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Although SARS-CoV-2 can infect human placental tissue, vertical transmission is rare. Therefore, the placenta may function as a barrier to inhibit viral transmission to the foetus, though the mechanisms remain unclear. In this study, we confirmed the presence of the SARS-CoV-2 genome in human placental tissue by in situ hybridization with antisense probes targeting the spike protein; tissue staining was much lower when using sense probes for the spike protein. To the best of our knowledge, this is the first evidence directly indicating inefficient viral replication in the SARS-CoV-2-infected placenta. Additional studies are required to reveal the detailed mechanisms.

Objectives: To investigate the spontaneous outcomes of vascularized retained products of conception (RPOC) detected by ultrasonography after second-trimester abortion, and to identify the predictiv...

Urine bags are commonly used to collect urine samples from neonates. However, the sample can be contaminated by stool, or detachment of the bag due to body movement can lead to failure of the collection. A qualitative urine collection kit containing ten filter papers of 3.2 mm diameter was developed and clinically verified among 138 neonates. During a single diaper change (approximately 3 h), the rate of urine collection was calculated. Urine collection was considered to be successful if any filter paper in the urine collection sheet turned from blue to white. Of the 127 neonates who passed urine, 122 had a change in the filter paper. The urine collection rate was 96%, with changes in all 10 filter papers observed in 98 neonates (80%). Urine collection rate was not influenced by sex (p = 1.00), age at collection (p = 0.72), preterm birth (p = 1.00), low birth weight (p = 0.92), or fecal contamination (p = 1.00). The incidence of dermatitis was not higher than in the group in which urine bags were used (urine collection kit: 2/68 [3%]; urine bag: 5/68 [7%]; p = 0.44). Novel urine collection kits using filter paper can collect samples from neonates safely and with a high probability of success.

The electrochemical behavior of uranium (IV) tetrachloride in ionic liquid–DMF mixture was studied for the first time in order to build a redox flow battery (RFB) using U as an electrode active mat...

Women with congenital amino acid disorders, including maple syrup urine disease (MSUD), are at risk of metabolic crisis at delivery. There are still only a few case reports of maternal MSUD globally, and we are the first to report the successful perinatal management of a woman with classical MSUD in Japan. A healthy baby was delivered by scheduled cesarean section despite the presence of several uterine fibroids. With precise diet therapy and accurate preparation, she completed the postpartum period without metabolic decompensation. Although her clinical outcome was favorable, she experienced hypoproteinemia at delivery because the available branched-chain amino acid-free medical food did not contain sufficient protein to meet the recommended nutrient intake. Therefore, this case also indicates a potential issue regarding a shortage of variations in specific amino acid-free medical food in Japan, which should be addressed to achieve a better nutrient status of adults with MSUD and other amino acid disorders.

Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV), high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy is available for CIN2-3 treatment. This study is a placebo-controlled randomized clinical trial of GLBL101c treatment for CIN2 in 40 patients with HPV16-positive CIN2 who were 1:1 randomized to receive GLBL101c (1 g/daily) or placebo for 5 days at 1, 2, 4, and 8 weeks. No differences were noted between the GLBL101c and placebo groups for patient background and adverse events. Moreover, no statistically significant difference was noted between the two groups at the primary endpoint, pathological regression after 16 weeks of the first oral dose, however, only in the GLBL101c group, two patients had complete regression (CR, regression to normal within 16 weeks). IFNγ production was significantly correlated with the number of spots identified by the interferon gamma enzyme-linked immunospot (IFNγ-ELISPOT) assay using cervical lymphocytes (CxLs) or peripheral blood mononuclear cells. In the two cases of CR, E7-specific Th1 immune responses were observed at week 16. Therefore, we concluded as a novel Lactobacillus-based vaccine with stronger immunogenicity than GLBL101c should be developed.

Background: X-ray pelvimetry is used for evaluation of pelvic inlet generally to diagnose cephalopelvic disproportion (CPD) or contracted inlet. Cesarean section delivery (C/S) is often performed for labor dystocia without CPD or contracted inlet. Here, we examined whether X-ray pelvimetry is useful to decide on mode of delivery in women with dystocia.Method: A total of 1118 pregnant women received X-ray pelvimetry before or during labor. Overall, 205 women with cesarean deliveries for indications except for dystocia were excluded. The remaining 913 women undergoing induction/augmentation were retrospectively investigated. Obstetrical and maternal variables were analyzed by univariate, multivariate or ROC analysis.Results: Among 913 women, 37 (4%), including three with contracted inlet and seven with CPD, gave birth by C/S, whereas 876 gave birth by vaginal delivery. Low maternal height, older age, small obstetrical conjugate, large weight and infant head size were significantly associated with risk of C/S for dystocia. Multivariate analysis revealed that the obstetrical conjugate was an independent variable for risk of C/S. The area under the ROC curve (AUC) and the optimal cut-off values, respectively, were as follows: obstetrical conjugate: 0.68 and 11.7 cm (odds ratio=4.27), transverse diameter: 0.59 and 11.4 cm (odds ratio=1.82), maternal height: 0.70 and 155.5 cm (odds ratio=4.33), and maternal weight before pregnancy: 0.55 and 49.7 kg (odds ratio=1.98).Conclusion: The obstetrical conjugate was an independent variable associated with risk of C/S for dystocia. Additionally, maternal height was comparable to the conjugate in term of diagnostic ability. Our data suggested that routine X-ray pelvimetry was not beneficial to identify women at risk of C/S for dystocia.

Aim Although the procedure of abdominal trachelectomy has been remarkably improved, preventing subsequent cervical stenosis remains challenging. In this study, we analyzed the clinicopathological risk factors for cervical stenosis to explore the appropriate surgical procedures for the prevention of cervical stenosis following trachelectomy. Methods Thirty-two patients who underwent abdominal extended and radical trachelectomy were assessed retrospectively (median follow-up period = 33 months). To evaluate the risk factors, the clinicopathological factors were analyzed by univariate and multivariate analyses. The reconstructed uterine length (UtL), that is, the length between the vaginal end of the neo-cervix and the uterine fundus, was measured by transvaginal ultrasound after surgery. The cut-off value for the UtL was assessed by a receiver operating characteristic (ROC) curve analysis. Results Cervical stenosis of any grade was observed in 12 patients (grade 1 = 9, grade 3b = 3). Among the various clinicopathological factors, the UtL and cervical length (CL) were significantly related to cervical stenosis following trachelectomy. The multivariate analysis revealed that the UtL, but not CL, is an independent risk factor for stenosis. The ROC curve analysis revealed that stenosis was significantly more likely to occur in patients with a UtL shorter than 53 mm (area under the ROC curve = 0.902). UtL in the patients who became pregnant was longer than that in the patients who did not. No evidence of recurrent cancer was observed during the follow-up period. Conclusion Our proposed method may provide a functional reconstructed uterus with preserving fertility by remaining UtL more than 53 mm.

Background: Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated.Methods: In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes—HPV 16, 18, 52, and 58—were investigated.Results: The detection rate of E6/E6* increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1.Conclusions: We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis.

The chemical behaviors of lead (Pb) based coolants in the air ingress accident of fast reactors were investigated by means of the thermodynamic considerations and the static oxidation experiments for Pb alloys at various chemical compositions. The results of the static oxidation tests for lead-bismuth (Pb-Bi) alloys indicated that Pb was depleted from the alloy due to the preferential formation of PbO in air at 773K. Bi was not involved in this oxidation procedure. Pb-Bi oxide and Bi2O3 were formed after the enrichment of Bi in the alloys due to the Pb depletion. The thickness of the oxide layer formed on liquid LBE at static condition was approximately 1mm. The oxidation rates of the alloys were much larger than that of the steels, and became larger with higher Pb concentration in the alloys. The compatibility of Pb-Bi alloys with stainless steel was worse when the Pb concentration in the alloys became low, since the dissolution type corrosion was promoted by the Bi composition in the alloy. The Pb-Li alloys were oxidized as they formed Li2PbO3 and Li2CO3. Then, Li was depleted from the alloy. These oxides of the coolant can be generated in the low temperature region of the reactor system after the increase of oxygen concentration in the coolant system in the air ingress accident.

Implantation is essential for successful reproduction. In humans, uterine receptivity is restricted to the mid-secretory phase, days 19 to 24 of the menstrual cycle; and this period is called the window of implantation (WOI). Large populations of decidual leukocytes infiltrate the implantation site, and the levels of cytokines, prostaglandins (PGs), and leukocytes are up-regulated in the endometrium during implantation. Implantation is like a local wound healing process which is characterized by a strong Th1, pro-inflammatory response in which high levels of pro-inflammatory cytokines such as IL-6, LIF, IL-8, and TNFα are involved. In addition, cyclooxygenase (COX)-2 expression increases between days 2 to 5, suggesting that PGs are necessary for the process of stromal cell decidualization in early pregnancy. Recently, it was reported that endometrial biopsies taken during spontaneous cycles that preceding IVF treatment improved the rate of implantation, clinical pregnancies, and live births in p...

Placental growth factor (PlGF), abundantly produced from trophoblasts is involved in placental angiogenesis. The regulatory mechanism of its expression is poorly understood. Hypoxia inducible factors (HIFs) are centrally involved in the modulation of cellular function in response to low oxygen conditions. This study aimed to clarify HIF1α and HIF2α expression patterns during cytotrophoblast differentiation into syncytiotrophoblast and the impact of any changes on PlGF expression. HIF proteins were induced remarkably under low oxygen condition (2%). HIF1α expression decreased and HIF2α expression increased when syncytialization of cultured cytotrophoblasts is progressed. Those expression changes of HIF proteins in the process of in-vitro syncytialization was congruent with the immunohistochemical findings in preeclamptic placenta as well as uncomplicated placenta. Low oxygen condition was also associated with reduced PlGF production in syncytializing primary cells and BeWo choriocarcinoma cells. Small interfering RNA-mediated HIF2α knockdown in BeWo cells abrogated hypoxia-associated decreases in PlGF secretion; HIF1α silencing had no significant effect on PlGF secretion. In summary, HIF2α, rather than HIF1α, is most affected by reduced oxygen level during syncytialization and increases in HIF2α trigger a reduction of PlGF production. Our findings suggest new and important connections between HIF proteins and PlGF pathways in the regulation of placental angiogenesis.

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth syndrome that is occasionally associated with hyperinsulinemic hypoglycemia (HH) in the neonatal period. Sotos syndrome (SS) and Kabuki syndrome (KS) are other malformation syndromes that may be complicated with HH, however, the detailed clinical characteristics of HH accompanied with these syndromes remain unclear. We herein conducted a nationwide questionnaire survey in Japan. We sent a primary questionnaire concerning the clinical experience for these syndromes to 347 perinatal care institutions. As a result, 222 departments or hospitals returned the questionnaires and the total numbers of BWS, SS, and KS patients were 113, 88, and 51, respectively. We sent a secondary questionnaire to 31 institutions where patients with these syndromes presented with HH during infancy. The secondary questionnaires were returned from the institutions and the numbers of patients were 16 for BWS, 9 for SS, and 3 for KS, respectively. Then, we compared the clinical characteristics of infants suffering from transient HH with and without these dysmorphic syndromes. As a result, BWS, SS, and KS patients showed significantly larger body size, lower Apgar scores, higher insulin levels at HH, and shorter durations of HH than non-dysmorphic infants with transient HH. We propose that a careful observation for the signs of HH, even if not specific to the syndromes, is important for the diagnosis of patients with BWS, SS, and KS in the postnatal period. © 2016 Wiley Periodicals, Inc.

金沢大学医薬保健研究域医学系, Background: Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epidemiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated. Methods: In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes-HPV 16, 18, 52, and 58-were investigated. Results: The detection rate of E6/E6*increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1. Conclusions: We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis. © 2020 The Author(s).

Therapeutic HPV vaccine is an agent to induce E7-specific Th1 immune responses to treat cervical neoplasia (CIN2-3). Our previous clinical trial has demonstrated that oral administration of HPV16 E7-expressing Lactobacillus casei (L. casei), GLBL101c, resulted in the regression of HPV16-related CIN3. Here we examined optimization of the E7-expressing L. casei for induction of the mucosal immune responses to E7. Various doses of HPV16 E7 molecule were displayed on the L. casei. Immunization with E7-bound L. casei showed the induction of E7-specific mucosal IFNγ-producing cells was dependent on displayed E7-doses but saturated beyond 0.3 μg/108 cells. A new agent, L. casei with endogenous expression of E7 (IGMKK16E7), showed the optimal amount of displayed-E7. Immunization with IGMKK16E7 demonstrated 4-fold higher induction of E7-specific mucosal IFNγ-producing cells when compared with the former one. Our new system provided the optimal E7-expressing L. casei for displayed-E7 amount and induction of mucosal Th1 immune response.

Background/Aim: We demonstrated that AT1 and AT2 are expressed and both pathways balance the renin-angiotensin system in endometriosis. MAS1, a specific receptor of angiotensin (1–7), opposes AT1 pathway-associated tissue remodelling. It is not known whether MAS1 has an effect on the pathogenesis of endometriosis or not. Materials and Methods: Ovarian endometriotic tissues (endo-Ov) and eutopic endometrial tissues (endo-Em) were obtained from 29 patients with endometrial cysts. Normal endometrial tissues (cont-Em) were obtained from patients without endometriosis. Immunohistochemical staining was performed for MAS1, AT1 and AT2 in the endometriosis-associated tissues. The mRNA levels of these receptors were examined by quantitative reverse transcription PCR. Results: MAS1 was immune-positive at the apical side of the glandular epithelium in the endometriotic lesions. The MAS1 mRNA levels in endo-Ov were increased significantly, irrespective of the menstrual cycle phase. The MAS1 mRNA levels were significantly higher in the proliferative-tissues of the endometriosis patients than in those of the controls. The ratio of the MAS1 to the AT1 mRNA in the proliferative tissues was increased predominantly in the endometriosis patients compared with that in the controls. Conclusion: High MAS1 expression in the endometrium might promote the initiation of endometriosis via migration of proliferative tissue.

Cancer cell metabolism is currently considered to be context dependent, and metabolic reprogramming is being widely investigated. It is known that ovarian cancer often metastasizes to the omentum. Given that the omentum itself contains a high concentration of adipocytes, ovarian cancer is thought to be a good model for research into metabolic reprogramming (particularly the shift to lipid metabolism). The present study investigated the switch to lipid metabolism in the metabolic reprogramming of ovarian cancer cells. The present study first considered the possibility of epigenetic involvement. Using an open database (GSE 85293 and GSE2109), the methylation status and gene expression patterns of the primary tumor site (ovary) and the metastatic tumor site (omentum) were compared. However, no evidence was obtained regarding the involvement of epigenetics (at least in terms of DNA methylation). The influence of suspension in ascites on metabolism was then considered, and a suspension culture was used as an in vitro model. It was demonstrated that ovarian cancer cells that are detached from the primary site and suspended in ascites have enhanced lipid metabolism. Additionally, it was demonstrated that these cells express high levels of the cancer stem cell (CSC) marker cluster of differentiation 44 and c-kit in a balanced manner as they approach the omentum. Accordingly, these cells activate the mammalian target of rapamycin pathway, which is thought to be advantageous for cancer cell metastasis. In conclusion, the present study proposed one explanation for why ovarian cancer cells are likely to disseminate to the peritoneal cavity, and in particular to the omentum.

To evaluate the potential impact of adenomyosis on the pregnancy outcomes by retrospectively investigating adenomyosis-complicated pregnancy cases.We performed a retrospective case-control study. Forty-nine singleton pregnancy cases complicated with adenomyosis were included in this study. The controls (n = 245) were singleton pregnant women without adenomyosis and were frequency matched to adenomyosis cases by age, parity, and the need for assisted reproductive technology for this conception. The incidence of obstetrical complications and delivery and neonatal outcomes were examined.Patients in the adenomyosis group were significantly more likely to have a second trimester miscarriage (12.2% versus 1.2%, odds ratio (OR): 11.2, 95% confidence interval (95% CI): 2.2-71.2), preeclampsia (18.3% versus 1.2%, OR: 21.0, 95% CI: 4.8-124.5), placental malposition (14.2% versus 3.2%, OR: 4.9, 95% CI: 1.4-16.3), and preterm delivery (24.4% versus 9.3%, OR: 3.1, 95% CI: 1.2-7.2), compared with the control group.Adenomyosis was associated not only with an increased incidence of preterm delivery, as previously reported, but also with an increased risk of second trimester miscarriage, preeclampsia, and placental malposition, which could lead to poor perinatal outcomes.

We investigated the effect of radiolysis on pit initiation of zircaloy-2 in water containing sea salt. Changes in the composition of water containing sea salt were analyzed as well, both before and after gamma-ray irradiation. The characteristics of the resultant oxide films formed on zircaloy-2 were evaluated by X-ray photoelectron spectroscopy and electrochemical impedance spectroscopy. The experimental results showed that the pitting potential under irradiation was slightly higher than that under conditions in which no radiation was present, and that the pitting potential decreased with increasing chloride concentration in the presence as well as the absence of radiation. Solution analyses for water containing sea salt showed that hydrogen peroxide was generated by irradiation. The oxide film was composed of zirconium oxide and was made thicker during the irradiation. Under gamma-ray irradiation, the zircaloy-2 surface with an oxide film formed by radiolysis products was found to be resistant to pitting in the presence of chloride., 著者所属: 日本原子力研究開発機構(JAEA)

Dilated cardiomyopathy 1X (CMD1X) is characterized by dilated cardiomyopathy (DCM) with mildest limb-girdle muscle symptoms and normal intelligence. Compound heterozygous mutation in fukutin gene is known as its genetic cause. Here, we report a pregnancy case complicated with CMD1X. A 25-year-old primiparous woman, who had been diagnosed as CMD1X at the age of 19, was referred to our hospital at 6 weeks of gestation. In early pregnancy, the evaluation of her cardiac function showed ejection fraction 47% and NYHA class II. Worsening of cardiac function was observed from 30 weeks, manifesting reduced cardiac load with left ventricular dilatation and in-hospital bed rest was necessary. Elective cesarean section was performed at 35 weeks to prevent deterioration of cardiac function. The parameters of her cardiac function returned to the pre-pregnancy status in a month after delivery, whereas she realized persistent worsening of muscular weakness at postpartum.

The ionic conductivity of solid electrolyte may insufficient, and the sensor output signal will deviate from the theoretical one in low temperature. The performance of oxygen sensor with Ag/air reference electrode (RE) and liquid Bi/Bi2O3 RE was tested in low-temperature LBE at 300°– 450°C and the charge transfer reactions impedance at the electrode-electrolyte interface was analyzed by electrochemical impedance analysis (EIS). After steady state condition, both of the sensors performed well and can be used at 300°– 450°C. Bi/Bi2O3 RE has lower impedance than Ag/air RE. Therefore, the response time of the oxygen sensor with Bi/Bi2O3 RE is faster than the oxygen sensor with Ag/air RE in the low-temperature region.

Amniotic fluid 'sludge' (AFS) is defined as the presence of dense aggregates of hyperechogenic material in close proximity to the internal cervical os. The presence of AFS is an independent risk factor for impending preterm delivery, histological chorioamnionitis, and microbial invasion of the amniotic cavity in patients with spontaneous preterm labor with intact membranes, and preterm prelabor rupture of membranes. We describe a case showing enlarging AFS on transvaginal ultrasound in a patient with impending preterm labor, followed by chorioamnionitis and emergency cesarean section at 28 weeks of gestation, resulting in a severe course of sepsis and recurrent tension pneumothorax in the infant. Such a case has not been reported as far as we know. Based on our case, sonographic findings of enlarging AFS may be a predictor of severe neonatal outcomes in a case with preterm labor even though the maternal symptoms of inflammation are not obvious.

Congenital chloride diarrhea (CLD) is a rare hereditary disease. The basic defect of CLD is massive loss of Cl− and fluid into the ileum and colon. Prenatal diagnosis of this disease is quite important because the infant requires electrolyte supplementation from the early postnatal period. Two cases in which prenatal diagnoses of CLD were made in siblings are reported. Extreme electrolyte imbalance may cause fetal cardiac dysfunction or a poor general condition leading to a non-reassuring fetal status in cases with CLD. Therefore, frequent fetal monitoring using cardiotocograms and ultrasound may be beneficial to some fetuses with CLD to detect fetal deterioration. In addition, repeated amnioreduction may be required to treat severe polyhydramnios and threatened preterm delivery. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound, 2012

The perinatal mortality rate of vasa previa is high if it is not prenatally diagnosed. In this report, a case of vasa previa diagnosed prenatally is presented. Antepartum hemorrhage at 24 weeks of gestation prompted a close investigation of the uterine cervix, internal os, and placenta. We detected a low-lying bilobed placenta with umbilical cord insertion in the lower uterine segment. Furthermore, one of the connecting vessels of the bilobed placenta passed directly above the internal os. Vasa previa was suspected and confirmed with color Doppler and MRI. The fetus was delivered uneventfully by planned Cesarean section at 38 weeks of gestation. It should be considered that placenta previa (including low-lying placenta), bilobed placenta, and umbilical cord insertion in the lower uterine segment are associated with high risk of vasa previa. Ultrasound screening for cord insertion and placenta around the internal os enables efficient and certain detection of vasa previa.

熱処理条件の異なる共析鋼に蓄積した水素量を電気化学的方法を用いて測定した．この方法では昇温分析法に比べて水素量が約30％少なく見積もられた．乾湿1サイクルあたりに蓄積する水素量は0.01から0.1 ppm程度であり，金属組織に依存した．ミクロ組織の異なる鋼に蓄積する水素量はマルテンサイト＞パーライト＞球状化セメンタイトの順に減少した．複数回の連続した乾湿サイクルで蓄積する水素量は1サイクルのときに比べて多くなり，金属組織による違いも大きくなった．