Transcriptome Analysis by RNA Sequencing of Mouse Embryonic Stem Cells Stocked on International Space Station for 1584 Days in Frozen State after Culture on the Ground.

As a space project, in "Stem Cells" by the Japan Aerospace Exploration Agency (JAXA), frozen mouse ES cells were stored on the International Space Station (ISS) in the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) for 1584 days. After taking these cells back to the ground, the cells were thawed and cultured, and their gene expressions were comprehensively analyzed using RNA sequencing in order to elucidate the early response of the cells to long-time exposure to space radiation consisting of various ionized particles. The comparisons of gene expression involved in double-stranded break (DSB) repair were examined. The expressions of most of the genes that were involved in homologous recombination (HR) and non-homologous end joining (NHEJ) were not significantly changed between the ISS-stocked cells and ground-stocked control cells. However, the transcription of Trp53inp1 (tumor protein 53 induced nuclear protein-1), Cdkn1a (p21), and Mdm2 genes increased in ISS-stocked cells as well as Fe ion-irradiated cells compared to control cells. This suggests that accumulated DNA damage caused by space radiation exposure would activate these genes, which are involved in cell cycle arrest for repair and apoptosis in a p53-dependent or -independent manner, in order to prevent cells with damaged genomes from proliferating and forming tumors.

The Impact of Assisted Reproductive Technology on Umbilical Cord Insertion: Increased Risk of Velamentous Cord Insertion in Singleton Pregnancies Conceived through ICSI.

Background and Objectives: Vasa previa (VP) is a significant perinatal complication that can have serious consequences for the fetus/neonate. Velamentous cord insertion (VCI) is a crucial finding in prenatal placental morphology surveillance as it is indicative of comorbid VP. Assisted reproductive technology (ART) has been identified as a risk factor for VCI, so identifying risk factors for VCI in ART could improve VP recognition. This study aims to evaluate the displacement of umbilical cord insertion (CI) from the placental center and to examine the relationship between the modes of conception. Materials and Methods: We conducted a retrospective study at the Obstetrics Department of Osaka Metropolitan University Hospital in Japan between May 2020 and June 2022. The study included a total of 1102 patients who delivered after 22 weeks of gestation. They were divided into three groups: spontaneous pregnancy, conventional in vitro fertilization (cIVF), and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). We recorded patient background information, perinatal complications, perinatal outcomes, and a numerical "displacement score", indicating the degree of separation between umbilical CI and the placental center. Results: The displacement score was significantly higher in the cIVF and IVF/ICSI groups compared with the spontaneous conception group. Additionally, the IVF/ICSI group showed a significantly higher displacement score than the cIVF group. Conclusions: Our study provides the first evidence that the methods of ART can affect the location of umbilical CI on the placental surface. Furthermore, we found that IVF/ICSI may contribute to greater displacement of CI from the placental center.

The Hematopoietic Effect of Ninjinyoeito (TJ-108), a Traditional Japanese Herbal Medicine, in Pregnant Women Preparing for Autologous Blood Storage.

Background and Objectives: There are no reports showing the hematopoietic effect of TJ-108 on pregnant women. The aim of this study was to investigate the effect of TJ-108 on the hemoglobin and hematocrit levels, and white blood cell and platelet counts of pregnant women complicated with placenta previa who were managed with autologous blood storage for cesarean section. Materials and Methods: We studied two groups of patients who were complicated with placenta previa and who underwent cesarean delivery. Group A consisted of women who were treated with oral iron medication (100 mg/day), and Group B consisted of women who were treated with TJ-108 at a dose of 9.0 g per day, in addition to oral iron medication, from the first day of blood storage until the day before cesarean delivery. To evaluate the effect of TJ-108, the patients' red blood cell (RBC); Hb; hematocrit (Ht); white blood cell (WBC); and platelet count (PLT) levels were measured 7 days after storage and at postoperative days (POD) 1 and 5. Results: The study included 65 individuals, 38 in group A and 27 in group B. At the initial storage, a 0.2 g/dL reduction in Hb levels was observed, as compared to the initial Hb levels, in the TJ-108 treated patients, whereas a 0.6 g/dL reduction in Hb levels was observed in the non-TJ-108 treated group. On the other hand, regarding the second and subsequent storages, no significant difference was found in the decrease in the Hb levels of both groups. Conclusions: This study is the first report showing the effect of TJ-108 on improving anemia in pregnant women, presumably by its boosting effect on myelohematopoiesis. Therefore, the combined administration of both iron and TJ-108 is effective as a strategy for pregnant women at a high risk of PPH due to complications such as placenta previa.

Upregulation of PTK7 and ß-catenin after vaginal mechanical dilatation: an examination of fibulin-5 knockout mice.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) in women is associated with deficiency of elastic fibers, and fibulin-5 is known to be a critical protein in the synthesis of elastin. The purpose of this study is to investigate the related pathway for the synthesis of elastin via fibulin-5 using fibulin-5 knockout mice. METHODS: Fibulin-5 knockout mice were generated using the CRISPR/Cas9 system, and vaginal dilatation was used to mimic vaginal delivery. We divided the mice into three groups: Fbln5+/+ mice immediately after dilatation (Fbln5+/+ day0), Fbln5+/+ mice 3 days after dilatation (Fbln5+/+ day3) and Fbln5-/- mice 3 days after dilatation (Fbln5-/- day3). Proteins related to elastogenesis in the vaginal wall were measured by liquid chromatography mass spectrometry (LC-MS/MS) analysis, and differences in the expression of these proteins between the Fbln5-/- mice and the Fbln5+/+ mice were analyzed using western blotting. RESULTS: In the LC-MS/MS analysis, protein tyrosine kinase 7 (PTK7) was not detected in the Fbln5-/- day3 group, although the expression increased by > 1.5 times between the Fbln5+/+ day0 and day3 groups. PTK7 and ß-catenin are known to act in the Wnt/ß-catenin pathway, and both were upregulated after dilatation in the Fbln5+/+ mice, though not in the Fbln5-/- mice. CONCLUSION: Our findings suggest that these proteins are involved in elastogenesis via fibulin-5, and the impairment of these proteins might be the underlying cause of POP manifestation.

Time interval analysis of ductus venosus and cardiac cycles in relation with umbilical artery pH at birth in fetal growth restriction.

BACKGROUND: The aims of this study were to evaluate the time intervals of flow velocity waveforms (FVW) of ductus venosus (DV) and cardiac cycles, as well as the pulsatility index of DV-FVW (DV-PI), in correlation with umbilical artery (UA) pH at birth in fetal growth restriction (FGR) complicated with placental insufficiency. METHODS: Data were retrospectively retrieved from pregnancies complicated by FGR. FGR was defined as an estimated fetal weight below - 2.0 S.D. with an elevated UA-PI. Time interval assessments of DV-FVW were as follows: the duration of systolic wave was divided by the duration of diastolic wave and defined as DV-S/D. We also measured the following time intervals of ventricular inflow through tricuspid valve (TV) and mitral valve (MV): (iii), from the second peak of ventricular inflow caused by atrial contraction (A-wave) to the opening of atrio-ventricular valves and: (iv), from the opening of atrio-ventricular valves to the peak of A-wave. (iii)/(iv) was expressed as TV-S/D and MV-S/D, for TV and MV, respectively. The time interval data were transformed into z-scores. RESULTS: Thirty-one FGR fetuses were included in this study. Both DV-PI and DV-S/D showed significant correlation with UA-pH (r = - 0.677, p = < 0.001 and r = 0.489, p = 0.005 for DV-PI and z-score of DV-S/D, respectively) and more significances were observed in FGR ≤ 28 + 6 gestational weeks (r = - 0.819, p < 0.001 and r = 0.726, p = 0.005, for DV-PI and z-score of DV-S/D, respectively) than in FGR > 28 + 6 gestational weeks (r = - 0.634, p = 0.007 and r = 0.635, p = 0.020, for DV-PI and z-score of DV-S/D, respectively). On the other hand, TV-S/D and MV-S/D showed no significant correlation with UA-pH, although these z-scores indicated significant decreases compared with normal references. CONCLUSIONS: Time interval analysis of DV-FVW might be a valuable parameter, as well as DV-PI, for the antenatal prediction of fetal acidemia in the management of FGR fetuses.

Preliminary evaluation of the short-term outcomes of polytetrafluoroethylene mesh for pelvic organ prolapse.

AIM: Tension-free vaginal mesh (TVM) surgery using synthetic polypropylene (PP) soft mesh had spread rapidly. However, the frequency of mesh-related postoperative complications had increased, and PP was banned in April 2019. In Japan, however, transvaginal surgery using polytetrafluoroethylene (PTFE) mesh had been approved. In this study, we evaluated the clinical outcome and quality of life (QOL) of the postoperative course using PP mesh and PTFE mesh (named "ORIHIME™" ) in a combination surgery for utero-sacral ligament suspension and anterior vaginal support using anterior TVM. METHODS: The vaginal hysterectomy and utero-sacral ligament colpopexy augmented by anterior vaginal mesh implants using PP mesh and PTFE mesh were performed on patients with stage III to IV cystocele and uterine prolapse. The clinical outcome and QOL changes in their postoperative course were evaluated by comparing 15 cases of PP mesh and 13 cases of PTFE mesh. RESULTS: There was no difference between the PP group and PTFE group in characteristics. No mesh-related complications occurred during the follow-up period. With regard to the pelvic organ prolapse quantification (POP-Q) score, no significant difference was found between the two groups. Comparing the postoperative QOL of both groups, the PTFE group had significantly higher values in two domains than PP group (SF-12v2 questionnaire). CONCLUSIONS: We used the world's first PTFE mesh to compare PP mesh with postoperative POP-Q and QOL after the same surgery, with the same operator, and at the same institution. The results showed no significant difference between both mesh materials in the short-term.

Low-dose irradiation of mouse embryos increases Smad-p21 pathway activity and preserves pluripotency.

PURPOSE: To study the outcomes of mouse preimplantation embryos irradiated with low doses of X-rays (≤ 1 Gy) and investigate apoptosis and pluripotency of the irradiated embryos. METHODS: Mouse embryos at the 2-cell stage were collected for in vitro culture. After reaching the 8-cell stage, embryos were irradiated with various low doses of X-rays (0-1 Gy). Blastocysts with a normal appearance were transferred into a pseudopregnant uterus. The developmental rate to blastocysts and the survival rate following embryo transfer were examined. Expression levels of p21, Smad2, Foxo1, Cdx2, Oct4, and Nanog genes were measured by RT-PCR. Apoptotic cells in mouse blastocysts were examined immunofluorescently by staining for cleaved caspase-3. RESULTS: More than 90% of non-irradiated and low-dose X-ray-irradiated preimplantation embryos developed to morphologically normal blastocysts that could be implanted and survive in the uterus. However, embryos irradiated with X-rays had more apoptotic cells in a dose-dependent manner. Expression of p21, Smad2, and Foxo1 genes in X-ray-irradiated embryos was increased significantly, while expression of Cdx2, Oct4, and Nanog genes was maintained in comparison with non-irradiated embryos. CONCLUSIONS: Although irradiated embryos contained apoptotic cells, the low doses of irradiation did not disturb development of 8-cell stage embryos to blastocysts or their survival in utero. The underlying mechanisms might involve anti-apoptotic systems, including the Smad-p21 pathway, and preservation of pluripotency.

Characteristic differences and reference ranges for mitral, tricuspid, aortic, and pulmonary Doppler velocity waveforms during fetal life.

OBJECTIVES: We aimed to construct reference ranges for time intervals of each component of cardiac flow velocity waveforms in normal fetuses, comparing those variables between right and left ventricles. METHODS: In 359 fetuses at the gestational age of 17-38 weeks, the durations of atrioventricular (AV) valve opening (AVVO), AV valve closure (AVVC), total E- (total-E) and A- (total-A) waves, total ejection time (total-ET), acceleration time (acc-E for E-wave, acc-A for A-wave, and acc-ET for ejection time), and deceleration time (dec-E for E-wave, dec-A for A-wave, and dec-ET for ejection time) were studied cross sectionally. RESULTS: Both right and left acc-E showed the strongest correlations with gestational age (r = 0.478 and r = 0.519, respectively). Left AVVO showed a stronger correlation (r = 0.474) than right AVVO (r = 0.282) and, conversely, right AVVC showed a stronger correlation (r = 0.399) than left AVVC (r = 0.195) with gestational age. Significant differences (all P values <0.001) were observed for all right and left parameters other than total-A and acc-E. CONCLUSIONS: Characteristic differences between right and left ventricles were found in the reference ranges, suggesting the developmental properties of the fetal heart. © 2014 John Wiley & Sons, Ltd.

Successful Management of Uterine Prolapse in Pregnancy: A Case Report of Avoiding a Cervical Laceration by the Reduction of Massive Edema.

We report a case of uterine prolapse in pregnancy, which was successfully managed before delivery. A 35-year-old woman (G2P1) complained consistently of a protruding uterus at 36 weeks gestation, and an engorged uterine cervix without tenderness, urinary disturbance, and incontinence were recognized (Pelvic Organ Prolapse Quantification (POP-Q) score C: +7). Manual retraction of the edematous cervix was gently performed with gauze packing, and strikingly improved edema of the cervix with a POP-Q score of C: -2 was observed one day after the gauze packing. Induction of labor was planned due to a suspected large-for-gestational-age infant, and the patient uneventfully delivered at 39 weeks gestation without any obstacles to delivery and cervical laceration. Cervical edema in pregnancy increases the risk of cervical dystocia and cervical lacerations. However, lacerations with edema are predicted to have a poor wound-healing process. The technique with gauze packing presented in this case may be useful in the protective handling of the uterine cervix during pregnancy.

Spontaneous Pregnancy After the Removal of Long-Term Retained Laminaria.

We report the case of a woman with laminaria retention up to six years, followed by spontaneous pregnancy after the removal by hysteroscope of the intrauterine retained laminaria. A 26-year-old woman (G1P0) visited our hospital with complaints of prolonged menstrual bleeding, dyspareunia, and infertility. She had a history of dilatation and evacuation (D&E) at nine weeks of gestation six years earlier. A transvaginal ultrasound showed an artifact, and hysteroscopy revealed a long foreign body, which was suspected to be a laminaria retained after the prior abortion. In the hysteroscopic surgical procedure, the laminaria was cut, and the two halves were excised using resectoscope electrodes and hooked to the electrodes for removal. Thereafter, a year later, she conceived spontaneously and gave birth to a baby by cesarean delivery due to the arrest of labor progress. We are the first to present a pregnant case after the removal of a six-year retained laminaria.

Elevated 12,13-diHOME level in maternal and umbilical cord blood complicated with preeclampsia.

Background: Preeclampsia (PE) is a condition in pregnancy characterized by hypertension and proteinuria, thus leading to severe complications for both mother and fetus, including fetal growth restriction (FGR). However, there are still unclear aspects regarding the pathogenesis, prevention, and treatments. This study aimed to elucidate the characteristics of lipid metabolism in maternal and umbilical cord plasma complicated with PE using liquid chromatography-mass spectrometry (LC-MS). Method: The study included singleton pregnant women at Osaka Metropolitan University Hospital from March 2023 to February 2024. PE was diagnosed based on new-onset hypertension after 20 weeks of gestation and other symptoms such as proteinuria and organ dysfunction. FGR was defined by ultrasound measurements below -1.5 standard deviation (SD). Plasma samples were collected from maternal and umbilical cord blood within 24 hours before delivery. Lipid metabolites were comprehensively analyzed using LC-MS, and the lipokine 12,13-diHOME, identified as elevated in the comprehensive analysis, was quantified. Immunohistochemistry was conducted on placental samples to assess soluble epoxide hydrolase (sEH) expression. Results: The study involved 31 participants, with 20 in the control group and 11 in the PE group. A comprehensive analysis of maternal plasma samples identified a significant increase in 12,13-diHOME levels in the PE group compared to the control group. Quantification of 12,13-diHOME showed a significant increase in maternal plasma, umbilical venous plasma, and umbilical arterial plasma in the PE group compared to the control group (p = 0.007, p = 0.008, p = 0.005). PE with FGR showed significantly higher 12,13-diHOME concentrations in the umbilical arterial/venous ratio compared to the PE without FGR group (p = 0.03). Negative correlations were observed between 12,13-diHOME levels and birth weight in the PE group. Immunohistochemistry did not show significant differences in the sEH expression between the groups. Conclusion: This study demonstrated that 12,13-diHOME levels were significantly elevated in maternal and umbilical cord blood in PE patients, particularly in PE with FGR. Elevated 12,13-diHOME may reflect the progression of placental ischemia due to PE pathogenesis. This lipid metabolite could serve as a marker for the severity of preeclampsia, thus providing new insights into perinatal lipidomics and the potential role of 12,13-diHOME in PE.

Barbed Sutures and Their Potential Role in Reducing Inflammatory Reaction After Cesarean Delivery: A Single-Center Experience.

Objectives The aim of this study was to investigate the short-term outcomes of knotless barbed sutures used for both closures of myometrium and subcuticular tissues in patients with various operative indications and who underwent cesarean delivery (CD) in a single tertiary center. Materials and methods A retrospective cohort study was conducted, and the patients were divided into two groups. The barbed suture group consisted of patients who underwent CD using barbed sutures for uterine closure (0 Stratafix® Spiral PDS Plus, Ethicon, Somerville, NJ, USA) and subcuticular closure (4-0 Stratafix® Spiral PDS Plus). The non-barbed group consisted of patients who underwent CD using monofilament sutures for uterine closure (0-Monocryl®, Ethicon) and subcuticular closure (3-0 Opepolyx®, Alfresa, Tokyo, Japan). Results White blood cell count on post-operative day 1 was statistically lower in the barbed suture group (p=0.01), while there were no other significant differences between the two groups. Conclusion Barbed sutures can be used without major complications in patients who have undergone CD, including high-risk pregnancies.

Transcatheter Arterial Embolization (TAE) Using N-Butyl-2-cyanoacrylate (NBCA) as the First Choice for Postpartum Vulvovaginal Hematoma; Case Series and Reviews of the Literature.

Transcatheter arterial embolization (TAE) has long been reported to be safe, effective, and to have a high clinical and technical success rate for vulvovaginal hematoma. We used a permanent embolic material, diluted N-butyl-2-cyanoacrylate (NBCA), for the first choice intervention for six cases of vulvovaginal hematoma, in order to confirm the effectiveness of NBCA. Regarding post-embolization adverse events, we did not observe any fever nor necrosis or pain in the vaginal wall or vulva, in all cases. The use of NBCA as a first-line treatment for TAE of vulvovaginal hematoma is considered to be effective, in the following two ways: First, hemostasis can be achieved by adjusting the mixing ratio of NBCA and lipiodol, according to the distance between the tip of the catheter and the site of injury. Second, NBCA does not cause complications such as pain, necrosis, or infection, and it can be used safely. There are no reports clearly recommending NBCA as the first choice in the treatment of TAE for vulvovaginal hematoma. This is the first report to examine the efficacy and safety of NBCA as the first-line intervention for such cases.

Changes of Coagulation and Fibrinolytic Status Detected by Thromboelastography (TEG6s®) in Pregnancy, Labor, Early Postpartum, Postpartum Hemorrhage and Heparin Treatment for Perinatal Venous Thrombosis.

The aims of this study are to evaluate coagulation and fibrinolytic features using TEG6s® in normal pregnant courses, in the early postpartum period and in cases with postpartum hemorrhage (PPH) caused by uterine atony. We also analyze cases with deep venous thrombosis (DVT) and/or pulmonary embolism (PE) under treatment with unfractionated heparin. The non-pregnant women (n = 13) and healthy pregnant women (at 9-13 weeks of gestation (n = 13), at 27-30 weeks of gestation (n = 14), at 35-38 weeks of gestation (n = 14)) were cross-sectionally studied, while the normal pregnant women at delivery (n = 14) were sequentially investigated. Blood samples from those patients with PPH (n = 15) and DVT and/or PE (n = 11) were also obtained and compared with those of normal women. Significant changes of clot formation parameters were observed in all parameters and, interestingly, fibrinolytic parameter (LY30) was maintained at a low value even within 120 min after placental delivery (median of LY30; 0) and also in cases with uterine atony (median of LY30; 0.1). The parameter that indicates the effectiveness of heparin showed strong correlation (R = 0.788) with activated partial thromboplastin time. Thromboelastography may be less sensitive to fibrinolysis in the conditions of uterine atonic bleeding.

Preliminary Outcomes of Cervical Cerclage for Shortened Cervix with Decidual Polyp.

The aim of this study was to elucidate the nature of decidual polyp (DP) and to compare DP outcomes treated with cervical cerclage for a shortened cervix with the outcomes of cases treated with cervical cerclage without DP. The medical records of pregnant women who were complicated with cervical polyps were retrospectively reviewed. Cervical cerclage was considered for those cases with a shortened cervical length of under 25 mm and before 25 gestational weeks. We also reviewed pregnant women who had no cervical polyps, and who underwent cervical cerclage during the same study period, and defined them as the control group. A total of 56 pregnant women with cervical polyps were identified. All of the polyps in the 14 cases that had undergone cervical cerclage migrated into the cervical canal. Of the thirty seven cases with cervical polyps that did not necessitate cervical cerclage, eight women delivered preterm and six of these cases were diagnosed as DP. In all of the women studied, polyp migration was observed in 68.6 %. Cervical cerclage was performed significantly earlier in the DP group than in the control group of 46 cases (p < 0.001; 18.4 weeks vs. 21.4 weeks, respectively). Cervical cerclage is effective in DP cases with a shortened cervical length and polypectomy should not be performed during pregnancy because of the risk of miscarriage.

Non-invasive continuous blood pressure monitoring using the ClearSight system for pregnant women at high risks of post-partum hemorrhage: comparison with invasive blood pressure monitoring during cesarean section.

OBJECTIVE: This study aimed to investigate the accuracy and precision of continuous, non-invasive blood pressure obtained using the ClearSight system by comparing it with invasive arterial blood pressure, and to assess the hemodynamic changes using invasive methods and the ClearSight system in patients undergoing cesarean section. METHODS: Arterial pressure was measured invasively with an intra-arterial catheter and non-invasively using the ClearSight system during cesarean section in patients with placenta previa or placenta accreta. Blood pressure measurements obtained using these two means were then compared. RESULTS: Total 1,277 blood pressure measurement pairs were collected from 21 patients. Under Bland-Altman analysis, the ClearSight system demonstrated an acceptable accuracy with a bias and standard deviation of 8.8±13.4 mmHg for systolic blood pressure, -6.3±7.1 mmHg for diastolic blood pressure, and -2.7±8.0 mmHg for median blood pressure. Cardiac index levels were significantly elevated during fetal delivery and 5 minutes after placental removal, and systemic vascular resistance index levels were significantly decreased during fetal delivery and 40 minutes after placental removal. CONCLUSION: In patients undergoing cesarean section, the ClearSight system showed excellent accuracy and precision compared to that of the currently used invasive monitoring system.

Effect of Thrombopoietin Receptor Agonist on Pregnant Mice.

Thrombopoietin receptor agonists (TPO-RAs) are an effective treatment for refractory immune thrombocytopenia (ITP). However, the use of TPO-RAs is limited for ITP in pregnant women due to concerns about fetal toxicity. In this study, we examined the effects of romiplostim, one of the TPO-RAs, on pregnant mice. The mice were injected subcutaneously with romiplostim (1, 5, 10, 30, and 100 µg/kg) on gestational days (GD) 1, 8, and 15. We evaluated maternal and fetal platelet and megakaryocyte counts (MK), fetal weight at birth, placental morphology, and miscarriage rates. Romiplostim increased platelet and MK counts in pregnant mice at all doses and in fetuses at doses above 10 µg/kg. Fetal weight at birth was slightly reduced at a dose of 100 µg/kg, but there were no significant differences in placental weight, spiral artery wall thickness, placental growth factor signal changes, or the rate of resorption at that dosage. The dose of romiplostim used clinically for ITP patients (1-10 µg/kg) did not show any adverse effects on pregnant mice. Although the results of the present study are encouraging, until there are more conclusive data, the use of romiplostim should be evaluated individually in severe, life-threatening cases, and all relevant ethical aspects should be considered.

Comparison of biological measurement and physical estimates of space radiation in the International Space Station.

Nowadays, ordinary people can travel in space, and the possibility of extended durations in an environment such as moon of the Earth and Mars with higher space radiation exposures compared to past missions, is increasing. Until now, the physical doses of space radiation have been measured, but measurement of direct biological effects has been hampered by its low dose and low dose-rate effect. To assess the biological effects of space radiation, we launched and kept frozen mouse embryonic stem (ES) cells in minus eighty degree Celsius freezer in ISS (MELFI) on the International Space Station (ISS) for a maximum of 1,584 days. The passive dosimeter for life science experiments in space (PADLES) was attached on the surface of the sample case of the ES cells. The physical dosimeter measured the absorbed dose in water. After return, the frozen cells were thawed and cultured and their chromosome aberrations were analyzed. Comparative experiments with proton and iron ion irradiation were performed at particle accelerators on Earth. The wild-type ES cells showed no differences in chromosomal aberrations between the ground control and ISS exposures. However, we detected an increase of chromosome aberrations in radio-sensitized histone H2AX heterozygous-deficient mouse ES cells and found that the rate of increase against the absorbed dose was 1.54-fold of proton irradiation at an accelerator. On the other hand, we estimated the quality factor of space radiation as 1.48 ± 0.2. using formulas of International Commission of Radiation Protection (ICRP) 60. The relative biological effectiveness (RBE) observed from our experiments (1.54-fold of proton) was almost equal (1.04-fold) to the physical estimation (1.48 ± 0.2). It should be important to clarify the relation between biological effect and physical estimates of space radiation. This comparative study paves a way to reveal the complex radiation environments to reduce the uncertainty for risk assessment of human stay in space.

Reply to Orsi, M.; Somigliana, E. Incarceration of the Gravid Uterus: Proposal for a Shared Definition. Comment on "Tachibana et al. Incarcerated Gravid Uterus: Spontaneous Resolution Is Not Rare. Diagnostics 2021, 11, 1544".

We appreciate the interest in our paper, and we are grateful for the comment by Orsi et al. [...].