Use of clinical variables for preoperative prediction of lymph node metastasis in endometrial cancer.

OBJECTIVE: Endometrial cancer is the most common gynaecological cancer, and most patients are identified during early disease stages. Noninvasive evaluation of lymph node metastasis likely will improve the quality of clinical treatment, for example, by omitting unnecessary lymphadenectomy. METHODS: The study population comprised 611 patients with endometrial cancer who underwent lymphadenectomy at four types of institutions, comprising seven hospitals in total. We systematically assessed the association of 18 preoperative clinical variables with postoperative lymph node metastasis. We then constructed statistical models for preoperative lymph node metastasis prediction and assessed their performance with a previously proposed system, in which the score was determined by counting the number of high-risk variables among the four predefined ones. RESULTS: Of the preoperative 18 variables evaluated, 10 were significantly associated with postoperative lymph node metastasis. A logistic regression model achieved an area under the curve of 0.85 in predicting lymph node metastasis; this value is significantly higher than that from the previous system (area under the curve, 0.74). When we set the false-negative rate to ~1%, the new predictive model increased the rate of true negatives to 21%, compared with 6.8% from the previous one. We also provide a spreadsheet-based tool for further evaluation of its ability to predict lymph node metastasis in endometrial cancer. CONCLUSIONS: Our new lymph node metastasis prediction method, which was based solely on preoperative clinical variables, performed significantly better than the previous method. Although additional evaluation is necessary for its clinical use, our noninvasive system may help improve the clinical treatment of endometrial cancer, complementing minimally invasive sentinel lymph node biopsy.

Kikuchi-Fujimoto disease during early pregnancy.

Kikuchi-Fujimoto disease (KFD) is rare during pregnancy. It is characterized by necrotizing lymphadenitis and often occurs in young Asian women. We report a case of KFD during pregnancy, which was difficult to diagnose. A 37-year-old pregnant female (gestational week [GW] 7+5) was admitted to our hospital because of hyperemesis gravidarum. On the eighth day of hospitalization (GW 8+6), she suddenly developed a fever (38.0°C) with skin rash and posterior pharynx redness. Blood tests showed pancytopenia and abnormal liver function. The patient was misdiagnosed with severe Epstein-Barr virus infection and administered with prednisolone. Subsequently, cervical lymphadenopathy was observed, and biopsy results led to the diagnosis of KFD. Thereafter, her symptoms improved, and she was discharged at GW 13+4. KFD must be included as a differential diagnosis for patients with fever, abnormal liver function, and pancytopenia during pregnancy.

Application of Synephrine to Grape Increases Anthocyanin via Production of Hydrogen Peroxide, Not Phytohormones.

Global warming has caused such problems as the poor coloration of grape skin and the decreased production of high-quality berries. We investigated the effect of synephrine (Syn) on anthocyanin accumulation. Anthocyanin accumulation in cultured grape cells treated with Syn at concentrations of 1 mM or higher showed no significant difference, indicating that the accumulation was concentration-independent. On the other hand, anthocyanin accumulation was dependent on the compound used for treatment. The sugar/acid ratio of the juice from berries treated with Syn did not differ from the control. The expression of anthocyanin-biosynthesis-related genes, but not phytohormones, was increased by the treatment with Syn at 24 h or later. The Syn treatment of cultured cells increased SOD3 expression and hydrogen peroxide (H2O2) production from 3 to 24 h after treatment. Subsequently, the expression of CAT and APX6 encoding H2O2-scavenging enzymes was also increased. Treatment of cultured cells with Syn and H2O2 increased the expression of the H2O2-responsive gene Chit4 and the anthocyanin-biosynthesis-related genes mybA1 and UFGT 4 days after the treatment and increased anthocyanin accumulation 7 days after the treatment. On the other hand, the treatment of berries with Syn and H2O2 increased anthocyanin accumulation after 9 days. These results suggest that Syn increases anthocyanin accumulation through H2O2 production without changing phytohormone biosynthesis. Syn is expected to improve grape skin coloration and contribute to high-quality berry production.

Diketopiperazine cyclo(-l-Leu-l-Phe) with plant elicitation activity and anti-oomycete activity against Plasmopara viticola.

The aim of this study was to contribute to the reduction of synthetic chemical fungicide application in viticulture by using cyclo(-l-Leu-l-Phe) (cLF) produced by Bacillus subtilis KS1, a candidate for biological control agent. cLF is a diketopiperazine and belongs to the family of 2,5-diketopiperazines. KS1 secreted micromolar levels of cLF into culture medium. Micromolar concentrations of cLF structure-dependently decreased by ∼90% both disease severity and lesion density of downy mildew in grapevine cultivated in a growth chamber. Microscopic observation demonstrated that cLF inhibited Plasmopara viticola haustorium formation by 80% but not zoospore germination on leas disks. Interestingly, millimolar concentrations of cLF induced plant defense response, such as expression of genes encoding chitinase and ß-1,3-glucanase, in grapevine leaves through the salicylic acid and jasmonate signaling pathways. We demonstrated that cLF was a weapon against P. viticola infection. Further evaluation of cLF in field trials is required to uncover its inherent characteristics.

Hysteroscopic resection of retained products of conception combined with uterine artery balloon occlusion: A novel case report.

Retained products of conception can cause massive bleeding that can be prevented by uterine artery embolization before resection; however, uterine artery balloon occlusion is less invasive. While scattered reports of its use for postpartum hemorrhage exist, no indications have been described. We report a case of hysteroscopic resection of retained products of conception using uterine artery balloon occlusion instead of uterine artery embolization. A 29-year-old woman, gravida 2 para 0, noted an intrauterine mass after an abortion at 7 weeks' gestation. Follow-up visits showed insufficient lowering of human chorionic gonadotropin levels, necessitating surgical treatment. Considering the patient's desire to conceive, we performed uterine artery balloon occlusion to reduce the risk of perinatal complications associated with uterine artery embolization. The operation was completed without complications. The patient conceived spontaneously and had a live baby 7 months after surgery, thus proving the benefits of uterine artery balloon occlusion before hysteroscopic resection.

Significance of positive peritoneal cytology for recurrence and survival in patients with endometrial cancer.

AIM: This study aims to examine the association between malignant peritoneal cytology and prognosis in women with endometrial cancer. METHODS: We retrospectively analyzed the records of patients with endometrial cancer who underwent surgery with intraoperative peritoneal cytology at our hospital between January 1988 and December 2012. All results were reclassified according to the 2009 International Federation of Gynecology and Obstetrics (FIGO) system, and the relation between intraoperative peritoneal cytology results and recurrence and prognosis was examined. RESULTS: Of the 908 patients analyzed, 205 (22.6%) had positive peritoneal cytology. Patients with positive peritoneal cytology had significantly lower rates of recurrence-free survival (RFS) and overall survival (OS) than those in the negative cytology group (both p < 0.001). Subgroup analysis of patients with FIGO stage I/II showed significantly lower RFS in the positive-cytology group (p = 0.005), but there was no significant difference in OS (p = 0.637). In the patients with FIGO stage III/IV or patients classified as "high risk," the RFS and OS were significantly lower in the positive-cytology group (both p < 0.001). Cox regression analysis identified positive peritoneal cytology as a significant predictor of recurrence in patients with FIGO stage I/II disease. CONCLUSIONS: Patients with positive peritoneal cytology for endometrial cancer have a high risk of recurrence, regardless of histopathologic type or FIGO stage. Peritoneal cytology has already been removed from the 2009 FIGO classification of endometrial cancer, but it may deserve reconsideration.

Cephalic version by postural management in the lateral position without the knee-chest position for primiparous breech presentation: A retrospective cohort study.

AIM: This study aimed to determine the efficacy of postural management in the lateral position for primiparous breech presentation. METHODS: A retrospective cohort study was conducted at a single institution from January 2020 through December 2020. Participants were singleton primiparous pregnant women diagnosed with breech presentation between 28 + 0 and 29 + 6 weeks of gestation. The exclusion criteria were scheduled cesarean delivery, uterine malformation, transverse position, and scheduled delivery at another hospital. A doctor instructed the women in the intervention group to lie on their right sides several times a day if the fetal back was on the left side or lie on their left sides if the fetal back was on the right side. The knee-chest position and other methods were not recommended. The control group received expectant management care. The primary endpoint was the percentage of fetuses in a cephalic presentation 2 weeks later. RESULTS: Of the 56 women included in the study, 17 women were instructed to lie in the lateral position, and 39 women received expectant management care only. After 2 weeks, women who were instructed to lie in lateral position had a higher rate of fetal cephalic version than the control group (82.4% [14/17] vs. 43.6% [17/39], p = 0.017). No study participants experienced adverse effects. CONCLUSIONS: Two weeks of postural management in the lateral position without the knee-chest position significantly reduced the rate of primiparous breech presentation in the third trimester of pregnancy.

Maternal cell contamination in embryonic chromosome analysis of missed abortions.

AIM: The fetal sample used for embryonic chromosome analysis is often contaminated with maternal cells, making it difficult to evaluate the fetal chromosomes. We examined on the rate of maternal cell contamination and its relationship with maternal information in the embryonic chromosome analysis of missed abortions using the Giemsabanding method. METHODS: Chromosome analysis was performed in 200 cases of delayed miscarriages in first trimester between July 1, 2000 and May 31, 2019. Chorionic villi were collected and were analyzed using the Giemsa banding method. Among the 20 cells for which chromosomal examination was performed, cells wherein 46,XX chromosomes were found together with normal male karyotype or abnormal chromosomes were defined as maternal cell contamination. RESULTS: Of the 200 cases analyzed, 136 had abnormal chromosomes. The normal female karyotype (n = 52) was four times more prevalent than the normal male karyotype (n = 12). Maternal cell contamination was seen in 15.4% of the abnormal chromosome cases and 8.3% of the normal male karyotype cases. There was no significant difference in the gestational age between the contaminated and noncontaminated groups at the time of miscarriage diagnosis. However, miscarriage before fetal heartbeat confirmation was significantly associated with higher maternal cell contamination. CONCLUSION: We found maternal cell contamination in 15% of all the cases. Moreover, in many cases of the normal female karyotype, it was suspected that only maternal chromosomes were cultured. When performing embryonic chromosome analysis in recurrent miscarriages, we should pay attention to maternal cell contamination and interpret the results accordingly.

Clinical guide for women with mental health problems during the perinatal period.

Pregnancy and childbirth have various effects on the physical as well as mental aspects of women. Therefore, appropriate considerations must be given to the mental health of pregnant women. The Guideline Review Committee of the Japanese Society of Psychiatry and Neurology launched a liaison meeting for the Japanese Society of Psychiatry and Neurology and the Japan Society of Obstetrics and Gynecology, with a view to creating a "Clinical guide for women with mental health problems during the perinatal period" by cooperation of these two fields. After repeated discussions with input from both academic societies, they jointly formulated the "Clinical guide for women with mental health problems during the perinatal period: Overview" in May 2020, and reported its "Detailed Contents" in April 2021. We hope that this guide, which is the English overview of the detailed guide, will contribute to the mental health of pregnant women, facilitating healthy pregnancies and childbirth.

Upregulated serum granulysin levels in women with antiphospholipid antibody-associated recurrent miscarriage are downregulated by heparin treatment.

Purpose: Granulysin is a cytotoxic protein that simultaneously activates innate and cellular immunity. The authors aimed to evaluate whether granulysin is associated with the antiphospholipid antibody syndrome and whether heparin changes the granulysin levels. Methods: A cohort study was performed with women with antiphospholipid antibody-positive recurrent pregnancy loss (RPL). The authors examined granulysin levels under RPL and evaluated the changes in serum granulysin levels before and 1 week after the commencement of heparin treatment. Results: Serum granulysin levels before heparin treatment were significantly higher in women who tested positive for one or more types of antiphospholipid antibodies (2.75 ± 1.03 vs. 2.44 ± 0.69, p = 0.0341 by Welch's t test), particularly anti-phosphatidylethanolamine antibodies (IgG: 2.98 ± 1.09 vs. 2.51 ± 0.86, p = 0.0013; IgM: 2.85 ± 1.09 vs. 2.47 ± 0.77, p = 0.0024 by Welch's t test). After heparin treatment for 1 week, serum granulysin levels were significantly reduced (p = 0.0017 by the paired t test). The miscarriage rate was significantly higher in women whose serum granulysin levels were not reduced by heparin treatment (p = 0.0086 by Fisher's exact probability test). Conclusion: The results suggest that heparin may reduce the incidence of miscarriage by suppressing serum granulysin levels.

First report of grapevine rupestris vein feathering virus in Vitis vinifera L. from Japan.

The production of wine grapes is gaining widespread popularity and being carried out on approximately 2,200 hectares of land in Japan. Scions grafted onto rootstocks generally have been imported from the EU, USA, New Zealand, and Australia into Japan. Unfortunately, viruses have spread in Japanese vineyards by slipping through the net of plant quarantine. Grapevine rupestris vein feathering virus (GRVFV), which was detected in a Greek grapevine accessions, is a member of genus Marafivirus in family Tymoviridae (El Beaino et al. 2001). GRVFV has been detected in many countries such as USA, Canada, Australia, New Zealand, Italy, Spain, Switzerland, Czech Republic, Uruguay, and Pakistan (Jo et al. 2015; Eichmeier et al. 2016; Xiao and Meng 2016; Blouin and MacDiarmid 2017; Reynard et al. 2017; Cho et al. 2018; Mahmood et al. 2019; Wu et al. 2020). Herein we report GRVFV infection in Vitis vinifera L. grapevines from Japan. In February 2021, dormant canes from 18 V. vinifera cv. Cabernet Sauvignon with leafroll-like disease symptoms, growing in a vineyard located in Kanagawa Prefecture, were collected. No typical vein banding symptom by GRVFV were observed in the grapevines during the growing season. Total RNA was isolated from the canes using an RNeasy Plant Mini Kit and QIAshredder (Qiagen, Valencia, CA), and subjected to cDNA synthesis using a PrimeScript 1st Strand cDNA Synthesis Kit (Takara Bio, Shiga, Japan). RT-PCR was performed with GRVFV_6156F and GRVFV_6600R primers for GRVFV detection (Reynard et al. 2017). The expected 445 nucleotides (nt) amplification product was obtained from four of 18 grapevines. Sequence analysis of the products revealed 91% identities to corresponding sequences of GRVFV isolates CHASS (KY513702) and Mauzac (KY513701) from Switzerland. Genome walking to determine the whole-genome sequence of the GRVFV isolates from the four grapevines was performed. Briefly, the upstream and downstream of the 445 nt amplification product were amplified from first-strand cDNA using gene-specific primers designed from the product and CHASS-specific primers. Each amplified fragment was Sanger sequenced. Next, gene-specific primers were designed to obtain the complete genome of GRVFV as 13 overlapping DNA fragments from each of the four grapevine samples. An identical complete genome of 6,704 bp was assembled from the overlapping DNA fragments using MEGA 10 software and named as NA1 isolate (DDBJ accession no. LC619667). Phylogenetic analysis of the NA1 genome and corresponding sequences of GRVFV from other countries showed that NA1 formed a cluster with isolate NZ ChTK0004 from New Zealand (MF000326; Supplementary Figure 1). In pairwise comparisons, the complete NA1 genome was most identical at 88% and 87%, respectively to isolates NZ ChTK0004 and Mauzac. The predicted amino acid sequences of NA1 polyprotein shared high homologies (96%) to the corresponding polyprotein sequences of NZ ChTK0004 and Mauzac, suggesting that NA1 is genetically similar to GRVFV isolates from New Zealand and Switzerland. The NA1-infected Cabernet Sauvignon was co-infected with Grapevine leafroll-associated virus 3, Grapevine virus A, and Grapevine rupestris stem pitting-associated virus according to RT-PCR assay for grapevine virus detection (Nakaune and Nakano 2006). The results underscore the importance of intensifying quarantine measures to prevent introduction of exotic viruses via contaminated wine grape vegetative cuttings.

Implementation of nationwide screening of pregnant women for HTLV-1 infection in Japan: analysis of a repeated cross-sectional study.

BACKGROUND: Screening of pregnant women carrying human T-lymphotropic virus type 1 (HTLV-1) has a crucial role in reducing the number of HTLV-1 carriers. A national HTLV-1 screening program for pregnant women was started in 2011 in Japan. The purpose of this study is to report on the implementation of this nationwide screening program. METHODS: This was a retrospective repeated cross-sectional study. We used datasets from surveys of HTLV-1-antibody-positive pregnant women performed by the Japan Association of Obstetricians and Gynecologists in 2011, 2013, and 2016. Outcomes for evaluation included the number of persons (pregnant women) who conducted the screening test, the number of positive persons (women) identified by these tests, and the proportion of positive persons to the number of persons (women) who conducted the tests. RESULTS: Numbers of target facilities changed yearly: 1857 in 2011, 2544 in 2013, and 2376 in 2016. The mean number of screening-test participants increased per facility, but the median increased or decreased. The mean number of positive individuals identified decreased. Multivariate analysis results revealed the number of screenings was slightly reduced yearly, although areas (Kanto and Kinki) and high volume in facility types increased. Regarding the positive rates, some areas (Hokkaido/Tohoku, Kanto, and Chugoku/Shikoku) exhibited decreases or increases by facility type. The number of western blotting (WB) implementations decreased in 2016, positive rates identified by WB decreased in 2016 in all areas, and the number of facility types increased. The number of PCR participants increased in 2016 in Kanto and Kinki, but a decrease in facility type was observed. Positive rates were decreased in all areas (except the central region) but facility types were increased. CONCLUSIONS: The nationwide screening program for HTLV-1 in Japan was almost fully implemented. However, regional variations in screening tests were observed during this implementation. Thus, some incentives are needed to encourage proper implementation across all regions.

Correction to: Implementation of nationwide screening of pregnant women for HTLV-1 infection in Japan: analysis of a repeated cross-sectional study.

An amendment to this paper has been published and can be accessed via the original article.

Cytochrome P450 CYP71BE5 in grapevine (Vitis vinifera) catalyzes the formation of the spicy aroma compound (-)-rotundone.

(-)-Rotundone is a potent odorant molecule with a characteristic spicy aroma existing in various plants including grapevines (Vitis vinifera). It is considered to be a significant compound in wines and grapes because of its low sensory threshold and aroma properties. (-)-Rotundone was first identified in red wine made from the grape cultivar Syrah and here we report the identification of VvSTO2 as a α-guaiene 2-oxidase which can transform α-guaiene to (-)-rotundone in the grape cultivar Syrah. It is a cytochrome P450 (CYP) enzyme belonging to the CYP 71BE subfamily, which overlaps with the very large CYP71D family and, to the best of our knowledge, this is the first functional characterization of an enzyme from this family. VvSTO2 was expressed at a higher level in the Syrah grape exocarp (skin) in accord with the localization of (-)-rotundone accumulation in grape berries. α-Guaiene was also detected in the Syrah grape exocarp at an extremely high concentration. These findings suggest that (-)-rotundone accumulation is regulated by the VvSTO2 expression along with the availability of α-guaiene as a precursor. VvSTO2 expression during grape maturation was considerably higher in Syrah grape exocarp compared to Merlot grape exocarp, consistent with the patterns of α-guaiene and (-)-rotundone accumulation. On the basis of these findings, we propose that VvSTO2 may be a key enzyme in the biosynthesis of (-)-rotundone in grapevines by acting as a α-guaiene 2-oxidase.

Cyclic lipopeptide iturin A structure-dependently induces defense response in Arabidopsis plants by activating SA and JA signaling pathways.

Iturin A is the most well studied antifungal cyclic lipopeptide produced by Bacillus species that are frequently utilized as biological control agents. Iturin A not only shows strong antifungal activity against phytopathogens but also induces defense response in plants, thereby reducing plant disease severity. Here we report the defense signaling pathways triggered by iturin A in Arabidopsis salicylic acid (SA) or jasmonic acid (JA)-insensitive mutants. Iturin A activated the transcription of defense genes PR1 and PDF1.2 through the SA and JA signaling pathways, respectively. The role of iturin A as an elicitor was dependent on the cyclization of the seven amino acids and/or the ß-hydroxy fatty acid chain. The iturin A derivative peptide, NH2-(L-Asn)-(D-Tyr)-(D-Asn)-(L-Gln)-(L-Pro)-(D-Asn)-(L-Ser)-COOH, completely suppressed PR1 and PDF1.2 gene expression in wild Arabidopsis plants. The identification of target molecules binding to iturin A and its derivative peptide is expected to shed new light on defense response in plants through the SA and JA signaling pathways.

Trend analysis of primary midwife-led delivery care at a Japanese perinatal center.

OBJECTIVE: To perform trend analysis of primary midwife-led delivery care for 'low risk' pregnant women at our hospital. METHODS: A retrospective cohort study was performed to examine trends and outcomes of labor under primary midwife-led delivery care at the Japanese Red Cross Katsushika Maternity Hospital between 2008 and 2012. RESULTS: During the study period, the rate of deliveries initially considered 'low risk' decreased from 25 to 22% (p < 0.01). This change was associated with increased cases of previous Cesarean deliveries and preterm delivery. There were no significant changes in the neonatal outcomes; however, the rate of Cesarean delivery and incidence of severe perineal laceration in primary midwife-led delivery care were decreased from 2.1 and 3.3% to 0.3 (p = 0.02) and 1.1% (p = 0.04), respectively due to the close cooperation between midwives and obstetricians. CONCLUSION: The rate of deliveries initially considered 'low risk' decreased over the last 5-year period. Closer cooperation between midwives and obstetricians is important in primary midwife-led delivery care.

Guidelines for obstetrical practice in Japan: Japan Society of Obstetrics and Gynecology (JSOG) and Japan Association of Obstetricians and Gynecologists (JAOG) 2014 edition.

The 'Clinical Guidelines for Obstetrical Practice, 2011 edition' were revised and published as a 2014 edition (in Japanese) in April 2014 by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists. The aims of this publication include the determination of current standard care practices for pregnant women in Japan, the widespread use of standard care practices, the enhancement of safety in obstetrical practice, the reduction of burdens associated with medico-legal and medico-economical problems, and a better understanding between pregnant women and maternity-service providers. The number of Clinical Questions and Answers items increased from 87 in the 2011 edition to 104 in the 2014 edition. The Japanese 2014 version included a Discussion, a List of References, and some Tables and Figures following the Answers to the 104 Clinical Questions; these additional sections covered common problems and questions encountered in obstetrical practice, helping Japanese readers to achieve a comprehensive understanding. Each answer with a recommendation level of A, B or C was prepared based principally on 'evidence' or a consensus among Japanese obstetricians in situations where 'evidence' was weak or lacking. Answers with a recommendation level of A or B represent current standard care practices in Japan. All 104 Clinical Questions and Answers items, with the omission of the Discussion, List of References, and Tables and Figures, are presented herein to promote a better understanding among English readers of the current standard care practices for pregnant women in Japan.