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Purpose Giant leucaena is a tropical tree-legume that thrives in alkaline and calcareous soils. It contains large amounts of mimosine, the physiological role of which is not well understood. The goals of this study were to determine i) if mimosine is released by giant leucaena into the rhizosphere ii) if mimosine enhances solubility of Fe present in various forms in alkaline soil, and iii) if mimosine enhances transition metal uptake in giant leucaena. Methods Mimosine in the extracts of rhizosphere soil and root exudates was analyzed by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS) to determine if it is released by giant leucaena. Iron concentration in tissue and aqueous samples was determined by ICP-OES analysis. Results Mimosine was detected in both the rhizosphere eluates and root exudates. Mimosine added to samples of goethite, hematite and FeCl3 increased Fe solubility in water. Giant leucaena plants grown in alkaline soils and supplied with mimosine had higher levels of chlorophyll, Fe and Mn than the control plants. Conclusion Mimosine is released by giant leucaena roots into the rhizosphere, where it interacts with Fe. Mimosine enhances solubility of insoluble Fe-oxides and prevents conversion of ferric Fe to insoluble oxides at an alkaline pH. Mimosine enhances Fe and Mn uptake in plants growing in alkaline soil conditions.

On January 15, 2022, we observed various unusual atmospheric wave events over South America: Atmospheric pressure waves (Lamb mode) around 12:30 to 17:30 UT, tsunamis along the Chilean coast at around 17:00 to 19:00 UT, and ionospheric disturbances between 11:30 and 20:00 UT. We understand that these events were generated by the Tonga volcanic eruption that occurred at (20.55°S, 175.39°W) in South Pacific Ocean at 04:15 UT. Several traveling ionospheric disturbances (TIDs), the horizontal wavelengths of 330 to 1174 km and the phase speed of 275–544 m/s were observed before and after the Lamb wave passed over the continent and the arrival of the tsunami on the Chile coast. The observed TID characteristics suggest us that these waves might be generated by the two atmospheric events, Lamb wave and gravity waves induced by the tsunamis. This is the first time to report the signature of ionospheric disturbances over the South American continent generated by the huge volcanic eruption. Graphical Abstract

Introduction In the US phase 2 RESCUE trial, ziltivekimab, a fully human monoclonal antibody against the ligand of the pro-inflammatory cytokine interleukin-6, was shown to reduce biomarkers of inflammation in patients with chronic kidney disease (CKD) and elevated levels of high-sensitivity C-reactive protein (hsCRP), a marker of inflammation and cardiac risk.1 Here, we present outcomes from the phase 2 RESCUE-2 trial of ziltivekimab in a patient population from Japan. Purpose To evaluate the efficacy and safety of ziltivekimab 15 mg and 30 mg compared with placebo in Japanese patients with non-dialysis-dependent CKD (NDD-CKD). Methods We conducted a randomized, double-blind, placebo-controlled trial in 36 patients aged ≥20 years with stage 3–5 NDD-CKD and hsCRP ≥2 mg/L. Patients were randomly assigned to receive subcutaneous ziltivekimab 15 mg (n=11) or 30 mg (n=12), or placebo (n=13) at weeks 0, 4 and 8. The primary endpoint was percentage change in hsCRP levels from baseline to end of treatment (EOT) (average of week 10 and week 12 values); secondary endpoints included percentage change from baseline to EOT in levels of fibrinogen, serum amyloid A (SAA), N-terminal pro B-type natriuretic peptide (NT-proBNP) and lipids. Analysis of endpoints was performed using Wilcoxon two-sample test; differences between treatment groups were calculated using the Hodges–Lehmann estimator. Results Baseline characteristics are shown in the Table. At EOT, median hsCRP levels were reduced by 96% and 93% in the ziltivekimab 15 mg and 30 mg groups, respectively, compared with 27% for placebo (both p Conclusion Ziltivekimab effectively reduced inflammatory biomarkers associated with atherosclerosis in patients from Japan with CKD and residual inflammatory risk as measured by hsCRP. A significant reduction of more than 90% in hsCRP levels for both doses of ziltivekimab was demonstrated, with a safety profile similar to placebo. Overall, the results of the RESCUE-2 trial in Japan are consistent with the efficacy and safety results of the US-based RESCUE trial. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): This study was funded by Novo Nordisk A/S. Medical writing support was provided by Johanna Scheinost PhD, PharmaGenesis Oxford Central, Oxford, UK, with funding from Novo Nordisk A/S.

Iron deficiency conditions as well as iron supplied as a Fe(III)-mimosine complex induced a number of strategy I and strategy II genes for iron uptake in leucaena. Leucaena leucocephala (leucaena) is a tree-legume that can grow in alkaline soils, where metal-cofactors like Fe(III) are sparingly available. Mimosine, a known chelator of Fe(III), may facilitate Fe(III) uptake in leucaena by serving as a phytosiderophore. To test if mimosine can serve as a phytosiderophore, three sets of experiments were carried out. First, the binding properties and solubility of metal-mimosine complexes were assessed through spectrophotometry. Second, to study mimosine uptake in plants, pole bean, common bean, and tomato plants were supplied with mimosine alone and metal-mimosine complexes. Third, the expression of strategy I (S1) and strategy II (S2) genes for iron uptake from the soil was studied in leucaena plants exposed to different Fe(III) complexes. The results of this study show that (i) mimosine has high binding affinity for metallic cations at alkaline pH, Fe(III)-mimosine complexes are water soluble at alkaline pH, and that mimosine can bind soil iron under alkaline pH; (ii) pole bean, common bean, and tomato plants can uptake mimosine and transport it throughout the plant; and (iii) a number of S1 and S2 genes were upregulated in leucaena under iron-deficiency condition or when Fe(III) was supplied as a Fe(III)-mimosine complex. These findings suggest that leucaena may utilize both S1 and S2 strategies for iron uptake; and mimosine may play an important role in both strategies.

CONTEXT: Physical activity is important for the management of metabolic functions; however, little is known whether performing home-based moderate-intensity exercise (MIE) obtains further improvement on metabolic functions in adults with non-communicable diseases (NCDs) who already perform regular gym-based MIE. OBJECTIVE: The purpose of this study was to examine the effect of adding home-based MIE on metabolic functions in older adults with NCDs who have regularly performed gym-based MIE. DESIGN: This was a single-center randomized controlled study. The observation period was set for 24 weeks. SUBJECTS AND METHODS: Twenty-one older adults (age, 60–79 years) with uncomplicated NCDs, who have performed 30–40 min MIE, 2–3 days/week at a hospital gym for over 1 year, were randomly divided into two groups: performing home-based MIE, comprising aerobic and resistance exercises, at least 20 min/day, 3 days/week (HOME, n = 11), or not performing home-based MIE (CON, n = 10). All participants completed the study and continued their gym-based MIE as usual. RESULTS: After 24 weeks, there were no significant differences in the values of any outcomes. Conversely, the decrease in waist circumference (WC) was larger in the HOME group (–2.17 [–3.98, –0.36] cm) than in the CON group (0.57 [–1.42, 2.56] cm) (p < 0.05), although not in other outcomes. CONCLUSIONS: Although further studies are needed, we found that adding home-based MIE had a positive effect on WC, but little effect on other metabolic functions in older adults with NCDs who have continued regular gym-based MIE.

Keynote paper presented at the International Leucaena Conference, 1‒3 November 2018, Brisbane, Queensland, Australia.Leucaena leucocephala (leucaena) is a multipurpose tropical tree-legume that is highly resistant to many biotic and abiotic stresses. Leucaena is used primarily as an animal fodder owing to its protein-rich foliage. However, leucaena foliage also contains mimosine, a toxic non-protein amino acid that can cause alopecia, goiter and other thyroid problems, infertility, and fetal death. Considering its toxicity and abundance in leucaena, it is important to quantify the mimosine concentrations in leucaena under different environmental conditions. Mimosine was extracted from various types of leucaena tissue exposed to a range of environmental conditions and then quantified by HPLC. The mimosine concentrations in leucaena treated with NaCl increased after 6 days of treatment and remained relatively high when treatment continued for 18 days. Interestingly, leucaena exposed to complete darkness for up to 5 days had a higher mimosine concentration than control plants exposed to normal light/dark photoperiods. On the other hand, drying leucaena leaflets or macerating them in an alkaline buffer significantly lowered their mimosine concentration. Mature leaflets that had fallen off the plant and dried out also contained significantly less mimosine than fresh leaflets. The results of this study indicate that mimosine concentrations in leucaena are affected by environmental conditions and this knowledge can assist in managing to prevent toxicity.

Leucaena leucocephala (leucaena) is one of the 22 Leucaena species that originated in Central America. There are two major subspecies of leucaena, L. leucocephala subsp. glabrata (giant leucaena) and L. leucocephala subsp. leucocephala (common leucaena). Giant leucaena is a medium size fast-growing tree important for agroforestry while common leucaena is a small bushy shrub that is considered to be an invasive weed. Giant leucaena can be grown as a woody tree of up to ~ 20 m in height or maintained as a bushy fodder legume by repeated harvest of its foliage several times a year. Giant leucaena grown for fodder can produce forage dry mater yield of up to 34 Mg ha−1 year−1. High forage yield together with high protein content makes leucaena an ideal fodder legume for the tropical and subtropical regions of the world. Although mimosine present in the leucaena foliage has toxicity, it should not be a big concern because ruminants can be successfully inoculated with the mimosine-metabolizing rumen bacterium Synergistis jonesii. Alternatively, mimosine present in the leucaena foliage can be removed easily and inexpensively through simple processing. Giant leucaena cultivars are generally free from diseases and are highly tolerant to drought. Although infestation by psyllids may be a problem, a number of psyllid-resistant cultivars of giant leucaena have been developed through interspecies hybridization. The wood of giant leucaena can be used for timber, paper pulp, or biofuel production. Leucaena foliage and wood may serve as raw materials for development of new industry for production of phytochemicals such as mimosine, tannins and anthocyanins, wood products, and high-protein animal feed for farm animals in the future.

Recent treatment for type 2 diabetes mellitus (T2DM) has included glucagon-like peptide-1 receptor agonist (GLP-1 RA), indicating clinical efficacy for better glucose variability. Subjects were seven patients with T2DM associated with the obese tendency. Their average age was 63.8 ± 21.7 years old (5 males, 2 females) who received a new administration of GLP-1 RA (Mean ± standard deviation). For GLP-1 RA, dulaglutide (TRULICITY R, single-dose pen) was administered by subcutaneous injection 0.75 mg once a week. Basal data at 0 month revealed that body weight 76.0 ± 11.6 kg, body mass index (BMI) 29.2 ± 11.6, blood C-peptide immunoreactivity (CPR) 2.68 ± 0.49 ng/mL, respectively. After the intervention of dulaglutide, decreased value of BMI for 3 and 6-9 months was 0.78 ± 0.45 and 1.16 ± 0.85, and HbA1c for 3 and 6-9 months was 1.60 ± 1.52% and 2.01 ± 1.44%, respectively. Though these cases have various complications besides T2DM, they showed clinical effects of weight reduction and lowering blood glucose. Diabetic treatment for current cases would suggest that GLP-1 RA would be effective in various situations such as a super-aged patient, medical practice in the remote area, family care and visiting nursing.

Giant leucaena (Leucaena leucocephala subsp. glabrata) is an arboreal tree legume, which is widely grown as a source of high-protein fodder for animals. The goal of this research was to identify ge...

Mimosine is a non-protein amino acid of Fabaceae, such as Leucaena spp. and Mimosa spp. Several relevant biological activities have been described for this molecule, including cell cycle blocker, anticancer, antifungal, antimicrobial, herbivore deterrent and allelopathic activities, raising increased economic interest in its production. In addition, information on mimosine dynamics in planta remains limited. In order to address this topic and propose strategies to increase mimosine production aiming at economic uses, the effects of several stress-related elicitors of secondary metabolism and UV acute exposure were examined on mimosine accumulation in growth room-cultivated seedlings of Leucaena leucocephala spp. glabrata. Mimosine concentration was not significantly affected by 10 ppm salicylic acid (SA) treatment, but increased in roots and shoots of seedlings treated with 84 ppm jasmonic acid (JA) and 10 ppm Ethephon (an ethylene-releasing compound), and in shoots treated with UV-C radiation. Quantification of mimosine amidohydrolase (mimosinase) gene expression showed that ethephon yielded variable effect over time, whereas JA and UV-C did not show significant impact. Considering the strong induction of mimosine accumulation by acute UV-C exposure, additional in situ ROS localization, as well as in vitro antioxidant assays were performed, suggesting that, akin to several secondary metabolites, mimosine may be involved in general oxidative stress modulation, acting as a hydrogen peroxide and superoxide anion quencher.

Background Blood pressure (BP) variability has reportedly been a risk factor for various clinical events. To clarify the influence of BP visit‐to‐visit variability on adverse events in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐RHYTHM Registry was performed. Methods and Results Of 7406 outpatients with nonvalvular atrial fibrillation from 158 institutions, 7226 (age, 69.7±9.9 years; men, 70.7%), in whom BP was measured 4 times or more (14.6±5.0 times) during the 2‐year follow‐up period or until occurrence of an event, constituted the study group. SD and coefficient of variation of BP values were calculated as BP variability. Thromboembolism, major hemorrhage, and all‐cause death occurred in 110 (1.5%), 121 (1.7%), and 168 (2.3%) patients, respectively. When patients were divided into quartiles of systolic BP‐SD (P =0.015 for thromboembolism; HR, 2.60, 95% CI, 1.36–4.97, P =0.004 for major hemorrhage; and HR, 1.85, 95% CI, 1.11–3.07, P =0.018 for all‐cause death) after adjusting for components of the CHA 2 DS 2 ‐VASc score, warfarin and antiplatelet use, atrial fibrillation type, BP measurement times, and others. These findings were consistent when BP‐coefficient of variation was used instead of BP‐SD. Conclusions Systolic BP visit‐to‐visit variability was significantly associated with all adverse events in patients with nonvalvular atrial fibrillation. Further studies are needed to clarify the causality between BP variability and adverse outcomes in patients with nonvalvular atrial fibrillation. Registration URL: https://www.umin.ac.jp/ctr/ ; Unique Identifier: UMIN000001569.

A number of drought-induced genes have been identified from giant leucaena. Leucaena leucocephala subspecies glabrata (leucaena), which is also known as ‘giant leucaena’, is a multipurpose tree legume that can be grown and maintained as a woody tree for wood and paper pulp production, or as a shrubby legume through repeated harvest of foliage for use as a fodder. Leucaena is naturally resistant to most biotic and abiotic stresses including drought. The objective of this research was to identify drought-responsive genes in leucaena seedlings through microarray and qRT-PCR analyses. Ten thousand cDNA sequences selected from a leucaena transcriptome were screened for higher expression in a 4 × 180 k microarray using RNA isolated from drought-treated and untreated leucaena seedlings. Microarray analysis identified 73 and 39 drought-responsive genes sequences that were upregulated in the root and shoot, respectively. qRT-PCR analyses confirmed the root- and shoot-specific upregulation of some of the most highly expressed gene sequences identified in the microarray analysis. The proteins encoded by these genes could be grouped into four classes: (1) receptors that sense osmotic and oxidative stresses, (2) transcription factors, (3) degradation pathway enzymes, and (4) biosynthetic enzymes and structural proteins. The functions of these four classes of proteins can be used to explain the drought response in leucaena. The NB-LRR class of disease-resistance proteins may serve as receptors for detecting osmotic and oxidative stresses induced by drought, leading to induction of transcription factors such as zinc finger CCCH domain-containing protein and TCP14. As result, the genes for some degradative pathway enzymes, such as GDSL esterase/lipase, lipid acyl hydrolase patatin, and serine carboxypeptidase, were induced. Similarly, the expression of certain biosynthetic enzymes and structural proteins such as flavonoid 3-O-galactosyl transferase, caffeoyl-CoA O-methyltransferase, 9-cis-epoxy carotenoid dioxygenase, β-amyrin synthase, pentatricopeptide-containing protein, GPI-anchored protein COBRA, and peroxin, were also induced. High expression of some of these drought-inducible genes in leucaena seedlings may be used as a selection criterion in future breeding programs for drought resistance in leucaena and other legumes.

Introduction Coronary artery disease (CAD) is a major cause of the morbidity and mortality in diabetic patients, however aggressive screening for CAD in asymptomatic patients is not recommended in guidelines. Chronic kidney disease (CKD) is one of serious co-morbidity and such patients especially tends to be observed without angiography to avoid contrast induced nephropathy. It is well known that systemic atherosclerosis worsens renal function. Thus, chronic kidney disease (CKD) may be associated with potential myocardial ischemia and worse clinical outcomes in asymptomatic DM patients. Purpose To determine the impact of CKD on the incidence of silent myocardial ischemia (SMI) and the long-term outcomes in asymptomatic patients with DM. Methods A total of 461 consecutive patients with DM were prospectively studied from July 2011 to August 2017. All patients were asymptomatic and self-sufficient in daily life. They underwent the ergometer exercise test. Coronary angiography was performed when the stress test was positive, or the patients did not achieve 90% of target heart rate. Primary end point was major adverse cardiac and cerebrovascular events (MACCE) including death, non-fatal myocardial infarction and stroke. Results SMI was diagnosed in 81 patients. The incidence of SMI increased with higher stage of CKD as shown in Figure. The median follow-up duration from diagnosis was 35 (15–57) months in the overall cohort of 461 diabetic patients. SMI patients had worse clinical outcomes (Figure). Among 81 patients with SMI, severe CKD group (≥ stage 3a) had worse long-term outcomes. After adjustment of age, gender and coronary risk factors, eGFR was independently associated with MACCE in diabetic patients with SMI [HR0.96, 95% CI (0.923–0.996), p=0.028]. Incidence of SMI and Kaplan-Meier curves Conclusions The incidence of potential CAD was high in CKD and the long-term outcomes of those patients were poor in asymptomatic DM. CKD patients should be aggressively screened for CAD and more intensively treated in our daily practice of DM.

Although population characteristics and antimicrobial prescribing practices suggest that the hospitalized population in Japan is at high risk of Clostridioides difficile infection (CDI), the epidemiology of CDI in Japan is poorly understood.This prospective cohort study aimed to investigate the epidemiology of CDI at 12 hospitals in Japan.Patients with clinically significant diarrhoea (CSD) were enrolled. Stool specimens were tested for C. difficile by toxin A and/or B enzyme immunoassay (EIA) in the hospital laboratories, and a toxigenic culture and nucleic acid amplification tests were performed at a central laboratory. The risk factors of CDI and the impact of CDI on mortality were investigated.In total, 566 patients with CSD were included in the analyses. A total of 152 patients received the diagnosis of CDI by Toxin A/B EIA, toxigenic culture, or nucleic acid amplification test. Factors associated with CDI included low albumin (adjusted odds ratio (aOR): 1.56; 95% confidence interval (CI): 1.03-2.34) and length of hospital stay before stool collection18 days (aOR: 1.73; 95% CI: 1.09-2.75). CDI was associated with an increased mortality on univariate analysis (OR: 1.6, 95% CI: 1.0-2.6) but was not associated with an increased risk of mortality on multivariable analysis.Risk factors for CDI in Japan were similar to those identified in the USA and Europe. However, CDI was not associated with an increased risk of mortality in this population of patients with CSD.

p130Cas translocates into the nucleus upon fluid shear stress application and alleviates NF-κB activity in osteocytes., Mechanical loading plays an important role in bone homeostasis. However, molecular mechanisms behind the mechanical regulation of bone homeostasis are poorly understood. We previously reported p130Cas (Cas) as a key molecule in cellular mechanosensing at focal adhesions. Here, we demonstrate that Cas is distributed in the nucleus and supports mechanical loading–mediated bone homeostasis by alleviating NF-κB activity, which would otherwise prompt inflammatory processes. Mechanical unloading modulates Cas distribution and NF-κB activity in osteocytes, the mechanosensory cells in bones. Cas deficiency in osteocytes increases osteoclastic bone resorption associated with NF-κB–mediated RANKL expression, leading to osteopenia. Upon shear stress application on cultured osteocytes, Cas translocates into the nucleus and down-regulates NF-κB activity. Collectively, fluid shear stress–dependent Cas-mediated alleviation of NF-κB activity supports bone homeostasis. Given the ubiquitous expression of Cas and NF-κB together with systemic distribution of interstitial fluid, the Cas–NF-κB interplay may also underpin regulatory mechanisms in other tissues and organs.

The International Forum, established by the European Society of Radiology (ESR), aims to discuss important topics in the field of radiology with radiological partner societies from outside Europe. Value-based healthcare is currently a hot topic around the world and has been addressed in many papers. The ESR chose the topic “value-based radiology” for the ESR International Forum at ECR 2018 to discuss the trend within radiology to move from volume-based to value-based practice. The value-based healthcare (VBH) concept defined “value” as health outcomes achieved for patients relative to the costs of achieving them (European Society of Radiology (ESR) 2017, Insights Imaging 8: 566). Value should increase the health outcome and decrease the cost of delivering the outcomes. Radiology is simply counted as a cost and therefore, it is important that the radiologists themselves have an active role in the transition to be recognised as clinicians taking care of the patients.

Effective conservation of globally distributed marine species relies on identification of demographically independent populations to ensure that management actions are directed at the appropriate scale. This identification is particularly challenging for species with complex life histories when local breeding populations have not been adequately sampled. We used mtDNA to analyze the population structure of loggerhead turtles from a total of 555 samples collected from 12 nesting sites in Japan in the Northwest Pacific, including previously unsampled rookeries in the Ryukyu Archipelago, for a comprehensive coverage of the nesting distribution. We identified a total of 9 haplotypes based on 820 bp of the mtDNA control region, including 5 variants of a single previously described 380 bp haplotype. We discovered that 1 haplotype (CcP1.1) previously rare in the North Pacific is common in the Ryukyu Archipelago. Based on analysis of haplotype frequencies, we found significant differentiation among regionally grouped nesting populations (analysis of molecular variance p < 0.0001, df = 8; pairwise FST ranging from 0.033 to 0.145). Our results provide evidence to support the recognition of 3 management units (MU) within the NW Pacific Regional Management Unit (RMU). These include (1) the Ryukyu MU that includes Okinawa, Okinoerabu and Amami, (2) Yakushima Island MU and (3) a Mainland MU that includes Bousou, Enshu-nada, Shikoku, Kii and Eastern Kyushu. These new data from Japan will provide important baseline data for global genetic stock assessments and contribute to our understanding of the population structure, ecology and life history of this migratory marine species in the northern Pacific.

Leucaena leucocephala is divided into two subspecies: (i) L. leucocephala subsp. leucocephala, which is known as “common leucaena” or “koa haole,” and (ii) L. leucocephala subsp. glabrata, which is known as “giant leucaena.” Common leucaena is a small bushy shrub that forms a lot of seeds, because of which it can spread easily and is considered invasive. Giant leucaena, on the other hand, is a tree with large branches. It produces much less seeds and is not considered invasive. Giant leucaena can grow to become big trees of up to ~20 m in height, or it can be grown as a legume fodder by maintaining the plants as dwarf bushes through repeated harvest of foliage, up to ten times a year. The wood of giant leucaena can be used for timber, paper pulp, or biofuel production. In the Hawaiian Islands, many eroded habitats, such as roadsides, hill slopes, and barren lands, are generally occupied by common leucaena. Replacing common leucaena with giant leucaena in these locations may create new opportunities for cattle farming, animal feed production, and development of other related industry. Dr. James Brewbaker and his colleagues at the University of Hawaii developed many high-yielding cultivars of giant leucaena suitable for both fodder and wood production. Besides growing in Hawaii, these cultivars are also widely grown in many other tropical and subtropical countries.

Background To clarify the influence of hypertension and blood pressure ( BP ) control on thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation, a post hoc analysis of the J‐ RHYTHM Registry was performed. Methods and Results A consecutive series of outpatients with atrial fibrillation was enrolled from 158 institutions. Of 7937 patients, 7406 with nonvalvular atrial fibrillation (70.8% men, 69.8±10.0 years) were followed for 2 years or until an event occurred. Hypertension was defined as a systolic BP ≥140 mm Hg, a diastolic BP ≥90 mm Hg, a history of hypertension, and/or antihypertensive drug use. Hypertension was an independent risk factor for major hemorrhage (hazard ratio 1.52, 95% CI 1.05–2.21, P =0.027) but not for thromboembolism (hazard ratio 1.05, 95% CI 0.73–1.52, P =0.787). When patients were divided into quartiles according to their systolic BP at the time closest to the event or at the end of follow‐up (Q1, CI 1.75–4.74, P CI 1.02–2.53, P =0.041) after adjustment for components of CHA 2 DS 2 ‐ VAS c score, warfarin use, and antiplatelet use. A systolic BP of ≥136 mm Hg was an independent risk factor for thromboembolism and major hemorrhage. Conclusions BP control appears to be more important than a history of hypertension and baseline BP values at preventing thromboembolism and major hemorrhage in patients with nonvalvular atrial fibrillation. Clinical Trial Registration URL : http://www.umin.ac.jp/ctr . Unique identifier: UMIN 000001569.

Leucaena leucocephala (leucaena) is a fast-growing tree legume highly tolerant to various abiotic and biotic stresses. Because of its abilities to withstand high temperature and prolonged drought and to grow as a disease-free plant, it is an interesting model plant to investigate genetics of stress resistance. The high-level stress resistance may be correlated with higher expression of certain genes in the root, which is the primary site for nutrient and water uptake and also infection by soil-borne pathogens. The objectives of this study were to characterize the transcriptome of leucaena and to identify root-specific genes that may be involved in drought tolerance and disease resistance. Transcriptomes of leucaena were analyzed through Illumina-based sequencing and de novo assembly, which generated 62,299 and 61,591 unigenes (≥ 500 bp) from the root and shoot, respectively. Through a 4 x 180,000 microarray analysis, the expression of 10,435 unigenes were compared between the root and shoot. Upregulated sequences in the root were mostly represented by unigenes that were related to secondary metabolism, while in the shoot, upregulated sequences were mostly represented by unigenes that were involved in carbohydrate and lipid metabolism. The unigenes sharing homology with terpenoid biosynthesis genes and a nicotianamine synthase gene were upregulated more than 100-fold in the root, which indicates that these genes may have important roles in high stress tolerance of leucaena. Cataloging of actively transcribed sequences in the root and shoot will lead to identification of genes for drought tolerance and disease resistance in leucaena.

We Review Our Dynamical Property Measurements of Rattling Phonons in Type-I Clathrate Compounds, the Quasi-on-Center Ba8Ga16Ge30 (BGG) and Off-Center Ba8Ga16Sn30 (BGS), Using a Terahertz Time-Domain Spectrometer. The Lowest-Lying Vibrational Modes of Rattling Ba Ions in the Oversized Cage Show Anomalous Temperature Dependence in their Spectra. For BGG, the Temperature Dependence Is Mostly Consistent with a Local Anharmonic Potential Approximation that Predicts Softening towards Low Temperature. On the other Hand, for BGS, a Single Broad Peak of Off-Center Rattling Phonons Splits into Two Subpeaks below 120 K, and, with Further Lowering Temperature, the Spectra Show Anomalous Broadening. While the Splitting Can Be Understood by the Double Well Potential, the Linewidth Broadening Must Be Attributed to some Relevant Interactions with such Excitations as Acoustic Phonons and Doped Carriers.

Objective: In this study, we develop methods to measure galvanotaxis of fibroblasts and determined the optimum conditions of electrical stimulation. Method: an inverted 35mm dish containing cell suspensions (3×10 5 primary human skin fibroblasts, DMEM, and 10% FBS) was placed on the centre of a 100mm dish. The 35mm dish was removed 24 hours later, and culture medium was added to the 100mm dish. Fibroblasts were randomised (double-blind) into three groups, where electrical stimulation was given at varying intensities: 0μa (control), 50μa, and 100μa. Electrical stimulation (frequency = 0.3Hz) was conducted, for a duration of 4 hours, with platinum electrodes in a Co2 incubator. We took pictures immediately before and 20 hours after stimulation. We calculated the migration ratio to the negative pole by dividing the area of attached fibroblasts after stimulation with that before stimulation. Results: The migration ratio to the negative pole was significantly higher in the 100μa group than in the control group (p < 0.05). The ratios were 0.902 ± 0.292 in the control group, 1.128 ± 0.253 in the 50μA group, and 1.245 ± 0.300 in the 100μA group. Conclusion: This study observed the change in cell proliferation during the initial 24-hour period after plating and was thus able to quantitatively evaluate the migration. The results suggest that a low-intensity direct current promotes migration to the negative pole of human dermal fibroblasts, which is charged with positive electricity. Several clinical reports using the methods in this study showed the microcurrent efficacy for pressure ulcer healing. Electrical stimulation based on our in vitro experiment might be important for the development of physical therapy for pressure ulcers. Declaration of interest: The authors have no conflict of interest to declare. There were no external sources of funding for this study.

Various placcntal and leucocyte enzyme activities were determined in a male newborn whose mother had decreased urinary E3 and serum total E3 levels during the course of pregnancy, suggesting placental sulfatase deficiency (PSD). Tests revealed that both placental steroid sulfatase (SS) and arylsulfatase C (ASC) were deficient but arylsulfatases A and 15 were normal. SS activity, as well as the levels of arylsulfatases A, B and C, were also determined in the newborn and his family members using leucocytes. SS and ASC activities were deficient in the newborn and one of his male cousins. Both cases had cutaneous ichthyosis several weeks after birth. Leucocyte SS and ASC activities in the mother and grandmother of these two cases with steroid sulfatase deficiency (SSD) were 38% to 69% of the mean levels in the control. This, coupled with the results of the family investigation, strongly suggests that the deficiency is a sex-linked recessive hereditary condition. Control values for SS and ASC were higher in females than in males. These results indicate that the diagnosis of SSD and the screening of carriers can be made using both leucocytic SS and ASC activities. Estrogen E1, E2 and E3 levels were low in maternal and umbilical cord blood.

Thermal stress, which is caused by the difference in thermal expansion coefficients of different materials, is a serious problem for large scale integrated (LSI) circuit packaging. The stress causes damage to LSI devices, especially those that have low-k materials in their LSI layer, and packaging substrates. We have developed a helical-micro-spring (HMS) to reduce damage due to thermal stress. The spring has a helical wiring structure that relieves any thermal stress. We have fabricated the HMS using a negative-type photopolymers or a positive-type photopolymer as dielectric layers. We have also simulated the spring's mechanical and electrical properties and compared the properties with other stress relaxation structure.

We present a patient with posterior cortical atrophy in whom positron emission tomography (PET) showed unusual findings. This 65-year-old man had a 5-year history of slowly progressive apperceptive visual agnosia and Balint syndrome, but with a relatively well-preserved intelligence and language ability even in the later stages of illness. No relevant features in this patient or his family were identified. Laboratory and radiographic investigations indicated that cerebral damage was due to primary degeneration. His symptoms resembled those of patients with posterior cortical atrophy. A PET study revealed that cerebral metabolism was reduced in the dorsal regions of the entire cortex and asymmetrical with the main site of damage on the right. The severity in asymmetry increased dorsally. These 2 types of predilection for dorsal regions had not previously been reported in such patients. These unusual PET findings may indicate the presence of pathological changes not yet identified.

The mdx mouse, a model of muscular dystrophy, lacks dystrophin, a cell membrane protein. It is known that the lack of dystrophin causes muscle fiber necrosis from 2 weeks after birth, and the majority of necrotic muscle fibers are replaced by regenerated muscle fibers by 4 weeks after birth. A recent study indicated the possibility that mitochondria-mediated intracellular stress, a phenomenon similar to apoptosis, may be produced during muscle fiber necrosis, but did not analyze endoplasmic reticulum-mediated intracellular stress. Therefore, we examined the expression of the caspase-12 gene involved in the endoplasmic reticulum stress pathway and the Bax, caspase-9, and caspase-3 genes involved in the mitochondrial stress pathway in the mdx masseter muscle. We found over-expression of caspase-12 in cells at 2-3 weeks after birth when muscle fiber necrosis was not prominent. This suggests that stress occurs in the endoplasmic reticulum to maintain cell morphology in the absence of dystrophin. In addition, Bax was abundantly expressed in the mdx masseter muscle at 3 weeks after birth, and the expression of caspase-9 and -3 was prominent at 3-4 weeks after birth when necrosis and regeneration were marked. These results indicate that endoplasmic reticulum and mitochondrial stresses are produced during necrosis of the mdx masseter muscle, and suggest that these events are a phenomenon similar to apoptosis.

Summary It is still controversial whether patients with a history of gastrectomy have high risk of esophageal carcinogenesis. On the other hand, the treatment strategy for esophageal cancer patients after gastrectomy is complicated. The association between histories of gastrectomy and esophageal carcinogenesis was retrospectively analyzed, and the treatment of esophageal cancer patients after gastrectomy was evaluated based on questionnaire data collected from multiple centers in Kyushu, Japan. The initial subject population comprised 205 esophageal cancer patients after gastrectomy. Among them, 108 patients underwent curative surgical treatment, and 70 patients underwent chemoradiation therapy (CRT). The time between gastrectomy and esophageal cancer development was longer in peptic ulcer patients (28.3 years) than in gastric cancer patients (9.6 years). There were no differences in the location of esophageal cancer according to the gastrectomy reconstruction method. There were no significant differences in the clinical background characteristics between patients with and without a history of gastrectomy. Among the 108 patients in the surgery group, the 5‐year overall survival rates for stages I (n = 30), II (n = 18), and III (n = 60) were 68.2%, 62.9%, and 32.1%, respectively. In the CRT group, the 5‐year overall survival rate of stage I (n = 29) was 82.6%, but there were no 5‐year survivors in other stages. The 5‐year overall survival rate of patients with CR (n = 33) or salvage surgery (n = 10) was 61.2% or 36%, respectively. For the treatment of gastrectomized esophageal cancer patients, surgery or CRT is recommended for stage I, and surgery with or without adjuvant therapy is the main central treatment in advanced stages, with surgery for stage II, neoadjuvant therapy + surgery for stage III, and CRT + salvage surgery for any stage, if the patient's condition permits.

The subject of this research was a concrete T-girder bridge which had been exposed for 40 years to the sub-tropical archipelago environment off the east coast of Okinawa, with large amounts of windblown salt, high temperatures and high humidity, a harsh environment for salt damage and steel corrosion. It had suffered damage in the forms of 1) concrete spalling due to reinforcing bar corrosion, 2) internal loss of cross section and severance in internal reinforcing bars, and was therefore removed. Various tests and inspections were applied to analyze the state of deterioration of a real salt-damaged bridge, with the aim of providing technical reference material of use in formulating appropriate maintenance management methods. Distant visual inspection was performed prior to removal of the girder. After the removal, close visual inspection and non-distractive inspections were performed. Compressive strength, elastic modulus and chloride ion content of the concrete were measured. Corrosion of reinforcing bar was observed after chipping the concrete. Chloride-induced deterioration inside the concrete and competence of non-destructive inspection for the deterioration were studied. Static loading test and fatigue-test were performed.

Aims In this prospective observational study, we investigated the time-dependent changes and correlations of upper arm performance tests (ten-second test and Simple Test for Evaluating Hand Function (STEF), the Japanese Orthopaedic Association (JOA) score, and the JOA Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) in 31 patients with cervical myelopathy who had undergone surgery. Patients and Methods We hypothesised that all the indices correlate with each other, but show slightly different recovery patterns, and that the newly described JOACMEQ is a sensitive outcome measure. Results Peak recoveries were achieved one month post-operatively in the ten-second test and JOACMEQ upper extremity function (UEF) subscale, and at three months in the JOA and STEF scores. The recoveries of all indices were maintained until six months post-operatively. The upper extremity function (UEF) subscale in the JOACMEQ showed the strongest correlation with STEF although all the indices correlated with each other. Patients with ≥ 20 and < 20 acquired points in the UEF subscale were classified into the UEF-improved and UEF-unimproved groups. Comparisons between the groups showed that pre-operative evaluation of “coordinated motion” of the STEF was significantly low in the UEF-unimproved group. Conclusion These results indicate that the JOACMEQ is a concise, sensitive, patient-based outcome measure for evaluating functional recovery in patients with cervical myelopathy who have undergone surgery. Cite this article: Bone Joint J 2016;98-B:990–6.