Dose of nafamostat mesylate during continuous kidney replacement therapy in critically ill patients: a two-centre observational study.

BACKGROUND: Nafamostat mesylate is an anticoagulant used for critically ill patients during continuous kidney replacement therapy (CKRT), characterised by its short half-life. However, its optimal dosage remains unclear. This study aimed to explore the optimal dosage of nafamostat mesylate during CKRT. METHODS: We conducted a two-centre observational study. We screened all critically ill adult patients who required CKRT in the intensive care unit (ICU) from September 2013 to August 2021; we included patients aged ≥ 18 years who received nafamostat mesylate during CKRT. The primary outcome was filter life, defined as the time from CKRT initiation to the end of the first filter use due to filter clotting. The secondary outcomes included safety and other clinical outcomes. The survival analysis of filter patency by the nafamostat mesylate dosage adjusted for bleeding risk and haemofiltration was performed using a Cox proportional hazards model. RESULTS: We included 269 patients. The mean dose of nafamostat mesylate was 15.8 mg/hr (Standard deviation (SD), 8.8; range, 5.0 to 30.0), and the median filter life was 18.3 h (Interquartile range (IQR), 9.28 to 36.7). The filter survival analysis showed no significant association between the filter life and nafamostat mesylate dosage (hazard ratio 1.12; 95 CI 0.74-1.69, p = 0.60) after adjustment for bleeding risk and addition of haemofiltration to haemodialysis. CONCLUSIONS: We observed no dose-response relationship between the dose of nafamostat mesylate (range: 5 to 30 mg/h) and the filter life during CKRT in critically ill patients. The optimal dose to prevent filter clotting safely needs further study in randomised controlled trials. TRIAL REGISTRATION: Not applicable.

Does salivary pH affect postoperative sore throat in the head-down position of general anesthesia?

BACKGROUND: Tracheal intubation sometimes causes postoperative sore throat (POST) due to laryngeal damage. However, clinical observations suggest that the environment of the oral cavity may also affect POST. OBJECTIVE: The purpose of this study was to investigate whether salivary pH in the oral cavity affects POST. METHODS: After obtaining ethical approval, informed consent was obtained from all patients. Patients who underwent surgery in the supine position were enrolled as the control group. Patients who underwent laparoscopic surgery in the head-down position were enrolled as the intervention group. Immediately before both groups of patients were anaesthetised, expelled saliva was collected, and salivary pH was measured. Immediately postoperatively, the same measurement was carried out before the patient regained consciousness. The primary outcome was the change in salivary pH. The secondary outcome was POST. In our study, POST was defined as pharyngeal and swallowing pain in the glossopharyngeal and superior laryngeal nerves. The normal distribution of pH was tested using the Shapiro-Wilk test followed by analysis using repeated-measurements and one-way analysis of variance. Statistical significance was set at p < .05. RESULTS: A total of 62 patients were enrolled, of whom two were excluded based on the exclusion criteria. Salivary pH in the intervention group was significantly lower than that in the control group. Five patients had POST in the intervention group, whereas none had POST in the control group had POST. CONCLUSION: Acidotic-shifted saliva is considered one of the causes of POST.

Myxomycetes on the bark of living Metasequoia glyptostroboides trees and their distribution along a rural-urban gradient.

Myxomycete distribution along urban-rural gradients remains to be studied in detail. The ancient plant Metasequoia glyptostroboides has been mainly planted in urban parks and green areas in Japan, and it provides new habitats for myxomycetes on its growing tree bark. Here, we examined myxomycetes on bark along urbanization gradients, estimated by land-use coverage types. Survey sites were selected at 20 locations in western Japan, where the bark was sampled from 10 trees at each site. The bark samples were cultured in 10 Petri dishes per tree using the moist chamber technique. Myxomycete fruiting colonies occurred in 71% of cultures, and 44 species were identified across surveys. Diderma chondrioderma occurred at all sites, with the next most abundant species being Licea variabilis and Perichaena vermicularis. Twenty-two myxomycete communities ordinated using non-metric multidimensional scaling showed a significant negative correlation with building coverage and bark pH, increasing along the first axis. Relative abundances of Physarum crateriforme and Licea biforis positively correlated with increasing building coverage. Overall, urbanization causes alternation of the myxomycete community structure without diversity loss, and intermediate urbanization diversified species diversity on M. glyptostroboides tree bark.

Ecological aspects of myxomycetes associated with white and brown wood rot on coarse woody debris in subalpine coniferous forests in Central Japan.

We investigated factors affecting the community composition of lignicolous myxomycetes in dead wood with white and brown rot through summer and autumn surveys in a subalpine forest in Central Japan. In both seasons, wood had decayed to a softer state under brown rot than under white rot. The pH of wood with white rot was nearly neutral, while wood with brown rot was weakly acidic. Wood pH was lower in summer than in autumn. Forty-two myxomycetes taxa in 19 genera were identified in 302 fruiting-body colonies; white rot yielded 31 taxa and brown rot 24 taxa. Species diversity was higher on wood with white rot than on wood with brown rot. The effect of wood hardness on species composition depended on season. Several species exhibited a preference for one of the rot types. The substrate conditions associated with brown rot limit myxomycetes species diversity.

ß-Amyrin Biosynthesis: The Methyl-30 Group of (3S)-2,3-Oxidosqualene Is More Critical to Its Correct Folding To Generate the Pentacyclic Scaffold than the Methyl-24 Group.

Oxidosqualene cyclases catalyze the transformation of oxidosqualene (1) into numerous cyclic triterpenes. Enzymatic reactions of 24-noroxidosqualene (8) and 30-noroxidosqualene (9) with Euphorbia tirucalli ß-amyrin synthase were conducted to examine the role of the branched methyl groups of compound 1 in the ß-amyrin biosynthesis. Substrate 8 almost exclusively afforded 30-nor-ß-amyrin (>95.5 %), which was produced through a normal cyclization pathway, along with minor products (<4.5 %). However, a lack of the Me-30 group (analogue 9) resulted in significantly high production of premature cyclization products, including 6/6/6/5-fused tetracyclic and 6/6/6/6/5-fused pentacyclic skeletons (64.6 %). In addition, the fully cyclized product (35.4 %) having the 6/6/6/6/6-fused pentacycle was produced; however, the normally cyclized product, 29-nor-ß-amyrin was present in only 18.6 % of these products. The conversion yield of substrate 8 possessing a Z-Me group at the terminus was approximately twofold greater than that of compound 9 with an E-Me group. Thus, the Me-30 group is essential for the correct folding of a chair-chair-chair-boat-boat conformation of compound 1 for the production of the ß-amyrin scaffold, whereas the Me-24 group exerts little influence on the normal polycyclization cascade. Here, we show that the Me-30 group plays critical roles in constructing the ordered architecture of a chair-chair-chair-boat-boat structure, in facilitating the ring-expansion reactions, and in performing the final deprotonation reaction at the correct position.

Impact of mild hypercapnia in critically ill patients with metabolic acidosis.

PURPOSE: Clinical trials focusing on critically ill patients with metabolic acidosis, a common exclusion criterion is the presence of a PaCO2 > 45 mmHg. The aim of this study was to assess the impact of mild hypercapnia on patient characteristics, severity, and clinical outcomes in critically ill patients with metabolic acidosis. MATERIAL AND METHODS: Multicentre, retrospective, observational study conducted in 12 intensive care units (ICUs) in Queensland, Australia. Patients with metabolic acidosis and concurrent vasopressor requirement were included and the exposure of interest was the PaCO2 level at the time of meeting the eligibility criteria divided in two groups: PaCO2 ≤ 45 mmHg and PaCO2 46-50 mmHg. Primary clinical outcome was major adverse kidney events within 30 days (MAKE30). RESULTS: We studied 5601 patients, with 3605 (64.4 %) in the PaCO2 ≤ 45 mmHg group and 1996 (35.6 %) in the PaCO2 46-50 mmHg group. The incidence of MAKE30 was lower in the PaCO2 46-50 mmHg group (29 % vs. 34 %; OR, 0.79 [95 %CI, 0.69 to 0.90]; p < 0.001) as was the use of renal replacement therapy, and the incidence of acute kidney injury. After adjustment for confounders, no outcome was different between the groups. The maximum fall of pH associated with an increase of 1 mmHg of PaCO2 in the PaCO2 46-50 mmHg group was 0.006. CONCLUSION: In patients with metabolic acidosis, after adjustment for potential confounders, mild hypercapnia does not increase the MAKE-30 rate and does not have a major impact on pH.

Optimal timing for intubation in patients on non-invasive ventilation: A retrospective cohort study.

Background and Aims: The timing of transition from non-invasive ventilation (NIV) to invasive ventilation in the intensive care unit (ICU) is uncertain due to a lack of clinical evidence. This study aimed to identify the optimal timing of intubation in patients with respiratory failure managed with NIVs. Methods: A single-center observational study was conducted in Tokyo, Japan. Patients in the ICU managed with NIV between 2013 and 2022 were screened. The primary outcome was 28-day invasive ventilator-free days. Statistical analyses used locally estimated scatter plot smoothing (LOESS) and generalized linear mixed models to estimate the association between the timing of transition and prolonged intubation duration. Results: During the study period, 139 of 589 adult ICU patients receiving NIV transitioned to invasive ventilation. The LOESS curve indicated the longest 28-day ventilator-free days around 24 h after NIV initiation, after which the primary outcome decreased linearly. Late intubation after 24 h of NIV initiation was associated with fewer 28-day ventilator-free days (adjusted mean difference: -0.22 days [95% confidence interval: -0.31, -0.13]). Conclusion: We identified a non-linear association between the timing of intubation and 28-day invasive ventilator-free days. The critical 24-h time window for patients on NIV was associated with longer 28-day invasive ventilator-free days.

Comparison of wood-inhabiting myxomycetes in subalpine and montane coniferous forests in the Yatsugatake Mountains of Central Japan.

To demonstrate altitudinal gradients (and resulting temperatures) that affect myxomycete biodiversity and species composition, we statistically compared myxomycete assemblages between a subalpine coniferous forest and a montane pine forest within the region of the Yatsugatake Mountains, Nagano Prefecture, Central Japan. In summer and autumn field surveys during 2003-2010, 53 myxomycete taxa (with varieties treated as species) were observed from 639 records of fruiting bodies in the subalpine forest and 32 taxa were detected from 613 records in the montane forest. There were 20 species in common between the assemblages and the percentage similarity index was 0.400. Myxomycete biodiversity was higher in the subalpine than in the montane forest. Nine myxomycete species were statistically frequent occurrences in the subalpine forest and appeared in autumn: Lamproderma columbinum, Cribraria macrocarpa, Trichia botrytis, Physarum newtonii, Diderma ochraceum, Enteridium splendens, Elaeomyxa cerifera, Trichia verrucosa, and Colloderma oculatum. Five species were restricted to appear in the subalpine forest: Cribraria purpurea, Cribraria rufa, Cribraria ferruginea, Cribraria piriformis, and Lepidoderma tigrinum. Dead wood in the subalpine forest provided a breeding habitat for specific myxomycetes that inhabit cold areas; that is those areas having geographical features of decreasing temperature and increasing elevation, such as the temperate area of Central Japan.

Association between corticolous myxomycetes and tree vitality in Cryptomeria japonica.

The bark of live trees provides an important microhabitat for corticolous myxomycetes. However, the association between the presence of myxomycetes and health of host trees has not been studied in detail. In this study, we aimed to investigate the relationship between tree vitality and myxomycetes on the bark of Cryptomeria japonica trees in a montane forest in western Japan. The vitality of trees was categorized into four grades based on the visual assessment of tree shape and leaf density in the upper branches. Myxomycetes on the bark surface were examined using the moist chamber culture method. A decline in tree vitality increased bark pH and decreased electrical conductivity of the bark exudates. Seventeen myxomycete species were recorded in 74 C. japonica trees. The structure of myxomycete communities varied between healthy and unhealthy trees, and species diversity increased as the vitality declined. The relative abundance of Cribraria confusa decreased as the vitality declined, while that of Paradiacheopsis solitaria increased. The results showed that acidophilic myxomycetes grew on healthy C. japonica bark, but changes in bark pH associated with vitality decline led to the weakening of acidity and shifted the community structure; thus, corticolous myxomycete diversity was enhanced as tree vitality decline.

Transfer free graphene growth on SiO2 substrate at 250 °C.

Low-temperature growth, as well as the transfer free growth on substrates, is the major concern of graphene research for its practical applications. Here we propose a simple method to achieve the transfer free graphene growth on SiO2 covered Si (SiO2/Si) substrate at 250 °C based on a solid-liquid-solid reaction. The key to this approach is the catalyst metal, which is not popular for graphene growth by chemical vapor deposition. A catalyst metal film of 500 nm thick was deposited onto an amorphous C (50 nm thick) coated SiO2/Si substrate. The sample was then annealed at 250 °C under vacuum condition. Raman spectra measured after the removal of the catalyst by chemical etching showed intense G and 2D peaks together with a small D and intense SiO2 related peaks, confirming the transfer free growth of multilayer graphene on SiO2/Si. The domain size of the graphene confirmed by optical microscope and atomic force microscope was about 5 µm in an average. Thus, this approach will open up a new route for transfer free graphene growth at low temperatures.

ß-Amyrin biosynthesis: the critical role of steric volume at C-19 of 2,3-oxidosqualene for its correct folding to generate the pentacyclic scaffold.

The effect of the steric volume at C-19 of (3S)-2,3-oxidosqualene 1 on the polycyclization reaction by ß-amyrin synthase was examined. The substrate analogs, in which the methyl group at C-19 of 1 was substituted by an ethyl group and hydrogen atom, were converted into the following three new compounds: (17ß-H, 20S)-20-ethyl-dammara-12,24-diene 9, ß-amyrin homologue 10, and the 6,6,6,6-fused tetracycle 11. The folding conformations leading to these products are discussed.

Expression patterns of genes encoding carbohydrate-metabolizing enzymes and their relationship to grain filling in rice (Oryza sativa L.): comparison of caryopses located at different positions in a panicle.

In rice, caryopses located at the base of the panicle have a lower growth rate than those at the tip of the panicle. The former and latter types of caryopses are called inferior and superior caryopses, respectively. Taking the different growth rate into consideration, sugar status and the expression of genes encoding carbohydrate-metabolizing enzymes in inferior caryopses were compared with those in superior caryopses. During the first 5 d after flowering, superior caryopses elongated rapidly, but inferior caryopses did not. At this phase, inferior caryopses had a low ratio of hexose to sucrose, high activity of acid invertase and the absence of the expression of the genes encoding the above enzymes except for two isoforms of cell wall invertase, OsCIN4 and INV1, in comparison with superior caryopses. At the start of caryopsis elongation in both superior and inferior caryopses, the hexose/sucrose ratio increased accompanied by gene expression of vacuolar invertase (INV3), sucrose synthase (RSus1) and ADP-glucose pyrophosphorylase (AGP-L2: D50317). Furthermore, the genes related to endospermal starch accumulation were expressed highly with the decrease in the hexose/sucrose ratio after its peak. Based on the comparison of superior and inferior caryopses, the possible mechanism of grain filling in rice is discussed.

Family 19 chitinase of Streptomyces griseus HUT6037 increases plant resistance to the fungal disease.

Chitinase C (ChiC) is the first bacterial family 19 chitinase discovered in Streptomyces griseus HUT6037. In vitro, ChiC clearly inhibited hyphal extension of Trichoderma reesei but a rice family 19 chitinase did not. In order to investigate the effects of ChiC as an increaser of plant resistance to fungal diseases, the chiC gene was introduced into rice plants under the control of the increased CaMV 35S promoter and a signal sequence from the rice chitinase gene. Transgenic plants were morphologically normal. Resistance to leaf blast disease caused by Magnaporthe grisea was evaluated in R1 and R2 generations using a spray method. Ninety percent of transgenic rice plants expressing ChiC had higher resistance than non-transgenic plants. Disease resistance of sibling plants within the same line was correlated with the ChiC expression levels. ChiC produced in rice plants accumulated intercellularly and had the hydrolyzing activity against glycol chitin.