Risk factors of menopause after allogeneic hematopoietic cell transplantation in premenopausal adult women.

OBJECTIVES: Allogeneic hematopoietic stem-cell transplantation (HCT) is the only curative option for most hematologic malignancies. However, HSCT can cause early menopause and various complications in premenopausal women. Therefore, we aimed to investigate risk factors predicting early menopause and its clinical implications among survivors post HCT. METHODS: We retrospectively analyzed 30 adult women who had received HCT at premenopausal status between 2015 and 2018. We excluded patients who had received autologous stem cell transplantation, had relapsed, or died of any cause within 2 years of HCT. RESULTS: The median age at HCT was 41.6 years (range, 22-53). Post-HCT menopause was identified in 90% of myeloablative conditioning (MAC) HCT and 55% of reduced-intensity conditioning (RIC) HCT (p = .101). In the multivariate analysis, the post-HCT menopausal risk was 21 times higher in a MAC regimen containing 4 days of busulfan (p = .016) and 9.3 times higher in RIC regimens containing 2-3 days of busulfan (p = .033) than that of non-busulfan-based conditioning regimens. CONCLUSIONS: Higher busulfan dose in conditioning regimens is the most significant risk factor affecting post-HCT early menopause. Considering our data, we need to decide on conditioning regimens and individualized fertility counseling before HCT for premenopausal women.

Chimeric Singleton Placenta Comprising Placental Mesenchymal Dysplasia and Complete Hydatidiform Mole with Live Birth and Postpartum Diagnosis of Gestational Trophoblastic Neoplasia.

INTRODUCTION: Placental mesenchymal dysplasia (PMD) is a benign lesion that is often misdiagnosed as complete (CHM) or partial hydatidiform mole. PMD usually results in live birth but can be associated with several fetal defects. Herein, we report PMD with CHM in a singleton placenta with live birth. CASE PRESENTATION: A 34-year-old gravida 2, para 1, living 1 (G2P1L1) woman was referred on suspicion of a molar pregnancy in the first trimester. Maternal serum human chorionic gonadotrophin levels were increased during early pregnancy, with multicystic lesions and placentomegaly observed on ultrasonography. Levels decreased to normal with no fetal structural abnormalities observed. A healthy male infant was delivered at 34 gestational weeks. Placental p57KIP2 immunostaining and short tandem repeat analysis revealed three distinct histologies and genetic features: normal infant and placenta, PMD, and CHM. Gestational trophoblastic neoplasia was diagnosed and up to fourth-line chemotherapy administered. CONCLUSION: Distinguishing PMD from hydatidiform moles is critical for avoiding unnecessary termination of pregnancy. CHM coexisting with a live fetus rarely occurs. This case is unique in that a healthy male infant was born from a singleton placenta with PMD and CHM.

Use of the Endometriosis Fertility Index to Predict Natural Pregnancy after Endometriosis Surgery: A Single-Center Study.

AIMS: Our objective was to predict natural pregnancy after endometriosis surgery using the endometriosis fertility index (EFI). METHODS: A retrospective medical records review was conducted, examining patients surgically treated for endometriosis at a single center in Korea between January 2009 and February 2015. In total, 68 women attempting natural conception were analyzed by assessing age, preoperative serum CA-125, body mass index, revised American Fertility Society (rAFS) stage, EFI, and pregnancy outcome. Kaplan-Meier estimates and log-rank tests were used to generate cumulative natural pregnancy rate curves based on an EFI cut-point. A receiver-operating characteristic (ROC) curve was plotted for EFI. RESULTS: Seventy-seven patients attempted conceptions, resulting in 33 natural and 9 assisted conceptions. Excluding assisted conceptions, the mean EFI scores of 68 women who were not pregnant and pregnant were 5.43 ± 0.36 and 6.88 ± 0.28 respectively. The relation between EFI and natural pregnancy was significant (cumulative overall pregnancy rate, p = 0.006), whereas rAFS stage was not (univariate logistics, p = 0.853). The cut-point for maximum natural pregnancy outcomes was 6 (area under ROC curve = 0.710, 95% CI 0.586-0.835). CONCLUSION: The EFI is a reliable staging system for predicting natural pregnancy after endometriosis surgery. EFI scores can be used to guide postoperative treatment of women with endometriosis.

Effects of an evidence-based practice education program using multifaceted interventions: a quasi-experimental study with undergraduate nursing students.

BACKGROUND: Although Evidence-Based Practice (EBP) should be introduced early on in nursing education to develop students' independence and self-learning ability, there are few such courses for undergraduate nursing students in Korea. This study examined the effects of the EBP education program for undergraduate nursing students (EBP-EPUNS) on nursing students' knowledge, skills, attitudes, competencies, and future use of EBP. METHODS: A quasi-experimental study design with pre-test, intervention, and post-test was used. The participants were 44 nursing students (experimental: 22, control: 22). A 20-h long EBP-EPUNS consisting of 5-step EBP components was provided through 8 sessions spread across 4 weeks. RESULTS: An independent t-test and a repeated-measures ANOVA showed that the experimental group had statistically significant higher post-test scores on EBP knowledge (p < 0.001), skills (p < 0.001), attitudes (p < 0.001), competencies (p < 0.001), future use of EBP (p = 0.001), and critical thinking (p < 0.001), compared to the control group. CONCLUSION: The EBP education program was effective in improving the knowledge, skills, attitudes, competencies, and future use of EBP among nursing students. Hence, we recommend the EBP education program as a general education course for undergraduate nursing students to promote needed proficiency in EBP.

Role of B-Cell Translocation Gene 1 in the Pathogenesis of Endometriosis.

Estrogen affects endometrial cellular proliferation by regulating the expression of the c-myc gene. B-cell translocation gene 1 (BTG1), a translocation partner of the c-myc, is a tumor suppressor gene that promotes apoptosis and negatively regulates cellular proliferation and cell-to-cell adhesion. The aim of this study was to determine the role of BTG1 in the pathogenesis of endometriosis. BTG1 mRNA and protein expression was evaluated in eutopic and ectopic endometrium of 30 patients with endometriosis (endometriosis group), and in eutopic endometrium of 22 patients without endometriosis (control group). The effect of BTG1 downregulation on cellular migration, proliferation, and apoptosis was evaluated using transfection of primarily cultured human endometrial stromal cells (HESCs) with BTG1 siRNA. BTG1 mRNA expression level of eutopic and ectopic endometrium of endometriosis group were significantly lower than that of the eutopic endometrium of the control group. Migration and wound healing assays revealed that BTG1 downregulation resulted in a significant increase in migration potential of HESCs, characterized by increased expression of matrix metalloproteinase 2 (MMP2) and MMP9. Downregulation of BTG1 in HESCs significantly reduced Caspase 3 expression, indicating a decrease in apoptotic potential. In conclusion, our data suggest that downregulation of BTG1 plays an important role in the pathogenesis of endometriosis.

GABAergic excitation of vasopressin neurons: possible mechanism underlying sodium-dependent hypertension.

RATIONALE: Increased arginine-vasopressin (AVP) secretion is a key physiological response to hyperosmotic stress and may be part of the mechanism by which high-salt diets induce or exacerbate hypertension. OBJECTIVE: Using deoxycorticosterone acetate-salt hypertension model rats, we sought to test the hypothesis that changes in GABA(A) receptor-mediated inhibition in AVP-secreting magnocellular neurons contribute to the generation of Na(+)-dependent hypertension. METHODS AND RESULTS: In vitro gramicidin-perforated recordings in the paraventricular and supraoptic nuclei revealed that the GABAergic inhibition in AVP-secreting neurons was converted into excitation in this model, because of the depolarization of GABA equilibrium potential. Meanwhile, in vivo extracellular recordings in the supraoptic nuclei showed that the GABAergic baroreflexive inhibition of magnocellular neurons was transformed to excitation, so that baroreceptor activation may increase AVP release. The depolarizing GABA equilibrium potential shift in AVP-secreting neurons occurred progressively over weeks of deoxycorticosterone acetate-salt treatment along with gradual increases in plasma AVP and blood pressure. Furthermore, the shift was associated with changes in chloride transporter expression and partially reversed by bumetanide (Na(+)-K(+)-2Cl(-) cotransporter inhibitor). Intracerebroventricular bumetanide administration during deoxycorticosterone acetate-salt treatment hindered the development of hypertension and rise in plasma AVP level. Muscimol (GABA(A) agonist) microinjection into the supraoptic nuclei in hypertensive rats increased blood pressure, which was prevented by previous intravenous V1a AVP antagonist injection. CONCLUSIONS: We conclude that the inhibitory-to-excitatory switch of GABAA receptor-mediated transmission in AVP neurons contributes to the generation of Na(+)-dependent hypertension by increasing AVP release. We speculate that normalizing the GABA equilibrium potential may have some utility in treating Na(+)-dependent hypertension.

Long-lasting forms of plasticity through patterned ultrasound-induced brainwave entrainment.

Achieving long-lasting neuronal modulation with low-intensity, low-frequency ultrasound is challenging. Here, we devised theta burst ultrasound stimulation (TBUS) with gamma bursts for brain entrainment and modulation of neuronal plasticity in the mouse motor cortex. We demonstrate that two types of TBUS, intermittent and continuous TBUS, induce bidirectional long-term potentiation or depression-like plasticity, respectively, as evidenced by changes in motor-evoked potentials. These effects depended on molecular pathways associated with long-term plasticity, including N-methyl-d-aspartate receptor and brain-derived neurotrophic factor/tropomyosin receptor kinase B activation, as well as de novo protein synthesis. Notably, bestrophin-1 and transient receptor potential ankyrin 1 play important roles in these enduring effects. Moreover, pretraining TBUS enhances the acquisition of previously unidentified motor skills. Our study unveils a promising protocol for ultrasound neuromodulation, enabling noninvasive and sustained modulation of brain function.

Chronic hyperosmotic stress converts GABAergic inhibition into excitation in vasopressin and oxytocin neurons in the rat.

In mammals, the increased secretion of arginine-vasopressin (AVP) (antidiuretic hormone) and oxytocin (natriuretic hormone) is a key physiological response to hyperosmotic stress. In this study, we examined whether chronic hyperosmotic stress weakens GABA(A) receptor-mediated synaptic inhibition in rat hypothalamic magnocellular neurosecretory cells (MNCs) secreting these hormones. Gramicidin-perforated recordings of MNCs in acute hypothalamic slices prepared from control rats and ones subjected to the chronic hyperosmotic stress revealed that this challenge not only attenuated the GABAergic inhibition but actually converted it into excitation. The hyperosmotic stress caused a profound depolarizing shift in the reversal potential of GABAergic response (E(GABA)) in MNCs. This E(GABA) shift was associated with increased expression of Na(+)-K(+)-2Cl(-) cotransporter 1 (NKCC1) in MNCs and was blocked by the NKCC inhibitor bumetanide as well as by decreasing NKCC activity through a reduction of extracellular sodium. Blocking central oxytocin receptors during the hyperosmotic stress prevented the switch to GABAergic excitation. Finally, intravenous injection of the GABA(A) receptor antagonist bicuculline lowered the plasma levels of AVP and oxytocin in rats under the chronic hyperosmotic stress. We conclude that the GABAergic responses of MNCs switch between inhibition and excitation in response to physiological needs through the regulation of transmembrane Cl(-) gradients.

Successful Full-Term Delivery via Selective Ectopic Embryo Reduction Accompanied by Uterine Cerclage in a Heterotopic Cesarean Scar Pregnancy: A Case Report and Literature Review.

Heterotopic cesarean scar pregnancy (HCSP) is a combination of cesarean scar pregnancy (CSP) and intrauterine pregnancy (IUP). Cesarean scar pregnancy is accompanied by life-threatening complications, such as uterine rupture and massive bleeding. Herein, we present a case of HCSP treated with selective potassium chloride injection into the CSP under ultrasonography in association with uterine cerclage to control vaginal bleeding; this led to a successful IUP preservation and full-term delivery. Additionally, we will review several previous reports on HCSP management, including our case.

The novel role of mast cells in the microenvironment of acute myocardial infarction.

Mast cells are multifunctional cells containing various mediators, such as cytokines, tryptase, and histamine, and they have been identified in infarct myocardium. Here, we elucidated the roles of mast cells in a myocardial infarction (MI) rat model. We studied the physiological and functional roles of mast cell granules (MCGs), isolated from rat peritoneal fluid, on endothelial cells, neonatal cardiomyocytes, and infarct heart (1-hour occlusion of left coronary artery followed by reperfusion). The number of mast cells had two peak time points of appearance in the infarct region at 1day and 21days after MI induction in rats (p<0.05 in each compared with sham-operated heart). Simultaneous injection of an optimal dose of MCGs modulated the microenvironment and resulted in the increased infiltration of macrophages and decreased apoptosis of cardiomyocytes without change in the mast cell number in infarct myocardium. Moreover, MCG injection attenuated the progression of MI through angiogenesis and preserved left ventricular function after MI. MCG-treated cardiomyocytes were more resistant to hypoxic injury through phosphorylation of Akt, and MCG-treated endothelial cells showed enhanced migration and tube formation. We have shown that MCGs have novel cardioprotective roles in MI via the prolonged survival of cardiomyocytes and the induction of angiogenesis.

Minimally invasive adenomyomectomy via a laparoscopic-assisted approach compared to a laparoscopic or laparotomic approach.

OBJECTIVE: The present study assessed the safety and benefits of laparoscopic-assisted adenomyomectomy compared to laparoscopic or laparotomic adenomyomectomy. MATERIALS AND METHODS: This study was a retrospective comparative study. A total of 277 patients underwent adenomyomectomy between January 2016 and January 2019 at the Department of Obstetrics and Gynaecology, Ulsan University Hospital, including 25 with laparoscopic-assisted adenomyomectomy, 82 with laparoscopic adenomyomectomy, and 170 with laparotomic adenomyomectomy. Laparoscopic-assisted adenomyomectomy consisted of a laparoscopic uterine artery procedure to reduce blood loss and a minimal incisional for laparotomic adenomyomectomy. An additional laparoscopic surgery was performed for possible pelvic pathology. RESULTS: Data on patient demographics, surgical indications, operative times, estimated blood loss (EBL), short-term complications, and postoperative hospital stays were compared. The laparoscopic-assisted surgery (LAS) and laparotomic groups were comparable in average EBL (208.0 ± 128.8 vs. 193.6 ± 193.0 ml, p = 0.11), weight of removed mass (85.5 ± 71.7 vs. 108.2 ± 91.9 g, p = 0.39), and postoperative hospital days (HDs) (4.5 ± 1.0 vs. 4.7 ± 0.8 days, p = 0.27). These values were lower in the laparoscopic group (EBL 119.5 ± 79.6 ml, mass weight 39.3 ± 25.9 g, HD 3.6 ± 0.8 days). Additional procedures, including myomectomy and combined severe endometriosis surgery, were more frequently performed in the LAS group than the laparotomic group. The mean operating time was longer in the LAS group (179.8 ± 36.6 min) than the other groups (laparoscopy 99.9 ± 40.6 min, p < 0.00; laparotomy 133.0 ± 41.1 min, p < 0.00). The three groups did not differ significantly in transfusion rates, hemoglobin changes, or perioperative complications. However, febrile morbidity was lower in the laparoscopic group than the LAS and laparotomic groups. CONCLUSION: LAS adenomyomectomy allows for maximal debulking of adenomyosis via extracorporeal and intracorporeal procedures while retaining the advantages of the laparoscopic approach. Additional pelvic surgery for benign uterine and adnexal pathology may easily be performed with this approach.

Ruptured Hemorrhagic Ectopic Pregnancy Implanted in the Diaphragm: A Rare Case Report and Brief Literature Review.

The mortality and morbidity rates of non-tubal ectopic pregnancies with abdominal hemorrhaging are 7-8 times higher than those of tubal pregnancies. Diaphragmatic pregnancy is a rare non-tubal ectopic form, causing acute abdominal hemoperitoneum. Here, we present a case of a primary diaphragmatic ectopic pregnancy with hemorrhage that was immediately diagnosed and successfully managed with laparoscopic surgery. Rapid and accurate diagnosis using appropriate imaging modalities is critical for improving the prognosis of a child-bearing woman with an abdominal pregnancy.

Maternal Bochdalek Hernia during Pregnancy: A Systematic Review of Case Reports.

BACKGROUND: Since the first report of a diaphragmatic hernia from Ambroise Paré's necropsy in 1610, the Bochdalek hernia (BH) of the congenital diaphragmatic hernia (CDH) has been the most common types with high morbidity and mortality in the neonatal period. Due to the nature of the disease, CDH associated with pregnancy is too infrequent to warrant reporting in the literature. Mortality of obstruction or strangulation is mostly due to failure to diagnose symptoms early. DATA SOURCES AND STUDY SELECTION: A systematic literature search of maternal BH during pregnancy was conducted using the electronic databases (PubMed and EMBASE) from January 1941 to December 2020. Because of the rarity of the disease, this review included all primary studies, including case reports or case series that reported at least one case of maternal BH in pregnant. Searches, paper selection, and data extraction were conducted in duplicate. The analysis was performed narratively regardless of the control groups' presence due to their rarity. RESULTS: The search retrieved 3450 papers, 94 of which were deemed eligible and led to a total of 43 cases. Results of treatment showed 16 cases in delayed delivery after hernia surgery, 10 cases in simultaneous delivery with hernia surgery, 3 cases in non-surgical treatment, and 14 cases in hernia surgery after delivery. Of 16 cases with delayed delivery after hernia surgery, 13 (81%) cases had emergency surgery and three (19%) cases had surgery after expectant management. Meanwhile, 10 cases underwent simultaneous delivery with hernia surgery, 6 cases (60%) had emergent surgery, and 4 cases (40%) had delayed hernia surgery after expectant management. 3 cases underwent non-surgical treatment. In this review, the maternal death rate and fetal/neonatal loss rate from maternal BH was 5% (2/43) and 16% (7/43), respectively. The preterm birth rate has been reported in 35% (15/43) of maternal BH, resulting from maternal deaths in 13% (2/15) of cases and 6 fetal loss in 40% (6/15) of cases; 44% (19/43) of cases demonstrated signs of bowel obstruction, ischemia, or perforation of strangulated viscera in the operative field, resulting from maternal deaths in 11% (2/19) of cases and fetal-neonatal loss in 21% (4/19) of cases. CONCLUSION: Early diagnosis and surgical intervention are imperative, as a gangrenous or non-viable bowel resection significantly increases mortality. Therefore, multidisciplinary care should be required in maternal BH during pregnancies that undergo surgically repair, and individualized care allow for optimal results for the mother and fetus.

Aberrant Expression of Sodium-Potassium-Chloride Cotransporter in Endometriosis.

Cell membrane ion channels have important roles in cell migration during cancer development and metastasis. Although endometriosis is a benign gynecological disease, some migration and invasion characteristics of endometriosis are similar to those of cancer. However, only a few studies have examined cell membrane ion channels and their associations with endometriosis. This study aimed to investigate the effects of these ion channels on development of endometriosis. A total of 39 women who underwent laparoscopic ovarian cyst enucleation were included in the study population. Eutopic endometrium or ectopic endometrium tissues were obtained from each patient based on allocation to an endometriosis group (n=21) or a control group (n=18). Quantitative real-time PCR (qRT-PCR) and western blot analyses were performed to quantify NKCC1, NKCC2, and CLCN3 mRNA expression and protein concentrations. SiRNA transfection and migration assays of the endometrial stromal cells were performed to test the effects of the ion channels on the migration ability. The qRT-PCR and western blot analyses revealed significantly elevated mRNA expression and protein expression of NKCC1, NKCC2, and CLCN3 in the ectopic endometrial tissue from the patients with endometriosis (p < 0.05). Migration assay of siRNA transfected cells suggested a decreased migratory potential of the endometrial stromal cells (p < 0.001). The magnitudes of expression of NKCC1, NKCC2, and CLCN3 were positively correlated with endometrioma size. The increased expression of NKCC1, NKCC2, and CLCN3 in endometriosis offers opportunities to understand mechanisms of endometriosis and develop novel therapeutic approaches.

Cygnus X-1 contains a 21-solar mass black hole-Implications for massive star winds.

The evolution of massive stars is influenced by the mass lost to stellar winds over their lifetimes. These winds limit the masses of the stellar remnants (such as black holes) that the stars ultimately produce. We used radio astrometry to refine the distance to the black hole x-ray binary Cygnus X-1, which we found to be [Formula: see text] kiloparsecs. When combined with archival optical data, this implies a black hole mass of 21.2 ± 2.2 solar masses, which is higher than previous measurements. The formation of such a high-mass black hole in a high-metallicity system (within the Milky Way) constrains wind mass loss from massive stars.

Serum phosphorus levels are associated with carotid intima-media thickness in asymptomatic postmenopausal women.

OBJECTIVE: Serum phosphorous is a significant risk factor for increased carotid intima-media thickness. Increased thickness of the carotid intima is a known cause of cardiovascular disease. Coronary heart disease is a significant cause of mortality and morbidity in postmenopausal women. This study aimed to compare the relationship between serum phosphorous concentration and carotid intima-media thickness in healthy asymptomatic postmenopausal women. METHODS: A retrospective review of the medical records from a health checkup center in Gangnam Severance hospital between March 2007 and September 2017 was conducted. We examined asymptomatic postmenopausal female patients with age range between 56 and 66 (N = 361) who underwent measurement of carotid intima-media thickness by B-mode ultrasonography. The physiological variables analyzed included mean blood pressure, body mass index, renal function (serum creatinine and estimated glomerular filtration rate), cholesterol levels (total cholesterol, triglyceride, and high- and low-density lipoprotein), serum phosphorous, calcium, electrolytes, diabetic status, hypertension, and albumin. RESULTS: Pearson correlation test showed that carotid intima-media thickness was significantly associated with age (r = 0.192, P < 0.001), mean blood pressure (r = 0.116, P = 0.029), diastolic blood pressure (r = 0.146, P = 0.029), serum phosphorous (r = 0.134, P = 0.012), and lactate dehydrogenase (r = 0.106, P = 0.047). On the basis of age-adjusted multivariate linear regression analysis, carotid intima-media thickness was significantly correlated with serum phosphorous levels (ß = 0.273, P = 0.022) in asymptomatic menopausal women. Increased carotid intima-media thickness (cut-off 1.5 mm) was detected, although serum phosphorous was within the normal range (2.8-4.5 mg/dL). CONCLUSIONS: Serum phosphorus concentration is significantly associated with carotid intima-media thickness in asymptomatic menopausal women.

The Diagnostic Accuracy of Magnetic Resonance Imaging for Maternal Acute Adnexal Torsion during Pregnancy: Single-Institution Clinical Performance Review.

BACKGROUND: For acute adnexal torsion of pregnant women, appropriate treatment based on an accurate diagnosis is especially important for fertility preservation and timely treatment. The 2017 American College of Obstetricians and Gynecologists (ACOG) Committee Opinion No. 723 announced its practice-changing guidelines to ensure that diagnostic magnetic resonance imaging (MRI) conducted during the first trimester and gadolinium exposure at any time during pregnancy are safe for fetal stability. Unfortunately, few studies have been performed to evaluate the usefulness of the diagnostic accuracy of MRI for acute adnexal torsion during pregnancy. OBJECTIVE: We sought to determine the efficacy of diagnostic MRI modality using multiparameter for maternal adnexal torsion during pregnancy. METHODS: From 1 January 2007 to 31 January 2019, 131 pregnant with MRI tests were reviewed. In this retrospective cohort study, 94 women were excluded due to conditions other than an adnexal mass, and 37 were identified through MRI analyses conducted before surgery for suspected adnexal torsion. The primary outcome was the diagnostic accuracy of sonography and MRI, and the secondary outcome was the usefulness of Apparent diffusion coefficient (ADC) values for predicting the severity of hemorrhagic infarction between the medulla and cortex of the torsed ovarian parenchyma. RESULTS: Our study demonstrates that in the diagnosis of adnexal torsion during pregnancy, the sensitivity, specificity, positive predictive value, and negative predictive value are 62.5%, 83.3%, 90.9%, and 45.5% for sonography and 100%, 77.8%, 90.5%, and 100% for MRI. MRI results in surgical-proven adnexal torsion patients revealed unilocular ovarian cysts (36.8% (7/19)), multilocular ovarian cysts (31.6% (6/19)), and near normal-appearing ovaries (31.6% (6/19)). Pathology in adnexal torsion revealed a corpus luteal ovarian cyst (63.2% (12/19)) and underlying adnexal pathology (46.8% (7/19)). Maternal adnexal torsion during pregnancy was more likely to occur in corpus luteal ovarian cysts than in underlying adnexal masses (odds ratio, 2.14; 95% confidence interval (CI), 0.428-10.738). MRI features for adnexal torsion were as follows: tubal wall thickness, 100% (19/19); ovarian stromal (medullary) edema, 100% (19/19); symmetrical or asymmetrical ovarian cystic wall, 100%(19/19); prominent follicles in the ovarian parenchyma periphery, 57.9% (11/19); periadenxal fat stranding, 84.2% (16/19); uterine deviation to the twisted side, 21.1% (4/19); and peritoneal fluid, 42.1% (8/19). The signal intensity of the ADC values of the ovarian medulla and cortex were compared between the cystectomy and detorsion (CD) and salpingo-oophorectomy (SO) groups. The ADC values of the CD and SO groups were 1.81 ± 0.09 × 10-3 mm2/s and 1.91 ± 0.18 × 10-3 mm2/s, respectively (P = 0.209), in the ovarian medulla and 1.37 ± 0.32 × 10-3 mm2/s and 0.96 ± 0.36 × 10-3 mm2/s, respectively (P = 0.022), in the ovarian cortex. The optimal cut-off value of ADC values for predictable total necrosis in the torsed ovarian cortex was ≤ 1.31 × 10-3 mm2/s (area under the curve (AUC) = 0.81; 95% CI 0.611-1.0; P = 0.028). CONCLUSION: Our data showed that maternal adnexal torsion during pregnancy occurred in most corpus luteal cystic ovary cases and some normal-appearing ovary during the 1st and 2nd trimesters of gestation. Therefore, this study is the first study to elaborate on the existence or usefulness of the diagnostic MRI for acute maternal adnexal torsion during pregnancy and to provide a predictive diagnosis of the severity of hemorrhagic infarction for deciding surgical radicality.

Identification of Serum Biomarkers for Diagnosis of Endometriosis Using Multiplex Immunoassays.

Endometriosis is a common gynecologic disorder characterized by chronic pelvic pain, dysmenorrhea, and infertility. Although this condition places significant financial burden on the healthcare system and negatively affects patient's quality of life, the pathophysiology of the disease remains unclear, and noninvasive diagnostic methods are insufficient. The object of this study was to identify potential biomarkers for endometriosis from peripheral blood. We hypothesized that serum biomarkers modified in endometriosis patients would be detected by multiplex cytokine panel, and identification of a combination of these biomarkers would improve diagnostic power. A total of 141 women, aged 15-52 years with regular menstruation, participated in this study. Twenty-one serum cytokines were detected using the commercially available MILLIPLEX MAP Human Cytokine/Chemokine Kit Panel IV. Among these cytokines, breast- and kidney-expressed chemokine (BRAK)/chemokine (C-X-C motif) ligand 14 (CXCL14) was significantly decreased, and proliferation-inducing ligand (APRIL)/tumor necrosis factor ligand superfamily member 13 (TNFSF13) was significantly increased in endometriosis group. APRIL/TNFSF13 and BRAK/CXCL14 alone or in combination, however, failed to show adequate sensitivity or specificity for the diagnosis of endometriosis. Combination of APRIL/TNFSF13 and BRAK/CXCL14 with serum CA-125 levels yielded significantly higher sensitivity (71.2%) for detecting endometriosis without compromising specificity (80.8%) than CA-125 alone in a logistic regression model (P = 0.050). In conclusion, we identified a biomarker combination that detects endometriosis better than CA125 alone. Therefore, we conclude that multiplex cytokine panel is an efficient method for detecting endometriosis, and analysis of additional cytokine panels may lead to identification of a novel biomarker combination with superior diagnostic power.

Excitatory actions of GABA in the suprachiasmatic nucleus.

Neurons in the suprachiasmatic nucleus (SCN) are responsible for the generation of circadian oscillations, and understanding how these neurons communicate to form a functional circuit is a critical issue. The neurotransmitter GABA and its receptors are widely expressed in the SCN where they mediate cell-to-cell communication. Previous studies have raised the possibility that GABA can function as an excitatory transmitter in adult SCN neurons during the day, but this work is controversial. In the present study, we first tested the hypothesis that GABA can evoke excitatory responses during certain phases of the daily cycle by broadly sampling how SCN neurons respond to GABA using extracellular single-unit recording and gramicidin-perforated-patch recording techniques. We found that, although GABA inhibits most SCN neurons, some level of GABA-mediated excitation was present in both dorsal and ventral regions of the SCN, regardless of the time of day. These GABA-evoked excitatory responses were most common during the night in the dorsal SCN region. The Na(+)-K(+)-2Cl(-) cotransporter (NKCC) inhibitor, bumetanide, prevented these excitatory responses. In individual neurons, the application of bumetanide was sufficient to change GABA-evoked excitation to inhibition. Calcium-imaging experiments also indicated that GABA-elicited calcium transients in SCN cells are highly dependent on the NKCC isoform 1 (NKCC1). Finally, Western blot analysis indicated that NKCC1 expression in the dorsal SCN is higher in the night. Together, this work indicates that GABA can play an excitatory role in communication between adult SCN neurons and that this excitation is critically dependent on NKCC1.

Improving virtual screening performance against conformational variations of receptors by shape matching with ligand binding pocket.

In this report, we present a novel virtual high-throughput screening methodology to assist in computer-aided drug discovery. Our method, designated as SLIM, involves ligand-free shape and chemical feature matching. The procedure takes advantage of a negative image of a binding pocket in a target receptor. The negative image is a set of virtual atoms representing the inner shape and chemical features of the binding pocket. Using this image, SLIM implements a shape-based similarity search based on molecular volume superposition for the ensemble of conformers of each molecule. The superposed structures, prioritized by shape similarity, are subjected to comparison of chemical feature similarities. To validate the merits of the SLIM method, we compared its performance with those of three distinct widely used tools ROCS, GLIDE, and GOLD. ROCS was selected as a representative of the ligand-centric methods, and docking programs GLIDE and GOLD as representatives of the receptor-centric methods. Our data suggest that SLIM has overall hit ranking ability that is comparable to that of the docking method, retaining the high computational speed of the ligand-centric method. It is notable that the SLIM method offers consistently reliable screening quality against conformational variations of receptors, whereas the docking methods have limited screening performance.