Disease burden of main bacterial infections in Japan, 2015-2020: A population-level study.

INTRODUCTION: Comprehensive evidence about the burden of infectious diseases in the Western Pacific Region is scarce. We thus examined the disease burden of infectious diseases in Japan in terms of disability-adjusted life years (DALYs). METHODS: We extracted national claims data from Japan's universal health insurance system to estimate the burden of disease for selected infections between 2015 and 2020 using DALYs. The mortality rate, disability duration and severity weight of each disease were estimated based on national data and literature reviews. RESULTS: Disease burden per 100,000 population was 1307.0 in 2015 and 972.1 in 2020 for bloodstream infections (BSI), 796.5 DALYs in 2015 and 498.9 DALYs in 2020 for pneumonia, 171.5 in 2015 and 149.4 in 2020 for meningitis and 11.6 in 2015 and 11.4 in 2020 for urinary tract infections (UTI). Only surgical site infections (SSI) showed a slightly increasing trend over the 5-year period, from 2.2 in 2015 to 2.8 in 2020. CONCLUSIONS: Our results showed that the disease burden of the five major infectious diseases was higher in Japan than in other countries. However, while the burden of SSI increased, the burden of pneumonia, meningitis, BSI and UTI gradually decreased year on year. The possible causes of the decreased morbidity should be examined in future work.

Trends in healthcare visits and antimicrobial prescriptions for acute infectious diarrhea in individuals aged 65 years or younger in Japan from 2013 to 2018 based on administrative claims database: a retrospective observational study.

BACKGROUND: The inappropriate use of antimicrobials for acute infectious diarrhea is widespread and leads to the problem of antimicrobial resistance. To improve the use of antimicrobials, it is first necessary to understand the actual situation of diarrheal disease and to identify potential targets for intervention. This study aimed to investigate the recent epidemiological characteristics of and antimicrobial prescriptions for acute infectious diarrhea in Japan. METHODS: This was a retrospective observational study of outpatients aged 0-65 years, separated into children (age 0-17 years) and adults (age 18-65 years), diagnosed with acute infectious diarrhea, using the administrative claims database of the Japan Medical Data Center from 2013 to 2018. We evaluated the number of eligible visits/number of database registrants (defined as the visit rate). The analysis of the antimicrobial prescription rate was restricted to otherwise healthy individuals diagnosed with acute infectious diarrhea alone by excluding patients with multiple disease diagnoses and with medical backgrounds of chronic bowel diseases or immunocompromised conditions. We further classified them by diagnosis of bacterial or nonbacterial acute infectious diarrhea. RESULTS: The total number of eligible visits for acute infectious diarrhea was 2,600,065. The visit rate, calculated based on the number of eligible visits by database registrants, was higher in children (boys, 0.264; girls, 0.229) than in adults (men, 0.070; women, 0.079), with peaks in early summer and winter. The peaks for visits in adults lagged those of children. In total, 482,484 visits were analyzed to determine the antimicrobial prescription rate; 456,655 (94.6%) were diagnosed with nonbacterial acute infectious diarrhea. Compared with children (boys, 0.305; girls, 0.304), the antimicrobial prescription rate was higher in adults, and there were differences between sexes in adults (men, 0.465; women, 0.408). Fosfomycin and fluoroquinolone were most frequently used for nonbacterial acute infectious diarrhea in children (44.1%) and adults (50.3%), respectively. CONCLUSIONS: These results revealed overprescription of antimicrobials for acute infectious diarrhea in this administrative claims database in Japan and contribute to the development of antimicrobial stewardship strategies and the identification of targets for efficiently reducing inappropriate antimicrobial use.

Distinguishing between isomeric neoxanthin and violaxanthin esters in yellow flower petals using liquid chromatography/photodiode array atmospheric pressure chemical ionization mass spectrometry and tandem mass spectrometry.

RATIONALE: Liquid chromatography/photodiode array atmospheric pressure chemical ionization mass spectrometry (LC/PDA-APCI-MS) is used for the analysis of various carotenoid pigments in plants. Among them, it is difficult to distinguish between the isomeric violaxanthin/neoxanthin esters. METHODS: The yellow pigments of tomato petals were extracted with acetone, and the extracts were kept at -30°C to allow the contaminating triacylglycerols to settle out physically. The supernatants were analyzed using LC/PDA-APCI-MS with a high-resolution orbitrap mass spectrometer for their exact masses. The expected carotenoid esters were calculated with the combination of carotenoids and fatty acids, and they were matched with the experimental exact masses. The fatty acid structures in the carotenoid esters were also identified using collision-induced dissociation (CID) tandem mass spectrometry (MS/MS). The isomeric violaxanthin/neoxanthin esters were distinguished using CID MS/MS from their in-source dehydrated product ions as pseudoprecursor ions. RESULTS: The in-source dehydrated ions [M - H2 O + H]+ of neoxanthin diesters predominated over their protonated molecules [M + H]+ in LC/MS. By contrast, the protonated molecules of violaxanthin diesters predominated. The 92 u loss product ions [M - H2 O - C7 H8 + H]+ were observed from the dehydrated violaxanthin diesters, but they were not generated from the dehydrated neoxanthin diesters in the CID MS/MS of their dehydrated pseudoprecursor ion [M - H2 O + H]+ . CONCLUSIONS: The allene allyl carbocation in neoxanthin diesters was generated from dehydration after preferential protonation at the hydroxy group. The epoxide group of violaxanthin diesters opens easily after protonation; however, the dehydration did not proceed at this stage. The 92 u loss of C7 H8 was explained by an intramolecular [2 + 2] cycloaddition, which proceeded preferentially in dehydrated violaxanthin diesters because the carbocations in the dehydrated species were conjugated to the polyene and those double bonds were depolarized during CID MS/MS. Therefore, the isomeric neoxanthin/violaxanthin diesters were distinguished using LC/PDA-APCI-MS and MS/MS. This method was a practical and useful method of profiling the carotenoid esters of the yellow petals.

Author Correction: Identification of a binding protein for sesamin and characterization of its roles in plant growth.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Author Correction: Identification of a binding protein for sesamin and characterization of its roles in plant growth.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Identification of a binding protein for sesamin and characterization of its roles in plant growth.

Sesamin is a furofuran-type lignan that is found abundantly in seeds of Sesamum indicum (sesame) and has been widely accepted as a dietary supplement with positive effects on human health. The biological activity of sesamin in human cells and organs has been analysed extensively, although comparatively few studies show biological functions for sesamin in planta. Herein we screened sesamin-binding proteins (SBP) from sesame seedling extracts using sesamin-immobilized nano-beads. In subsequent peptide mass fingerprinting analyses, we identified a SBP, Steroleosin B, which is one of the membrane proteins found in oil bodies. In addition, pull-down assays and saturation transfer difference-nuclear magnetic resonance (STD-NMR) experiments demonstrated that sesamin binds directly to recombinant Steroleosin B in vitro. Finally, ectopic accumulations of sesamin and Steroleosin B in transgenic Arabidopsis thaliana plants induced severe growth defects including suppression of leaf expansion and root elongation. Collectively, these results indicate that sesamin influences tissue development in the presence of Steroleosin B.

Author Correction: Oxidative rearrangement of (+)-sesamin by CYP92B14 co-generates twin dietary lignans in sesame.

The original version of of the Supplementary Information associated with this Article inadvertently omitted oligonucleotide primer sequences from Supplementary Table 3 and Supplementary Methods describing the molecular cloning of CYP92B14, CPR1 and CYP81Q cDNA fragments. The HTML has been updated to include a corrected version of the Supplementary Information.

Oxidative rearrangement of (+)-sesamin by CYP92B14 co-generates twin dietary lignans in sesame.

(+)-Sesamin, (+)-sesamolin, and (+)-sesaminol glucosides are phenylpropanoid-derived specialized metabolites called lignans, and are rich in sesame (Sesamum indicum) seed. Despite their renowned anti-oxidative and health-promoting properties, the biosynthesis of (+)-sesamolin and (+)-sesaminol remained largely elusive. Here we show that (+)-sesamolin deficiency in sesame is genetically associated with the deletion of four C-terminal amino acids (Del4C) in a P450 enzyme CYP92B14 that constitutes a novel clade separate from sesamin synthase CYP81Q1. Recombinant CYP92B14 converts (+)-sesamin to (+)-sesamolin and, unexpectedly, (+)-sesaminol through an oxygenation scheme designated as oxidative rearrangement of α-oxy-substituted aryl groups (ORA). Intriguingly, CYP92B14 also generates (+)-sesaminol through direct oxygenation of the aromatic ring. The activity of CYP92B14 is enhanced when co-expressed with CYP81Q1, implying functional coordination of CYP81Q1 with CYP92B14. The discovery of CYP92B14 not only uncovers the last steps in sesame lignan biosynthesis but highlights the remarkable catalytic plasticity of P450s that contributes to metabolic diversity in nature.

Inhibitory activity of Filipendula ulmaria constituents on recombinant human histidine decarboxylase.

Histidine decarboxylase (HDC) catalyses the formation of histamine, a bioactive amine. Agents that control HDC activity are beneficial for treating histamine-mediated symptoms, such as allergies and stomach ulceration. We searched for inhibitors of HDC from the ethyl acetate extract of the petal of Filipendula ulmaria, also called meadowsweet. Rugosin D, rugosin A, rugosin A methyl ester (a novel compound), and tellimagrandin II were the main components; these 4 ellagitannins exhibited a non-competitive type of inhibition, with K(i) values of approximately 0.35-1 µM. These K(i) values are nearly equal to that of histidine methyl ester (K(i)=0.46 µM), an existing substrate analogue inhibitor. Our results show that food products contain potent HDC inhibitors and that these active food constituents might be useful for designing clinically available HDC inhibitors.

Phenolic glycosides from Kaempferia parviflora.

Three phenolic glycosides were isolated together with two known flavonol glycosides from the H2O-soluble fraction of rhizomes of Kaempferia parviflora. Their structures were determined to be rel-(5aS,10bS)-5a,10b-dihydro-1,3,5a,9-tetrahydroxy-8-methoxy-6H-benz[b]indeno[1,2-d]furan-6-one 5a-O-[alpha-L-rhamnopyranosyl-(1-->6)-beta-d-glucopyranoside] (1), its rel-5aS,10bR isomer (2), and (2R,3S,4S)-3-O-[alpha-L-rhamnopyranosyl-(1-->6)-beta-d-glucopyranosyl]-3'-O-methyl-ent-epicatechin-(2alpha-->O-->3,4alpha-->4)-(5aS,10bS)-5a,10b-dihydro-1,3,5a,9-tetrahydroxy-8-methoxy-6H-benz[b]indeno[1,2-d]furan-6-one 5a-O-[alpha-L-rhamnopyranosyl-(1-->6)-beta-D-glucopyranoside] (3). The structures were elucidated on the basis of analyses of chemical and spectroscopic evidence.