Recognition of pathogen-derived sphingolipids in Arabidopsis.

In plants, many invading microbial pathogens are recognized by cell-surface pattern recognition receptors, which induce defense responses. Here, we show that the ceramide Phytophthora infestans-ceramide D (Pi-Cer D) from the plant pathogenic oomycete P. infestans triggers defense responses in Arabidopsis. Pi-Cer D is cleaved by an Arabidopsis apoplastic ceramidase, NEUTRAL CERAMIDASE 2 (NCER2), and the resulting 9-methyl-branched sphingoid base is recognized by a plasma membrane lectin receptor-like kinase, RESISTANT TO DFPM-INHIBITION OF ABSCISIC ACID SIGNALING 2 (RDA2). 9-Methyl-branched sphingoid base is specific to microbes and induces plant immune responses by physically interacting with RDA2. Loss of RDA2 or NCER2 function compromised Arabidopsis resistance against an oomycete pathogen. Thus, we elucidated the recognition mechanisms of pathogen-derived lipid molecules in plants.

Regulation of nursing professionals in Cambodia: strategies to overcome underpinning challenges.

AIMS: To elucidate (i) the challenges and constraints in the development and implementation of the regulatory framework for nursing professionals in Cambodia and (ii) the specific strategies adopted to address the challenges experienced in Cambodia. INTRODUCTION: The health workforce will be critical to achieving the health-related and wider Sustainable Development Goals in the years up to 2030. BACKGROUND: In 2006, the countries of the Association of Southeast Asian Nations signed a Mutual Recognition Arrangement in relation to nursing services in the region with the main aim of facilitating the mobility of nursing professionals between countries. To ensure the competency of the health workforce and the quality and safety of health services, member states are required to establish an appropriate regulatory framework. METHODS: This is a qualitative descriptive study. Eighteen key informant interviews were conducted in Cambodia in 2018. Walt and Gilson's policy analysis model was applied to organize and synthesize the data. FINDINGS: Major challenges were identified such as conceptual and cultural issues, limited capacity of Cambodian stakeholders and an unstandardized system with limited coordination. DISCUSSION: In Cambodia, the nursing regulatory environment has expanded greatly over the last decade. Strategies adopted were 'political leadership', optimal utilization of 'outsider's capacity', strengthening 'insider's capacity', and 'dedicated consultation and collaboration and consensus building' involving all players. IMPLICATIONS FOR NURSING AND HEALTH POLICIES: Policymakers in similar resource-limited countries could apply and adapt similar strategic efforts when formulating and implementing health policies, legislation and regulations. 'Outsiders', in this case, represented by development partners can play a vital role in the process, but should not be leading the charge. They should be aligned with national priority to support recipient countries. It is imperative for these countries and development partners to invest in increasing the quantity and quality of nursing leaders who can develop and advance regulatory functions.

Visualization of ferroaxial domains in an order-disorder type ferroaxial crystal.

Ferroaxial materials that exhibit spontaneous ordering of a rotational structural distortion with an axial vector symmetry have gained growing interest, motivated by recent extensive studies on ferroic materials. As in conventional ferroics (e.g., ferroelectrics and ferromagnetics), domain states will be present in the ferroaxial materials. However, the observation of ferroaxial domains is non-trivial due to the nature of the order parameter, which is invariant under both time-reversal and space-inversion operations. Here we propose that NiTiO3 is an order-disorder type ferroaxial material, and spatially resolve its ferroaxial domains by using linear electrogyration effect: optical rotation in proportion to an applied electric field. To detect small signals of electrogyration (order of 10-5 deg V-1), we adopt a recently developed difference image-sensing technique. Furthermore, the ferroaxial domains are confirmed on nano-scale spatial resolution with a combined use of scanning transmission electron microscopy and convergent-beam electron diffraction. Our success of the domain visualization will promote the study of ferroaxial materials as a new ferroic state of matter.

Gene Polymorphism of Tacrolimus-Metabolizing Enzymes Associated With Impaired Absorption of Tacrolimus Following Allogeneic Hematopoietic Stem Cell Transplantation: A Case Report.

OBJECTIVE: To elucidate the mechanisms by which orally administered tacrolimus was not absorbed in a patient following allogeneic hematopoietic stem cell transplantation. CLINICAL COURSE: A 17-year-old girl with acute myeloid leukemia underwent HLA-haploidentical peripheral blood stem cell transplantation following fludarabine, busulfan, and total-body irradiation. Graft-vs-host disease prophylaxis was post-transplant cyclophosphamide, followed by intravenous tacrolimus and mycophenolate mofetil. When tacrolimus was switched to oral administration, its blood level declined rapidly, resulting in development of acute graft-vs-host disease, which was ameliorated by switching back to intravenous administration. METHODS/RESULTS: To elucidate if impaired tacrolimus absorption could be related to genetic polymorphism of tacrolimus-metabolizing enzymes, we analyzed gene polymorphisms of cytochrome P450 3A4, cytochrome P450 3A5, and multidrug resistance 1 (MDR1). The patient had wild-type cytochrome P450 3A4 (*1/*1) and variant-type cytochrome P450 3A5 (*3/*3), while MDR1 genes (2677A/G, 3435C/C) were wild-type. CONCLUSION: Wild-type MDR1 gene product P-glycoprotein expressed in the intestine reduces drug absorption from the gastrointestinal tract and may have contributed to low blood levels of tacrolimus in this patient when tacrolimus was orally administered.

The importance of accounting for testing and positivity in surveillance by time and place: an illustration from HIV surveillance in Japan.

The number of tests performed is an important surveillance indicator. We illustrate this point using HIV surveillance data, focusing on Tokyo and Okinawa, two prefectures with high HIV notification rates in Japan. Restricting to data reported from local public health centres and affiliate centres where testing data are accessible, we assessed HIV surveillance data during 2007-2014, based on the annual HIV notification rate (per 100 000 population), HIV testing rate (per 100 000 population) and proportion testing HIV-positive (positivity). Nationally, testing activity and positivity showed an inverse relationship; in 2008, the testing rate peaked, but positivity was lowest. While notification rates were higher for Tokyo (median = 0.98, range = 0.89-1.33) than Okinawa (median = 0.61, range = 0.42-1.09), Okinawa had slightly higher testing rates (median = 187, range = 158-274) relative to Tokyo (median = 172, range = 163-210). Positivity was substantially lower in Okinawa (median = 0.34%, range = 0.24-0.45%) compared with Tokyo (median = 0.57%, range = 0.46-0.67%). Relative to the national testing rate (median = 85, range = 80-115) and positivity (median = 0.34%, range = 0.28-0.36%), Tokyo had higher positivity, despite more testing. In 2014 in Okinawa, all three indicators increased, providing a strong reason to be concerned as positivity increased despite more testing. Together with other information, accounting for testing and positivity improve interpretation of surveillance data to guide public health assessments.

Talbot interferometry for imaging two-dimensional electron density distribution over discharge plasma with higher sensitivity.

The basic properties of a Talbot interferometer implementing pinhole arrays were experimentally and numerically investigated for the improvement of measurement sensitivity of laser wavefront sensors utilized for electron density imaging over discharge plasmas. A numerical simulation using a plane wave decomposition method indicated that the pinhole arrays with a pitch of 300 µm and a pinhole diameter of 150 µm were most suitable for the measurement of the millimetre-scale discharge plasmas, in consideration of the spatial resolution and measurement accuracy. The plane wave decomposition simulation expected that the measurement sensitivity of the 8th-Talbot-length interferometer could be improved by a factor of 4 compared with the previously developed Shack-Hartmann type laser wavefront sensors, which was experimentally verified by the self-image behavior of the pinhole arrays. The Talbot interferometric system was successfully used for electron density imaging over the vacuum arcs generated between a 3-mm gap. The electron density image observed by the Talbot interferometers was in excellent agreement with that visualized by the previously developed Shack-Hartmann sensors. The practical notification for the pinhole array fabrication was also presented.

Follow-up study of symptomatic submucous fibroids after hysteroscopic myomectomy.

PURPOSE OF INVESTIGATION: This study aimed to estimate the effectiveness of hysteroscopic myomectomy for symptomatic submucous uterine fibroids and to identify prognostic factors for persistent or recurrent symptoms. MATERIALS AND METHODS: A total of 237 patients who underwent hysteroscopic myomectomy were divided into three groups according to the classification of the European Society for Gynaecological Endoscopy: Type 0 (n=116), Type I (n=97), and Type II (n=24). Medical records and videotape records of all patients were retrospectively reviewed. RESULTS: Improvement of symptoms was achieved in 100% of Types 0 and I, and 66.7% of Type II. The five-year cumulative symptom-free rates after hysteroscopic myomectomy were 96.7% ± 1.9%, 87.8% 6.7%, and 44.5% ± 12.7% in Types 0, I, and II, respectively. The mean symptom-free periods were 46.2 ± 2.6, 47.7 ± 2.7, and 24.7 ± 6.3 months in Types 0, I, and II, respectively. Logistic regression analysis showed that co-existence of other myomas and Type II were independent prognostic factors for recurrence of symptoms. CONCLUSION: Type I fibroids are a good indication for hysteroscopic myomectomy. In Type II, some patients feel that their symptoms improve, but this curative effect could be temporary.

The relation between causes and onset time of polyhydramnios.

The aim of this analysis was to investigate the onset time and significance of maximum volume of polyhydraminios and whether the tter was associated with causes. This was a retrospective cohort study between 2012 and 2014. A total number of 68 singleton pregancies were analyzed. Gestational age at onset of polyhydramnios was 30.0 ± 2.8 (25-36) weeks in maternal factor, 30.0 ± 3.5 (25- 7) weeks in fetal factor, and 32.3 ± 2.0 (27-37) weeks in idiopathic factor. Median of maximum amniotic fluid index (AFI) was gnificantly late onset in idiopathic factor. Diabetes, gestational or pre-existing, was present in all of women (ten cases) in maternal facror. Higher AFI was found to be associated with an increased frequency of prenatally detected congenital anomalies. Abnormal fetal kary- type noted in 18/45 (40%) cases of polyhydramnios. Polyhydramnios diagnosed on ultrasound requires further maternal and fetal iagnostic tests.

Histologic chorioamnionitis prevalence in patients with premature rupture membranes.

This was a retrospective cohort study between 2002 and 2011. A total number of 150 singleton pregnancies with preterm premature rupture of membranes (PROM) (before 34 weeks) were analyzed. Histological chorioamnionitis (Blanc grade III) was significantly increased over three days from onset of premature rupture of membranes. The positive relationship was strengthened (odds ratios, 3.5; 95% confidence intervals, 1.5-5.2) over three days from onset of preterm PROM. PROM is a risk factor important for histological chorioamnionitis. To avoid neonatal infection, early termination is recommended in preterm PROM patients.

Retroperitoneal leiomyosarcoma: a case report.

Retroperitoneal leiomyosarcoma is a relatively rare and aggressive tumor. Because of its rarity, it is difficult to arrive at a definite diagnosis preoperatively and to design an effective strategy. Here the authors report a case of peritoneal leiomyosarcoma in which diagnosis was difficult because the clinical course resembled that of ovarian cancer. A 77-year-old woman diagnosed with ovarian cancer underwent laparotomy. The excised tumor contained a necrotic polypoid mass that histologically displayed the features of leiomyosarcoma. The patient received adjuvant chemotherapy with a combination of gemcitabine and docetaxel but died two months after surgery owing to the aggressive behavior of the tumor. Because the preoperative diagnosis in this case was ovarian cancer, arriving at a treatment strategy assuming peritoneal leiomyosarcoma was difficult. If complete surgical resection of tumor is not performed, as in the present case, the prognosis can be extremely poor.

Rupture risk factors of fallopian tubal pregnancy.

The present authors analyzed patients' backgrounds and pre-surgical findings to clarify the risk factors of rupture of fallopian tubal pregnancy. The surgical findings 113 cases were clearly diagnosed as fallopian tubal pregnancy with or without rupture. Twenty-six cases of fallopian tubal pregnancy were ruptured and 87 cases were not ruptured at the time of operation. The risk factors of fallopian tubal rupture were assessed by Chi-square for independence test and multiple regression analysis. Obesity (BMI over 26), prior birth history, social welfare entitlement, ultrasonography findings of fetal heart movement, and pre-surgical serum beta-hCG level more than 3,000 mIU/ml patient were significantly higher risk in fallopian tubal rupture. Fertility treatment patient were at significantly lower risk for fallopian tubal rupture. Higher beta-hCG levels, especially >3,000 mIU/ml is associated with increased risk of fallopian tubal rupture in ectopic pregnancy.

Projecting boreal bird responses to climate change: the signal exceeds the noise.

For climate change projections to be useful, the magnitude of change must be understood relative to the magnitude of uncertainty in model predictions. We quantified the signal-to-noise ratio in projected distributional responses of boreal birds to climate change, and compared sources of uncertainty. Boosted regression tree models of abundance were generated for 80 boreal-breeding bird species using a comprehensive data set of standardized avian point counts (349,629 surveys at 122,202 unique locations) and 4-km climate, land use, and topographic data. For projected changes in abundance, we calculated signal-to-noise ratios and examined variance components related to choice of global climate model (GCM) and two sources of species distribution model (SDM) uncertainty: sampling error and variable selection. We also evaluated spatial, temporal, and interspecific variation in these sources of uncertainty. The mean signal-to-noise ratio across species increased over time to 2.87 by the end of the 21st century, with the signal greater than the noise for 88% of species. Across species, climate change represented the largest component (0.44) of variance in projected abundance change. Among sources of uncertainty evaluated, choice of GCM (mean variance component = 0.17) was most important for 66% of species, sampling error (mean= 0.12) for 29% of species, and variable selection (mean =0.05) for 5% of species. Increasing the number of GCMs from four to 19 had minor effects on these results. The range of projected changes and uncertainty characteristics across species differed markedly, reinforcing the individuality of species' responses to climate change and the challenges of one-size-fits-all approaches to climate change adaptation. We discuss the usefulness of different conservation approaches depending on the strength of the climate change signal relative to the noise, as well as the dominant source of prediction uncertainty.

Viper bite during pregnancy: case report.

Viper bites in pregnant women have rarely been reported thus far. Moreover, there is no consensus regarding the treatment of such cases. In this paper, the authors report the successful treatment of viper bite during pregnancy without using antivenom.

Susceptibility quantitative trait loci for pathogenic leucocytosis in SCG/Kj mice, a spontaneously occurring crescentic glomerulonephritis and vasculitis model.

The spontaneous crescentic glomerulonephritis-forming/Kinjoh (SCG/Kj) mouse, a model of human crescentic glomerulonephritis (CrGN) and systemic vasculitis, is characterized by the production of myeloperoxidase-specific anti-neutrophil cytoplasmic autoantibody (MPO-ANCA) and marked leucocytosis. This study was performed to identify the specific populations of leucocytes associated with CrGN and susceptibility loci for pathogenic leucocytosis. Four hundred and twenty female (C57BL/6 × SCG/Kj) F2 intercross mice were subjected to serial flow cytometry examination of the peripheral blood (PB). Kidney granulocytes and monocytes were examined histopathologically. Linkage analyses were performed with 109 polymorphic microsatellite markers. Correlation studies revealed that increase of the granulocytes, F4/80(+) cells, CD3(+) CD4(-) CD8(-) T cells and dendritic cells (DCs) in peripheral blood (PB) were associated significantly with glomerulonephritis, crescent formation and vasculitis. In kidney sections, F4/80(low) cells were observed in crescent, while F4/80(high) cells were around the Bowman's capsules and in the interstitium. Numbers of F4/80(+) cells in crescents correlated significantly with F4/80(+) cell numbers in PB, but not with numbers of F4/80(+) cells in the interstitium. Genome-wide quantitative trait locus (QTL) mapping revealed three SCG/Kj-derived non-Fas QTLs for leucocytosis, two on chromosome 1 and one on chromosome 17. QTLs on chromosome 1 affected DCs, granulocytes and F4/80(+) cells, but QTL on chromosome 17 affected DCs and granulocytes. We found CrGN-associated leucocytes and susceptibility QTLs with their positional candidate genes. F4/80(+) cells in crescents are considered as recruited inflammatory macrophages. The results provide information for leucocytes to be targeted and genetic elements in CrGN and vasculitis.

Minimum Information about a Cardiac Electrophysiology Experiment (MICEE): standardised reporting for model reproducibility, interoperability, and data sharing.

Cardiac experimental electrophysiology is in need of a well-defined Minimum Information Standard for recording, annotating, and reporting experimental data. As a step towards establishing this, we present a draft standard, called Minimum Information about a Cardiac Electrophysiology Experiment (MICEE). The ultimate goal is to develop a useful tool for cardiac electrophysiologists which facilitates and improves dissemination of the minimum information necessary for reproduction of cardiac electrophysiology research, allowing for easier comparison and utilisation of findings by others. It is hoped that this will enhance the integration of individual results into experimental, computational, and conceptual models. In its present form, this draft is intended for assessment and development by the research community. We invite the reader to join this effort, and, if deemed productive, implement the Minimum Information about a Cardiac Electrophysiology Experiment standard in their own work.

Mesothelin gene expression and promoter methylation/hypomethylation in gynecological tumors.

PURPOSE: Mesothelin is a cell surface glycoprotein that is present on normal mesothelial cells and overexpressed in several cancers. In this study, we investigated the methylation/hypomethylation status in the promoter region of the mesothelin gene in gynecological tumors. METHODS: Forty-four ovarian tumor specimens and 16 cases of uterine endometrial carcinoma, and normal tissue specimens were used. Monoclonal antibody (5B2) was employed for the immunohistochemical analysis. The methylation-sensitive single-nucleotide primer extension (Ms-SNuPE) technique was used to quantify the methylation/hypomethylation status at 20 CpG sites in the mesothelin promoter region. RESULTS: Mesothelin was expressed in 100% of serous cystadenocarcinoma and 100% of serous borderline tumor of the ovary. None of the germ cell tumors and sexcord-stromal tumors was immunoreactive. Fifty percent of endometrial carcinoma was immunoreactive for mesothelin. The average methylation of CpG sites in ovarian tumors ranged from 6-56% (median: 31%) in mesothelin-positive and 13-79% (median: 43%) in mesothelin-negative samples. In endometrial tumors, the average methylation ranged from 5-52% (median: 28%) in mesothlin-positive and from 15-67% (median: 22%) in mesothlin-negative samples. A correlation was found between mesothelin expression and the average methylation/hypomethylation status as well as methylation/hypomethylation status at four of 20 CpG sites in ovarian samples. No correlation was found in endometrial samples. CONCLUSION: We detected diverse levels of methylation/hypomethylation at CpG sites in the mesothelin promoter region in ovarian and endometrial tumors. We speculate that, although methylation/hypomethylation changes may affect its transcription, other mechanisms may synergically operate in tissue-specific expression and tumor-related mesothelin overexpression.

Ruptured cornual pregnancy: case report.

Cornual pregnancy is uncommon among ectopic pregnancies. A diagnosis of cornual pregnancy remains challenging, and rupture of a cornual pregnancy causes catastrophic consequence due to massive bleeding. We report a case of a ruptured cornual pregnancy occurring at 12 weeks of gestation. A 34-year-old woman was suspected of having a left cornual pregnancy at 11 weeks of gestation. Transabdominal ultrasound and magnetic resonance imaging revealed an eccentric localization of a gestational sac containing a viable fetus outside the uterine cavity adjacent to the left uterine cornua. The gestational sac was surrounded with a thin myometrial layer. The patient developed a rupture of the left cornual pregnancy with unstable hemodynamics. She underwent emergency laparotomy, which revealed the ruptured left cornual pregnancy with a hemoperitoneum. Cornual resection was performed. The pathological examination confirmed a ruptured cornual pregnancy.