The TGF-ß/UCHL5/Smad2 Axis Contributes to the Pathogenesis of Placenta Accreta.

Placenta accreta is a high-risk condition causing obstetric crisis and hemorrhage; however, its pathogenesis remains unknown. We aimed to identify the factors contributing to trophoblast invasiveness and angiogenic potential, which in turn drive the pathogenesis of placenta accreta. We focused on the transforming growth factor (TGF)-ß1-Smad pathway and investigated the intrinsic relationship between the time- and dose-dependent inhibition of the ubiquitinating enzyme UCHL5 using bAP15, a deubiquitinase inhibitor, after TGF-ß1 stimulation and the invasive and angiogenic potential of two cell lines, gestational choriocarcinoma cell line JEG-3 and trophoblast cell line HTR-8/SVneo. UCHL5 inhibition negatively regulated TGF-ß1-induced Smad2 activation, decreasing extravillous trophoblast invasiveness. Smad1/5/9 and extracellular signal-regulated kinase (ERK) were simultaneously activated, and vascular endothelial growth factor was secreted into the trophoblast medium. However, extravillous trophoblast culture supernatant severely impaired the vasculogenic potential of human umbilical vein endothelial cells. These results suggest that the downstream ERK pathway and Smad1/5/9 potentially regulate the TGF-ß1-Smad pathway in extravillous trophoblasts, whereas Smad2 contributes to their invasiveness. The abnormal invasive and angiogenic capacities of extravillous cells, likely driven by the interaction between TGF-ß1-Smad and ERK pathways, underlie the pathogenesis of placenta accreta.

The role of transperineal ultrasonography for perinatal management: A review.

BACKGROUND: Transperineal ultrasound (TPUS) has become an increasingly popular tool in obstetrics due to its objective, non-invasive, and real-time imaging capabilities. AIM: This review aims to describe the basic approaches, current utilization, and potential future applications of TPUS. MATERIALS & METHOD: A comprehensive literature review on TPUS was conducted. In addition, discussions at academic meetings and congress focused on TPUS were also considered. RESULTS: TPUS was initially used in prostate biopsies and is currently applied to evaluating fetal head descent in labor, with the angle of progression being the most widely used parameter. It is more tolerated than conventional invasive or expensive methods, such as digital vaginal examinations or MRIs. Additionally, TPUS can assess the internal rotation of the fetal head in the birth canal. DISCUSSION: Compared to other imaging modalities like MRI and CT scans, TPUS is easier to perform and more cost-effective. It also provides real-time imaging, allowing for quick and accurate assessments. It also help clinicians make critical decisions regarding the mode of delivery and identify patients at high risk for fecal incontinence postpartum. With its many benefits, TPUS has the potential to become a standard tool in urogynecology and obstetrics. CONCLUSIONS: Transperineal ultrasound is a non-invasive imaging modality that is well-tolerated and easy to understand for patients and their family and help medical staff support the patients. Transperineal ultrasound can be applied in real-time monitoring of labor progress, helping predict the possibility of vaginal delivery during labor, and further research in this area is warranted.

Effect of Different Educational Interventions on Knowledge of HPV Vaccination and Cervical Cancer among Young Women: A Preliminary Report.

The incidence and mortality rates of cervical cancer are rising among young women in Japan. In November 2021, the Japanese Ministry of Health, Labour, and Welfare reinstated the active recommendation for the human papillomavirus (HPV) vaccine, which was discontinued in June 2013 due to reports of adverse reactions, including chronic pain and motor dysfunction, following vaccination. However, vaccine hesitancy among the younger generation remains, and it is essential to identify the barriers in vaccination uptake. Therefore, we aimed to conduct a randomized study using different methods of providing educational contents to improve health literacy regarding cervical cancer and HPV vaccination among female students in Japan. Here, we present the results of our preliminary report and discuss current topics related to HPV vaccination in Japan. Data were collected from 27 female students-divided into three groups: no intervention, print-based intervention, and social networking service-based intervention-using the health literacy scale and communicative and critical health literacy scale. Our primary results indicate that participants' knowledge and health literacy improved post-intervention. Therefore, medical professionals must provide accurate scientific knowledge regarding routine HPV vaccination and the risk of cervical cancer to young women to improve their health literacy and subsequently increase the HPV vaccination rates.

Evaluating the Angiogenetic Properties of Ovarian Cancer Stem-like Cells using the Three-dimensional Co-culture System, NICO-1.

Cancer stem cells (CSCs) reside in a supportive niche, constituting a microenvironment comprised of adjacent stromal cells, vessels, and extracellular matrix. The ability of CSCs to participate in the development of endothelium constitutes an important characteristic that directly contributes to the general understanding of the mechanisms of tumorigenesis and tumor metastasis. The purpose of this work is to establish a reproducible methodology to investigate the tumor-initiation capability of ovarian cancer stem cells (OCSCs). Herein, we examined the neovascularization mechanism between endothelial cells and OCSCs along with the morphological changes of endothelial cells using the in vitro co-culture model NICO-1. This protocol allows visualization of the neovascularization step surrounding the OCSCs in a time course manner. The technique can provide insight regarding the angiogenetic properties of OCSCs in tumor metastasis.

Elevated Expression of Vascular Adhesion Molecule-1, Plasminogen Activator Inhibitor-1, Cyclooxygenase-2, and Thrombomodulin in Human Umbilical Vein Endothelial Cells from Hospitalized Gestational Diabetes Mellitus Patients.

Protein expression in human umbilical vein endothelial cells (HUVECs) is a useful indicator of maternal condition and the intrauterine environment during pregnancy. Therefore, we investigated protein expression in HUVECs obtained from patients with gestational diabetes mellitus (GDM). HUVECs were prepared from the umbilical cords of GDM patients and controls who underwent planned cesarean section between 2013 and 2014 at Teikyo University Hospital (Tokyo, Japan). There were no differences in blood glucose levels between the GDM patients and controls at admission. However, pre-pregnancy body mass index (BMI) was higher in GDM patients, although the changes in gestational BMI were smaller during hospitalization. To evaluate the state of the endothelium, we examined the protein expression levels of vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1, thrombomodulin (TM), endothelial nitric oxide synthase, plasminogen activator inhibitor-1 (PAI-1), cyclooxygenase-2 (COX-2), and VE-cadherin, which are altered by various factors in endothelial tissue. VCAM-1, PAI-1, and COX-2 expression was higher in HUVECs from patients with GDM than the controls. Because the pre-pregnancy BMI was higher in GDM patients, we examined the relationship between BMI and protein expression. However, the expression levels of these proteins were not correlated with pre-pregnancy BMI and were higher in HUVECs from BMI-matched GDM patients than from BMI-matched controls. Intriguingly, TM expression was also higher in HUVECs from BMI-matched GDM patients. Thus, expression of VCAM-1, PAI-1, COX-2, and TM may reflect certain factors in the intrauterine environment that are altered in hospitalized GDM patients with controlled body weight.

Spinal cord infarction in diabetic pregnancy: a case report.

Spinal cord infarction (SCI) is uncommon as compared to cerebral stroke. Moreover, SCI during pregnancy is rare. Here, we report a case of SCI in diabetic pregnancy, properly diagnosed, promptly treated, and a good prognosis achieved. A 38-year-old, pregnant woman, para 1, with type 1 diabetes mellitus on insulin since 14 years of age, was admitted to our hospital for paresthesia and numbness in the lower left side of the body, with movement disturbances. On the basis of the temporal profile of the onset and the multiple resonance imaging scans, SCI was diagnosed. Steroid pulse therapy and low-dose aspirin administration was initiated. Her symptoms were improved and discharged. A repeat cesarean section was performed at 37 weeks of gestation and her postoperative course was uneventful. Her daily activities were not hindered severely, though she experienced defecation discomfort.

Erythematous and bullous rash strongly indicating toxic epidermal necrolysis associated with the use of intravenous ritodrine hydrochloride.

Toxic epidermal necrolysis (TEN) is a very rare drug reaction associated with a high mortality rate. This condition warrants prompt recognition, diagnosis and treatment. Only one case report of TEN that was possibly induced by ritodrine hydrochloride, a tocolytic agent, was found in English literature. Here, we report the case of a 26-year-old pregnant woman who was suspected with TEN following the intravenous administration of ritodrine hydrochloride in the 35(th) week of gestation. An emergency cesarean section was performed because the labor pains caused systemic intolerable haphalgesia. After the surgery, intensive dermatological treatment commenced, which helped her recover from the serious condition. The result of the drug-induced lymphocyte stimulation test for ritodrine hydrochloride was positive. When a skin eruption appears during the administration of ritodrine, we must consider the benefits as well as the risks of continuous use of tocolytic agents because there is a risk of Stevens-Johnson syndrome or TEN.

Endoluminal ultraflex stent for palliative treatment of malignant rectosigmoidal obstruction.

Rectosigmoidal obstruction due to a malignant tumor usually requires emergency surgical treatment, and colostomy is usually inevitable. This report describes our experience with the use of endoluminal self-expanding metallic stents in the treatment for rectosigmoidal obstruction in patients with unresectable recurrent colorectal cancer or intra-abdominal dissemination. A total of 5 cases were included (4 male and 1 female) with a mean age of 70.8 (range, 63-80) years. A self-expanding noncovered Ultraflex, 10 cm in length and 22 mm in diameter, was emplaced at the site of the obstruction under both endoscopic and fluoroscopic guidance. Each patient had a recurrent malignancy (colorectal cancer, 3; ovarian cancer, 1; gastric cancer, 1). No subsequent surgery was planned due to ascites or extensive intra-abdominal dissemination. There was no mortality related to the procedure. Immediate decompression with symptomatic relief was achieved. One stent later became obstructed due to tumor ingrowth, and in two cases there was intermittent bleeding from the tumor and these were treated by argon plasma coagulation (APC) endoscopically. The use of self-expanding Ultraflex stent provides good palliation for unresectable advanced tumors that cause left colonic obstruction.

Transanal dilation using circular stapling for benign rectal stenosis: report of a case.

When a simple procedure such as bougie, balloon dilation and transanal incision are not effective for severe stenosis after colorectal anastomotic leakage, a surgical operation is required. We report a case of transanal dilation using circular stapling for severe stricture in the colorectal anastomosis following low anterior resection.