Layer thickness dependence of the terahertz emission based on spin current in ferromagnetic heterostructures.

The emission with a bandwidth of 1.5 terahertz based on the spin current in the ferromagnetic heterostructure Co/Pt is demonstrated. The spin transient launched by the NIR femtosecond laser pulse in the Co/Pt is converted into the in-plane charge current due to the inverse spin Hall effect, which gives rise to the terahertz emission towards free space. The dependence of the terahertz emission on the Pt-layer thickness is investigated. To optimize the geometry structure of the new type of emitter, we developed the theoretical model by carefully analyzing the spin transport. Our model reveals the importance to take into account the interfacial spin loss. It can be used to analyze more complex heterostructures.

Postoperative laryngeal morbidity and intubating conditions using the McGRATH™ MAC videolaryngoscope with or without neuromuscular blockade: a randomised, double-blind, non-inferiority trial.

Tracheal intubation without neuromuscular blockade may be associated with worse intubating conditions and increased laryngeal morbidity. We hypothesised that tracheal intubation using the McGRATH™ MAC videolaryngoscope would not increase postoperative hoarseness, even without neuromuscular blockade. In this prospective, randomised, parallel-group, double-blind, non-inferiority trial, 248 patients were randomly assigned to tracheal intubation with or without neuromuscular blockade using rocuronium. Hoarseness and sore throat were evaluated at 24 h and 48 h postoperatively. The primary outcome was the incidence of hoarseness at 48 h postoperatively with a pre-defined non-inferiority margin of 10%. Hoarseness at 48 h did not differ between the non-paralysed group and the paralysed group (8.1% vs. 13.6%; absolute difference: -5.4%; 95%CI: -13.3 to 2.4). Also, no significant differences were found between the two groups for hoarseness at 24 h (22.8% vs. 27.1%) or for sore throat at 24 h (12.2% vs. 9.3%) and 48 h postoperatively (1.6% vs. 0.8%). Although more patients in the non-paralysed group showed an adducted position of the vocal cords (29.3% vs. 0%), there were no significant group differences in the ease of laryngoscopy (96.7% vs. 98.3%), Cormack grade laryngeal view 1 (97.6% vs. 96.6%) or first-pass success rate (100% vs. 100%). We conclude that when using the McGRATH MAC videolaryngoscope for tracheal intubation, the incidence of postoperative hoarseness was not inferior if neuromuscular blockade was avoided.

A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. INTRODUCTION: The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture. METHODS: A patient-level state transition model was developed to predict the outcomes of Japanese women with no previous fracture. Lifetime costs and quality-adjusted life years (QALYs) were estimated for women who receive osteoporosis screening and alendronate therapy for 5 years and those who do not receive the screening and treatments. The incremental cost-effectiveness ratio (ICER) of the screening option compared with the no screening option was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. RESULTS: The ICERs of osteoporosis screening and treatments for Japanese women aged 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years were estimated to be $89,242, $64,010, $40,596, $27,697, $17,027, and $9771 per QALY gained, respectively. Deterministic sensitivity analyses showed that several parameters such as the disutility due to vertebral fracture had a significant influence on the base case results. Applying a willingness to pay of $50,000 per QALY gained, the probability that the screening option became cost-effectiveness estimated to 50.9, 56.3, 59.1, and 64.7 % for women aged 60-64, 65-69, 70-74, and 75-79 years, respectively. Scenario analyses showed that the ICER for women aged 55-59 years with at least one clinical risk factor was below $50,000 per QALY. CONCLUSIONS: In conclusion, dual energy X-ray absorptiometry (DXA) screening and alendronate therapy for osteoporosis would be cost-effective for postmenopausal Japanese women over 60 years. In terms of cost-effectiveness, the individual need for osteoporosis screening should be determined by age and clinical risk factors.

On the mechanism of gas adsorption for pristine, defective and functionalized graphene.

Defects are no longer deemed an adverse aspect of graphene. Contrarily, they can pave ways of extending the applicability of graphene. Herein, we discuss the effects of three types of defects in graphene including carbon deficiency, adatom (single Fe) dopants and the introduction of functional groups (carbonyl, ether group) on the NO2 gas adsorption via density functional theory methods. We have observed that introducing Fe on graphene can enhance the NO2 adsorption process. Adsorption energy calculations suggest that the enhancement in NO2 adsorption is more profound for Fe-doped mono- and tetra-vacant graphene than that for Fe doped bi- and tri-vacant graphene, which is favourable for NO2 gas capture applications. The unsaturated carbons in defected graphene as well as the oxygenated functional groups are very active to attract NO2 molecules. However, though the gas binding strength was not as high as the that found in the Fe-doped graphene structure, the relatively low NO2 gas adsorption energy is suitable for the practical gas sensors both for gas sensitivity and the sensor recovery rate factor. This theoretical study can potentially be useful for developing adsorption-based applications of graphene.

Monocyte CD64 expression as a novel biomarker for the disease activity of systemic lupus erythematosus.

OBJECTIVE: Interferon alpha (IFN-α) is a key cytokine associated with systemic lupus erythematosus (SLE). IFN-α induces the expression of CD64 on monocytes (mCD64). Although enhanced mCD64 expression has been reported in patients with SLE, it has never been assessed quantitatively. The aim of this study was to investigate whether or not mCD64 expression correlates with SLE disease activity. METHODS: The mCD64 expression levels were assessed quantitatively in 40 patients with active or inactive SLE by using flow cytometry. The mCD64 expression levels were subsequently compared with the SLE disease activity index (SLEDAI) and levels of existing SLE activity biomarkers, such as anti-DNA antibody, complements, and so on. RESULTS: The mCD64 expression was significantly higher in active disease than in inactive disease SLE (median molecules/cell, interquartile range: 34,648, 8174-24,932 and 20,865, 6357-21,503, respectively; p < 0.001). The levels of mCD64 expression strongly correlated with SLEDAI (r = 0.68, p < 0.001). CONCLUSION: The mCD64 expression is a simple and useful biomarker for evaluating disease activity in patients with SLE.

Chronic hypoxia remodels the tumor microenvironment to support glioma stem cell growth.

Cerebral organoids co-cultured with patient derived glioma stem cells (GLICOs) are an experimentally tractable research tool useful for investigating the role of the human brain tumor microenvironment in glioblastoma. Here we describe long-term GLICOs, a novel model in which COs are grown from embryonic stem cell cultures containing low levels of GSCs and tumor development is monitored over extended durations (ltGLICOs). Single-cell profiling of ltGLICOs revealed an unexpectedly long latency period prior to GSC expansion, and that normal organoid development was unimpaired by the presence of low numbers of GSCs. However, as organoids age they experience chronic hypoxia and oxidative stress which remodels the tumor microenvironment to promote GSC expansion. Receptor-ligand modelling identified astrocytes, which secreted various pro-tumorigenic ligands including FGF1, as the primary cell type for GSC crosstalk and single-cell multi-omic analysis revealed these astrocytes were under the control of ischemic regulatory networks. Functional validation confirmed hypoxia as a driver of pro-tumorigenic astrocytic ligand secretion and that GSC expansion was accelerated by pharmacological induction of oxidative stress. When controlled for genotype, the close association between glioma aggressiveness and patient age has very few proposed biological explanations. Our findings indicate that age-associated increases in cerebral vascular insufficiency and associated regional chronic cerebral hypoxia may contribute to this phenomenon.

Solid tumor size on high-resolution computed tomography and maximum standardized uptake on positron emission tomography for new clinical T descriptors with T1 lung adenocarcinoma.

BACKGROUND: To better describe clinical T descriptors using solid tumor size (the maximum dimension of the solid component of the tumor) on high-resolution computed tomography (HRCT) and maximum standardized uptake value (SUVmax) on F-18-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT). PATIENTS AND METHODS: We examined 610 consecutive patients with clinical stage IA lung adenocarcinoma who underwent complete resection. Recurrence-free survival (RFS) was assessed on the basis of whole tumor size (maximum dimension of the tumor), solid tumor size, or a combination of solid tumor size and SUVmax. RESULTS: RFS based on whole tumor size was not significantly different between patients with tumors measuring ≤2 cm and 2-3 cm (P = 0.089), whereas RFS based on solid tumor size was significantly different (P < 0.0001). We divided patients into four groups on the basis of solid tumor size and SUVmax: group 1: solid tumor size ≤2 cm, SUVmax ≤1.8; group 2: solid tumor size ≤2 cm, SUVmax >1.8; group 3: solid tumor size 2-3 cm, SUVmax ≤3.6; and group 4: solid tumor size 2-3 cm, SUVmax >3.6. Groups 2 and 3 were combined because they showed similar RFS each other. RFS was significantly different among these groups: group 1 versus groups 2 + 3, P < 0.0001; groups 2 + 3 versus group 4, P = 0.019. CONCLUSIONS: Both solid tumor size on HRCT and SUVmax on FDG-PET/CT reflect prognosis well in patients with clinical stage IA lung adenocarcinoma and may support new clinical T descriptors.

Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase.

The Sod2 gene for Mn-superoxide dismutase (MnSOD), an intramitochondrial free radical scavenging enzyme that is the first line of defense against superoxide produced as a byproduct of oxidative phosphorylation, was inactivated by homologous recombination. Homozygous mutant mice die within the first 10 days of life with a dilated cardiomyopathy, accumulation of lipid in liver and skeletal muscle, and metabolic acidosis. Cytochemical analysis revealed a severe reduction in succinate dehydrogenase (complex II) and aconitase (a TCA cycle enzyme) activities in the heart and, to a lesser extent, in other organs. These findings indicate that MnSOD is required for normal biological function of tissues by maintaining the integrity of mitochondrial enzymes susceptible to direct inactivation by superoxide.

Maize resistance to witchweed through changes in strigolactone biosynthesis.

Maize (Zea mays) is a major staple crop in Africa, where its yield and the livelihood of millions are compromised by the parasitic witchweed Striga. Germination of Striga is induced by strigolactones exuded from maize roots into the rhizosphere. In a maize germplasm collection, we identified two strigolactones, zealactol and zealactonoic acid, which stimulate less Striga germination than the major maize strigolactone, zealactone. We then showed that a single cytochrome P450, ZmCYP706C37, catalyzes a series of oxidative steps in the maize-strigolactone biosynthetic pathway. Reduction in activity of this enzyme and two others involved in the pathway, ZmMAX1b and ZmCLAMT1, can change strigolactone composition and reduce Striga germination and infection. These results offer prospects for breeding Striga-resistant maize.

Biphasic action of aldosterone on Akt signaling in cardiomyocytes.

Both aldosterone and Akt signaling play pivotal roles in the pathogenesis of heart failure. However, little is known about the correlation between them. We herein investigated whether aldosterone interacts with Akt signaling in a coordinated manner in cardiomyocytes. Neonatal rat cardiomyocytes were stimulated with aldosterone for either a short (10-min) or long (24-h) time. The phosphorylation of Akt and its downstream effector, GSK3ß, were transiently increased after short-term stimulation, which was blocked by either PI3K or Na(+)/H(+) exchanger inhibitors, but not by the mineralocorticoid receptor antagonist, eplerenone. Long-term stimulation also significantly increased Akt-GSK3ß phosphorylation and this effect was reduced by eplerenone. Thus, these results suggest that aldosterone activates Akt signaling via a biphasic reaction that occurs through different cascades. To understand the significance of the rapid action of aldosterone, cardiomyocytes were exposed to hydrogen peroxide for from 10 to 60 min. A short-term aldosterone stimulation (for up to 30 min) significantly protected cardiomyocytes from oxidative stress-induced cellular damage. Eplerenone did not abrogate this beneficial effect, while a PI3K inhibitor did. Therefore, during the early phase, aldosterone has favorable effects on cardiomyocytes, partly by acute activation of a mineralocorticoid receptor-independent cascade through the Na(+)/H(+) exchanger, PI3K, and Akt. In contrast, its persistent activity produces pathological effects partly by chronic Akt activation in a mineralocorticoid receptor-dependent manner.

The effect of cross-reacting antigens on the tolerant state.

Rabbits were rendered tolerant to human albumin (HA) and were then injected with azo and oxazolonated derivatives of human albumin. These injections were continued to a time at which all animals would have lost tolerance if they had not been injected. Injection of cross-reacting antigens prolonged the duration of tolerance, as judged by the mode of elimination of lightly iodinated human albumin (HA.(131)I). Different derivatives of HA differed in their capacity to prolong tolerance. Those neonatally injected rabbits which were immunized with cross-reacting antigens and lost tolerance, responded much more promptly to HA.(131)I than animals which were not immunized. Animals immunized with cross-reacting antigen which went on to eliminate HA.(131)I triphasically, usually had responded earlier by making antibodies. These antibodies contained a fraction which was reactive with HA, and which was usually equally well adapted to determinants on HA and on the cross-reacting antigen.

[Treatment of superior sulcus tumor].

We reported on 34 patients with superior sulcus non-small-cell lung cancer and clinical outcome. It is necessary to select the most appropriate approach from preoperative examination and the degree of infiltration at the chest wall. Recently, various approach and preoperative chemoradiotherapy followed by surgical resection is effective for the treatment of superior sulcus tumor (SST), we should keep challenging for radical resection in mind.

Modulation of methotrexate-induced intestinal mucosal injury by dietary factors.

Methotrexate (MTX)-induced intestinal mucosal injury in animals has been studied to understand how MTX can cause gastrointestinal disorders, but the pathogenesis of gastrointestinal disorders is still uncertain. We have attempted to reveal how dietary factors influence intestinal toxicity due to MTX. Mice were fed normal chow (NC) or a high-fat high-sucrose diet (HFHSD) before oral administration of MTX. While MTX significantly decreased the survival rates of mice fed HFHSD, the intestinal epithelial injury was detected. MTX excretion in the feces of mice fed HFHSD was reduced. Change of diets between NC and HFHSD influences the survival. The survival rates of the mice fed a high-sucrose diet or control diet were higher than those fed HFHSD. Higher survival rates were observed in mice fed a high-fat high-sucrose diet modified (HFHSD-M) in which casein was replaced by soybean-derived proteins. The survival rates of mice treated with vancomycin were lower than those administered neomycin. Microbiome and metabolome analyses on feces suggest a similarity of the intestinal environments of mice fed NC and HFHSD-M. HFHSD may modify MTX-induced toxicity in intestinal epithelia on account of an altered MTX distribution as a result of change in the intestinal environment.

New MRI Findings in Fukuyama Congenital Muscular Dystrophy: Brain Stem and Venous System Anomalies.

BACKGROUND AND PURPOSE: Leptomeningeal glioneuronal heterotopia of the brain stem and cerebral migration abnormality were pathologically reported in Fukuyama congenital muscular dystrophy, but the radiologic assessments of the brain stem and cerebral venous system (which may be involved in the development of the anomaly) were insufficient. Here, we evaluated the brain stem and cerebral veins on MR imaging in patients with Fukuyama congenital muscular dystrophy. MATERIALS AND METHODS: We retrospectively reviewed the MR imaging findings of 27 patients with Fukuyama congenital muscular dystrophy. We visually assessed the hypoplasia, superficial structures, and signal intensity of the brain stem on T2WI, FLAIR, and double inversion recovery images and the cerebral, superficial, and deep veins with and without hemorrhage on T2WI and SWI. RESULTS: Brain stem fluffy structures were seen in 96.3% of the cases on T2WI. Superficial high signal intensity on T2WI and FLAIR images was seen in 96.3% and 92.6%, respectively. Abnormally located superficial vessels beneath the cortex were seen in 11.1% on T2WI. Hypoplasia of the superficial cerebral veins was noted in all patients who underwent SWI. Dilated and tortuous subependymal veins were seen in 40.0% on SWI. Hemorrhages were seen in 11.1% on T2WI and in 60.0% on SWI. CONCLUSIONS: Superficial brain stem structural and signal abnormalities would be useful MR imaging findings to diagnose Fukuyama congenital muscular dystrophy as well as venous system abnormalities. Clinicians must keep in mind that this disease has a high risk of hemorrhage.

Responses to 5-HT in morphologically identified neurons in the rat substantia gelatinosa in vitro.

Bath application of 5-HT (1-1000 muM) induced a tetrodotoxin (TTX)-resistant outward current at the holding membrane potential (V(H)) of -50 mV in 104/162 (64.2%) of substantia gelatinosa (SG) neurons from the rat spinal cord in vitro. The 5-HT-induced outward current was suppressed by an external solution containing Ba(2+), or a pipette solution containing Cs(2)SO(4) and tetraethylammonium. It was reversed near the equilibrium potential of the K(+) channel. The response to 5-HT was abolished 30 min after patch formation with a pipette solution containing guanosine-5-O-(2-thiodiphosphate)-S. The 5-HT-induced outward current was mimicked by a 5-HT(1A) agonist, (+/-)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide, and suppressed by a 5-HT(1A) antagonist, WAY100635, suggesting the 5HT(1A) receptor-mediated activation of K(+) channels in the outward current. In 11/162 (6.8%) SG neurons, 5-HT produced an inward current, which was mimicked by a 5-HT(3) agonist, 1-(m-chlorophenyl)-biguanide (mCPBG). The 5-HT-induced outward currents were observed in vertical cells (21/34) and small islet cells (11/34), while inward currents were induced in islet cells (1/5) and small islet (4/5) cells, but not in vertical cells. It is known that most vertical cells and islet cells in the SG are excitatory (glutamatergic) and inhibitory interneurons, respectively, while small islet cells consist of both excitatory and inhibitory neurons. Bath application of 5-HT or mCPBG increased the amplitude and the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), but no neurons showed a decrease in sIPSC. Furthermore, frequency, but not amplitude, of miniature IPSCs increased with perfusion with 5-HT in the presence of TTX. These findings, taken together, suggest that 5-HT induces outward currents through 5-HT(1A) receptors in excitatory SG neurons. These findings also suggest that the inward currents are post- and presynaptically evoked through 5-HT(3) receptors, probably in inhibitory neurons.

Important roles of tachykinins in the development of allergic nasal hyperresponsiveness in guinea-pigs.

BACKGROUND: Although it has been suggested that the use of tachykinin receptor antagonists might prove to be an effective treatment for allergic rhinitis (AR), they are not used clinically. Therefore, we decided to examine the effects of tachykinin receptor antagonists on AR symptoms in an appropriate experimental model. OBJECTIVE: To evaluate newly developed tachykinin receptor antagonists in a Japanese cedar pollen-induced AR model and to determine their effect on allergen-induced sneezing, nasal blockage, and nasal hyperresponsiveness (NHR). METHODS: Sensitized guinea-pigs were challenged by forced inhalation of pollen once every week. Sneezing and nasal blockage were observed after pollen challenges. NHR (nasal blockage) to an intranasal application of leukotriene D(4) was assessed 2 days after an antigen challenge. We also evaluated whether intranasal dosing with a tachykinin causes NHR. NK(1) and NK(2) receptor antagonists were administered before an intranasal treatment with antigen or tachykinin. Amounts of tachykinins present in nasal cavity lavage fluid were measured by an enzyme immunoassay. RESULTS: Although an NK(1) and NK(2) receptor dual antagonist showed no effect on pollen-induced sneezing and biphasic nasal blockage, it did completely suppress the development of NHR. Experiments using specific NK(1) or NK(2) receptor antagonists revealed that NK(2) receptor activation was preferentially involved in the development of hyperresponsiveness. Increases in the levels of substance P (SP) and neurokinin A (NKA) in the nasal tissue were noted 20 min-1 h after the challenge. Intranasal instillation of either SP or NKA-induced NHR, which was almost completely inhibited by NK(2) receptor antagonists and partially inhibited by NK(1) receptor antagonists. CONCLUSIONS: SP and NKA, which are released early after the challenge, mediate the development of NHR by preferentially activating NK(2) receptors. Therefore, NK(2) receptor antagonists might prove to be effective treatment of AR.