Usefulness of bicarbonate-based Impella purge solution in a patient with heparin-induced thrombocytopenia: the first case report of long-term management in Japan.

Percutaneous mechanical circulatory support utilizing micro-axial flow pumps, such as the Impella group of devices, has become a life-saving technique in the treatment of refractory cardiogenic shock, with ever-increasing success rates. A 30-year-old man presented with acute decompensated heart failure and a severely reduced left ventricular ejection fraction (17%). Despite initial treatment with inotropic drugs and intra-aortic balloon pump support, his hemodynamic status remained unstable. Transition to Impella CP mechanical circulatory support was made on day 6 owing to persistently low systolic blood pressure. A significant decline in platelet count prompted suspicion of heparin-induced thrombocytopenia (HIT), later confirmed by positive platelet-activated anti-platelet factor 4/heparin antibody and a 4Ts score of 6 points. Argatroban was initially used as the purge solution, but owing to complications, a switch to Impella 5.0 and a bicarbonate-based purge solution (BBPS) was performed. Despite additional veno-arterial extracorporeal membrane oxygenation support on day 24, the patient, aiming for ventricular assist device treatment and heart transplantation, died from infection and multiple organ failure. Remarkably, the Impella CP continued functioning normally until the patient's demise, indicating stable Impella pump performance using BBPS. This case highlights the usefulness of BBPS as an alternative to conventional Impella heparin purge solution when HIT occurs.

The ridge line of left pulmonary vein isolation from left atrial appendage can subsequently increase the completion rate of the mitral isthmus block line.

BACKGROUND AND OBJECTIVES: Mitral isthmus (MI) ablation for mitral flutter is technically difficult, and incomplete block line is not uncommon. The objective of this study is to investigate the effect of the ridge line of left pulmonary vein isolation (LPVI) from left atrial appendage (LAA) on completion rate of mitral isthmus (MI) block line and recurrence rate of atrial tachycardia (AT) or atrial flutter (AFL) after the first MI ablation. METHODS: We identified 611 patients who underwent first MI ablation for mitral flutter during the study period. Finally, 559 patients were enrolled and divided into two groups according to the method of ridge line ablation of LPVI (LAA group, n = 467, conventional group, n = 92). Outcome measures were the completion of MI block line by first MI ablation, the recurrence of AT/AFL, and repeat MI ablation after the first MI ablation. RESULTS: The first MI block line completion rate was significantly higher in the LAA group than the conventional group (95% vs. 85%, p < 0.001). The recurrence rate of AT/AFL after 3 months from first MI ablation was significantly lower in the LAA group. The requirement of additional MI ablation tended to be lower in the LAA group. CONCLUSIONS: Our novel approach of ablating LPV-LAA ridge from the LAA side during PVI can increase the success rate of MI block line completion, and reduce the recurrence rate of AT/AFL and the need for additional MI block line ablation. Graphical abstract Ablation of the left pulmonary vein-left atrial appendage ridge from the left atrial appendage side during PVI increased the success rate of mitral isthmus block line completion.

Does global warming decrease the correlation between cherry blossom flowering date and latitude in Japan?

In Japan, the geographical distribution of the first date of flowering (FFD) of Yoshino cherry trees (Cerasus ×yedoensis) in 2020, a year when temperatures were mild during the previous December and March, was different from the average FFD, which progresses northward along a latitudinal gradient. We hypothesized that global warming may have changed the average geographical pattern of the FFD. To test this hypothesis, we examined the relationship between the observed FFD and latitude at 42 sites during the period 1953-2020. We found that the correlation between FFD and latitude had decreased since 1980. This decrease may have been caused by a rise of temperatures in winter that delayed dormancy release and the subsequent FFD in areas where the annual mean temperature is high. Our results suggest that the correlation between FFD and latitude will decrease further as the climate warms in the future.

Peak autumn leaf colouring along latitudinal and elevational gradients in Japan evaluated with online phenological data.

We evaluated the spatial characteristics of the first day of peak leaf colouring (PLCstart) and their relationships with air temperature along latitudinal and elevational gradients in Japan from 2015 to 2017. Leaf colouring information collected from more than 740 sites via citizen science was analysed, representing elevations from 0 to 2800 m and latitudes from 32°N to 44°N. We found that locations with earlier PLCstart dates (day of year 265-294) displayed steeper slopes in elevation per degree of latitude than locations with later PLCstart dates (day of year 295-314). This statistically significant result indicates that the influence of elevation on PLCstart (vertical gradient) weakened as the leaf colouring season progressed in Japan. In addition to these spatial characteristics, the PLCstart and the warmth index (based on monthly mean air temperature) showed significant linear correlations for latitudinal and elevational gradients. This result suggests that the sensitivity of PLCstart to air temperature, as manifested in both latitudinal and elevational gradients, is constant. This study suggests that online phenological data may provide more accurate results for a regional scale (100-1000 km) than the datasets used by previous studies.

Improved Characterisation of Vegetation and Land Surface Seasonal Dynamics in Central Japan with Himawari-8 Hypertemporal Data.

Spectral vegetation index time series data, such as the normalized difference vegetation index (NDVI), from moderate resolution, polar-orbiting satellite sensors have widely been used for analysis of vegetation seasonal dynamics from regional to global scales. The utility of these datasets is often limited as frequent/persistent cloud occurrences reduce their effective temporal resolution. In this study, we evaluated improvements in capturing vegetation seasonal changes with 10-min resolution NDVI data derived from Advanced Himawari Imager (AHI), one of new-generation geostationary satellite sensors. Our analysis was focused on continuous monitoring sites, representing three major ecosystems in Central Japan, where in situ time-lapse digital images documenting sky and surface vegetation conditions were available. The very large number of observations available with AHI resulted in improved NDVI temporal signatures that were remarkably similar to those acquired with in situ spectrometers and captured seasonal changes in vegetation and snow cover conditions in finer detail with more certainty than those obtained from Visible Infrared Imaging Radiometer Suite (VIIRS), one of the latest polar-orbiting satellite sensors. With the ability to capture in situ-quality NDVI temporal signatures, AHI "hypertemporal" data have the potential to improve spring and autumn phenology characterisation as well as the classification of vegetation formations.

Cultural ecosystem services provided by flowering of cherry trees under climate change: a case study of the relationship between the periods of flowering and festivals.

In Japan, cherry blossoms are an important tourism resource and provide many cultural ecosystem service benefits. Under future warming conditions, we will require adaptions such as changing the timing of flower festivals to account for changes in the flowering phenology. In this study, we evaluated the coincidence between the flowering phenology of cherry blossoms and the associated festival periods in two Japanese cities under past, recent, and future climate conditions. We examined the situation in Shinhidaka, where the flower festival period changes every year, and Takayama, where the festival period is fixed to coincide with a shrine's annual spring festival. Currently, the average dates of beginning of flowering (more than four or five flowers open in an index tree; ~BBCH60) and full bloom (equal to or more than 80% of flowers open in an index tree; after BBCH65) in Shinhidaka (day of year (DOY) 126 and 130) are later than the long national holiday of Golden Week (DOY 119 to 125). The respective dates in Takayama (DOY 106 and 111, respectively) are later than the local a festival period (DOY 104 and 105). Under a scenario of 1.0 to 2.0 °C warming, the full blooming dates in Shinhidaka will coincide with Golden Week, whereas under 1.0 to 1.5 °C warming, the full blooming dates in Takayama will coincide with the spring festival period. Thus, moderate warming may increase the value of cherry blossoms to the tourism industry. Under more than 3.5 °C warming in Shinhidaka and 2.5 °C warming in Takayama, however, cherry blossoms will have already dropped by Golden Week and the spring festival period, respectively, suggesting that greater warming may decrease the value of this tourism resource.

Composite Lymphoma Comprising Extranodal NK/T-Cell Lymphoma and Diffuse Large B-Cell Lymphoma.

We report a rare case of composite lymphoma comprising extranodal NK/T-cell lymphoma, nasal type, (ENKL) and diffuse large B-cell lymphoma (DLBCL) in a 70-year-old man complaining of fatigue. Computed tomography showed multiple consolidations in both lungs, and ENKL was diagnosed from transbronchial lung biopsy. Positron emission tomography also detected abnormal uptake in the stomach, and DLBCL was diagnosed from subsequent gastroscopy. Two courses of chemotherapy including rituximab achieved reduction in DLBCL, but ENKL proved resistant to this treatment and progressed. Concomitant ENKL and DLBCL have not been previously described among reports of composite lymphomas.

Simple method to detect year-to-year variability of blooming phenology of Cerasus × yedoensis by digital camera.

The year-to-year variability of the blooming phenology of cherry trees is important as a proxy climate indicator and strongly affects cultural ecosystem services. Observation of blooming phenology at multiple points requires a simple and flexible approach. We examined changes in the canopy gap fraction extracted from binarized upward images taken periodically beneath a Cerasus × yedoensis 'Somei-yoshino' tree. The gap fraction decreased rapidly after the start of bloom, reached a minimum value at full bloom, and began to increase again, but then decreased rapidly during leaf flush. These changes reflect the phenology of blooming and leaf flush after flower drop of 'Somei-yoshino'. These characteristics allow detection of the year-to-year variability of the bloom and leaf-flush phenology of cherry and other deciduous tree species that show the same patterns.

Review: advances in in situ and satellite phenological observations in Japan.

To accurately evaluate the responses of spatial and temporal variation of ecosystem functioning (evapotranspiration and photosynthesis) and services (regulating and cultural services) to the rapid changes caused by global warming, we depend on long-term, continuous, near-surface, and satellite remote sensing of phenology over wide areas. Here, we review such phenological studies in Japan and discuss our current knowledge, problems, and future developments. In contrast with North America and Europe, Japan has been able to evaluate plant phenology along vertical and horizontal gradients within a narrow area because of the country's high topographic relief. Phenological observation networks that support scientific studies and outreach activities have used near-surface tools such as digital cameras and spectral radiometers. Differences in phenology among ecosystems and tree species have been detected by analyzing the seasonal variation of red, green, and blue digital numbers (RGB values) extracted from phenological images, as well as spectral reflectance and vegetation indices. The relationships between seasonal variations in RGB-derived indices or spectral characteristics and the ecological and CO2 flux measurement data have been well validated. In contrast, insufficient satellite remote-sensing observations have been conducted because of the coarse spatial resolution of previous datasets, which could not detect the heterogeneous plant phenology that results from Japan's complex topography and vegetation. To improve Japanese phenological observations, multidisciplinary analysis and evaluation will be needed to link traditional phenological observations with "index trees," near-surface and satellite remote-sensing observations, "citizen science" (observations by citizens), and results published on the Internet.

Spatio-temporal distribution of the timing of start and end of growing season along vertical and horizontal gradients in Japan.

We detected the spatio-temporal variability in the timing of start (SGS) and end of growing season (EGS) in Japan from 2003 to 2012 by analyzing satellite-observed daily green-red vegetation index with a 500-m spatial resolution. We also examined the characteristics of SGS and EGS timing in deciduous broadleaf and needleleaf forests along vertical and horizontal gradients and then evaluated the relationship between their timing and daily mean air temperature. We found that for the timing of SGS and EGS, changes along the vertical gradient in deciduous broadleaf forest tended to be larger than those in deciduous needleleaf forest. For both forest types, changes along the vertical and horizontal gradients in the timing of EGS tended to be smaller than those of SGS. Finally, in both forest types, the sensitivity of the timing of EGS to air temperature was much less than that of SGS. These results suggest that the spatio-temporal variability in the timing of SGS and EGS detected by satellite data, which may be correlated with leaf traits, photosynthetic capacity, and environment conditions, provide useful ground-truthing information along vertical and horizontal gradients.

Unmanned aerial survey of fallen trees in a deciduous broadleaved forest in eastern Japan.

Since fallen trees are a key factor in biodiversity and biogeochemical cycling, information about their spatial distribution is of use in determining species distribution and nutrient and carbon cycling in forest ecosystems. Ground-based surveys are both time consuming and labour intensive. Remote-sensing technology can reduce these costs. Here, we used high-spatial-resolution aerial photographs (0.5-1.0 cm per pixel) taken from an unmanned aerial vehicle (UAV) to survey fallen trees in a deciduous broadleaved forest in eastern Japan. In nine sub-plots we found a total of 44 fallen trees by ground survey. From the aerial photographs, we identified 80% to 90% of fallen trees that were >30 cm in diameter or >10 m in length, but missed many that were narrower or shorter. This failure may be due to the similarity of fallen trees to trunks and branches of standing trees or masking by standing trees. Views of the same point from different angles may improve the detection rate because they would provide more opportunity to detect fallen trees hidden by standing trees. Our results suggest that UAV surveys will make it possible to monitor the spatial and temporal variations in forest structure and function at lower cost.

The ratio of transmitted near-infrared radiation to photosynthetically active radiation (PAR) increases in proportion to the adsorbed PAR in the canopy.

The daily total photosynthetically active radiation (400-700 nm, PAR) and near-infrared radiation (700-1000 nm, NIR) were measured in the understory beneath the canopy (PARt and NIRt) and above the canopy (PARi and NIRi) of a Japanese cool-temperate deciduous broad-leaved forest during the snow-free period (May to November). The integration of spectral radiation for NIR and that for PAR, and the daily integrations of instantaneous NIR and PAR, reduced the noises from the optical difference in spectrum and from canopy structure heterogeneity, sky condition and solar elevation. PARi/PARt was linearly related to NIRt/PARt (R² = 0.96). The effect of cloudiness was negligible, because the fluctuation of NIRi/PARi was quite small regardless of season and weather conditions compared with the range of NIRt/PARt in the forest. The ratio of NIRt/PARt beneath the canopy was log-linearly related to the in situ leaf area index (LAI) with a wide range from 0 to 5.25 (R² = 0.97). We conclude that seasonal changes in fAPAR (= 1 - PARt/PARi) and LAI of a canopy can be estimated with high accuracy by transmitted NIRt and PARt beneath the canopy.

Effects of seasonal and interannual variations in leaf photosynthesis and canopy leaf area index on gross primary production of a cool-temperate deciduous broadleaf forest in Takayama, Japan.

Revealing the seasonal and interannual variations in forest canopy photosynthesis is a critical issue in understanding the ecological mechanisms underlying the dynamics of carbon dioxide exchange between the atmosphere and deciduous forests. This study examined the effects of temporal variations of canopy leaf area index (LAI) and leaf photosynthetic capacity [the maximum velocity of carboxylation (V (cmax))] on gross primary production (GPP) of a cool-temperate deciduous broadleaf forest for 5 years in Takayama AsiaFlux site, central Japan. We made two estimations to examine the effects of canopy properties on GPP; one is to incorporate the in situ observation of V (cmax) and LAI throughout the growing season, and another considers seasonality of LAI but constantly high V (cmax). The simulations indicated that variation in V (cmax) and LAI, especially in the leaf expansion period, had remarkable effects on GPP, and if V (cmax) was assumed constant GPP will be overestimated by 15%. Monthly examination of air temperature, radiation, LAI and GPP suggested that spring temperature could affect canopy phenology, and also that GPP in summer was determined mainly by incoming radiation. However, the consequences among these factors responsible for interannual changes of GPP are not straightforward since leaf expansion and senescence patterns and summer meteorological conditions influence GPP independently. This simulation based on in situ ecophysiological research suggests the importance of intensive consideration and understanding of the phenology of leaf photosynthetic capacity and LAI to analyze and predict carbon fixation in forest ecosystems.

Evaluation of 3-substituted arginine analogs as selective inhibitors of human nitric oxide synthase isozymes.

Nitric oxide (NO), a mediator of various physiological and pathophysiological processes, is synthesized by three isozymes of nitric oxide synthase (NOS). In developing candidate clinical drugs, it is very important not to inhibit endothelial NOS, because it plays an important role in maintaining normal blood pressure and flow. Here, we describe the design, synthesis and human NOS-inhibitory activities of S-methyl-L-isothiocitrulline-based 3-substituted arginine analogs. The 3R*-methyl compound 4, which has an S-methyl isothiourea moiety, inhibited nNOS and iNOS, but not eNOS (IC(50) > 1 mM). However, the 3R*-methyl compound 7, bearing a 5-iminoethyl moiety, did not inhibit any of the NOS isozymes, although L-N-iminoethylornithine (L-NIO) potently inhibited all three. A computational docking study was carried out to investigate the mechanism of the isozyme selectivity.

Involvement of NLK and Sox11 in neural induction in Xenopus development.

BACKGROUND: The Wnt signal transduction pathway regulates various aspects of embryonal development and has been implicated in promoting cancer. Signalling by Wnts leads to the stabilization of cytosolic beta-catenin, which then associates with TCF transcription factors to regulate expression of Wnt-target genes. The Wnt pathway is further subject to cross-regulation at various levels by other components. RESULTS: Recent evidence suggests that a specific MAP kinase pathway involving the MAP kinase kinase kinase TAK1 and the MAP kinase NLK counteract Wnt signalling. In particular, it has been shown that TAK1 activates NLK, which phosphorylates TCFs bound to beta-catenin. This phosphorylation down-regulates the DNA-binding activity of a TCF-4/beta-catenin complex, and blocks activation of their target genes. To investigate the role of NLK in Xenopus development, we isolated xNLK, a Xenopus homologue of NLK. Our findings indicate that xNLK is expressed in neural tissues and induces the anterior-neural marker gene, Otx-2. Moreover, xSox11, which is induced by the expression of Chordin, co-operates with xNLK to induce neural development. These molecules also interact in mammalian cells, and expression of a mutant of xNLK lacking kinase activity was found to suppress the induction of neural marker gene expression by xSox11. CONCLUSIONS: Our findings indicate that xNLK may play a role in neural development together with xSox11 during early Xenopus embryogenesis.