differences between the two cell lines to study the mechanisms involved in liver metastasis. Results: There was no difference between NECS-P and NECS-L in the morphological, ultrastructural and immunohistochemical studies. After addition of TGF-β[sub 1] , the doubling times of NECS-P were increased in a dose-dependent manner relative to untreated cells, whereas TGF-β[sub 1] had no effect on NECS-L. The attachment and chemotactic response of the two cell lines were not enhanced by TGF-β[sub 1] . The invasive capacity and the production of matrix metalloproteinase-2 (MMP-2) were significantly increased only in NECS-L following the addition of TGF-β[sub 1] . When anti-MMP-2 antibody was added to the medium with TGF-β[sub 1] , NECS-L invasion was inhibited. Conclusion: It is considered that these differences are important to understand the mechanisms of liver metastasis of NEC.Copyright © 2000 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objective: Individuals with Dravet syndrome (DS) exhibit progressive gait disturbance. No quantitative studies have been conducted to evaluate the effectiveness of medication for gait disturbance. Therefore, the aim of this study was to evaluate the effectiveness of levodopa for pathological gait in people with DS using three‐dimensional gait analysis (3DGA). Methods: Nine individuals with DS, ages 6–20 years, participated in a crossover study of levodopa and were randomly assigned to the levodopa precedence or no levodopa precedence group. Levodopa/carbidopa hydrate was prescribed at a dose of 5 mg/kg/day (body weight <60 kg) or 300 mg/day (body weight ≥60 kg). The medication was taken for 4–6 weeks (4‐week washout period). 3DGA was performed three times before the study, with and without levodopa. A mixed‐effects model was used to evaluate the effectiveness of levodopa. The primary outcome was the change in the Gait Deviation Index (GDI). In addition, spatiotemporal gait parameters, 6‐minute walking distance (6MD), and balance were evaluated. The correlation between the effectiveness of levodopa and age or gait performance before starting levodopa was analyzed. Results: Levodopa improved the GDI by 4.2 points, (p =.029), 6MD by 52 m (p =.002), and balance test result by 4.1 mm (p =.011) in participants with DS. No severe adverse events were observed, with the exception of one participant, who exhibited fever and consequently stopped taking levodopa. Levodopa was more effective in younger participants with a higher baseline gait performance. Significance: Our randomized crossover trial showed that levodopa has the potential to improve gait disturbance in people with DS. [ABSTRACT FROM AUTHOR]

[Display omitted] • Nickel-catalyzed hydroalkylation of 1,3-dienes. • A homoallyl carbonate as a surrogate for the 1,3-diene and hydride source. • Malonates were used as a carbon pronucleophile. The use of a malonate nucleophile in the transition metal-catalyzed hydroalkylation of 1,3-dienes remains immature. Herein, we report the nickel-catalyzed hydroalkylation of 1,3-dienes with malonates using a homoallyl carbonate as the 1,3-diene and hydride source. A broad range of homoally carbonates and malonate derivatives were well tolerated under a Ni/DPEphos catalyst system, providing the corresponding 1,2-hydroalkylation products in 40–94% yields with excellent regioselectivity (32 examples). We also suggested the possible reaction mechanism for the nickel-catalyzed hydroalkylation of in situ generated 1,3-dienes with malonates. [ABSTRACT FROM AUTHOR]

The introduction of varicella vaccines into routine pediatric immunization programs has led to a considerable reduction in varicella incidence. However, there have been reports of varicella, herpes zoster, and meningitis caused by the vaccine strain of varicella-zoster virus (VZV), raising concerns. Establishing the relationship between the wild-type and vaccine strains in VZV infections among previously vaccinated individuals is crucial. Differences in the single nucleotide polymorphisms (SNPs) among vaccine strains can be utilized to identify the strain. In this study, we employed nanopore sequencing to identify VZV strains and analyzed clinical samples. We retrospectively examined vesicle and cerebrospinal fluid samples from patients with VZV infections. One sample each of the wild-type and vaccine strains, previously identified using allelic discrimination real-time PCR and direct sequencing, served as controls. Ten samples with undetermined VZV strains were included. After DNA extraction, a long PCR targeting the VZV ORF62 region was executed. Nanopore sequencing identified SNPs, allowing discrimination between the vaccine and wild-type strains. Nanopore sequencing confirmed SNPs at previously reported sites (105,705, 106,262, 107,136, and 107,252), aiding in distinguishing between wild-type and vaccine strains. Among the ten unknown samples, nine were characterized as wild strains and one as a vaccine strain. Even in samples with low VZV DNA levels, nanopore sequencing was effective in strain identification. This study validates that nanopore sequencing is a reliable method for differentiating between the wild-type and vaccine strains of VZV. Its ability to produce long-read sequences is remarkable, allowing simultaneous confirmation of known SNPs and the detection of new mutations. Nanopore sequencing can serve as a valuable tool for the swift and precise identification of wild-type and vaccine strains and has potential applications in future VZV surveillance. [ABSTRACT FROM AUTHOR]

Aim: This study aimed to describe children developing late gastrointestinal (GI) complications after allogeneic hematopoietic stem cell transplantation (allo‐HSCT), focusing on Kampo medicine. Methods: At the Nagoya University Hospital Department of Pediatrics, 179 consecutive patients underwent allo‐HSCT over five years, of whom 167 achieved engraftment and survived at least 100 days post transplant and therefore were included in the study. Results: Thirteen patients (7.8%) developed late GI symptoms. Among these, three had upper GI symptoms, three had lower GI symptoms, while seven had upper/lower GI symptoms. Total parenteral nutrition was administered in 10 (77%) patients for a median of 81 days (range: 20–303). Four (31%) had histologically proven graft‐versus‐host‐disease (GVHD), two (15%) had adverse drug reactions, and one (8%) had a viral infection. All three patients with lower GI symptoms responded to Kampo formulas' warming interior [TM1]. Two patients with upper GI symptoms had epigastric rigidity and responded to Aurantii Fructus Immaturus‐based formulas. One patient developed severe cachexia, which was successfully reversed with Kampo medicines. There were no adverse effects due to Kampo medicines. Conclusions: Late GI complications may be a burden on children after allo‐HSCT. Kampo medicines may provide a safe and promising therapy to resolve GI symptoms not otherwise specified. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) infection can lead to infectious mononucleosis (EBV-IM) and, more rarely, EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), which is characterized by a life-threatening hyperinflammatory cytokine storm with immune dysregulation. Interferon-gamma (IFNγ) has been identified as a critical mediator for primary HLH; however, the detailed role of IFNγ and other cytokines in EBV-HLH is not fully understood. In this study, we used single-cell RNA sequencing to characterize the immune landscape of EBV-HLH and compared it with EBV-IM. Three pediatric patients with EBV-HLH with different backgrounds, one with X-linked lymphoproliferative syndrome type 1 (XLP1), two with chronic active EBV disease (CAEBV), and two patients with EBV-IM were enrolled. The TUBA1B + STMN1 + CD8 + T cell cluster, a responsive proliferating cluster with rich mRNA detection, was explicitly observed in EBV-IM, and the upregulation of SH2D1A—the gene responsible for XLP1—was localized in this cluster. This proliferative cluster was scarcely observed in EBV-HLH cases. In EBV-HLH cases with CAEBV, upregulation of LAG3 was observed in EBV-infected cells, which may be associated with an impaired response by CD8 + T cells. Additionally, genes involved in type I interferon (IFN) signaling were commonly upregulated in each cell fraction of EBV-HLH, and activation of type II IFN signaling was observed in CD4 + T cells, natural killer cells, and monocytes but not in CD8 + T cells in EBV-HLH. In conclusion, impaired responsive proliferation of CD8 + T cells and upregulation of type I IFN signaling were commonly observed in EBV-HLH cases, regardless of the patients’ background, indicating the key features of EBV-HLH. [ABSTRACT FROM AUTHOR]

Introduction: The effects of hydrocortisone (HDC) administration to extremely low birth weight (ELBW) infants on later development remain unclear. This study examined the association between HDC dosage during neonatal period and neurodevelopmental outcomes in ELBW infants. Methods: This study was a retrospective cohort study conducted in eight centers in Japan. The subjects of this study were ELBW infants born between April 2015 and March 2017. The association between postnatal total HDC dosage up to 36 weeks postmenstrual age and the developmental quotient (DQ) at 3 years of age was examined. Multiple linear regression evaluated the association, adjusting for weeks of gestation, birth weight, and the presence of bronchopulmonary dysplasia, late-onset circulatory collapse, intracranial hemorrhage, necrotizing enterocolitis, and sepsis. Results: This study included 218 ELBW infants, of whom 144 underwent a developmental test at 3 years of age. Simple linear regression analysis revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: −2.65, 95% CI: −3.73, −1.57). Multiple linear regression analysis adjusted for the presence of bronchopulmonary dysplasia and late-onset circulatory collapse also revealed a significant association between total HDC dosage and DQ at 3 years of age (coefficients: −2.66, 95% CI: −3.89, −1.42). Conclusion: Higher total HDC dosage up to 36 weeks postmenstrual age in ELBW infants was associated with impaired neurodevelopmental outcomes. Although HDC is often needed in the treatment of ELBW infants, clinicians should be aware that an increased dose of HDC may be associated with impaired neurodevelopmental outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor differentiation therapy using retinoids has a long history of clinical development and an established role as a part of the standard treatment for high-risk neuroblastoma. However, basic and clinical science related to this treatment is still immature in multiple respects. In the present review, we systematically expand on the basic and clinical science of retinoids for neuroblastoma treatment, off-label issues related to the treatment and possible countermeasures, and finally, prospects for this therapy. Retinoids are vitamin A derivatives and include trans-retinoic acid, isotretinoin, tamibarotene, and bexarotene, all of which are currently available for clinical use. The clinical development of retinoid therapy for neuroblastoma has a history spanning more than four decades. The most promising agent is isotretinoin, which can contribute to improving event-free survival in patients with high-risk neuroblastoma by approximately 10% when administered over six months as maintenance therapy. Although isotretinoin is regarded as an essential component in the standard clinical management of high-risk neuroblastoma, its use for this purpose in the US and EU is off-label. To promote isotretinoin use in Japan as a treatment for neuroblastoma, our clinical research team is planning to launch an investigator-initiated, registration-directed clinical trial. The present review article discusses the basic science behind retinoid therapy, pre-clinical/clinical evidence on neuroblastoma, the concept of the proposed clinical trial, and prospects for this therapy. [ABSTRACT FROM AUTHOR]

The method of "modulated driving force" has been applied to the kinetics of ferroelectric-paraelectric transition in copolymers of vinylidene fluoride (VDF) with trifluoroethylene (TrFE). The method examines the response of transition kinetics to a periodically modulated driving force, e.g., supercooling or superheating. The response to the modulation in temperature appears in the apparent heat capacity obtained by a temperature-modulated differential scanning calorimeter. By examining the frequency dispersion and its dependence on underlying linear heating (or cooling) rate, the mean time required for the completion of transition in each crystallite and the dependence of transition rate on superheating (or supercooling) are obtainable. In VDF/TrFE copolymers, it is known that the transition behavior undergoes a drastic change from reversible transition with low VDF content to nucleation-controlled transition with higher content. Several types of compositions (VDF/TrFE=47/53, 52/48, 59/41, 65/35, 69/31 and 73/27 by mol %) have been examined experimentally with this method in terms of the crossover of transition behaviors. © 2001 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Emergency drills and drills against terrorism have been held at nuclear facilities. Shortcomings of these drills are that the numbers of emergency scenarios and roles are limited because many workers must participate in them simultaneously. The times during which all employees can participate simultaneously are limited. As a means of solving these problems, augmented reality (AR) training has been increasingly adopted in recent years, but difficulties of creating contents and the inadequate degrees of freedom in the created contents are becoming problematic. For this study, we developed an AR training environment construction system for users to create scenarios easily by simply assembling and placing blocks representing scenario components in a real-world environment. To realize the construction system, we also developed the "Program Block," which enables users to create scenarios in a puzzle-like style. The system can create and simulate various scenarios involving interaction between trainees and a real-world environment. To evaluate the ease of system usage and flexibility for scenario creation, a subjective experiment was conducted at a nuclear facility. Results indicate that users can construct an AR training environment easily. [ABSTRACT FROM AUTHOR]

Multilineage-differentiating stress-enduring (Muse) cells are endogenous reparative pluripotent stem cells present in the bone marrow, peripheral blood, and organ connective tissues. We assessed the homing and therapeutic effects of systemically administered nafimestrocel, a clinical-grade human Muse cell-based product, without immunosuppressants in a neonatal hypoxic–ischemic (HI) rat model. HI injury was induced on postnatal day 7 (P7) and was confirmed by T2-weighted magnetic resonance imaging on P10. HI rats received a single dose nafimestrocel (1 × 106 cells/body) or Hank's balanced salt solution (vehicle group) intravenously at either three days (on P10; M3 group) or seven days (on P14; M7 group) after HI insult. Radioisotope experiment demonstrated the homing of chromium-51-labeled nafimestrocel to the both cerebral hemispheres. The cylinder test (M3 and M7 groups) and open-field test (M7 group) showed significant amelioration of paralysis and hyperactivity at five weeks of age compared with those in the vehicle group. Nafimestrocel did not cause adverse events such as death or pathological changes in the lung at ten weeks in the both groups. Nafimestrocel attenuated the production of tumor necrosis factor-α and inducible nitric oxide synthase from activated cultured microglia in vitro. These results demonstrate the potential therapeutic benefits and safety of nafimestrocel. [ABSTRACT FROM AUTHOR]

We report a case of bone metastasis arising from lung cancer, including quantitative values obtained with bone single-photon emission computed tomography/computed tomography (SPECT/CT), which were useful to evaluate the treatment response. The first bone SPECT/CT during pembrolizumab therapy for lung cancer recurrence showed intense 99mTc-HMDP uptake of the right femur head and mild uptake of the left ribs. After the palliative radiotherapy for the right femur head metastasis and chemotherapy, the second bone SPECT/CT showed a decrease in focal uptake of the right femur hip and increasing uptake of the left ribs. There was also new uptake appearance in the sternum, right rib, spine (Th2, Th9, Th12, L4, S1), and bilateral pelvic bone (left ilium, acetabular cartridge, femur, right ilium and ischium). The change of maximum standardized uptake values (SUVmax) for the right femur head and left third and eighth rib bony metastases were −72.6% (from 22.96 to 6.28), +407.7% (from 2.97 to 15.08), and +229.2% (from 2.60 to 8.56), respectively. The change of whole-lesion metabolic bone volume and total bone uptake was +235.4% (from 22.75 to 76.3 cm3) and +219.1% (from 205.0 to 654.09), respectively. Two quantitative bone SPECT/CT images clearly showed the good response of femur head metastasis due to radiotherapy, and progression of other bone metastases regardless of chemotherapy. [ABSTRACT FROM AUTHOR]