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Periodontal disease is an inflammatory disease caused by infection with periodontopathogenic bacteria. Oral care is essential to prevent and control periodontal disease, which affects oral and systemic health. However, many oral hygiene products currently on the market were developed as disinfectants, and their intense irritation makes their use difficult for young children and older people. This study investigated the antibacterial effects of prunin laurate (Pru-C12) and its analogs on periodontopathogenic bacteria, Porphyromonas gingivalis ( P. gingivalis ). Pru-C12 and its analogs inhibited in vitro bacterial growth at more than 10 μM and biofilm formation at 50 µM. Among its analogs, only Pru-C12 showed no cytotoxicity at 100 µM. Three of the most potent inhibitors also inhibited the formation of biofilms. Furthermore, Pru-C12 inhibited alveolar bone resorption in a mouse experimental periodontitis model by P. gingivalis infection. These findings may be helpful in the development of oral hygiene products for the prevention and control of periodontal disease and related disorders.

Staphylococcus aureus produces large amounts of toxins and virulence factors. In patients with underlying diseases or compromised immune systems, this bacterium can lead to severe infections and potentially death. In this study, the crystal structure of the complex of S. aureus lipase (SAL), which is involved in the growth of this bacterium, with petroselinic acid (PSA), an inhibitor of unsaturated fatty acids, was determined by X-ray crystallography. Recently, PSA was shown to inhibit S. aureus biofilm formation and the enzymatic activity of SAL. To further characterize the inhibitory mechanism, we determined the half-inhibitory concentration of SAL by PSA and the crystal structure of the complex. The IC 50 of the inhibitory effect of PSA on SAL was 3.4 μm. SAL and PSA inhibitors were co-crystallized, and diffraction data sets were collected to 2.19 Å resolution at SPring-8 to determine the crystal structure and elucidate the detailed structural interactions. The results show that the fatty acid moiety of PSA is tightly bound to a hydrophobic pocket extending in two directions around the catalytic residue Ser116. Ser116 was also covalently bonded to the carbon of the unsaturated fatty acid moiety, and an oxyanion hole in SAL stabilized the electrons of the double bond. The difference in inhibitory activity between PSA and ester compounds revealed a structure-activity relationship between SAL and PSA. Additional research is required to further characterize the clinical potential of PSA., (© 2024 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Late kidney injury (LKI) in patients with acute heart failure (AHF) requiring intensive care is poorly understood.We analyzed 821 patients with AHF who required intensive care. We defined LKI based on the ratio of the creatinine level 1 year after admission for AHF to the baseline creatinine level. The patients were categorized into 4 groups based on this ratio: no-LKI (< 1.5, n = 509), Class R (risk; ≥ 1.5, n = 214), Class I (injury; ≥ 2.0, n = 78), and Class F (failure; ≥ 3.0, n = 20). Median follow-up after admission for AHF was 385 (346-426) days. Multivariate logistic regression analysis revealed that acute kidney injury (AKI) during hospitalization (Class R, odds ratio [OR]: 1.710, 95% confidence interval [CI]: 1.138-2.571, P = 0.010; Class I, OR: 6.744, 95% CI: 3.739-12.163, P < 0.001; and Class F, OR: 9.259, 95% CI: 4.078-18.400, P < 0.001) was independently associated with LKI. Multivariate Cox regression analysis showed that LKI was an independent predictor of 3-year all-cause death after final follow-up (hazard ratio: 1.545, 95% CI: 1.099-2.172, P = 0.012). The rate of all-cause death was significantly lower in the no-AKI/no-LKI group than in the no-AKI/LKI group (P = 0.048) and in the AKI/no-LKI group than in the AKI/LKI group (P = 0.017).The incidence of LKI was influenced by the presence of AKI during hospitalization, and was associated with poor outcomes within 3 years of final follow-up. In the absence of LKI, AKI during hospitalization for AHF was not associated with a poor outcome.

The fibrinogen-to-albumin ratio (FAR) in the acute phase of acute heart failure (AHF) has seldom been evaluated.A total of 1,402 hospitalized AHF patients were analyzed. We calculated FAR using the following formula: plasma fibrinogen (g/L) /serum albumin (g/L) × 1,000. Patients were divided into 3 groups according to FAR value quartiles (low-FAR [Q1, FAR ≤ 564, n = 352], middle-FAR [Q2/Q3, 565 ≤ FAR ≤ 1,071, n = 700], and high-FAR [Q4, FAR ≥ 1,072, n = 350]). The median (interquartile range) FAR value was 855 (710-1,103). A multivariate logistic regression model showed that C-reactive protein (per 1 mg/dL increase; odds ratio [OR]: 1.307, 95% CI: 1.250-1.3366, P < 0.001), ischemic heart disease etiology (OR: 1.691, 95%CI: 1.227-2.331, P = 0.001), and diabetes mellitus (DM; OR: 1.624, 95%CI: 1.188-2.220, P = 0.002) were independently associated with high FAR values. Kaplan-Meier curve analysis showed that prognosis of all-cause mortality within 730 days was significantly poorer (P = 0.033) in the high-FAR group than in the other 2 groups. Conversely, in the low-albumin group, the prognosis of all-cause mortality was significantly poorer (P = 0.006) in the low-FAR group than in the other groups. A Cox regression model revealed that in the low-albumin group, a low FAR value was an independent predictor of 730-day mortality (hazard ratio [HR]: 0.503, 95% CI: 0.287-0.881, P = 0.016) and HF events (HR: 0.444, 95%CI 0.276-0.712, P = 0.001).Elevated FAR was associated with inflammation, DM, and ischemic etiology, and with adverse outcomes in the whole AHF group, whereas low FAR was independently associated with adverse outcomes in the low-albumin group.

Background: Balloon kyphoplasty (BKP) is a useful treatment performed in patients with painful osteoporotic vertebral body fracture (OVF). However, in cases with large intra-vertebral clefts and cases with posterior spinal tissue damage, adjacent vertebral body fractures (AVFs), and cement migration may occur early after BKP, which may be a factor for poor results. In such cases, percutaneous vertebroplasty (PVP) combined with percutaneous pedicle screw (PPS) is useful treatment. This study compared BKP combined with PPS (BKP + PPS) compared to PVP using hydroxyapatite (HA) block combined with PPS (HAVP + PPS) for thoracolumbar OVF (TLOVF)., Methods: Twenty-eight patients who sustained painful TLOVFs without neurologic deficits underwent HAVP + PPS (group H, n=14) or BKP + PPS (group B, n=14). We evaluated time from injury to surgery, pre- and post-operative visual analogue scale (VAS) of low back pain, wedging angle of fractured vertebra, duration of operation, intraoperative blood loss, number of instrumented vertebra, and length of stay at hospital., Results: Group B had significantly less surgery time and less blood loss during surgery. VAS of low back pain improved equally in both groups, but at 1 year and 2 years postoperatively, wedging angle of fractured vertebra progressed significantly in group H compared with group B., Conclusions: PPS fixation combined with percutaneous vertebral cement augmentation with BKP for OVF was suggested to be minimally invasive in the elderly patients. In addition, there is no correction loss of the fractured vertebral body after BKP + PPS, which is considered to be a useful surgical procedure.

Two new felt scale species (Hemiptera: Coccomorpha: Eriococcidae) collected in Japan, Acanthococcus torikurai Tanaka sp. nov. and Anophococcus koguchii Tanaka sp. nov., are described and illustrated based on the morphological characteristics of the adult females. Acanthococcus torikurai is similar to A. spiraeae Borchsenius 1949 but lacks small pores on hind legs, spinulae on the meso- and metathoracic coxae, a cauda on abdominal segment VIII and capitate ventral setae. Anophococcus koguchii is similar to An. socialis (Goux 1931) but differs in having seven-segmented antennae, two different sizes of macrotubular ducts on the venter, multilocular pores mostly with five loculi rather than seven or eight, and in lacking large pores on the metathoracic coxae and a cauda on abdominal segment VIII. A key to the 17 Eriococcidae species found in Japan is also provided.

Introduction: The bacterial protein toxin Pasteurella multocida toxin (PMT) mediates RANKL-independent osteoclast differentiation. Although these osteoclasts are smaller, their resorptive activity is high which helps in efficient destruction of nasal turbinate bones of pigs., Methods: The proteome of bone marrow-derived macrophages differentiated into osteoclasts with either RANKL or PMT was analysed. The results were verified by characterizing the metabolic activity using Seahorse analysis, a protein translation assay, immunoblots, real-time PCR as well as flow cytometry-based monitoring of mitochondrial activity and ROS production. A Gαq overexpression system using ER-Hoxb8 cells was used to identify Gαq-mediated metabolic effects on osteoclast differentiation and function., Results: PMT induces the upregulation of metabolic pathways, which included strong glycolytic activity, increased expression of GLUT1 and upregulation of the mTOR pathway. As OxPhos components were expressed more efficiently, cells also displayed increased mitochondrial respiration. The heterotrimeric G protein Gαq plays a central role in this hypermetabolic cell activation as it triggers mitochondrial relocalisation of pSerSTAT3 and an increase in OPA1 expression. This seems to be caused by a direct interaction between STAT3 and OPA1 resulting in enhanced mitochondrial respiration. Overexpression of Gαq mimicked the hypermetabolic phenotype observed for PMT-induced osteoclasts and resulted in higher glycolytic and mitochondrial activity as well as increased bone resorptive activity. In addition, rheumatoid arthritis (RA) patients showed an increase in GNAQ expression, especially in the synovial fluid., Discussion: Our study suggests that Gαq plays a key role in PMT-induced osteoclastogenesis. Enhanced expression of GNAQ at the site of inflammation in RA patients indicates its pathophysiological relevance in the context of inflammatory bone disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chakraborty, Handrick, Yu, Bode, Hafner, Schenz, Schaack, Uhle, Tachibana, Kamitani, Vogl and Kubatzky.)

Mealybug species found in Japan belonging to the genus Crisicoccus Ferris (Hemiptera: Coccomorpha: Pseudococcidae) are reviewed and the adult female of each valid species is described or update described and illustrated. Crisicoccus seruratus (Kanda 1933) and C. matsumotoi (Shiraiwa 1935) are found to be the same species, and are synonymized. A neotype is designated for C. seruratus for the purpose of taxonomic stability. A species from Japan previously identified by Ezzat & McConnell (1956) as C. matsumotoi is found to differ from specimens of C. matsumotoi from Japan and is described as a new species, Crisicoccus ezzati sp. nov. Other Crisicoccus species recorded from Japan (C. azaleae (Tinsley 1898) and C. pini (Kuwana 1902)) are characterized based on recently collected specimens. A species in South Korea that was misidentified as C. matsumotoi for over 40 years is identified as Spilococcus pacificus (Borchsenius 1949) and an updated description and an illustration of the adult female are provided. Identification keys to relevant genera and to adult females of species of Crisicoccus in Japan and Spilococcus Ferris in South Korea are provided.

Two new mealybug species (Hemiptera: Coccomorpha: Pseudococcidae), namely, Dysmicoccus kunaw Tanaka sp. nov. and Phenacoccus miruku Tanaka Choi sp. nov., collected in Japan, are described based on the morphological characteristics of the adult females. Dysmicoccus kunaw resembles D. trispinosus (Hall 1923) and D. furcillosus Williams 2004, but differs from them in having two conical cerarian setae in each anal lobe cerarius, a considerable number of dorsal multilocular pores on the abdominal segments, and two types of oral collar tubular ducts on the venter. Phenacoccus miruku is similar to P. sisymbriifolium Granara de Willink 2007 and P. similis Granara de Willink 1983, but differs by lacking quinqelocular pores anterior to the mouthparts and translucent pores on the hind tibiae, and in the shape of the circulus. A molecular phylogenetic analysis was used to investigate the phylogenetic placements of the two new species. Keys to the species of Dysmicoccus Ferris and Phenacoccus Cockerell found in Japan are provided.

The soft scale, Pulvinaria floccifera (Westwood 1870) (Hemiptera: Coccidae) is a well-known agricultural and horticultural plant pest; however, there is some confusion surrounding its true taxonomic identity. The type specimens of P. floccifera differ morphologically from specimens described under this name in several recent studies. This confusion has arisen because the original description is too brief, and subsequent redescriptions were based on non-conspecific material. This taxonomically problematic situation has led to further confusion regarding the identity of P. floccifera. Herein, the oldest junior synonym of P. floccifera, i.e., Pulvinaria camelicola Signoret 1873 stat. rev., is revived to confer taxonomic stability to P. floccifera. The revived name, P. camelicola, is applied to a distinct species hitherto misidentified as P. floccifera. Morphological details of the adult female of P. camelicola stat. rev. are updated; and the adult female of P. floccifera is redescribed, based on specimens collected in Japan and some type specimens. A lectotype of P. floccifera are designated to stabilise the species identity. A key to the species of Pulvinaria found in Japan, and a table of diagnostic morphological character states of P. floccifera, P. camelicola stat. rev. and the type species of the genus, P. vitis (Linnaeus 1758), are provided to facilitate further taxonomic revision of the genus in the future.

Purpose: Postoperative diarrhea, including high-output stoma (HOS), frequently occurs after colorectal surgery; its risk factors and clinical implications on subsequent complications remain unknown. This study aimed to evaluate the risk factors and clinical implications of postoperative diarrhea after primary colorectal cancer (CRC) surgery., Methods: This prospective observational study included patients with CRC who underwent radical surgery at six hospitals between June 2016 and December 2017. The patients were categorized into three groups (non-stoma, colostoma, and ileostoma groups)., Results: A total of 178 patients participated in the study. In the non-stoma group, the incidence of postoperative diarrhea was 18.4% (27/147). The incidence of HOS was 28.6% (4/14) in the ileostoma group, and 0% in the colostoma group. Multivariable analyses of the incidence of diarrhea in the non-stoma group indicated that habitual smoking and hypertension were significantly associated with postoperative diarrhea (P = 0.012 and P = 0.0274, respectively). Postoperative diarrhea was more likely to occur in patients with rectal cancer than in those with colon cancer (P = 0.0501). In the non-stoma and ileostoma groups, the probability of the occurrence of other complications with Clavien-Dindo (C-D) grades II or higher was significantly higher in patients with C-D grade I diarrhea, including HOS, than in patients without diarrhea (39.3% vs. 14.6%, P = 0.0061)., Conclusions: Smoking and hypertension are the independent predictors of postoperative diarrhea after an elective CRC surgery. Rectal cancer surgery seems to be associated with postoperative diarrhea more than colon cancer surgery does. Mild postoperative diarrhea may lead to more severe complications., (© 2022. The Author(s).)

This study aims to investigate six food additives (octanoic acid, decanoic acid, acesulfame K, aspartame, saccharin, and sucralose) used in foods for the elderly or people with dysphagia because of the effect of these food additives on Porphyromonas gingivalis ( P. gingivalis ), which is a keystone pathogen of periodontal diseases. The growth of P. gingivalis was inhibited by 5 mM octanoic acid, 1.25 mM decanoic acid, 1.25% acesulfame K, 0.0625% aspartame, 0.03125% saccharin, and 0.625% sucralose. In addition, these food additives showed bactericidal activity for planktonic P. gingivalis (5 mM octanoic acid, 5 mM decanoic acid, 0.25% aspartame, 0.25% saccharin, and 5% sucralose). Moreover, biofilm formation was inhibited by 10 mM octanoic acid, 10 mM decanoic acid, 10% acesulfame K, 0.35% aspartame, 0.5% saccharin, and 7.5% sucralose. Moreover, the same concentration of these food additives without aspartame killed P. gingivalis in the biofilm. Aspartame and sucralose did not show cytotoxicity to human cell lines at concentrations that affected P. gingivalis. These findings may be useful in clarifying the effects of food additives on periodontopathogenic bacteria.

Six Japanese species of the genus Pulvinaria Targioni Tozzetti (Hemiptera: Coccomorpha; Coccidae): P. aurantii Cockerell, 1896, P. hazeae Kuwana, 1902, P. idesiae Kuwana, 1914, P. kuwacola Kuwana, 1907, P. nipponica Lindinger, 1933 and P. photiniae Kuwana, 1914, are redescribed and illustrated based on type specimens and some newly collected adult females. In addition, Pulvinaria decorata Borchsenius, 1957 syn. nov. and P. ornata Froggatt, 1921 (nec Hempel, 1912) syn. nov. are proposed as new junior synonyms of P. aurantii, and Pulvinaria fujisana Kanda, 1960 syn. nov. and P. hydrangeae Steinweden, 1946 syn. nov. are proposed as new junior synonyms of P. kuwacola. Lectotypes are designated for P. idesiae, P. nipponica and P. photiniae from the syntypes of these species and, in the absence of any original material, neotypes are designated for P. hazeae and P. kuwacola, respectively, using specimens collected from the type localities. To facilitate comparisons, a table containing diagnostic morphological character states of the redescribed species and the type species of the genus, P. vitis (Linnaeus, 1758), is provided.

A new species of the genus Formicoccus Takahashi (Hemiptera, Coccomorpha, Pseudococcidae) collected from the holoparasitic plant Balanophorafungosa J. R. & G. Forst (Balanophoraceae), on Ishigaki Island, Japan, is described as Formicoccusyoshinoi Tanaka, sp. nov. based on the morphology of adult females. This species is similar to F.formicarius (1900) and F.erythrinae Williams, 2004, but differs from them by having fewer than six cerarii, and only one type of ventral oral collar tubular duct distributed on the medial area of the posterior abdominal segments. Keys to the Oriental species of the genus Formicoccus are provided., (Hirotaka Tanaka, Kenji Suetsugu, Satoshi Kamitani.)

A new species of soft scale insect (Hemiptera: Coccomorpha: Coccidae), Luzulaspis kinakikir Tanaka sp. nov., collected from Carex miyabei (Cyperaceae), on Hokkaido Island, Japan, is described and illustrated based on adult female morphology. The new species, which belongs to the Scotica group of Luzulaspis, is similar to L. filizae Kaydan, 2015, but can be distinguished from it by possessing multilocular pores with fewer loculi; numerous dorsal tubular ducts, obviously wider than the ventral tubular ducts, and by lacking dorsal tubular ducts on the head apex. An updated diagnosis of Luzulaspis and two identification keys, one to the Japanese species of Luzulaspis and the other to the species of the Scotica group of Luzulaspis, are provided.

Two new species of Coccomorpha collected from Japanese silver grass, Miscanthus sinensis Andersson (Poaceae), in Okinawa Island, Japan, are described based on the morphology of adult females: Aspidiella kijimuna sp. nov. (Diaspididae) and Dysmicoccus bunagaya sp. nov. (Pseudococcidae). Aspidiella kijimuna is similar to A. phragmitis (Takahashi, 1931) but differs from it by having relatively well-developed and recognisable third lobes, and median lobes with rounded apices. Dysmicoccus bunagaya is similar to Trionymus okiensis Tanaka, 2018 but differs from it by having more than eight pairs of cerarii. Keys to all the Japanese species of Aspidiella and Dysmicoccus are provided.

Biological invasion has been a serious global threat due to increasing international trade and population movements. Tracking the source and route of invasive species and evaluating the genetic differences in their native regions have great significance for the effective monitoring and management, and further resolving the invasive mechanism. The spotted lanternfly Lycorma delicatula is native to China and invaded South Korea, Japan, and the United States during the last decade, causing severe damages to the fruits and timber industries. However, its global phylogeographic pattern and invasion history are not clearly understood. We applied high-throughput sequencing to obtain 392 whole mitochondrial genome sequences from four countries to ascertain the origin, dispersal, and invasion history of the spotted lanternfly. Phylogenomic analyses revealed that the spotted lanternfly originated from southwestern China, diverged into six phylogeographic lineages, and experienced northward expansion across the Yangtze River in the late Pleistocene. South Korea populations were derived from multiple invasions from eastern China and Japan with two different genetic sources of northwestern (Loess Plateau) and eastern (East Plain) lineages in China, whereas the each of Japan and the United States had only one. The United States populations originated through single invasive event from South Korea, which served as a bridgehead of invasion. The environmental conditions, especially the distribution of host Ailanthus trees, and adaptability possibly account for the rapid spread of the spotted lanternfly in the native and introduced regions., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.)

All four species of the soft scale insect genus Pulvinaria Targioni Tozzetti (Hemiptera: Coccomorpha: Coccidae) known from the Ryukyu Islands, Japan, are reviewed. For each species, the detailed morphology of the adult female is redescribed from specimens recently collected in the Ryukyu Islands and is compared with previous descriptions. A key to the species of Pulvinaria in the Ryukyu Islands is provided. A table of diagnostic morphological character states of the reviewed species and the type species of the genus, P. vitis (Linnaeus, 1758), is provided for use in future taxonomic revision of the genus; this comparison indicates that all four species of Pulvinaria in this region and the type species of the genus, P. vitis can be distinguished clearly from each other by several diagnostic morphological character states.

Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor and may be a therapeutic target for infectious diseases. Herein, we determined the 3D structure of native SAL, the mutated S116A inactive form, and the inhibitor complex using the anti-obesity drug orlistat to aid in drug development. The determined crystal structures showed a typical α/β hydrolase motif with a dimeric form. Fatty acids bound near the active site in native SAL and inactive S116A mutant structures. We found that orlistat potently inhibits SAL activity, and it covalently bound to the catalytic Ser116 residue. This is the first report detailing orlistat-lipase binding. It provides structure-based information on the production of potent anti-SAL drugs and lipase inhibitors. These results also indicated that orlistat can be repositioned to treat bacterial diseases.

Background: We aimed to develop quality indicators (QIs) related to primary and comprehensive stroke care and examine the feasibility of their measurement using the existing Diagnosis Procedure Combination (DPC) database., Methods and results: We conducted a systematic review of domestic and international studies using the modified Delphi method. Feasibility of measuring the QI adherence rates was examined using a DPC-based nationwide stroke database (396,350 patients admitted during 2013-2015 to 558 hospitals participating in the J-ASPECT study). Associations between adherence rates of these QIs and hospital characteristics were analyzed using hierarchical logistic regression analysis. We developed 17 and 12 measures as QIs for primary and comprehensive stroke care, respectively. We found that measurement of the adherence rates of the developed QIs using the existing DPC database was feasible for the 6 QIs (primary stroke care: early and discharge antithrombotic drugs, mean 54.6% and 58.7%; discharge anticoagulation for atrial fibrillation, 64.4%; discharge antihypertensive agents, 51.7%; comprehensive stroke care: fasudil hydrochloride or ozagrel sodium for vasospasm prevention, 86.9%; death complications of diagnostic neuroangiography, 0.4%). We found wide inter-hospital variation in QI adherence rates based on hospital characteristics., Conclusions: We developed QIs for primary and comprehensive stroke care. The DPC database may allow efficient data collection at low cost and decreased burden to evaluate the developed QIs.

Methods for the robust quantification of bacterial communities are still under development. In this context, the present study aimed to evaluate a method combining competitive PCR (cPCR) and microarray assays for the determination of absolute content of total bacteria and individual bacterial species in samples. For this, a competitor DNA for cPCR and microarrays containing three types of DNA probes was prepared. A calibration curve was generated with genomic DNA samples as standards, which was then utilized for cPCR-based determination of the total number (in moles) of 16S rRNA genes in other bacterial samples. Moreover, scatter plots of species-specific probes versus total bacteria probe for each genomic DNA of known concentration was fit to the regression model, and the obtained slope value was defined as the hybridization affinity ratio. The cPCR assay was performed for both a commercially available mixed genomic DNA sample and human oral bacterial DNA samples, and the total number of moles of 16S rRNA genes was determined. These values were distributed among each species on the basis of the signal intensities of species-specific probes and the hybridization affinity ratio. The total number of bacterial genomes and those of individual species were determined by dividing the copy number of 16S rRNA genes per genome. The obtained results were confirmed by quantitative real-time PCR (qPCR). For values of >1 × 10 2 copies determined by qPCR, the ratio of the values measured by DNA chips to by qPCR was 1.53-fold on average and <2.6-fold for all data. These results show that the combined method of cPCR and microarray is useful to quantify the absolute numbers of several types of bacteria in a sample at one time., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Introduction: To the best of our knowledge, no quality indicators (QIs) for primary care provided by local clinics have yet been developed in Japan. We aimed to develop valid and applicable QIs to evaluate primary care in Japan., Methods: Two focus group interviews were held to identify conceptual categories. Existing indicators for these categories were identified, and initial sets of potential QIs were developed. Using a modified Delphi appropriateness method, a multidisciplinary expert panel then developed and selected the QIs. Feasibility and applicability of these QIs were then confirmed in pilot testing at six local clinics in Hokkaido, Japan. To determine patient acceptance of these quality improvement activities, the survey asked two questions, "Do you think it is preferable that the patients of this clinic be periodically surveyed?" and "Do you think it is preferable that this clinic periodically undergo an external quality review by an independent body?", Results: Seven categories emerged from the focus group discussions as key components of primary care in Japan. Thirty-nine QIs under five categories (Comprehensive care/Standardized care, Access, Communication, Co-ordination, and Understanding of patient background) were finally selected and named the QIs for Primary Care Practice in Japan. In pilot testing at six primary care clinics in 2015, 65.4% of patients answered favorably to the idea that clinics should conduct regular patient surveys, and 71.8% answered favorably to the idea that clinics should undergo periodic external quality review by an independent body., Conclusions: We developed QIs to assess primary care services provided by clinics in Japan, for the first time. Although further refinement is required, establishment of these QIs is the first step in quality improvement for primary care practices in Japan., Competing Interests: None, (Copyright © Japan Medical Association.)

A new genus, Stictotettix gen. nov. and two new species of Dikraneurini, S. cleyerae sp. nov. and S. morishimai sp. nov., are described and illustrated, based on the specimens from Japan. This new genus is unique in the male genital features of the aedeagal atrium. The two new species live on pentaphylacacean trees, Cleyera japonica and Eurya japonica, respectively.

Cutinases are enzymes known to degrade polyester-type plastics. Est119, a plastic-degrading type of cutinase from Thermobifida alba AHK119 (herein called Ta&#95;cut), shows a broad substrate specificity toward polyesters, and can degrade substrates including polylactic acid (PLA). However, the PLA-degrading mechanism of cutinases is still poorly understood. Here, we report the structure complexes of cutinase with ethyl lactate (EL), the constitutional unit. From this complex structure, the electron density maps clearly showed one lactate (LAC) and one EL occupying different positions in the active site cleft. The binding mode of EL is assumed to show a figure prior to reaction and LAC is an after-reaction product. These complex structures demonstrate the role of active site residues in the esterase reaction and substrate recognition. The complex structures were compared with other documented complex structures of cutinases and with the structure of PETase from Ideonella sakaiensis. The amino acid residues involved in substrate interaction are highly conserved among these enzymes. Thus, mapping the precise interactions in the Ta&#95;cut and EL complex will pave the way for understanding the plastic-degrading mechanism of cutinases and suggest ways of creating more potent enzymes by structural protein engineering., (© 2019 Federation of European Biochemical Societies.)

Bordetella pertussis , B. parapertussis , and B. bronchiseptica cause respiratory infections, many of which are characterized by coughing of the infected hosts. The pathogenesis of the coughing remains to be analyzed, mainly because there were no convenient infection models of small animals that replicate coughing after Bordetella infection. Here, we present a coughing model of rats infected with B. bronchiseptica Rats, which are one of natural hosts of B. bronchiseptica , were readily infected with the organisms and showed frequent coughing. B. pertussis also caused coughing in rats, which is consistent with previous reports, but the cough response was less apparent than the B. bronchiseptica -induced cough. By using the rat model, we demonstrated that adenylate cyclase toxin, dermonecrotic toxin, and the type III secretion system are not involved in cough production, but BspR/BtrA (different names for the same protein), an anti-σ factor, regulates the production of unknown factor(s) to cause coughing. Rat coughing was observed by inoculation of not only the living bacteria but also the bacterial lysates. Infection with bspR ( btrA )-deficient strains caused significantly less frequent coughing than the wild type; however, intranasal inoculation of the lysates from a bspR ( btrA )-deficient strain caused coughing similarly to the wild type, suggesting that BspR/BtrA regulates the production of the cough factor(s) only when the bacteria colonize host bodies. Moreover, the cough factor(s) was found to be heat labile and produced by B. bronchiseptica in the Bvg + phase. We consider that our rat model provides insight into the pathogenesis of cough induced by the Bordetella infection. IMPORTANCE Whooping cough is a contagious respiratory disease caused by Bordetella pertussis This disease is characterized by severe paroxysmal coughing, which becomes a heavy burden for patients and occasionally results in death; however, its pathogenesis remains largely unknown. The major obstacle to analyzing Bordetella -induced coughing is the lack of conventional animal models that replicate coughing. As Bordetella pertussis is highly adapted to humans, infection models in experimental animals are not considered to be well established. In the present study, we examined coughing in rats infected with B. bronchiseptica , which shares many virulence factors with B. pertussis Using this rat model, we demonstrated that some of the major virulence factors of Bordetella are not involved in cough production, but an anti-σ factor, BspR/BtrA, of B. bronchiseptica regulates the production of unknown cough-causing bacterial factor(s). Our results provide important clues to understand the mechanism by which Bordetella induces cough., (Copyright © 2019 Nakamura et al.)

The assassin bug, Sphedanolestes impressicollis (Hemiptera: Reduviidae), is widely distributed in East Asia. It is an ideal model for evaluating the effects of climatic fluctuation and geographical events on the distribution patterns of East Asian reduviids. Here, we used two mitochondrial genes and one nuclear gene to investigate the phylogeographic pattern of the assassin bug based on comprehensive sampling in China, Japan, South Korea, Vietnam, and Laos. High levels of genetic differentiation were detected among the geographic populations classified into the northern and southern groups. A significant correlation was detected between genetic and geographical distances. The East China Sea land bridge served as a "dispersal corridor" during Pleistocene glaciation. The estimated divergence time indicated that the northern group may have separated from the eastern Chinese populations when the sea level rapidly rose during the "Ryukyu Coral Sea Stage" and the East China Sea land bridge was completely submerged. Demographic history and ecological niche modeling suggested that appropriate climatic conditions may have accounted for the rapid spread across the Korean Peninsula and Japan during the late Pleistocene. Our study underscores the pivotal roles of the Pleistocene sea level changes and climatic fluctuations in determining the distribution patterns of East Asian reduviids.

Background: Quality indicators (QIs) for primary care are used worldwide. To date, however, the use of QIs to assess the quality of primary care in Japan has not been reported besides diabetes care. Here, we used QIs to evaluate the quality of primary care services provided by local clinics in Japan., Methods: Four primary care clinics participated in the retrospective medical chart review in 2015. To assess primary care quality, we used 18 process-oriented QIs from the Quality Indicators for Primary Care practice in Japan (QIPC-J) those we previously developed by using a modified Delphi appropriateness method, which comprises 39 QIs in five categories (Comprehensive care/Standardized care, Access, Communication, Coordination, and Understanding of patient's background). Adult subjects were selected from among patients who visited each clinic within the previous one year using medical claims data. We collected data by reviewing medical charts, and calculated the quality score for each QI and clinic., Results: A cumulative total of 4330 medical charts were reviewed. The overall quality score was 31.5%. Adherence to QIs ranged from 3.2% to 85.6%. Some quality scores varied substantially between clinics but the overall quality of care among clinics varied less, from 29.2% to 34.0%., Conclusions: The quality of primary care services provided by local clinics in Japan varies by both QI and clinic. Strategies to improve the quality of care are warranted., Competing Interests: The authors have stated explicitly that there are no conflicts of interest in connection with this article.

An alien bamboo leafhopper, Branchana xanthota Li, is recorded from Japan for the first time. Three species of bamboos are recognized as host plants: Phyllostachys bambusoides, Phyllostachys edulis and Pleioblastus simonii.

Objective: We aimed to propose a set of quality indicators (QIs) based on the clinical guidelines for cervical cancer treatment published by The Japan Society of Gynecologic Oncology, and to assess adherence to standard-of-care as an index of the quality of care for cervical cancer in Japan., Methods: A panel of clinical experts devised the QIs using a modified Delphi method. Adherence to each QI was evaluated using data from a hospital-based cancer registry of patients diagnosed in 2013, and linked with insurance claims data, between October 1, 2012, and December 31, 2014. All patients who received first-line treatment at the participating facility were included. The QI scores were communicated to participating hospitals, and additional data about the reasons for non-adherence were collected., Results: In total, 297 hospitals participated, and the care provided to 15,163 cervical cancer patients was examined using 10 measurable QIs. The adherence rate ranged from 50.0% for 'cystoscope or proctoscope for stage IVA' to 98.8% for 'chemotherapy using platinum for stage IVB'. Despite the variation in care, hospitals reported clinically valid reasons for more than half of the non-adherent cases. Clinically valid reasons accounted for 75%, 90.9%, 73.4%, 44.5%, and 88.1% of presented non-adherent cases respectively., Conclusion: Our study revealed variations in pattern of care as well as an adherence to standards-of-care across Japan. Further assessment of the causes of variation and non-adherence can help identify areas where improvements are needed in patient care., Competing Interests: Dr. Hirashima received grant from ONO PHARMACEUTICAL CO., LTD, TAIHO PHARMACEUTICAL CO., LTD, AbbVie, AstraZeneca, TAKEDA PHARMACEUTICAL CONPANY LIMITED, EIZAI CO., LTD during the 36 months prior to publication. Other authors declare that there is no potential conflict of interest relevant to this article., (Copyright © 2018. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology.)

A large-sized assassin bug Agriosphodrus dohrni (Signoret), has been recorded from India, Vietnam, China and Japan. It is one of the potential biological control agents against some important agricultural and forest pests. This species is speculated to have invaded Japan from its native range in China about 60 years ago. We used three mitochondrial gene fragments (COI, Cytb, and ND5) and one nuclear gene fragment (EF-1α) to clarify the invasion history of A. dohrni and assess the effects of geographic events and associated ecological adaptation on the distribution pattern. The native populations of A. dohrni in China are divided into three distinct groups, which might be molded by the Early Pleistocene glaciation event and diverged during the Calabrian Stage. However, consistent with the hypothesis of a recent invasion, extremely low level of genetic variation was detected in the Japanese populations, with only two haplotypes for the combined mitochondrial genes. Both the splits network and the ML/BI phylogenetic trees revealed that haplotypes of Japan were more closely-related to those from eastern China. Therefore, we postulate that there has been only one introduction event, probably from somewhere around the Nanjing (NJ) and Lin'an (LA) populations of eastern China., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Staphylococcus aureus lipase (SAL), a triacylglycerol esterase, is an important virulence factor in S. aureus and may be a therapeutic target for infectious diseases caused by S. aureus. For the purposes of anti-SAL drug development using structure-based drug design, X-ray crystallographic analysis of SAL overexpressed in Escherichia coli was performed. The recombinant protein was purified using a three-step protocol involving immobilized metal-affinity chromatography, cation-exchange chromatography and anion-exchange chromatography flowthrough methods, yielding 40 mg of protein per litre of bacterial culture. Crystals were obtained using the sitting-drop vapor-diffusion technique. Diffraction data to 3.0 Å resolution were collected on the BL44XU beamline at SPring-8 at the zinc peak of 1.2842 Å for SAD phasing. The crystals belonged to space group P4 1 22 or P4 3 22, with unit-cell parameters a = 131.0, b = 131.0, c = 250.6 Å, and are likely to contain four SAL molecules (408 residues) per asymmetric unit.

OBJECTIVE Although heterogeneity in patient outcomes following subarachnoid hemorrhage (SAH) has been observed across different centers, the relative merits of clipping and coiling for SAH remain unknown. The authors sought to compare the patient outcomes between these therapeutic modalities using a large nationwide discharge database encompassing hospitals with different comprehensive stroke center (CSC) capabilities. METHODS They analyzed data from 5214 patients with SAH (clipping 3624, coiling 1590) who had been urgently hospitalized at 393 institutions in Japan in the period from April 2012 to March 2013. In-hospital mortality, modified Rankin Scale (mRS) score, cerebral infarction, complications, hospital length of stay, and medical costs were compared between the clipping and coiling groups after adjustment for patient-level and hospital-level characteristics by using mixed-model analysis. RESULTS Patients who had undergone coiling had significantly higher in-hospital mortality (12.4% vs 8.7%, OR 1.3) and a shorter median hospital stay (32.0 vs 37.0 days, p < 0.001) than those who had undergone clipping. The respective proportions of patients discharged with mRS scores of 3-6 (46.4% and 42.9%) and median medical costs (thousands US$, 35.7 and 36.7) were not significantly different between the groups. These results remained robust after further adjustment for CSC capabilities as a hospital-related covariate. CONCLUSIONS Despite the increasing use of coiling, clipping remains the mainstay treatment for SAH. Regardless of CSC capabilities, clipping was associated with reduced in-hospital mortality, similar unfavorable functional outcomes and medical costs, and a longer hospital stay as compared with coiling in 2012 in Japan. Further study is required to determine the influence of unmeasured confounders.

Objectives: This cross-sectional survey explored the characteristics and outcomes of direct oral anticoagulant (DOAC)-associated nontraumatic intracerebral hemorrhages (ICHs) by analyzing a large nationwide Japanese discharge database., Methods: We analyzed data from 2,245 patients who experienced ICHs while taking anticoagulants (DOAC: 227; warfarin: 2,018) and were urgently hospitalized at 621 institutions in Japan between April 2010 and March 2015. We compared the DOAC- and warfarin-treated patients based on their backgrounds, ICH severities, antiplatelet therapies at admission, hematoma removal surgeries, reversal agents, mortality rates, and modified Rankin Scale scores at discharge., Results: DOAC-associated ICHs were less likely to cause moderately or severely impaired consciousness (DOAC-associated ICHs: 31.3%; warfarin-associated ICHs: 39.4%; p = 0.002) or require surgical removal (DOAC-associated ICHs: 5.3%; warfarin-associated ICHs: 9.9%; p = 0.024) in the univariate analysis. Propensity score analysis revealed that patients with DOAC-associated ICHs also exhibited lower mortality rates within 1 day (odds ratio [OR] 4.96, p = 0.005), within 7 days (OR 2.29, p = 0.037), and during hospitalization (OR 1.96, p = 0.039)., Conclusions: This nationwide study revealed that DOAC-treated patients had less severe ICHs and lower mortality rates than did warfarin-treated patients, probably due to milder hemorrhages at admission and lower hematoma expansion frequencies., (Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Dendritic cells (DC) are antigen-presenting cells that connect the innate and adaptive immune system to ensure an efficient immune response during the course of an infection. Recently, DC came into the spotlight as a potential source of osteoclast progenitors, especially under (auto)inflammatory conditions. The virulence factor Pasteurella multocida Toxin (PMT) causes atrophic rhinitis in pigs, a disease characterised by a severe reduction of nasal bone. Our group and others have shown the potential of PMT in mediating differentiation of monocytes/macrophages into bone-resorbing osteoclasts. However, whether DC are target cells for PMT-induced osteoclast differentiation, is currently unknown. Using different murine DC model systems, we investigated the ability of PMT to induce osteoclast formation in DC. Similar to our previous observations in macrophages, PMT was endocytosed by DC and triggered intracellular deamidation of residue Q209 of the Gq alpha subunit. Still, PMT failed to induce prolonged secretion of osteoclastogenic cytokines and osteoclast formation; instead PMT-treated DC secreted interleukin-12 (IL-12), an inhibitor of osteoclastogenesis. In this study, we show that in comparison to bone marrow-derived macrophages, PMT induces maturation of DC through increased expression of the activation markers CD80 and CD86. As maturation of DC prevents their transdifferentiation into osteoclasts, we hypothesize that PMT, a potent osteoclastogenic toxin, fails to trigger osteoclastogenesis in DC due to its effect on DC maturation and IL-12 production., (Copyright © 2017 Elsevier GmbH. All rights reserved.)

Background: Although the Brain Attack Coalition recommended establishing centers of comprehensive care for stroke and cerebrovascular disease patients, a scoring system for such centers was lacking. We created and validated a comprehensive stroke center (CSC) score, adapted to Japanese circumstances., Methods: Of the selected 1369 certified training institutions in Japan, 749 completed an acute stroke care capabilities survey. Hospital performance was determined using a 25-item score, evaluating 5 subcategories: personnel, diagnostic techniques, specific expertise, infrastructure, and education. Consistency and validity were examined using correlation coefficients and factorial analysis., Results: The CSC score (median, 14; interquartile range, 11-18) varied according to hospital volume. The five subcategories showed moderate consistency (Cronbach's α = 0.765). A strong correlation existed between types of available personnel and specific expertise. Using the 2011 Japanese Diagnosis Procedure Combination database for patients hospitalized with stroke, four constructs were identified by factorial analysis (neurovascular surgery and intervention, vascular neurology, diagnostic neuroradiology, and neurocritical care and rehabilitation) that affected in-hospital mortality from ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The total CSC score was related to in-hospital mortality from ischemic stroke (odds ratio [OR], 0.973; 95% confidence interval [CI], 0.958-0.989), intracerebral hemorrhage (OR, 0.970; 95% CI, 0.950-0.990), and subarachnoid hemorrhage (OR, 0.951; 95% CI, 0.925-0.977), with varying contributions from the four constructs., Conclusions: The CSC score is a valid measure for assessing CSC capabilities, based on the availability of neurovascular surgery and intervention, vascular neurology, diagnostic neuroradiology, and critical care and rehabilitation services.

Objectives: To elucidate the association between antiplatelet use in patients with non-haemorrhagic moyamoya disease before hospital admission and good functional status on admission in Japan., Design: Retrospective, multicentre, non-randomised, observational study., Setting: Nationwide registry data in Japan., Participants: A total of 1925 patients with non-haemorrhagic moyamoya disease admitted between 1 April 2012 and 31 March 2014 in Japan., Main Outcome Measure: We performed propensity score-matched analysis to examine the association between prehospital antiplatelet use and no significant disability on hospital admission, as defined by a modified Rankin Scale score of 0 or 1., Results: Propensity-matched patients who received prehospital antiplatelet drugs were associated with a good outcome on hospital admission (OR adjusted for all covariates, 3.82; 95% CI 1.22 to 11.99) compared with those who did not receive antiplatelet drugs prior to hospital admission., Conclusions: Prehospital antiplatelet use was significantly associated with good functional status on hospital admission among patients with non-haemorrhagic moyamoya disease in Japan. Our results suggest that prehospital antiplatelet use should be considered when evaluating outcomes of patients with non-haemorrhagic moyamoya disease., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)