Right heart reserve function assessed with fluid loading predicts late right heart failure after left ventricular assist device implantation.

BACKGROUND: A left ventricular assist device (LVAD) is an effective therapeutic option for advanced heart failure. Late right heart failure (LRHF) is a complication after LVAD implantation associated with increasing morbidity and mortality; however, the assessment of right heart function, including right heart reserve function after LVAD implantation, has not been established. We focused on a fluid loading test with right heart catheterization (RHC) to evaluate right heart pre-load reserve function and investigate its impact on LRHF. METHODS: Patients aged > 18 who received continuous-flow LVAD between November 2007 and December 2022 at our institution and underwent RHC with saline loading (10ml/kg for 15 min) 1 month after LVAD implantation were included. RESULTS: Overall, 31 LRHF or deaths (RHF group) have occurred in 149 patients. Comparing the RHF and non-RHF groups, pulmonary artery pulsatility index (PAPi) at rest (1.8±0.89 vs. 2.5±1.4, p=0.02) and right ventricular stroke work index (RVSWi) change ratio with saline loading (0.96±0.32 vs. 1.1±0.20, p=0.03) was significantly different. The PAPi at rest and RVSWi change ratio with saline loading were identified as the postoperative risks for LRHF or death. The cohort was divided into three groups based on whether the PAPi at rest and RVSWi change ratio were low. The event-free curve significantly differed between the three groups (p<0.001). CONCLUSIONS: Hemodynamic assessment with saline loading can evaluate the right ventricular pre-load reserve function of patients with LVAD. The low RVSWi change with saline loading was a risk factor for LRHF following LVAD implantation.

Prophylactic negative pressure wound therapy is not effective for preventing driveline infection following left ventricular assist device implantation.

BACKGROUND: Driveline infection (DLI) following left ventricular assist device (LVAD) implantation remains an unresolved problem. Negative pressure wound therapy (NPWT) promotes wound healing by applying negative pressure on the surface of the wound. Recently, the prophylactic application of NPWT to closed surgical incisions has decreased surgical site infections in various postsurgical settings. Therefore, we evaluated the efficacy and safety of prophylactic NPWT for preventing DLI in patients with LVAD implantation. METHODS: Prophylactic NPWT was provided to 50 patients who received continuous-flow LVADs as bridge-to-transplant therapy at our institution between May 2018 and October 2020 (NPWT group). The negative pressure dressing was applied immediately after surgery and retained on the driveline exit site for 7 days with a continuous application of -125 mm Hg negative pressure. The primary outcome was DLI within 1 year of LVAD implantation. We compared the rate of DLI incidence in the NPWT group with that in the historical control cohort (50 patients) treated with the standard dressing (SD) who received LVAD implantation between July 2015 and April 2018 (SD group). RESULTS: No severe complications were associated with the NPWT. During the follow-up period, DLI was diagnosed in 16 participants (32%) in the NPWT group and 21 participants (42%) in the SD group. The rates of DLI incidence and freedom from DLI did not differ between groups (p = 0.30 and p = 0.63). CONCLUSIONS: Prophylactic NPWT at the driveline exit site was safe following LVAD implantation. However, it did not significantly reduce the risk of DLI.

Sarcopenia and risk of infection in adult heart transplant recipients in Japan.

AIMS: Heart transplantation (HT) is an effective therapeutic option for end-stage heart failure. Infection is a major cause of morbidity and mortality after HT. Sarcopenia, defined as the loss of muscle mass and strength, is a common comorbidity in HT candidates with end-stage heart failure. However, the effects of sarcopenia on the occurrence of post-HT infections are not well understood. Therefore, we explored the association between the skeletal muscle mass and post-transplant infections in adult HT recipients. METHODS AND RESULTS: We retrospectively examined the records of 135 patients who underwent HT between August 2007 and November 2019 at our institution. Pre-transplant computed tomography was used to calculate the skeletal muscle index (SMI) at the level of the third lumbar vertebra. Muscle wasting was defined as the SMI of the lowest sex-based tertiles. The primary endpoint was infections within 6 months of HT. The study included 109 patients (80 men, mean age: 41.6 ± 12.0 years): 37 patients in the muscle wasting group and 72 patients in the non-muscle wasting group. The mean SMI values in the muscle wasting and non-muscle wasting groups were 29.9 ± 4.8 cm2 /m2 and 40.7 ± 6.7 cm2 /m2 , respectively. Prior to HT, 108 (99.1%) patients were on left ventricular assist device support, and during that support, the rate of late right heart failure was significantly higher in the muscle wasting group than non-muscle wasting group (P = 0.012). Sixteen infections occurred within 6 months of HT. The most common infection sites included the respiratory tract (n = 5) and the upper gastrointestinal tract (n = 5), followed by the urinary tract (n = 4). Overall, 10 patients experienced infections in the muscle wasting group (27.0%) and 6 in the non-muscle wasting group (8.3%) (P = 0.009). Two patients in the muscle wasting group required intensive care unit admission, compared to none in the non-muscle wasting group. Low skeletal muscle mass was associated with infections in the univariate and multivariate logistic regression models (hazard ratio: 3.68, 95% confidence interval: 1.19-11.3; P = 0.023). However, the duration of all-cause mortality within 3 years did not differ between the groups (P = 0.56). CONCLUSIONS: Low skeletal muscle mass is a predictor of post-HT infections within 6 months of HT.

Radiochemical analysis of the drain water sampled at the exhaust stack shared by Units 1 and 2 of the Fukushima Daiichi Nuclear Power Station.

Radioactive gas of Unit 1 of the Fukushima Daiichi Nuclear Power Station was released from the exhaust stack shared by Units 1 and 2 through the venting line on March 12th, 2011. In the present study, radiochemical analysis of drain water sampled at the drain pit of the exhaust stack was conducted to study radionuclides released during venting of the Unit 1. Not only volatile 129I, 134Cs and 137Cs but also 60Co, 90Sr, 125Sb and Unit 1-originated stable Mo isotopes were detected. Although Unit 1-originated stable Mo isotopes were clearly detected, their amounts were quite low compared to Cs, suggesting that the formation of Cs2MoO4 was suppressed under the accident condition. Approximately 90% of iodine existed as I- and 10% as IO3- in November 2020. Furthermore, larger amount of 129I than 137Cs was observed, suggesting major chemical form of 131I was molecular iodine rather than CsI at the accident time. The 134Cs/137Cs radioactivity ratio decay-corrected to March 11th, 2011 was 0.86, supported the results that Unit 1 originated radiocesium in environment has smaller 134Cs/137Cs radioactivity ratio than Unit 2 and 3 originated radiocesium.

Dose Estimation of Landfill Disposal of Removed Soil Generated Outside Fukushima Prefecture.

ABSTRACT: Dose estimation was conducted by assuming landfill disposal of removed soil generated outside the Fukushima Prefecture by each local town and in a lump sum. Because the radioactivity of removed soil is lower than that of specified waste that was generated at Fukushima Prefecture and the radioactivity concentration is 100,000 Bq kg-1 or less, simple landfill covered with 30 cm of non-contaminated soil was used. The exposure doses of loading/unloading, transportation, and landfill workers and the public residing near the repository site were estimated. Furthermore, migration of cesium into groundwater because of precipitation and using the contaminated groundwater for drinking and agricultural water was evaluated, and exposure doses regarding farmers and the ingestion of agricultural products were estimated. It was confirmed that estimated exposure doses during landfill were less than 1 mSv y-1, and those for after landfill were 0.01 mSv y-1.

DOSE ESTIMATION FOR CONTAMINATED SOIL STORAGE IN LIVING ENVIRONMENT.

After the Fukushima Nuclear Power Plant accident, most of radiocesium-contaminated soil generated from decontamination activities outside Fukushima prefecture has been stored at decontamination sites such as schools, parks and residential lands (storage at sites) according to the Decontamination Guidelines. However, additional exposure due to the present storage has not been evaluated. Moreover, entering storage sites, which is not restricted for storage at sites, was not considered in safety assessment conducted in the guidelines. To continue the storage and confirm the effectiveness, understanding of present possible exposures is important. In this study, we evaluated exposure doses for residents and users of storage sites based on the present situation. As a result, annual doses due to residence were 10-2 to 10-3 mSv y-1 and doses due to annual entries were of the order of 10-3 mSv y-1. Hence, we confirmed that the exposure due to present storage outside Fukushima is significantly <1 mSv y-1.

Development of a separation method for molybdenum from zirconium, niobium, and major elements of rubble samples.

A method for separation of Mo from Zr, Nb, and other major elements of rubble samples from the Fukushima Daiichi Nuclear Power Station (FDNPS) was developed to enable 93Mo assay of the rubble samples. Although (93)Mo analysis has been reported in a few studies, the known separation method is tedious and time consuming, or the target is a simple material. Therefore, a simple and rapid protocol for the separation of a complex material, i.e., the rubble sample, was developed in this study. Firstly, loss of Mo during the digestion of simulated rubble samples was evaluated. Next, weight distribution coefficients (Kd's) of Zr, Nb, and Mo between an extraction chromatographic resin (tetra valent actinide resin, TEVA resin) and acid solutions (HF-HCl and HF-HNO3 solutions) were determined to obtain suitable solution conditions for the separation of Mo from Zr and Nb. Based on the obtained Kd's, a chromatographic separation scheme was designed and applied to the digested solution of the simulated rubble sample. Consequently, Mo was successfully separated from Zr, Nb and other major metal ions of the simulated rubble sample.

A new method to analyze 242mAm in low-level radioactive waste based on extraction chromatography and ß-ray spectrometry.

A new method for identifying (242m)Am in low-level radioactive waste (LLW) using ß-ray spectrometry is proposed. First, (152)Eu, (241+242m+243)Am, and (244)Cm in a digested solution of simulated LLW were separated from the major components of the digested solution and Pu using a transuranium element resin (TRU resin). Next, Am and Cm were separated from Eu using a tetravalent actinide element resin (TEVA resin). A ß-ray spectrum of the fraction containing Am and Cm was recorded and the contribution of (239)Np, which is a daughter nuclide of (243)Am, was subtracted to determine the radioactivity of (242m)Am. Also mutual separation of Am, Cm, and Eu was carried out using a tertiary pyridine resin to determine (242m)Am by analyzing the increase of (242)Cm in the Am fraction just after separation of Am from Cm, which is the traditional method. The isotope ratio of (242m)Am/(241)Am determined by ß-ray spectrometry agreed with that obtained by analyzing the traditional method.

Structural basis for gibberellin recognition by its receptor GID1.

Gibberellins (GAs) are phytohormones essential for many developmental processes in plants. A nuclear GA receptor, GIBBERELLIN INSENSITIVE DWARF1 (GID1), has a primary structure similar to that of the hormone-sensitive lipases (HSLs). Here we analyse the crystal structure of Oryza sativa GID1 (OsGID1) bound with GA(4) and GA(3) at 1.9 A resolution. The overall structure of both complexes shows an alpha/beta-hydrolase fold similar to that of HSLs except for an amino-terminal lid. The GA-binding pocket corresponds to the substrate-binding site of HSLs. On the basis of the OsGID1 structure, we mutagenized important residues for GA binding and examined their binding activities. Almost all of them showed very little or no activity, confirming that the residues revealed by structural analysis are important for GA binding. The replacement of Ile 133 with Leu or Val-residues corresponding to those of the lycophyte Selaginella moellendorffii GID1s-caused an increase in the binding affinity for GA(34), a 2beta-hydroxylated GA(4). These observations indicate that GID1 originated from HSL and was further modified to have higher affinity and more strict selectivity for bioactive GAs by adapting the amino acids involved in GA binding in the course of plant evolution.

The rice SPINDLY gene functions as a negative regulator of gibberellin signaling by controlling the suppressive function of the DELLA protein, SLR1, and modulating brassinosteroid synthesis.

SPINDLY (SPY) encodes an O-linked N-acetylglucosamine transferase that is considered to be a negative regulator of gibberellin (GA) signaling through an unknown mechanism. To understand the function of SPY in GA signaling in rice, we isolated a rice SPINDLY homolog (OsSPY) and produced knockdown transgenic plants in which OsSPY expression was reduced by introducing its antisense or RNAi construct. In knockdown plants, the enhanced elongation of lower internodes was correlated with decreased levels of OsSPY expression, similar to the spindly phenotype of Arabidopsis spy mutants, suggesting that OsSPY also functions as a negative factor in GA signaling in rice. The suppressive function of OsSPY in GA signaling was supported by the findings that the dwarfism was partially rescued and OsGA20ox2 (GA20 oxidase) expression was reduced in GA-deficient and GA-insensitive mutants by the knockdown of OsSPY function. The suppression of OsSPY function in a GA-insensitive mutant, gid2, also caused an increase in the phosphorylation of a rice DELLA protein, SLR1, but did not change the amount of SLR1. This indicates that the function of OsSPY in GA signaling is not via changes in the amount or stability of SLR1, but probably involves control of the suppressive function of SLR1. In addition to the GA-related phenotypes, OsSPY antisense and RNAi plants showed increased lamina joint bending, which is a brassinosteroid-related phenotype, indicating that OsSPY may play roles both in GA signaling and in the brassinosteroid pathway.

GAMYB controls different sets of genes and is differentially regulated by microRNA in aleurone cells and anthers.

GAMYB is a component of gibberellin (GA) signaling in cereal aleurone cells, and has an important role in flower development. However, it is unclear how GAMYB function is regulated. We examined the involvement of a microRNA, miR159, in the regulation of GAMYB expression in cereal aleurone cells and flower development. In aleurone cells, no miR159 expression was observed with or without GA treatment, suggesting that miR159 is not involved in the regulation of GAMYB and GAMYB-like genes in this tissue. miR159 was expressed in tissues other than aleurone, and miR159 over-expressors showed similar but more severe phenotypes than the gamyb mutant. GAMYB and GAMYB-like genes are co-expressed with miR159 in anthers, and the mRNA levels for GAMYB and GAMYB-like genes are negatively correlated with miR159 levels during anther development. Thus, OsGAMYB and OsGAMYB-like genes are regulated by miR159 in flowers. A microarray analysis revealed that OsGAMYB and its upstream regulator SLR1 are involved in the regulation of almost all GA-mediated gene expression in rice aleurone cells. Moreover, different sets of genes are regulated by GAMYB in aleurone cells and anthers. GAMYB binds directly to promoter regions of its target genes in anthers as well as aleurone cells. Based on these observations, we suggest that the regulation of GAMYB expression and GAMYB function are different in aleurone cells and flowers in rice.

Identification and characterization of Arabidopsis gibberellin receptors.

Three gibberellin (GA) receptor genes (AtGID1a, AtGID1b and AtGID1c), each an ortholog of the rice GA receptor gene (OsGID1), were cloned from Arabidopsis, and the characteristics of their recombinant proteins were examined. The GA-binding activities of the three recombinant proteins were confirmed by an in vitro assay. Biochemical analyses revealed similar ligand selectivity among the recombinants, and all recombinants showed higher affinity to GA(4) than to other GAs. AtGID1b was unique in its binding affinity to GA(4) and in its pH dependence when compared with the other two, by only showing binding in a narrow pH range (pH 6.4-7.5) with 10-fold higher affinity (apparent K(d) for GA(4) = 3 x 10(-8) m) than AtGID1a and AtGID1c. A two-hybrid yeast system only showed in vivo interaction in the presence of GA(4) between each AtGID1 and the Arabidopsis DELLA proteins (AtDELLAs), negative regulators of GA signaling. For this interaction with AtDELLAs, AtGID1b required only one-tenth of the amount of GA(4) that was necessary for interaction between the other AtGID1s and AtDELLAs, reflecting its lower K(d) value. AtDELLA boosted the GA-binding activity of AtGID1 in vitro, which suggests the formation of a complex between AtDELLA and AtGID1-GA that binds AtGID1 to GA more tightly. The expression of each AtGID1 clone in the rice gid1-1 mutant rescued the GA-insensitive dwarf phenotype. These results demonstrate that all three AtGID1s functioned as GA receptors in Arabidopsis.

Overexpression of a GRAS protein lacking the DELLA domain confers altered gibberellin responses in rice.

The rice SLR1 (SLENDER RICE 1) gene encodes a DELLA protein that belongs to a subfamily of the GRAS protein superfamily and that functions as a repressor of gibberellin (GA) signaling. Based on the constitutive GA response phenotype of slr1 mutants, SLR1 has been thought to be the sole DELLA-type protein suppressing GA signals in rice. However, in rice genome databases we identified two sequences homologous to SLR1: SLR1-like1 and -2 (SLRL1 and -2). SLRL1 and SLRL2 contain regions with high similarity to the C-terminal conserved domains in SLR1, but lack the N-terminal conserved region of the DELLA proteins. The expression of SLRL1 was positively regulated by GA at the mRNA level and occurred preferentially in reproductive organs, whereas SLRL2 was moderately expressed in mature leaf organs and was not affected by GA. Transformation of SLRL1 into the slr1 mutant rescued the slender phenotype of this mutant. Moreover, overexpression of SLRL1 in normal rice plants induced a dwarf phenotype with an increased level of OsGA20ox2 gene expression and diminished the GA-induced shoot elongation, suggesting that SLRL1 acts as a repressor of GA signaling. Consistent with the fact that SLRL1 does not have a DELLA domain, which is essential for degradation of DELLA proteins, a level of SLRL1 protein was not degraded by application of gibberellic acid. However, the repressive activity of SLRL1 against GA signaling was much weaker than a truncated SLR1 lacking the DELLA domain. Based on these characteristics of SLRL1, the functional roles of SLRL1 in GA signaling in rice are discussed.