Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction

Tensile deformation and failure behavior at room temperature of the open cell nickel and copper foams with high porosity (96%) fabricated with the slurry foaming process at Mitsubishi Materials Corporation, Japan, was studied. In-situ observation of the deformation and failure behavior was conducted with a digital microscope. Stress-strain curves were measured, in which a non-contact extensometer was employed to detect the strain of the samples accurately. Electric resistance was measured to monitor the damage evolution. Finite element stress analysis was conducted to calculate the morphological change of cells with applied strain and the stress distribution in cells. It was revealed that the deformation and failure progressed through the following four stages; stage I characterized by the elastic deformation, stage II by plastic deformation, stage III by the co-occurrence of plastic deformation and cumulative failure of struts and stage IV by the chain reaction of strut failure nearly in a limited cross-section, respectively. Also it was found that the distribution of failure strain of struts in stage III, measured from the serrations in the stress-strain curve, could be described by the Weibull distribution, with which the transition from stage II to III was identified. Also, the result of the statistical analysis suggested that the average failure strain of the struts in the foam is much higher than the strain at ultimate stress of the foam

Factors associated with motivation and hesitation to work among health professionals during a public crisis: a cross sectional study of hospital workers in Japan during the pandemic (H1N1) 2009

<p>Abstract</p> <p>Background</p> <p>The professionalism of hospital workers in Japan was challenged by the pandemic (H1N1) 2009. To maintain hospital function under critical situations such as a pandemic, it is important to understand the factors that increase and decrease the willingness to work. Previous hospital-based studies have examined this question using hypothetical events, but so far it has not been examined in an actual pandemic. Here, we surveyed the factors that influenced the motivation and hesitation of hospital workers to work in Japan soon after the pandemic (H1N1) 2009.</p> <p>Methods</p> <p>Self-administered anonymous questionnaires about demographic character and stress factors were distributed to all 3635 employees at three core hospitals in Kobe city, Japan and were collected from June to July, 2009, about one month after the pandemic (H1N1) in Japan.</p> <p>Results</p> <p>Of a total of 3635 questionnaires distributed, 1693 (46.7%) valid questionnaires were received. 28.4% (N = 481) of workers had strong motivation and 14.7% (N = 249) had strong hesitation to work. Demographic characters and stress-related questions were categorised into four types according to the odds ratios (OR) of motivation and hesitation to work: some factors increased motivation and lowered hesitation; others increased motivation only; others increased hesitation only and others increased both motivation and hesitation. The strong feeling of being supported by the national and local governments (Multivariate OR: motivation; 3.5; CI 2.2-5.4, hesitation; 0.2; CI 0.1-0.6) and being protected by hospital (Multivariate OR: motivation; 2.8; CI 2.2-3.7, hesitation; 0.5; CI 0.3-0.7) were related to higher motivation and lower hesitation. Here, protection included taking precautions to prevent illness among workers and their families, providing for the care of those who do become ill, reducing malpractice threats, and financial support for families of workers who die on duty. But 94.1% of the respondents answered protection by the national and local government was weak and 79.7% answered protection by the hospital was weak.</p> <p>Conclusions</p> <p>Some factors have conflicting effects because they increase both motivation and hesitation. Giving workers the feeling that they are being protected by the national and local government and hospital is especially valuable because it increases their motivation and lowers their hesitation to work.</p

Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer

BACKGROUND: Gefitinib, an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, has a certain efficacy against non-small cell lung cancer (NSCLC). Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we analyzed the response and disease progression of primary and metastatic lesions to gefitinib in responders and the results of gefitinib readministration following temporary cessation of gefitinib upon progression of initial gefitinib treatment and other treatments. METHOD: We retrospectively evaluated the clinical courses of 27 NSCLC patients who received gefitinib and achieved either a complete or partial response. RESULTS: The best-response rate and disease-control rate against the initial chemotherapy for the gefitinib-responders were 27.3% and 77.3%, respectively. Favorable efficacy was observed in the primary lesion and metastases to the lung, liver and brain, while there was no obvious effect on bone metastasis. The primary lesion and intrapulmonary metastasis were the sites of major recurrence. Median progression-free survival was 13.8 months, median duration of gefitinib treatment was 17.0 months and median overall survival was 29.2 months. Some of the patients who experienced disease progression after responding to gefitinib were again sensitive to readministration of gefitinib following temporary cessation of gefitinib and other treatments. CONCLUSION: Patients may still be expected to have prolonged survival if they once responded to gefitinib and then underwent various subsequent treatments followed by readministration of gefitinib. These findings might provide valuable information for the management of gefitinib-responders

Clinical benefit of readministration of gefitinib for initial gefitinib-responders with non-small cell lung cancer

BACKGROUND: Gefitinib, an oral agent of epidermal growth factor receptor tyrosine kinase inhibitor, has a certain efficacy against non-small cell lung cancer (NSCLC). Several predictive factors of gefitinib sensitivity have been well described. However, few studies have investigated the clinical features of gefitinib-responders. In the present study, we analyzed the response and disease progression of primary and metastatic lesions to gefitinib in responders and the results of gefitinib readministration following temporary cessation of gefitinib upon progression of initial gefitinib treatment and other treatments. METHOD: We retrospectively evaluated the clinical courses of 27 NSCLC patients who received gefitinib and achieved either a complete or partial response. RESULTS: The best-response rate and disease-control rate against the initial chemotherapy for the gefitinib-responders were 27.3% and 77.3%, respectively. Favorable efficacy was observed in the primary lesion and metastases to the lung, liver and brain, while there was no obvious effect on bone metastasis. The primary lesion and intrapulmonary metastasis were the sites of major recurrence. Median progression-free survival was 13.8 months, median duration of gefitinib treatment was 17.0 months and median overall survival was 29.2 months. Some of the patients who experienced disease progression after responding to gefitinib were again sensitive to readministration of gefitinib following temporary cessation of gefitinib and other treatments. CONCLUSION: Patients may still be expected to have prolonged survival if they once responded to gefitinib and then underwent various subsequent treatments followed by readministration of gefitinib. These findings might provide valuable information for the management of gefitinib-responders

51V-NMR study of charge order induced by cation order in δ-Ag2/3V2O5

51V-NMR experiments have been performed to investigate the local magnetic and electronic properties of the mixed-valence oxide δ-Ag2/3V2O5, which shows the novel V4+/V5+ charge ordering trigged by Ag ion ordering. We have observed the abrupt loss of 51V-NMR signal coming from the non-magnetic V5+-like ions above Tc = 225 K. It indicates that the majority of V ions are magnetic above Tc and that the phase transition is accompanied by the charge separation and the charge ordering of 3d electrons on V sites. In the low-temperature phase below Tc, the nuclear spin-lattice relaxation rate 1/T1 shows the thermal activation-type temperature dependence with the activation energy of about 130 K. It has been clarified that the ground state of this material is the charge ordered one with the spin singlet of 3d electrons on V4+-V4+ pair from a microscopic point of view

Alteration of the immune environment in bone marrow from children with recurrent B cell precursor acute lymphoblastic leukemia

Due to the considerable success of cancer immunotherapy for leukemia, the tumor immune environment has become a focus of intense research; however, there are few reports on the dynamics of the tumor immune environment in leukemia. Here, we analyzed the tumor immune environment in pediatric B cell precursor acute lymphoblastic leukemia by analyzing serial bone marrow samples from nine patients with primary and recurrent disease by mass cytometry using 39 immunophenotype markers, and transcriptome analysis. High-dimensional single-cell mass cytometry analysis elucidated a dynamic shift of T cells from naïve to effector subsets, and clarified that, during relapse, the tumor immune environment comprised a T helper 1-polarized immune profile, together with an increased number of effector regulatory T cells. These results were confirmed in a validation cohort using conventional flow cytometry. Furthermore, RNA transcriptome analysis identified the upregulation of immune-related pathways in B cell precursor acute lymphoblastic leukemia cells during relapse, suggesting interaction with the surrounding environment. In conclusion, a tumor immune environment characterized by a T helper 1-polarized immune profile, with an increased number of effector regulatory T cells, could contribute to the pathophysiology of recurrent B cell precursor acute lymphoblastic leukemia. This information could contribute to the development of effective immunotherapeutic approaches against B cell precursor acute lymphoblastic leukemia relapse

Influence of antimicrobial regimen on decreased in-hospital mortality of patients with MRSA bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most important causes of bacteremia. Recently, several epidemiological and microbiological changes have become evident in MRSA infections. The purposes of this study were to assess clinical characteristics of patients with MRSA bacteremia and microbiological changes in MRSA. We conducted a retrospective observational study on patients with MRSA bacteremia who were hospitalized between 2008 and 2011. We used univariate and multivariate analysis to evaluate the predictors associated with 30-day mortality. The 7-day and 30-day mortality rates were 12.0% and 25.3%, respectively. According to multivariate analysis, the independent predictors that associated with 30-day mortality were leukopenia, low serum albumin, high sequential organ failure assessment (SOFA) score, and quinolone use within 30 days. Compared to previous data (2003-2007), the SOFA score of the new data set remained unchanged, but in-hospital mortality decreased significantly. In particular, the mortality associated with use of vancomycin (VCM) was significantly lower. Although the minimuminhibitory concentration of VCM required to inhibit the growth of 90% of organisms (MIC90) had not changed, the trough value of VCM changed significantly; a VCM trough value of 10 or greater was significantly higher compared to previous data. Of the staphylococcal cassette chromosome mec (SCCmec) types, SCCmec II values decreased significantly, and SCCmec I and IV values increased significantly. Our results indicate that changes in VCM usage might contribute to decreased in-hospital mortality

Isotope production in proton-, deuteron-, and carbon-induced reactions on Nb 93 at 113 MeV/nucleon

Isotope-production cross sections for p-, d-, and C-induced spallation reactions on Nb93 at 113 MeV/nucleon were measured using the inverse-kinematics method employing secondary targets of CH2, CD2, and C. The measured cross sections for Mo90, Nb90, Y86,88 produced by p-induced reactions were found to be consistent with those measured by the conventional activation method. We performed benchmark tests of the reaction models INCL-4.6, JQMD, and JQMD-2.0 implemented in the Particle and Heavy Ion Transport code System (PHITS) and of the nuclear data libraries JENDL-4.0/HE, TENDL-2017, and ENDF/B-VIII.0. The model calculations also showed generally good agreement with the measured isotope-production cross sections for p-, d-, and C-induced reactions. It also turns out that, among the three nuclear data libraries, JENDL-4.0/HE provides the best agreement with the measured data for the p-induced reactions. We compared the present Nb93 data with the Zr93 data, that were measured previously by the same inverse kinematics method (Kawase et al., Prog. Theor. Exp. Phys. 2017, 093D03 (2017)2050-391110.1093/ptep/ptx110), with particular attention to the effect of neutron-shell closure on isotope production in p- and d-induced spallation reactions. The isotopic distributions of the measured production cross sections in the Zr93 data showed noticeable jumps at neutron number N=50 in the isotopic chains of ΔZ=0 and -1, whereas no such jump appeared in isotopic chain of ΔZ=0 in the Nb93 data. From INCL-4.6 + GEM calculations, we found that the jump formed in the evaporation process is smeared out by the intranuclear cascade component in Nb91 produced by the Nb93(p,p2n) and (d,d2n) reactions on Nb93. Moreover, for Nb93, the distribution of the element-production cross sections as a function of the change in proton number ΔZ is shifted to smaller ΔZ than for Zr93, because the excited Nb prefragments generated by the cascade process are more likely to emit protons than the excited Zr prefragments, due to the smaller proton-separation energies of the Nb isotopes

Coulomb breakup reactions of 93,94 Zr in inverse kinematics

Coulomb breakup reactions of 93,94 Zr have been studied in inverse kinematics at incident beam energies of about 200 MeV/nucleon in order to evaluate neutron capture reaction methods. The 93 Zr(n,γ) 94 Zr reaction is particularly important as a candidate nuclear transmutation reaction for the long-lived fission product 93 Zr in nuclear power plants. One- and two-neutron removal cross sections on Pb and C targets were measured to deduce the inclusive Coulomb breakup cross sections, 375 ± 29 (stat.) ± 30 (syst.) and 403 ± 26 (stat.) ± 31 (syst.) mb for 93 Zr and 94 Zr, respectively. The results are compared with estimates using the standard Lorentzian model and microscopic calculations. The results reveal a possible contribution of the pygmy dipole resonance or giant quadrupole resonance in the Coulomb breakup reactions of 94 Zr

Randomized controlled trial of daily teriparatide, weekly high-dose teriparatide, or bisphosphonate in patients with postmenopausal osteoporosis: The TERABIT study

Purpose: The effects of daily teriparatide (20 μg) (D-PTH), weekly high-dose teriparatide (56.5 μg) (W-PTH), or bisphosphonates (BPs) on areal bone mineral density (aBMD), bone turnover markers (BTMs), volumetric BMD (vBMD), microarchitecture, and estimated strength were investigated in postmenopausal osteoporosis patients.Methods: The study participants were 131 women with a history of fragility fractures. They were randomized to receive D-PTH, W-PTH, or BPs (alendronate or risedronate) for 18 months. Dual-energy X-ray absorptiometry (DXA), BTMs, and high-resolution peripheral quantitative CT (HR-pQCT) parameters were evaluated at baseline and after 6 and 18 months of treatment. The primary endpoint was the change (%) in cortical thickness (Ct.Th) after 18 months\u27 treatment compared with baseline.Results: DXA showed that D-PTH, W-PTH, and BPs increased lumbar spine aBMD (+12.0%, +8.5%, and +6.8%) and total hip aBMD (+3.0%, +2.1%, and +3.0%), but D-PTH and W-PTH decreased 1/3 radius aBMD (− 4.1%, − 3.0%, − 1.4%) after 18 months. On HR-pQCT, D-PTH increased trabecular vBMD (Tb.vBMD) at the distal radius and tibia after 18 months (+6.4%, +3.7%) compared with the BPs group, decreased cortical volumetric tissue mineral density (Ct.vTMD) (− 1.8%, − 0.9%) compared with the other groups, increased Ct.Th (+1.3%, +3.9%), and increased failure load (FL) (+4.7%, +4.4%). W-PTH increased Tb.vBMD (+5.3%, +1.9%), maintained Ct.vTMD (− 0.7%, +0.2%) compared with D-PTH, increased Ct.Th (+0.6%, +3.6%), and increased FL (+4.9%, +4.5%). The BPs increased Tb.vBMD only in the radius (+2.0%, +0.2%), maintained Ct.vTMD (− 0.6%, +0.3%), increased Ct.Th (+0.5%, +3.4%), and increased FL (+3.9%, +2.8%).Conclusions: D-PTH and W-PTH comparably increased Ct.Th, the primary endpoint. D-PTH had a strong effect on trabecular bone. Although D-PTH decreased Ct.vTMD, it increased Ct.Th and total bone strength. W-PTH had a moderate effect on trabecular bone, maintained Ct.vTMD, and increased Ct.Th and total bone strength to the same extent as D-PTH