Junctional Zone Research Articles

Placental glycosylation senses the anti-angiogenic milieu induced by human sFLT1 during pregnancy

Abnormal placental angiogenesis during gestation resulting from high levels of anti-angiogenic factors, soluble fms-like tyrosine kinase-1 (sFLT1) and soluble endoglin, has been implicated in the progression of preeclampsia (PE). This heterogeneous syndrome (defined by hypertension with or without proteinuria after 20 weeks of pregnancy) remains a major global health burden with long-term consequences for both mothers and child. Previously, we showed that in vivo systemic human (hsFLT1) overexpression led to reduced placental efficiency and PE-like syndrome in mice. Galectins (gal-1, −3 and −9) are critical determinants of vascular adaptation to pregnancy and dysregulation of the galectin-glycan circuits is associated with the development of this life-threatening disease. In this study, we assessed the galectin-glycan networks at the maternal-fetal interface associated with the hsFLT1-induced PE in mice. We observed an increase on the maternal gal-1 expression in the decidua and junctional zone layers of the placenta derived from hs FLT1high pregnancies. In contrast, placental gal-3 and gal-9 expression were not sensitive to the hsFLT1 overexpression. In addition, O- and N-linked glycan expression, poly-LacNAc sequences and terminal sialylation were down-regulated in hsFLT1 high placentas. Thus, the gal-1-glycan axis appear to play an important role counteracting the anti-angiogenic status caused by sFLT1, becoming critical for vascular adaptation at the maternal-fetal interface.

Manganese porphyrin-based treatment improves fetal-placental development and protects against oxidative damage and NLRP3 inflammasome activation in a rat maternal hypothyroidism model

Oxidative stress (OS) and endoplasmic reticulum stress (ERS) are at the genesis of placental disorders observed in preeclampsia, intrauterine growth restriction, and maternal hypothyroidism. In this regard, cationic manganese porphyrins (MnPs) comprise potent redox-active therapeutics of high antioxidant and anti-inflammatory potential, which have not been evaluated in metabolic gestational diseases yet. This study evaluated the therapeutic potential of two MnPs, [MnTE-2-PyP]5+ (MnP I) and [MnT(5-Br-3-E-Py)P]5+ (MnP II), in the fetal-placental dysfunction of hypothyroid rats. Hypothyroidism was induced by administration of 6-Propyl-2-thiouracil (PTU) and treatment with MnPs I and II 0.1 mg/kg/day started on the 8th day of gestation (DG). The fetal and placental development, and protein and/or mRNA expression of antioxidant mediators (SOD1, CAT, GPx1), hypoxia (HIF1α), oxidative damage (8-OHdG, MDA), ERS (GRP78 and CHOP), immunological (TNFα, IL-6, IL-10, IL-1β, IL-18, NLRP3, Caspase1, Gasdermin D) and angiogenic (VEGF) were evaluated in the placenta and decidua on the 18th DG using immunohistochemistry and qPCR. ROS and peroxynitrite (PRX) were quantified by fluorometric assay, while enzyme activities of SOD, GST, and catalase were evaluated by colorimetric assay. MnPs I and II increased fetal body mass in hypothyroid rats, and MnP I increased fetal organ mass. MnPs restored the junctional zone morphology in hypothyroid rats and increased placental vascularization. MnPs blocked the increase of OS and ERS mediators caused by hypothyroidism, showing similar levels of expression of HIFα, 8-OHdG, MDA, Gpx1, GRP78, and Chop to the control. Moreover, MnPs I and/or II increased the protein expression of SOD1, Cat, and GPx1 and restored the expression of IL10, Nlrp3, and Caspase1 in the decidua and/or placenta. However, MnPs did not restore the low placental enzyme activity of SOD, CAT, and GST caused by hypothyroidism, while increased the decidual and placental protein expression of TNFα. The results show that treatment with MnPs improves the fetal-placental development and the placental inflammatory state of hypothyroid rats and protects against oxidative stress and reticular stress caused by hypothyroidism at the maternal-fetal interface.

The association between sonographic features and clinical symptoms of adenomyosis.

To investigate the association of sonographic features and clinical symptoms of adenomyosis. This was a prospective observational study. Only reproductive age women who underwent standardized transvaginal ultrasound examination were included. The diagnosis of adenomyosis was based on sonographic features proposed by Morphological Uterus Sonographic Assessment (MUSA)group. Pictorial blood loss assessment chart (PBAC) and numerical rating scale (NRS) were respectively used for the evaluation of menstrual bleeding and pain. Fifty-three women were recruited. Adenomyosis group consisted of 33 (62.3%) representative cases, whereas control group consisted of 20 (37.7%). Women with adenomyosis experienced significantly heavier menstrual bleeding (p = 0.008) and more painful menstrual periods (p = 0.003). Significant positive correlation between the number of sonographic adenomyosis features and both PBAC (r = 0.613, p < 0.001) and NRS scores (r = 0.402, p = 0.022) was found. PBAC score was significantly higher if either fan-shaped shadowing (r = 0.548, p = 0.001), interrupted junctional zone (JZ) (r = 0.548, p = 0.001) or globular uterus (r = 0.445, p = 0.011) was detected. Interrupted JZ (r = 0.440, p = 0.012) was associated with higher NRS score. Significant positive correlation between PBAC score and adenomyosis spread in uterine layers (r = 0.495, p = 0.004) was established. Certain sonographic features of adenomyosis and assessment of its involvement in uterine layers may predict the severity of adenomyosis symptoms.

Maternal 129S1/SvImJ background attenuates the placental phenotypes induced by chronic paternal alcohol exposure

Paternal alcohol use is emerging as a plausible driver of alcohol-related growth and patterning defects. Studies from our lab using an inbred C57Bl/6 J mouse model suggest that these paternally-inherited phenotypes result from paternally programmed deficits in the formation and function of the placenta. The 129S1/SvImJ genetic background is typically more susceptible to fetoplacental growth defects due to strain-specific differences in placental morphology. We hypothesized that these placental differences would sensitize 129S1/SvImJ-C57Bl/6 J hybrid offspring to paternally-inherited fetoplacental growth phenotypes induced by paternal alcohol exposure. Using a limited access model, we exposed C57Bl/6 J males to alcohol and bred them to naïve 129S1/SvImJ dams. We then assayed F1 hybrid offspring for alterations in fetoplacental growth and used micro-CT imaging to contrast placental histological patterning between the preconception treatments. F1 hybrid placentae exhibit larger placental weights than pure C57Bl/6 J offspring but display a proportionally smaller junctional zone with increased glycogen content. The male F1 hybrid offspring of alcohol-exposed sires exhibit modest placental hyperplasia but, unlike pure C57Bl/6 J offspring, do not display observable changes in placental histology, glycogen content, or measurable impacts on fetal growth. Although F1 hybrid female offspring do not exhibit any measurable alterations in fetoplacental growth, RT-qPCR analysis of placental gene expression reveals increased expression of genes participating in the antioxidant response. The reduced placental junctional zone but increased glycogen stores of 129S1/SvImJ-C57Bl/6 J F1 hybrid placentae ostensibly attenuate the previously observed placental patterning defects and fetal growth restriction induced by paternal alcohol use in the C57Bl/6 J strain.

Venous Anatomy of the Superior and Inferior Sagittal Sinuses

The superior sagittal sinus(SSS)is contained within the dura, which consists of the dura propria and osteal dura at the junction of the falx cerebri, in addition to the attachment of the falx to the cranial vault. The SSS extends anteriorly from the foramen cecum and posteriorly to the torcular Herophili. The superior cerebral veins flow into the SSS, coursing under the lateral venous lacunae via bridging veins. Most of the bridging veins reach the dura and empty directly into the SSS. However, some are attached to the dural or existed in it for some distance before their sinus entrance. The venous structures of the junctional zone between the bridging vein and the SSS existed in the dura are referred to as dural venous channels. The SSS communicates with the lateral venous lacunae connecting the meningeal and diploic veins, as well as the emissary veins. These anatomical variations of the SSS are defined by the embryological processes of fusion and withdrawal of the sagittal plexus and marginal sinus.

Live birth from ovarian grafted tissue after pelvic radiation for rectal cancer

ObjectiveTo study the management of a woman who returned to conceive after high dose radiation treatment (RT), with documentation of uterine dosimetry, and the efficacy of ovarian tissue grafted into an irradiated pelvis. Design, setting, interventionA 26-year-old woman underwent RT to treat rectal cancer, with half of the uterus being exposed to a radiation dose of 50 Gy and 25 Gy to the fundus. We report details of the uterine assessment, determining suitability of conception with her own uterus, pregnancy surveillance and reproductive outcome. Main outcome measures, resultsThe results of MRI and pelvic ultrasound showed a small uterus with preserved junctional zone anatomy and while the endometrium was initially thin following administration of high oestrogen administration, endometrial thickness increased with time. Twelve grafted ovarian tissue stimulation cycles led to 4 embryo transfers, the last of which resulted in a live birth. She had two cervical cerclage procedures due to cervical shortening and delivered a 3.3kg healthy girl at 38/40 via LSCS. ConclusionsSuccessful pregnancy is possible from ovarian tissue grafted into an irradiated pelvis, with high dose uterine exposure. Careful uterine assessment needs to be undertaken to determine suitability of conception attempt with a patient’s own uterus, in consultation with the medical team. Further studies are needed to correlate imaging and biopsy findings with reproductive outcomes.

Label-free differentiation of functional zones in mature mouse placenta using micro-Raman imaging

In histopathology, it is highly crucial to have chemical and structural information about tissues. Additionally, the segmentation of zones within a tissue plays a vital role in investigating the functions of these regions for better diagnosis and treatment. The placenta plays a vital role in embryonic and fetal development and in diagnosing some diseases associated with its dysfunction. This study provides a label-free approach to obtain the images of mature mouse placenta together with the chemical differences between the tissue compartments using Raman spectroscopy. To generate the Raman images, spectra of placental tissue were collected using a custom-built optical setup. The pre-processed spectra were analyzed using statistical and machine learning methods to acquire the Raman maps. We found that the placental regions called decidua and the labyrinth zone are biochemically distinct from the junctional zone. A histologist performed a comparison and evaluation of the Raman map with histological images of the placental tissue, and they were found to agree. The results of this study show that Raman spectroscopy offers the possibility of label-free monitoring of the placental tissue from mature mice while simultaneously revealing crucial structural information about the zones.

Assessment of feto-placental oxygenation and perfusion in a rat model of placental insufficiency using T2* mapping and 3D dynamic contrast-enhanced MRI

IntroductionPlacental insufficiency may lead to preeclampsia and fetal growth restriction. There is no cure for placental insufficiency, emphasizing the need for monitoring fetal and placenta health. Current monitoring methods are limited, underscoring the necessity for imaging techniques to evaluate fetal-placental perfusion and oxygenation. This study aims to use MRI to evaluate placental oxygenation and perfusion in the reduced uterine perfusion pressure (RUPP) model of placental insufficiency. MethodsPregnant rats were randomized to RUPP (n = 11) or sham surgery (n = 8) on gestational day 14. On gestational day 19, rats imaged using a 7T MRI scanner to assess oxygenation and perfusion using T2* mapping and 3D-DCE MRI sequences, respectively. The effect of the RUPP on the feto-placental units were analyzed from the MRI images. ResultsRUPP surgery led to reduced oxygenation in the labyrinth (24.7 ± 1.8 ms vs. 28.0 ± 2.1 ms, P = 0.002) and junctional zone (7.0 ± 0.9 ms vs. 8.1 ± 1.1 ms, P = 0.04) of the placenta, as indicated by decreased T2* values. However, here were no significant differences in fetal organ oxygenation or placental perfusion between RUPP and sham animals. DiscussionThe reduced placental oxygenation without a corresponding decrease in perfusion suggests an adaptive response to placental ischemia. While acute reduction in placental perfusion may cause placental hypoxia, persistence of this condition could indicate chronic placental insufficiency after ischemic reperfusion injury. Thus, placental oxygenation may be a more reliable biomarker for assessing fetal condition than perfusion in hypertensive disorders of pregnancies including preeclampsia and FGR.

Clinical and ultrasonographic characteristics of pregnancy-related enhanced myometrial vascularity: prospective cohort study.

To assess the ultrasonographic, epidemiological, clinical and evolutive characteristics of enhanced myometrial vascularity (EMV) following a first-trimester termination of pregnancy (TOP) or management of non-viable pregnancy. This prospective study included women who underwent follow-up ultrasound examination 5-6 weeks after a first-trimester TOP or after management of a first-trimester non-viable pregnancy at the University Hospital Polyclinic San Martino of Genoa between March 2021 and March 2022. EMV was characterized using two- and three-dimensional ultrasound and Virtual Organ Computer-aided Analysis. Ultrasonographic diagnosis of EMV was made when an unusual, tortuous myometrial vessel structure, with high-velocity blood flow, protruding towards the endometrium was observed, while an abnormal junctional zone, absent endometrial midline and heterogeneous endometrium supported the diagnosis. Patients with EMV underwent expectant management with planned ultrasonographic follow-up every 2 weeks until resolution. During the study period, 305 women underwent TOP, of whom 132 attended the initial follow-up 5-6 weeks later, at which 52 were diagnosed with EMV. Ninety-six women were managed for a non-viable pregnancy, of whom 32 presented for follow-up, at which six had a diagnosis of EMV. Thus, overall, 164 of 401 women were included in the study and EMV was identified in 58 (35%) of these. The prevalence of EMV 5-6 weeks after a TOP was therefore between 52/305 (17%) and 52/132 (39%), and that after management of a non-viable pregnancy was between 6/96 (6%) and 6/32 (19%). Bleeding/pelvic pain was present in half (29/58) of the women with EMV, and serum human chorionic gonadotropin was detectable in 29% (17/58) at the first follow-up examination. At ultrasound assessment, all cases with EMV presented abundant tortuous myometrial vessels with high-velocity flow projecting from the myometrium towards the endometrium, along with non-uniform heterogeneous endometrium in 97% of cases, which often (67% of these) contained cystic areas, absence of the endometrial midline in 98% of cases and an abnormal junctional zone in 97% of cases (64% interrupted, 33% irregular). Most (67%) women with EMV were parous and 90% of them had undergone TOP rather than management for a non-viable pregnancy. Medical management of the TOP or non-viable pregnancy was more frequent in women with than those without EMV (93% vs 77%, P = 0.023). Multiple regression analysis showed the risk of EMV to be increased following TOP vs non-viable pregnancy (odds ratio (OR), 3.67 (95% CI, 1.16-11.56), P = 0.026) and in parous compared with nulliparous women (OR, 2.95 (95% CI, 1.45-6.01), P = 0.002). All women with EMV underwent expectant management. Eleven women did not return for subsequent follow-up examinations and did not present to our outpatient or emergency facilities, so were lost to further follow-up. Spontaneous resolution of the lesion was observed within 7-16 weeks after the procedure in 96% (45/47) of the remaining cases. Two women chose to undergo surgery for pelvic discomfort, and histology showed the presence of neovessels mixed with retained chorionic villi. EMV is a transient and common finding 5-6 weeks following first-trimester TOP or management of non-viable pregnancy. TOP and being parous are risk factors for EMV. Expectant management of EMV is appropriate, because, in almost all cases, this resolves spontaneously, without complications, within 2-4 months. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Maternal RNA transcription in Dlk1-Dio3 domain is critical for proper development of the mouse placental vasculature

The placenta is a unique organ for ensuring normal embryonic growth in the uterine. Here, we found that maternal RNA transcription in Dlk1-Dio3 imprinted domain is essential for placentation. PolyA signals were inserted into Gtl2 to establish a mouse model to prevent the expression of maternal RNAs in the domain. The maternal allele knock-in (MKI) and homozygous (HOMO) placentas showed an expanded junctional zone, reduced labyrinth and poor vasculature impacting both fetal and maternal blood spaces. The MKI and HOMO models displayed dysregulated gene expression in the Dlk1-Dio3 domain. In situ hybridization detected Dlk1, Gtl2, Rtl1, miR-127 and Rian dysregulated in the labyrinth vasculature. MKI and HOMO induced Dlk1 to lose imprinting, and DNA methylation changes of IG-DMR and Gtl2-DMR, leading to abnormal gene expression, while the above changes didn’t occur in paternal allele knock-in placentas. These findings demonstrate that maternal RNAs in the Dlk1-Dio3 domain are involved in placental vasculature, regulating gene expression, imprinting status and DNA methylation.

Parasagittal and Superior Sagittal Sinus Dural Arteriovenous Fistulas: Clinical Presentations, Imaging Characteristics, and Treatment Strategies.

Parasagittal and superior sagittal sinus (SSS) dural arteriovenous fistulas (DAVFs) are often inappropriately classified. We explore the clinical presentations, imaging characteristics, and endovascular treatment strategies of these 2 DAVF subtypes. Clinical and imaging data of 19 patients with SSS or parasagittal sinus DAVFs who underwent endovascular treatment in our institution between 2017 and 2022 were retrospectively analyzed. The angiographic findings, endovascular treatment strategies, and angiographic outcomes were evaluated and recorded. Among these 19 patients, 14 had a parasagittal DAVF, 4 had a SSS DAVF, and 1 patient had both parasagittal and SSS DAVF. Only 1 (1/19, 5.26%) patient presented with intracranial hemorrhage. For the parasagittal DAVF group, most of the shunts were located along the middle third of the SSS (12/15, 80%), on the dura in proximity with the junctional zone between the bridging vein and SSS (15/15, 100%), with ipsilateral cortical venous reflux (CVR) (15/15, 100%). For the SSS DAVF group, all 5 patients had shunting zone along the middle third of the SSS, on the sinus or parasinus wall, with bilateral CVR. Transarterial embolization, via the middle meningeal artery as the primary route of access, was the primary treatment approach in 95% of cases (19/20). Reflux of embolization material into the SSS was observed in 1 case (1/5, 20%) of SSS DAVF in which balloon sinus protection was not used during embolization. Our study found that parasagittal DAVFs have shunting point(s) centered on the junctional zone of the bridging vein and the SSS with ipsilateral CVR, while SSS DAVFs have shunting point(s) centered on the sinus or parasinus wall with bilateral CVR. Transarterial embolization via the middle meningeal artery can be used as the primary treatment strategy in most cases. Balloon sinus protection during embolization is not necessary in cases of parasagittal DAVF with occluded or stenosed connection with the SSS but its use should be considered in cases of SSS DAVF with patent sinus.

Modulatory effects of quercetin on histological changes, biochemical and oxidative stress of rat placenta induced by inhalation exposure to crude oil vapor

The inhalation exposure to crude oil vapor (COV) has been shown to have adverse effects on the placenta and fetal development. The modulatory effects of quercetin (QUE) as a natural phenolic compound with antioxidant properties are promising for the protection of placental structure. This study aimed to investigate the modulatory role of QUE in mitigating histopathological damage, oxidative stress, and biochemical alteration in the placenta of COV-exposed pregnant rats. Forty-eight pregnant rats were divided into eight groups (days 15 and 20) as follows: 1–2) Control groups, 3–4) COV groups, 5–6) COV+QUE groups, and 7–8) QUE-treated groups (50 mg/kg). The inhalation method was used to expose pregnant rats to COV, and QUE was administered orally. On the 15th and 20th days of gestation, placental tissue was analyzed using PAS and H&E staining and immunohistochemistry. The expression of the caspase-3 gene and oxidative stress biomarkers including TAC, CAT, MDA, GPx, and SOD were investigated in the placental tissue. The COV significantly decreased the weight, diameter, and thickness of the placenta as well as the thickness of the junctional zone and labyrinth and the number of trophoblast giant cells in 15- and 20-day-old placentas (P<0.05). Also, COV significantly increased placental expression of caspase-3 and the oxidative stress biomarkers (P<0.05). The administration of QUE along with exposure to COV reduced morphometric and histological alteration, oxidative stress, and caspase-3 expression (P<0.05). Our findings indicated that QUE in COV-exposed pregnant rats can prevent placental histopathological alternations by increasing the activity of the antioxidant system.

Perfusion magnetic resonance imaging in Asherman syndrome.

Microvascular scarring compromises the functionality of the endometrium, and vascular flow at the junctional zone (JZ) may be the key to understanding poor reproductive outcomes in women with Asherman syndrome (AS). To investigate whether vascular perfusion of the uterus, measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is impaired in women with intrauterine adhesions (IUA) and AS. A prospective observational cohort pilot study of 23 women with IUA treated with hysteroscopic synecholysis and a control group of two patients with cervix cancer were subject to DCE-MRI with gadolinium to assess uterine vascularity. Twelve regions of interest (ROIs) were allocated on the DCE-MRI image incorporating the JZ, with control ROI placed at the psoas muscle. Individual ROIs were compared to the mean total perfusion (TP) in the same uterus. Pre- and post-operative perfusion analyses were performed on five women. Receiver operator curves (ROC) were used to analyse MRI as a predictor of IUA. There was no significant difference in perfusion; a trend toward reduced perfusion was observed in women with IUA compared to the controls. The ROC was predictive of higher-grade and inoperable IUA. Reduced perfusion on DCE-MRI as assessed by ROC predicted higher-stage AS. The results of this study support further investigation of DCE-MRI as a prognostic tool for AS prior to surgical intervention to assist in providing prognostic guidance for women suffering from AS.

Visual Sensitivity Loss in Geographic Atrophy: Structure-Function Evaluation Using Defect-Mapping Microperimetry.

To examine the structure-function relationship in eyes with geographic atrophy (GA) using defect-mapping microperimetry, a testing strategy optimized to quantify the spatial extent of deep visual sensitivity losses. Fifty participants with GA underwent defect-mapping microperimetry testing of the central 8°-radius region (208 locations tested once with a 10-decibel stimuli) and fundus autofluorescence imaging in one eye. The GA extent in the corresponding central 8°-radius was derived by manual annotations and image co-registration to examine the global structure-function relationship. The distance of each test location from the GA margin was also derived, and regions defined, to examine the local structure-function relationship. GA extent in the central 8° explained a substantial proportion of variance in the percentage of locations missed (nonresponse) on microperimetry at the global level (R2=0.90). At a local level, the probability of missing stimuli at the outer junctional zone (0-500 µm outside the GA margin) and GA margin (probability=7% and 34%, respectively) was higher than at the outer nonlesional zone (>500 µm outside the GA margin; probability=2%; P<0.001 for both). The probability of missing stimuli at the inner junctional zone (0-250 µm inside the GA margin) was also lower than at the inner lesional zone (>250 µm inside the GA margin; probability=64% and 88%; P<0.001). This study confirms the expected functional relevance of the region with GA on fundus autofluorescence imaging and underscores the potential effectiveness of defect-mapping microperimetry testing for capturing visual function changes when evaluating new GA treatments.

Uterine peristalsis in women affected by adenomyosis: A step towards functional assessment.

The non-pregnant uterus shows an intrinsic contractility pattern, actively involved in early reproductive processes. Uterine contractility is characterized by endometrial waves that originate from the junctional zone and varies throughout the menstrual cycle due to fluctuations in the concentrations of hormones. The aim of this study was to compare the uterine contractility patterns in the periovulatory phase in a group of patients with isolated adenomyosis and a group of healthy women using transvaginal ultrasound (TVUS). From March 2019 to March 2021, we enrolled consecutive nulliparous patients in the periovulatory phase of the menstrual cycle, divided in patients with isolated adenomyosis (group A, n = 18) and healthy patients in the control group (group B, n = 18). Patients who met the inclusion criteria underwent TVUS for the study of uterine contractility: the uterus was scanned on sagittal plane for 3 min and all the movies were recorded. Then, static images and video were evaluated offline and the uterine contractility patterns were defined. The patients belonging to the study group had a higher incidence of painful symptoms (dysmenorrhea, 6.11 ± 2.81 vs 1.39 ± 2.17; chronic pelvic pain, 2.56 ± 3.01 vs 0.39 ± 1.04) and a larger uterine volume (137.48 ± 117.69 vs 74.50 ± 27.58 cm3; P = 0.04). Regarding the uterine contractility, a statistically significant difference was observed about the retrograde patterns (group A, 27.8% vs group B, 72.2%, P < 0.01) and opposing (group A, 38.9% vs, group B, 5.6%, P = 0.02). The study confirms the presence of altered uterine peristalsis in the periovulatory phase in patients with adenomyosis. The abnormal uterine peristalsis could lead to both structural and functional changes, which are the basis of the clinical manifestations of adenomyosis and the perpetuation of the anatomical damage.

Monitoring Contractility of Junctional Zone Endometrium across Menstrual Cycle Using the ElectroUteroGraph (EUG): A Clinical Evaluation

(1) Background: Abnormal uterine contractility for nonpregnant women has been associated with gynecological pathologies and infertility. The objective of this study was to evaluate the ability of a novel monitoring technique to assess the contractility of the nongravid uterus using a simple, standardized, direct, in vivo methodology during the different phases of the menstrual cycle. (2) Methods: Twenty-six healthy women of reproductive age (28–48 years) were recruited. An ElectroUteroGraph (EUG) was used to measure the electrical activity from the contractility of the junctional zone endometrium (JZE) across the menstrual cycle. Derived recordings were separated into the early proliferative (EP) (n = 10), late proliferative (LP) (n = 31), early luteal (EL) (n = 27), and late luteal (LL) (n = 12) phases of the menstrual cycle. EUG recordings were performed by inserting a flexible electrode array into the endometrial cavity. (3) Results: Waveforms that were measured from the electrode closer to the fundus (1 cm distance) were processed. The Root-Mean-Square (RMS) Voltage Amplitude (VJZE-RMS) (in μV) and the Mean Frequency (fJZE-mean) (in cycles/min) of the JZE’s electrical activity, as direct indicators of the intensity and frequency changes in the JZE’s contractions, were extracted from the recorded waveforms. There was a trend in the median values of the VJZE-RMS decreasing from the EP to the LP phase (247–158 μV). During the EL phase, an upward trend was observed (158–374 μV, p &lt; 0.05), reaching its highest value during the LL phase (374–477 μV, p &lt; 0.05) when compared to the LP phase. The fJZE-mean showed the opposite trend, increasing from 2.5 cycles/min during the EP phase to 2.96 cycles/min during the LP phase. During the EL phase, a downward trend was observed (2.96–2.37 cycles/min), continuing to fall to 1.33 cycles/min, in the LL phase, with p &lt; 0.05 when compared to the previous three phases. (4) Conclusions: The novel in vivo monitoring technique has shown clinically, for the first time, significant electrical activity differences in the different sub-phases of the menstrual cycle, recorded in a safe and painless way.

Nerve Sheath Tumours In and Around Spine—A Series of 50 Cases

Abstract Background: Nerve sheath tumours in and around the spine, especially in the junctional zones, are a challenging endeavour for the surgeon, because of the difficulty in approaching these structures as well as their close proximity to the major vessels and nerves. Most of these tumours are benign in nature. They are usually very slow growing, and hence the tumour may be detected very late in its clinical course unless it compresses or encircles any of the major neurovascular structures early in its course. The surgical results after the excision of these tumours are excellent. Most of the patients get completely cured by prompt treatment. Here we present a series of 50 nerve sheath tumours in and around the spine operated over a period of 21 years. Materials and Methods: A retrospective study was done for 50 patients who underwent an operation for nerve sheath tumours in and around the spine, over a period of 21 years. Patient’s clinical and radiological data were extracted from the Medical Record Department (MRD) of our hospital and analysed. Results: Out of the 50 cases of nerve sheath tumours, 40 patients (80%) were of schwannoma and 10 patients (20%) were of neurofibroma. Overall, 10 patients had dumbbell tumours (neurofibroma+schwannoma). The mean age group was between 4th and 6th decade. Patients were followed up for a minimum of 1 year and a maximum of 20 years period. All of these tumours were benign except one patient who had a malignant neurofibroma of the C-8 nerve root. 15 out of 50 patients presented with paraparesis, 5 with paraplegia and another 5 with quadriparesis. All these patients had complete neurological recovery after surgical removal of the tumours. Conclusion: This case series brings out the nuances in the management of nerve sheath tumours in and around the spine and their results.

Prediction of adenomyosis according to revised definitions of morphological uterus sonographic assessment features.

This study aimed to predict the diagnosis of adenomyosis by revised definitions of morphological uterus sonographic assessment (MUSA) features in individuals who had hysterectomy. This was retrospective cohort research conducted at a tertiary facility. Between January 2022 and January 2023, 196 individuals who had hysterectomy were analyzed in the research. The revised definitions of MUSA features of the adenomyosis approach were used to record the direct and indirect results of the sonography. The cases were classified as Group 1 (adenomyosis; n = 40, 20.4%) and Group 2 (control; n = 156, 79.6%) according to histopathology reports. Hyperechogenic islands and echogenic subendometrial buds and lines were the most predictive direct features (p = 0.02). Globular uterus and irregular junctional zone were the most predictive indirect features (p = 0.04; p = 0.03, respectively). Among all indirect features, the globular uterus was the most predictive (p = 0.02). Total feature >4 was determined as the significant cutoff value to predict adenomyosis (p < 0.001). This study shows that combinations with a total number of features >4 can be practically used in the evaluation of adenomyosis using the revised definitions of MUSA features.

Maternal nano-titanium dioxide inhalation exposure alters placental cyclooxygenase and oxidant balance in a sexually dimorphic manner

The placenta plays a critical role in nutrient-waste exchange between the maternal and fetal circulation, and thus impacts fetal growth and development. We have previously shown that nano-titanium dioxide (nano-TiO2) inhalation exposure during gestation decreased fetal female pup and placenta mass [1], which persists in the following generation [2]. In utero exposed females, once mated, their offspring's placentas had increased capacity for H2O2 production. Generation of oxidants such as hydrogen peroxide (H2O2), have been shown to impact cyclooxygenase activity, specifically metabolites such as prostacyclin (PGI2) or thromboxane (TXA2). Therefore, we hypothesized that maternal nano-TiO2 inhalation exposure during gestation results in alterations in placental production of prostacyclin and thromboxane mediated by enhanced H2O2 production in a sexually dimorphic manner. Pregnant Sprague-Dawley rats were exposed to nano-TiO2 aerosols or filtered air (sham-control) from gestational day (GD) 10–19. Dams were euthanized on GD 20, and fetal serum and placental tissue were collected based on fetal sex. Fetal placental zones (junctional zone (JZ) and labyrinth zone (LZ)) were assessed for xanthine oxidoreductase (XOR) activity, H2O2, and catalase activity, as well as 6-keto-PGF1α and TXB2 levels. Nano-TiO2 exposed fetal female LZ demonstrated significantly greater XOR activity compared to exposed males. Exposed fetal female LZ also demonstrated significantly diminished catalase activity compared to sham-control females. Exposed fetal female LZ had significantly increased abundance of 6-keto-PGF1α compared to sham-control females and increased TXB2 compared to exposed males. In the aggregate these data indicate that maternal nano-TiO2 inhalation exposure has a greater impact on redox homeostasis and PGI2/TXA2 balance in the fetal female LZ. Future studies need to address if treatment with an XO inhibitor during gestation can prevent diminished fetal female growth during maternal nano-TiO2 inhalation exposure.

Adenomyosis diagnosis among adolescents and young women with dysmenorrhoea and heavy menstrual bleeding

Research questionWhat is the prevalence of adenomyosis at ultrasonography among adolescents and young women reporting dysmenorrhoea and/or heavy menstrual bleeding (HMB)? DesignThis observational cohort study involved adolescents and young women referred for dysmenorrhoea and/or HMB to the Adolescent Medicine Unit at Careggi University Hospital, Italy. Patients with endometriosis and bleeding disorders were excluded. Transvaginal ultrasonography or transrectal sonography using a transvaginal probe was performed. The myometrium was described according to the Morphological Uterus Sonographic Assessment criteria. Details of baseline characteristics, clinical data and symptoms were collected. The presence of sonographic features of adenomyosis and the association between imaging findings and clinical symptoms were evaluated. ResultsThe cohort included 95 patients aged between 13 and 25 years, referred for dysmenorrhoea (88.4%), HMB (23.2%) or both (13.7%). According to the MUSA criteria the sonographic diagnosis of adenomyosis was made in 27.4% of patients, with the diffuse type the most prevalent. Uterine wall asymmetry, hyperechoic intramyometrial islands, translesional vascularity and an interrupted junctional zone were the most common features. Patients with imaging findings of adenomyosis had significantly higher rates of HMB than those with a normal myometrial appearance (38.5% versus 17.4%, P = 0.030). In addition, the coexistence of dysmenorrhoea and HMB was significantly associated with adenomyosis (odds ratio 5.68, 95% confidence interval 1.65–19.5). ConclusionsAdenomyosis may be diagnosed among teenagers and young women referred with dysmenorrhoea and/or HMB. The clinical presentation is relevant for the diagnosis, with HMB alone and HMB plus dysmenorrhoea significantly associated with the sonographic identification of adenomyosis.