During the course of generating derivatives of
N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, a synthetic calmodulin inhibitor, we came across several analogues with shorter alkyl chains that ...exhibited inhibition of serine/threonine protein kinase activities in an ATP-competitive manner. Certain derivatives proved to be selective inhibitors of protein kinases useful for elucidation of relevant functions of the enzymes. One of them turned out to be a unique vasodilator that preferentially suppresses delayed cerebral vasospasm, a critical complication of subarachnoid hemorrhage, without significant changes in systemic blood pressure. The compound in question, 1-(5-isoquinolinesulfonyl)-homopiperazine, was identified from sequential development of protein kinase inhibitors with isoquinolinesulfonyl structures, which occupy the adenine pocket of the ATP-binding site of the enzyme. It recently has been proposed that the target kinase responsible for vasodilation by 1-(5-isoquinolinesulfonyl)-homopiperazine may be Rho-kinase, which regulates phosphorylation of myosin light chains and vasocontraction. Because protein phosphorylation plays important roles in regulation of various cellular functions, the foregoing is a good example of current progress in the development of protein kinase inhibitors with potential clinical applications.
Background: Despite recommendations from clinical practice guidelines to initiate and titrate guideline-directed medical therapy (GDMT) during their hospitalization, patients with acute heart failure ...(AHF) are frequently undertreated. In this study we aimed to clarify GDMT implementation and titration rates, as well as the long-term outcomes, in hospitalized AHF patients.Methods and Results: Among 3,164 consecutive hospitalized AHF patients included in a Japanese multicenter registry, 1,400 (44.2%) with ejection fraction ≤40% were analyzed. We assessed GDMT dosage (β-blockers, renin-angiotensin inhibitors, and mineralocorticoid-receptor antagonists) at admission and discharge, examined the contributing factors for up-titration, and evaluated associations between drug initiation/up-titration and 1-year post-discharge all-cause death and rehospitalization for HF via propensity score matching. The mean age of the patients was 71.5 years and 30.7% were female. Overall, 1,051 patients (75.0%) were deemed eligible for GDMT, based on their baseline vital signs, renal function, and electrolyte values. At discharge, only 180 patients (17.1%) received GDMT agents up-titrated to >50% of the maximum titrated dose. Up-titration was associated with a lower risk of 1-year clinical outcomes (adjusted hazard ratio: 0.58, 95% confidence interval: 0.35–0.96). Younger age and higher body mass index were significant predictors of drug up-titration.Conclusions: Significant evidence-practice gaps in the use and dose of GDMT remain. Considering the associated favorable outcomes, further efforts to improve its implementation seem crucial.
Terpenoid is an important group of compounds not only as biocomponents but also as useful secondary metabolites. A volatile terpenoid 1,8-cineole, which is used as a food additive, flavoring agent, ...cosmetic, etc., is also attracting attention from a medical perspective due to its antiinflammation and antioxidation. The 1,8-cineole fermentation using a recombinant Escherichia coli strain has been reported, although a carbon source supplement is necessary for a high-yield 1,8-cineole production. We constructed the 1,8-cineole-producing cyanobacteria toward a carbon-free and sustainable 1,8-cineole production. cnsA, the 1,8-cineole synthase gene in Streptomyces clavuligerus ATCC 27064, was introduced and overexpressed in the cyanobacterium Synechococcus elongatus PCC 7942. We succeeded in producing an average of 105.6 µg g-1 wet cell weight of 1,8-cineole in S. elongatus 7942 without supplementing any carbon source. Using the cyanobacteria expression system is an efficient approach to producing 1,8-cineole by photosynthesis.
Norovirus is highly contagious, and a few particles of this virus are sufficient to make people sick. It is desirable to develop quick and accurate laboratory methods to detect norovirus.
We ...evaluated two commercial molecular diagnostic assays, the Xpert Norovirus and the TRCReady NV, using clinical fecal samples. A reference method was performed using in-house real-time reverse transcriptase polymerase chain reaction (real-time RT-PCR).
The results of the real-time RT-PCR analysis of 60 suspected cases of norovirus infection showed 5 cases of Genogroup I (GI) positives and 21 cases of GII positives, among which was 1 GI and GII coinfection. The viral titers of the norovirus-positive samples ranged from 1.54 × 101 to 3.14 × 108 copies/μL. Norovirus GII.17 (12 cases, 48%) was the most frequently detected genotype in this study, followed by GII.4 (6 cases, 24%), GII.13 (2 cases, 8%), GI.2 (2 cases, 8%), GI.3 (2 cases, 8%), GI.1 (1 case, 4%), and GII.2 (1 case, 4%). The kappa coefficient was 1.000 (95% CI: 1.000–1.000) for Xpert Norovirus and 0.966 (95% CI: 0.896–1.000) for TRCReady NV, indicating a strong agreement.
Norovirus detection using Xpert Norovirus and TRCReady NV is highly useful for diagnosis and infection control because these assays are easy to operate, quick, and exhibit almost the same performance as that of real-time RT-PCR.
Abstract
We report Atacama Large Millimeter/submillimeter Array Band 3 observations of CO(6−5), CO(7−6), and C
i
(2−1) in B14-65666 (“Big Three Dragons”), one of the brightest Lyman-break galaxies at
...z
> 7 in the rest-frame ultraviolet continuum, far-infrared continuum, and emission lines of O
iii
88
μ
m and C
ii
158
μ
m. CO(6−5), CO(7−6), and C
i
(2−1), whose 3
σ
upper limits on the luminosities are approximately 40 times fainter than the C
ii
luminosity, are all not detected. The
L
C
II
/
L
CO(6–5)
and
L
C
II
/
L
CO(7–6)
ratios are higher than the typical ratios obtained in dusty star-forming galaxies or quasar host galaxies at similar redshifts, and they may suggest a lower gas density in the photodissociated region in B14-65666. By using the (1) C
ii
luminosity, (2) dust mass-to-gas mass ratio, and (3) a dynamical mass estimate, we find that the molecular gas mass (
M
mol
) is (0.05–11) × 10
10
M
⊙
. This value is consistent with the upper limit inferred from the nondetection of mid-
J
CO and C
i
(2−1). Despite the large uncertainty in
M
mol
, we estimate a molecular gas-to-stellar mass ratio (
μ
gas
) of 0.65–140 and a gas depletion time (
τ
dep
) of 2.5–550 Myr; these values are broadly consistent with those of other high-redshift galaxies. B14-65666 could be an ancestor of a passive galaxy at
z
≳ 4 if no gas is fueled from outside the galaxy.
Anti-phosphatidylethanolamine antibody (aPE), an anti-phospholipid autoantibody (aPL), has been proposed as a factor in recurrent pregnancy loss (RPL). However, conflicting views exist on the ...pathogenicity of RPL, and aPE has not yet been included in the classification criteria for antiphospholipid syndrome (APS). Here, we aimed to determine the clinical importance of examining aPE. aPE (IgG, IgM) was measured in 1705 patients with a history of RPL and re-examined after a 12-week interval in patients who tested positive. Persistent positive patients were administered low-dose aspirin during the subsequent pregnancy and clinical outcomes depending on the presence, type, and persistence of aPE were evaluated. Among the patients positive for aPE IgG and aPE IgM in the first examination (n = 117; 6.87%, and n = 235; 13.6%, respectively), 31.5% and 37.6% were negative upon re-examination, respectively. Moreover, among the cases with known pregnancy outcome, the miscarriage rate in the cumulative positive aPE group was 32.6% (29/89), which did not differ significantly from that of the aPE negative group (27.7%; 80/209; P = 0.178). Alternatively, the miscarriage rate in the persistently positive group was 40.7% (22/54), which was significantly higher than that in the transient positive group, 20.0% (7/35) (P = 0.041). Particularly, this difference become more significant when focusing on aPE IgM, 46.9% (15/32) in the persistent, compared with 16.7% (4/24) in the transient positive group (P = 0.024). aPE IgM is suggested to serve as a pathogenic aPL together with anti-cardiolipin antibodies and lupus anticoagulants, particularly if these factors persist over an extended period of time.
Carbapenemase-producing Enterobacteriaceae (CPE) are increasing worldwide. Rapid and accurate detection of CPE is necessary for appropriate antimicrobial treatment and hospital infection control. ...However, CPE contains some strains that are difficult to detect depending on genotype and MIC value of carbapenem, and a detection method has not been established. The recently reported modified carbapenem inactivation method (mCIM) has been developed in CLSI M100-S27 as a phenotypic technique for detecting carbapenemase activity. In the present study, we examined mCIM as a new CPE detection method using 207 Enterobacteriaceae isolates in comparison with the three existing screening methods of modified Hodge test, Carba NP test and carbapenem inactivation method and evaluated its performance. Consequently, both the sensitivity and specificity of mCIM were 100%, indicating better results than the conventional screening methods. The mCIM is a useful tool for microbiology laboratories due to its simplicity, clear criteria, cost-effectiveness and availability at any laboratory.
Introduction
Rice leaves and stems, which can be used as rice straw for livestock feed, accumulate soluble oxalate. The oxalate content often reaches 5% of the dry weight leaves. Excess uptake of ...oxalate-rich plants causes mineral deficiencies in vertebrates, so it is important to reduce the oxalate content in rice leaves to produce high-quality rice straw. However, the mechanism of oxalate accumulation in rice has remained unknown.
Objectives
To understand metabolic networks relating oxalate accumulation in rice.
Methods
In this study, we performed metabolome analysis of rice M
2
population generated by ion-beam irradiation using CE-MS.
Results
The result showed wide variation of oxalate contents in M
2
plants compared with those of control plants. Multivariate analyses of metabolome dataset revealed that oxalate accumulation was strongly related with anionic compounds such as 2OG and succinate. For low-oxalate plants, four patterns of metabolic alterations affected oxalate contents in the M
2
leaves were observed. In M
3
plants, we found putative low-oxalate line obtained from low-oxalate M
2
mutant.
Conclusions
These findings would lead to produce the low-oxalate rice and to understand the oxalate synthesis in plants.These findings would lead to produce the low-oxalate rice and to understand the oxalate synthesis in plants.
Bronchopulmonary dysplasia (BPD) is the most common morbidity complicating preterm birth and affects long-term respiratory outcomes. The objectives of this study were to establish whether serum ...periostin at birth, day of life (DOL) 28, and corrected 36 weeks' gestational age could be potential biomarkers for BPD.
A total of 98 preterm Japanese infants born at <32 weeks and comparing 41 healthy controls born at term, were divided into BPD (n = 44) and non-BPD (n = 54) cohorts. Serum periostin levels were measured using an enzyme-linked immunosorbent assay.
Among 98 preterm infants, the median serum periostin levels at birth were higher with BPD (338.0 ng/mL) than without (275.0 ng/mL, P < 0.001). Multivariate analysis revealed that serum periostin levels at birth were significantly associated with BPD (P = 0.013). Serum periostin levels at birth with moderate/severe BPD (345.0 ng/mL) were significantly higher than those with non-BPD/mild BPD (283.0 ng/mL, P = 0.006).
Serum periostin levels were significantly correlated with birth weight and gestational age, and serum periostin levels at birth in BPD infants were significantly higher than that in non-BPD infants.
This study found higher serum periostin levels at birth in preterm infants subsequently diagnosed with bronchopulmonary dysplasia. It also emerged that serum periostin levels at birth significantly correlated with gestational age and birth weight. The mechanism by which serum periostin is upregulated in BPD infants needs further investigation.
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