Vasomotion in human arteries and their regulations based on ion channel regulations: 10 years study.

Vasomotion is the oscillation of vascular tone which gives rise to flow motion of blood into an organ. As is well known, spontaneous contractile organs such as heart, GI, and genitourinary tract produce rhythmic contraction. It imposes or removes pressure on their vessels alternatively for exchange of many substances. It was first described over 150 years ago, however the physiological mechanism and pathophysiological implications are not well understood. This study aimed to elucidate underlying mechanisms and physiological function of vasomotion in human arteries. Conventional contractile force measurement, immunohistochemistry, and Western blot analysis were employed to study human left gastric artery (HLGA) and uterine arteries (HUA). RESULTS: Circular muscle of HLGA and/or HUA produced sustained tonic contraction by high K+ (50 mM) which was blocked by 2 µM nifedipine. Stepwise stretch and high K+ produced nerve-independent spontaneous contraction (vasomotion) (around 45% of tested tissues). Vasomotion was also produced by application of BayK 8644, 5-HT, prostagrandins, oxytocin. It was blocked by nifedipine (2 µM) and blockers of intracellular Ca2+ stores. Inhibitors of Ca2+ -activated Cl- channels (DIDS and/or niflumic acid) and ATP-sensitive K+ (KATP ) channels inhibited vasomotion reversibly. Metabolic inhibition by sodium cyanide (NaCN) and several neuropeptides also regulated vasomotion in KATP channel-sensitive and -insensitive manner. Finally, we identified TMEM16A Ca2+ -activated Cl- channels and subunits of KATP channels (Kir 6.1/6.2 and sulfonylurea receptor 2B [SUR2B]), and c-Kit positivity by Western blot analysis. We conclude that vasomotion is sensitive to TMEM16A Ca2+ -activated Cl- channels and metabolic changes in human gastric and uterine arteries. Vasomotion might play an important role in the regulation of microcirculation dynamics even in pacemaker-related autonomic contractile organs in humans.

Awareness, intentions and attitudes towards planned oocyte cryopreservation among female medical staff.

RESEARCH QUESTION: What are the awareness, intentions and attitudes of female medical staff towards planned oocyte cryopreservation? DESIGN: A cross-sectional survey was conducted during June 2019 among 171 female medical staff at a single tertiary hospital. The self-administered questionnaire consisted of 39 questions. RESULTS: A total of 151 responses (88%) were received from 13 doctors and 138 nurses. The mean age of the respondents was 26.4 years. Fewer than half of the women (47.7%) answered correctly on the age at which female fertility markedly declines. The study demonstrated that 28.5% of respondents considered themselves as 'potential freezers' while 30.5% would not consider the procedure. Potential freezers (58.1% versus 21.7%, P < 0.001) and older age participants (44.2% versus 28.4, P = 0.014) were more interested in consulting about fertility preservation during an obstetrician/gynaecologist (OB/GYN) visit. If respondents were to consider oocyte cryopreservation, they thought that lack of information would be a major obstacle to accepting the procedure (57.6%). Of the respondents, 85.3% believed that oocyte cryopreservation is a woman's right. A strong majority of respondents (96.0%) agreed or were neutral on the statement that all women have the right to receive education on fertility preservation during OB/GYN visits, but none had ever received medical education about fertility preservation, reflecting lack of access to fertility preservation care. CONCLUSIONS: This study indicated that there was widespread awareness about planned oocyte cryopreservation among female medical staff. The majority of participants considered planned oocyte cryopreservation as a woman's right. There appears to be a critical need for proper education about fertility preservation.

Disparities in the Diagnosis, Treatment, and Survival Rate of Cervical Cancer among Women with and without Disabilities.

INTRODUCTION: Not much is known regarding the disparities in cancer care between women with and without disabilities. OBJECTIVES: The aim of this study was to investigate the potential disparities in the diagnosis, treatment, and survival of women with cervical cancer with and without disabilities. METHODS: We performed a retrospective cohort study and linked the National Disability Database, Korean Central Cancer Registry, and Korean National Health Insurance claims database. Charlson comorbidity index was used for adjusting the comorbidity. The study population comprised 3 185 women with disabilities (physical/brain, communication, mental, cardiopulmonary, and other impairment) who were diagnosed with cervical cancer and 13 582 age- and sex-matched women without disability who were diagnosed with cervical cancer for comparison. RESULTS: Distant metastatic stage (7.7% vs 3.7%) and unknown stage (16.1% vs 7.0%) were more common in cervical cancer women with grade 1 disabilities, compared with women without disabilities. Women with cervical cancer with disabilities were less likely to undergo surgery (adjusted odds ratio (aOR) 0.81, 95% confidence interval (CI) 0.73-0.90) or chemotherapy (aOR 0.86, 95% CI 0.77-0.97). Lower rate of surgery was more evident in patients with physical/brain impairment (aOR 0.46, 95% CI 0.37-0.58) and severe mental impairment (aOR 0.57, 95% CI 0.41-0.81). The overall mortality risk was also higher in patients with disabilities (adjusted hazard ratio (aHR) 1.36, 95% CI 1.25-1.48). CONCLUSION: Women with cervical cancer with disabilities, especially with severe disabilities, were diagnosed at later stages, received less treatment, and had higher mortality rates, compared with patients who lacked disabilities. Social support and policies, along with education for women with disabilities, their families, and healthcare professionals, are needed to improve these disparities.

Antenatal sonographic features of persistent extrahepatic vitelline vein aneurysm confused with umbilical vein varix.

Background: The persistent vitelline vein is a portal venous system malformation arising during the embryonic period. These abnormal blood vessels frequently thrombose and can lead superior mesenteric vein obstruction or portal hypertension. Case report: We visualized a fetal intra-abdominal cystic mass with turbulent flow on prenatal ultrasound at 28 weeks' gestation. Initially diagnosed as an umbilical vein varix, it was later determined to be an extrahepatic persistent vitelline vein with an internal thrombus by postnatal ultrasound. It was successfully surgically excised. Conclusion: When an abnormal abdominal vascular structure near the umbilicus is found during prenatal ultrasonography, the persistent vitelline vein should be included in the differential diagnosis to allow prompt evaluation and treatment after birth.

Structural and Electronic Origin of Bis-Lactam-Based High-Performance Organic Thin-Film Transistors.

We describe herein the comprehensive theoretical and experimental studies on the transistor mobility of organic semiconductors by correlating a two-dimensional (2D) intermolecular interaction with thin-film morphology and the electronic coupling structure. We developed a novel bis-lactam-based small molecule, 1,5-dioctyl-3,7-di(thiophen-2-yl)-1,5-naphthyridine-2,6-dione (C8-NTDT), with a 2D-type C-H···O═C intermolecular interaction along the in-plane directions of the crystal packing structure, which is characteristically different from the one-dimensional-type intermolecular interaction shown in the typical bis-lactam molecule of 2,5-dioctyl-3,6-di(thiophen-2-yl)pyrrolo[3,4- c]pyrrole-1,4-dione (C8-DPPT). Experimentally and theoretically, C8-NTDT exhibited more favorable thin-film morphology and an electronic coupling structure for charge transport because of its unique 2D intermolecular interactions compared with C8-DPPT. In fact, C8-NTDT exhibited a hole mobility of up to 1.29 cm2 V-1 s-1 and an on/off ratio of 107 in a vacuum-processed device. Moreover, the high solubility with the 2D electronic coupling structure of C8-NTDT enables versatile solution processing for device fabrication without performance degradation compared to the vacuum-processed device. As an example, we could demonstrate a hole mobility of up to 1.10 cm2 V-1 s-1 for the spin-coated devices, which is one of the best performances among the solution-processed organic field-effect transistors based on bis-lactam-containing small molecules.

Highly Luminescent 2D-Type Slab Crystals Based on a Molecular Charge-Transfer Complex as Promising Organic Light-Emitting Transistor Materials.

A new 2:1 donor (D):acceptor (A) mixed-stacked charge-transfer (CT) cocrystal comprising isometrically structured dicyanodistyrylbenzene-based D and A molecules is designed and synthesized. Uniform 2D-type morphology is manifested by the exquisite interplay of intermolecular interactions. In addition to its appealing structural features, unique optoelectronic properties are unveiled. Exceptionally high photoluminescence quantum yield (ΦF ≈ 60%) is realized by non-negligible oscillator strength of the S1 transition, and rigidified 2D-type structure. Moreover, this luminescent 2D-type CT crystal exhibits balanced ambipolar transport (µh and µe of ≈10-4 cm2 V-1 s-1 ). As a consequence of such unique optoelectronic characteristics, the first CT electroluminescence is demonstrated in a single active-layered organic light-emitting transistor (OLET) device. The external quantum efficiency of this OLET is as high as 1.5% to suggest a promising potential of luminescent mixed-stacked CT cocrystals in OLET applications.

Delayed postpartum hemoperitoneum due to uterine artery pseudoaneurysm rupture.

A 30-year-old woman experienced severe abdominal pain 8 days after vaginal delivery. The patient was diagnosed with hemoperitoneum due to rupture of the left uterine artery pseudoaneurysm, which was confirmed via ultrasound with color Doppler and computed tomography scans. This patient was treated with bilateral uterine artery embolization to maintain fertility. A uterine artery pseudoaneurysm that causes delayed postpartum hemorrhage can occur after cesarean section or vaginal delivery. A uterine artery pseudoaneurysm can be fatal, so its detection and diagnosis are critical. Herein, we report a case of delayed postpartum hemoperitoneum due to uterine artery pseudoaneurysm rupture.

Considerations of critical quality attributes in the analytical comparability assessment of biosimilar products.

Based on experience in clinical trial approvals and marketing authorizations for biosimilar products in Korea, we suggest principles for the analytical comparability assessment of biosimilar products with respect to regulatory considerations. The composition and manufacturing processes of biosimilar products can differ from those of the reference product depending on the information available for the reference product and the time of product development; however, the analytical characteristics of biosimilar products should be highly similar to those of the reference product. Although manufacturing an identical product in terms of the quality profile is nearly impossible due to the high molecular weight and complex structure of biological products, the developer of the biosimilar product should attempt to establish a quality level as similar to that of the reference product as possible. When comparing the similarity of quality attributes, the criticality of the quality attributes and the characteristics of orthogonal quality attributes need to be considered carefully. Based on the results from the analytical comparability assessment, the comparability results of non-clinical and clinical studies should be evaluated before claiming biosimilarity to the reference product. In this review, we focus on quality attribute evaluation based on our regulatory experience.

A case of spontaneous hemoperitoneum by uterine vessel rupture in pregnancy.

A 27-year-old pregnant woman, para 1, was transferred to our hospital at 29+3 weeks of gestation complaining of abdominal pain. She was diagnosed with hemoperitoneum based on ultrasonography. An emergency laparotomy was performed, and the bleeding was confirmed to be caused by ruptured surface blood vessels on the uterine fundus. Hemostasis with compression was successfully performed to sustain the pregnancy, and the patient delivered a full-term baby. Spontaneous hemoperitoneum during pregnancy caused by rupture of uterine blood vessels is very rare. It requires rapid diagnosis and surgical treatment because it increases the morbidity of the fetus and mother. In most incidences of spontaneous hemoperitoneum during pregnancy, a cesarean delivery is performed along with a simultaneous emergency laparotomy. However, in this case, the pregnancy was maintained to full term after surgical hemostasis, which prevented neonatal complications due to premature birth.

Myometrial relaxation of mice via expression of two pore domain acid sensitive K(+) (TASK-2) channels.

Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing K(+) channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward K(+) current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing K(+) channels (TASK-2). NIOK in the presence of K(+) channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.

A collaborative study of an alternative in vitro potency assay for the Japanese encephalitis vaccine.

The use of inactivated Japanese encephalitis (JE) vaccines has been ongoing in East Asia for 40 years. A mouse immunogenicity assay followed by a Plaque Reduction Neutralization (PRN) Test (PRNTest) is currently recommended for each lot release of the vaccine by many national authorities. We developed an alternative in vitro ELISA to determine the E antigen content of the Japanese encephalitis virus to observe the 3Rs strategy. A collaborative study for replacing the in vivo potency assay for the Japanese encephalitis vaccine with the in vitro ELISA assay was confirmed comparability between these two methods. The study demonstrated that an in vitro assay could perform faster and was more convenient than the established in vivo PRNTest. Moreover, this assay had better precision and reproducibility compared with the conventional in vivo assay. Additionally, the content of antigen determined using the in vitro ELISA correlated well with the potency of the in vivo assay. Furthermore, this method allowed discrimination between individual lots. Thus, we propose a progressive switch from the in vivo assay to the in vitro ELISA for JE vaccine quality control.

Regulation of myometrial contraction by ATP-sensitive potassium (KATP) channel via activation of SUR2B and Kir 6.2 in mouse.

ATP-sensitive potassium (KATP) channels are well characterized in cardiac, pancreatic and many other muscle cells. In the present study, functional expression of the KATP channel was examined in non-pregnant murine longitudinal myometrium. Isometric contraction measurements and Western blot were used. KATP channel openers (KCOs), such as pinacidil, cromakalim, diazoxide and nicorandil, inhibited spontaneous myometrial contractions in a reversible and glibenclamide-sensitive manner. KCOs inhibited oxytocin (OXT)- and prostaglandin F2α (PGF2α)-induced phasic contractions in a glibenclamide-sensitive manner. SUR2B and Kir6.2 were detected by Western blot, whereas SUR1, SUR2A and Kir6.1 were not. These results show that pinacidl, cromakalim, diazoxide and nicorandil-sensitive KATP channels exist in murine myometrium, which are composed of SUR2B and Kir6.2. Based on the modulatory effects of the KATP channel on spontaneous contraction, OXT- and PGF2α-induced contractions, KATP channels seem to play an essential role in murine myometrial motility via activation of SUR2B and Kir6.2.

Safety of cesarean delivery through placental incision in patients with anterior placenta previa.

OBJECTIVE: To demonstrate the safety of fetal delivery through placental incision in a placenta previa pregnancy. METHODS: We examined the medical records of 80 women with singleton pregnancy diagnosed with placenta previa who underwent cesarean section between May 2010 and May 2015 at the Department of Obstetrics and Gynecology, Chungbuk National University Hospital. Among the women with placenta previa, those who did not have the placenta in the uterine incision site gave birth via conventional uterine incision, while those with anterior placenta previa or had placenta attached to the uterine incision site gave birth via uterine incision plus placental incision. We compared the postoperative hemoglobin level and duration of hospital stay for the mother and newborn of the two groups. RESULTS: There was no difference between the placental incision group and non-incision group in terms of preoperative and postoperative hemoglobin change, the amount of blood transfusions required by the mother, newborns with 1-min or 5-min Apgar scores below 7 points or showing signs of acidosis on umbilical cord blood gas analysis result of pH below 7.20. Moreover, neonatal hemoglobin levels did not differ between the two groups. CONCLUSION: Fetal delivery through placental incision during cesarean section for placenta previa pregnancy does not negatively influence the prognosis of the mother or the newborn, and therefore, is considered a safe surgical technique.

Increased expression of nuclear factor kappa-B p65 subunit in adenomyosis.

OBJECTIVE: Nuclear factor kappa-B (NF-κB) is a critical proinflammatory regulator that has been suggested to play a pivotal role in the pathogenesis and pathophysiology of endometriosis. In the present study, we aimed to evaluate whether the expression of NF-κB p65 subunit is increased in the eutopic endometrium and/or in the adenomyosis nodule of women with adenomyosis. METHODS: Thirty-three women with histologically confirmed adenomyosis after laparoscopic or transabdominal hysterectomy were recruited. Women with carcinoma in situ of uterine cervix without evidence of adenomyosis or endometriosis (n=32) served as controls. Formalin-fixed, paraffin-embedded archival tissues were sectioned and immunostained utilizing a monoclonal anti-human NF-κB p65 subunit antibody, and the immunoreactivity of NF-κB p65 subunit was compared between women with and without adenomyosis. RESULTS: The immunoreactivities of both the nuclear and the cytoplasmic NF-κB p65 subunit were significantly increased in the stromal cells in the eutopic endometrium as well as in the adenomyosis nodule of women with adenomyosis compared with controls, respectively. The nuclear expression of NF-κB p65 subunit was significantly higher in the glandular cells in the eutopic endometrium as well as the adenomyosis nodule of women with adenomyosis compared with controls, respectively. CONCLUSION: The expression of NF-κB p65 is increased in the eutopic endometrium and adenomyosis nodule of women with adenomyosis, which strongly suggest that NF-κB plays a critical role in the pathogenesis and/or pathophysiology of adenomyosis.

Differences in cognitive ability and hippocampal volume between Alzheimer's disease, amnestic mild cognitive impairment, and healthy control groups, and their correlation.

The study investigated differences in cognitive ability and hippocampal volume between groups of patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI), and healthy control (HC) subjects, and explored the relationship between cognitive ability and hippocampal volume. Among the sub-tests of Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K), the Boston naming test score decreased in the order HC, aMCI, and AD. The hippocampal volumes of subjects with AD and aMCI were relatively smaller than those of HC individuals. There were strongly positive correlations between hippocampal volume and the scores for the Boston naming test. Discriminant analysis identified the Boston naming test as having the highest level of discrimination among the variables used to differentiate the three groups (89.9%). In conclusion, the Boston naming test accurately differentiated the three groups and was correlated with hippocampal volume. These results will be helpful for choosing an accurate and economically feasible test method that efficiently differentiates the three groups.

Comparison of HE4, CA125, and Risk of Ovarian Malignancy Algorithm in the Prediction of Ovarian Cancer in Korean Women.

This study is a multi-center clinical study, which aimed to compare CA125, HE4, and risk of ovarian malignancy algorithm (ROMA) in predicting epithelial ovarian cancer of Korean women with a pelvic mass. Prospectively, serum from 90 Korean women with ovarian mass was obtained prior to surgery. For control group, serum from 79 normal populations without ovarian mass was also obtained. The HE4 and CA125 data were registered and evaluated separately and ROMA was calculated for each sample. Total 67 benign tumors and 23 ovarian cancers were evaluated. Median serum levels of HE4 and CA125, and ROMA score were significantly higher in patients with ovarian cancer than those with benign ovarian tumor and normal population (P < 0.001). In ROC curve analysis for women with a pelvic mass, area under the curve (AUC) for HE4 and ROMA was higher than CA125. Statistical differences in each study compared to CA125 were marginal (P compared to CA125; 0.082 for HE4 and 0.069 for ROMA). Sub-analysis revealed that AUC for HE4 and ROMA was higher than AUC for CA125 in post-menopausal women with a pelvic mass, but there were no statistically significant differences (P compared to CA125; 0.160 for HE4 and 0.127 for ROMA). Our data suggested that both HE4 and ROMA score showed better performance than CA125 for the detection of ovarian cancer in women with a pelvic mass. HE4 and ROMA can be a useful independent diagnostic marker for epithelial ovarian cancer in Korean women.

Efficacy of the device combining high-frequency transcutaneous electrical nerve stimulation and thermotherapy for relieving primary dysmenorrhea: a randomized, single-blind, placebo-controlled trial.

OBJECTIVE: To investigate the efficacy and safety of the combined therapy with high-frequency transcutaneous electrical nerve stimulation (hf-TENS) and thermotherapy in relieving primary dysmenorrheal pain. STUDY DESIGN: In this randomized, single-blind, placebo-controlled study, 115 women with moderate or severe primary dysmenorrhea were assigned to the study or control group at a ratio of 1:1. Subjects in the study group used an integrated hf-TENS/thermotherapy device, whereas control subjects used a sham device. A visual analog scale was used to measure pain intensity. Variables related to pain relief, including reduction rate of dysmenorrheal score, were compared between the groups. RESULTS: The dysmenorrheal score was significantly reduced in the study group compared to the control group following the use of the devices. The duration of pain relief was significantly increased in the study group compared to the control group. There were no differences between the groups in the brief pain inventory scores, numbers of ibuprofen tablets taken orally, and World Health Organization quality of life-BREF scores. No adverse events were observed related to the use of the study device. CONCLUSIONS: The combination of hf-TENS and thermotherapy was effective in relieving acute pain in women with moderate or severe primary dysmenorrhea.