Causes and Effects of COVID-19 Vaccine Hesitancy Among Pregnant Women and its Association with Adverse Maternal, Placental, and Perinatal Outcomes.

Populations identified to be severely affected by COVID-19, such as pregnant patients, require special consideration in vaccine counseling, access, and provider education. Maternal infection with COVID-19 poses a significant risk to the maternal-fetal dyad with known adverse placenta destruction [1-5]. Despite the widespread access and availability of vaccinations, vaccine hesitancy continues to persist and is highly prevalent in pregnant populations [6-9]. Addressing the multitude of social ecological factors surrounding vaccine hesitancy can aid in providing holistic counseling [10]. However, such factors are foremost shaped by maternal concern over possible fetal effects from vaccination. While changes in policy can help foster vaccine access and acceptance, increasing global provider education and incorporation of motivational interviewing skills are the first steps towards increasing maternal acceptance.

Characteristics and treatment for severe postpartum haemorrhage in different midwifery hospitals in one district of Beijing in China: an institution-based, retrospective cohort study.

OBJECTIVE: To identify the characteristics and treatment approaches for patients with severe postpartum haemorrhage (SPPH) in various midwifery institutions in one district in Beijing, especially those without identifiable antenatal PPH high-risk factors, to improve regional SPPH rescue capacity. DESIGN: Retrospective cohort study. SETTING: This study was conducted at 9 tertiary-level hospitals and 10 secondary-level hospitals in Haidian district of Beijing from January 2019 to December 2022. PARTICIPANTS: The major inclusion criterion was SPPH with blood loss ≥1500 mL or needing a packed blood product transfusion ≥1000 mL within 24 hours after birth. A total of 324 mothers with SPPH were reported to the Regional Obstetric Quality Control Office from 19 midwifery hospitals. OUTCOME MEASURES: The pregnancy characteristics collected included age at delivery, gestational weeks at delivery, height, parity, delivery mode, antenatal PPH high-risk factors, aetiology of PPH, bleeding amount, PPH complications, transfusion volume and PPH management. SPPH characteristics were compared between two levels of midwifery hospitals and their association with antenatal PPH high-risk factors was determined. RESULTS: SPPH was observed in 324 mothers out of 106 697 mothers in the 4 years. There were 74.4% and 23.9% cases of SPPH without detectable antenatal PPH high-risk factors in secondary and tertiary midwifery hospitals, respectively. Primary uterine atony was the leading cause of SPPH in secondary midwifery hospitals, whereas placental-associated disorders were the leading causes in tertiary institutions. Rates of red blood cell transfusion over 10 units, unscheduled returns to the operating room and adverse PPH complications were higher in patients without antenatal PPH high-risk factors. Secondary hospitals had significantly higher rates of trauma compared with tertiary institutions. CONCLUSION: Examining SPPH cases at various institutional levels offers a more comprehensive view of regional SPPH management and enhances targeted training in this area.

Placental ontogeny in the Yucca Night Lizard, Xantusia vigilis.

Squamate placentas support physiological exchange between mothers and embryos. Uterine and embryonic epithelial cells provide sites for transporting mechanisms and extraembryonic membranes provide the scaffolding for embryonic epithelial cells and vascular systems. Diversity in placental structure involves variation in extraembryonic membrane development as well as epithelial cell specializations. Variation in placental ontogeny is known to occur and, although lineage specific patterns have been described, phylogenetic distribution of specific patterns is poorly understood. Xantusia vigilis is a viviparous lizard in a monophyletic clade, Xantusiidae, of predominantly viviparous species. Xantusiidae is one of two viviparous lineages within the clade Scincoidea that provides an important outgroup comparison for Scincidae, which includes the largest number of independent origins of viviparity among Squamata. Previous reports contain brief descriptions of placental structure of X vigilis but the developmental pattern is unknown including relevant details for comparison with skinks. We studied placental ontogeny in X. vigilis to address two hypotheses: (1) the pattern of development of placental architecture is similar to species of Scincidae and, (2) placental epithelial cell specializations are similar to species of Scincidae. The terminal placental stage of X. vigilis is similar to skinks in that it includes a chorioallantoic placenta and an omphaloplacenta. The chorioallantoic placenta is richly vascularized with thin, squamous epithelial cells separating the two vascular systems. This morphology differs from the elaborate epithelial cell specializations as occur in some skink species, but is similar to many species. Epithelial cells of the omphaloplacenta are enlarged, as they are in scincids, yet development of the omphaloplacenta includes a vascular pattern known to occur only in gerrhonotine lizards. Histochemical staining properties of the epithelium of the omphalopleure of the omphaloplacenta indicate the potential for protein transport, a function not previously reported for lizards.

A realistic aneurysm clipping simulation combining 3D-printed and placenta-based models-how I do it.

INTRODUCTION: Neurovascular surgery, particularly aneurysm clipping, is a critical skill for aspiring neurosurgeons. However, hands-on training opportunities are limited, especially with the growing popularity of endovascular techniques. To address this challenge, we present a novel neurovascular surgical training station that combines synthetic 3D-printed models with placental vascular structures to create a semi-realistic surgical field. METHODS: Our model consists of three components: a 3D-printed skull replica with anatomical landmarks, a malleable silicone parenchyma with a Sylvian fissure, and vascular layers (placenta). The placental vascular layer is catheterized and perfused to replicate pulsatile flow, offering a realistic aneurysm simulation. This innovative training station provides a cost-effective solution (approximately 200 USD once) without ethical constraints. Surgeons can practice essential skills such as Sylvian fissure dissection, managing anatomical constraints like bone, and achieving proximal vascular control. The model's realism allows for training in various scenarios, including clipping with different hand orientations and handling ruptures realistically. CONCLUSION: Our neurovascular surgical station bridges the gap between existing training models, offering affordability, ecological considerations, and minimal ethical concerns. It empowers neurosurgery residents to refine their skills in handling both emergencies and elective cases under close-to-real surgical conditions, with the potential for independent practice and senior supervision.

CircTHBS1 promotes trophoblast cell migration and invasion and inhibits trophoblast apoptosis by regulating miR-136-3p/IGF2R axis.

The precise molecular mechanism behind fetal growth restriction (FGR) is still unclear, although there is a strong connection between placental dysfunction, inadequate trophoblast invasion, and its etiology and pathogenesis. As a new type of non-coding RNA, circRNA has been shown to play a crucial role in the development of FGR. This investigation identified the downregulation of hsa_circ_0034533 (circTHBS1) in FGR placentas through high-sequencing analysis and confirmed this finding in 25 clinical placenta samples using qRT-PCR. Subsequent in vitro functional assays demonstrated that silencing circTHBS1 inhibited trophoblast proliferation, migration, invasion, and epithelial mesenchymal transition (EMT) progression and promoted apoptosis. Furthermore, when circTHBS1 was overexpressed, cell function experiments showed the opposite result. Analysis using fluorescence in situ hybridization revealed that circTHBS1 was primarily found in the cytoplasmic region. Through bioinformatics analysis, we anticipated the involvement of miR-136-3p and IGF2R in downstream processes, which was subsequently validated through qRT-PCR and dual-luciferase assays. Moreover, the inhibition of miR-136-3p or the overexpression of IGF2R partially reinstated proliferation, migration, and invasion abilities following the silencing of circTHBS1. In summary, the circTHBS1/miR-136-3p/IGF2R axis plays a crucial role in the progression and development of FGR, offering potential avenues for the exploration of biological indicators and treatment targets.

Umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia: a systematic review and meta-analysis.

BACKGROUND: Placental management strategies such as umbilical cord milking and delayed cord clamping may provide a range of benefits for the newborn. The aim of this review was to assess the effectiveness of umbilical cord milking and delayed cord clamping for the prevention of neonatal hypoglycaemia. METHODS: Three databases and five clinical trial registries were systematically reviewed to identify randomised controlled trials comparing umbilical cord milking or delayed cord clamping with control in term and preterm infants. The primary outcome was neonatal hypoglycaemia (study defined). Two independent reviewers conducted screening, data extraction and quality assessment. Quality of the included studies was assessed using the Cochrane Risk of Bias tool (RoB-2). Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Meta-analysis using a random effect model was done using Review Manager 5.4. The review was registered prospectively on PROSPERO (CRD42022356553). RESULTS: Data from 71 studies and 14 268 infants were included in this review; 22 (2 537 infants) compared umbilical cord milking with control, and 50 studies (11 731 infants) compared delayed with early cord clamping. For umbilical cord milking there were no data on neonatal hypoglycaemia, and no differences between groups for any of the secondary outcomes. We found no evidence that delayed cord clamping reduced the incidence of hypoglycaemia (6 studies, 444 infants, RR = 0.87, CI: 0.58 to 1.30, p = 0.49, I2 = 0%). Delayed cord clamping was associated with a 27% reduction in neonatal mortality (15 studies, 3 041 infants, RR = 0.73, CI: 0.55 to 0.98, p = 0.03, I2 = 0%). We found no evidence for the effect of delayed cord clamping for any of the other outcomes. The certainty of evidence was low for all outcomes. CONCLUSION: We found no data for the effectiveness of umbilical cord milking on neonatal hypoglycaemia, and no evidence that delayed cord clamping reduced the incidence of hypoglycaemia, but the certainty of the evidence was low.

Inadvertent antibiotic exposure during pregnancy may increase the risk for neural tube defects in offspring.

BACKGROUND: As emerging environmental contaminants, antibiotics pose potential threats to human health, in particular to pregnant women and infants. However, the potential harm of inadvertent antibiotic exposure (IAE) is often disregarded in light of the focus on intentional antibiotic use during pregnancy. Currently, little is known about the effects of IAE during pregnancy on fetal neural tube development. METHODS: In this case-control study, we used questionnaire data from 855 subjects to investigate the effects of intentional antibiotic use in early pregnancy on neural tube defects (NTDs). Then we tested for placental antibiotics in mothers who had not intentionally used antibiotics, and the compounds were detected in 379 subjects; these were considered IAE cases. We assessed the association between IAE during pregnancy and fetal NTDs using both multivariable logistic and multi-pollutant exposure models. We also analyzed the correlation between maternal dietary habits and placental antibiotics to explore possible sources of IAE. RESULTS: Only 50 of 855 participants (5.8%) intentionally used antibiotics and such use showed no significant association with NTD risk (odds ratio [OR] = 1.92, confidence interval [95%CI] = [0.66, 5.59]). However, 14 of 15 placental antibiotics were detected in 378 of 379 subjects (99.7%) and multivariable logistic analysis indicated that high levels of placental macrolides were significantly associated with increased NTD risk (4.42 [2.01-10.45]). Multi-pollutant exposure analysis suggested an increase in NTD risk with an increase in exposure to a mixture of placental antibiotics, among which macrolides were the most important contributor. In addition, the level of placental macrolides was positively correlated with the intake frequency of milk. Finally, mothers who drank river, well, or pond water had higher levels of placental macrolides than those who drank only tap water. CONCLUSIONS: Intentional antibiotic use during early pregnancy may not be associated with NTDs, while IAE during pregnancy is associated with higher NTD risk in offspring. Macrolides are crucial risk factors. Milk, and river, well, or pond water may be important sources of IAE.

Gestational diabetes mellitus enhances cobalt placental transfer efficiency between mother and infant.

Background: The fetal stage is pivotal for growth and development, making it susceptible to the adverse effects of prenatal metal(loid)s exposure. This study evaluated the influence of gestational diabetes mellitus (GDM) on the placental transfer efficiency (PTE) of metal(loid)s and thus assessed the associated risks of prenatal metal(loid)s exposure.Materials and method: Designed as a case-control study, it incorporated 114 pregnant participants: 65 without complications and 49 diagnosed with GDM. We utilized inductively coupled plasma mass spectrometry to quantify seven metal(loid)s - manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), gallium (Ga), arsenic (As), and cadmium (Cd) - in both maternal venous blood and umbilical cord blood.Result: We compared metal(loid)s concentrations and their PTE in the maternal and cord blood between the two groups. Notably, Cu, Ga, As, and Co levels in the umbilical cord blood of the GDM group (657.9 ± 167.2 µg/L, 1.23 ± 0.34 µg/L, 5.19 ± 2.58 µg/L, 1.09 ± 2.03 µg/L) surpassed those of the control group, with PTE of Co showing a marked increase in GDM group (568.8 ± 150.4 µg/L, 1.05 ± 0.31 µg/L, 4.09 ± 2.54 µg/L, 0.47 ± 0.91 µg/L), with PTE of Co showing a marked increase in GDM group (p < 0.05). The PTE of Ni exhibited a reduction in the GDM group relative to the control group, yet this decrease did not reach statistical significance.Conclusion: This study indicates that GDM can influence the placental transfer efficiency of certain metal(loid)s, leading to higher concentrations of Co, Cu, Ga, and As in the umbilical cord blood of the GDM group. The marked increase in the PTE of Co suggests a potential link to placental abnormal angiogenesis due to GDM.

The CD4 transmembrane GGXXG and juxtamembrane (C/F)CV+C motifs mediate pMHCII-specific signaling independently of CD4-LCK interactions.

CD4+ T cell activation is driven by five-module receptor complexes. The T cell receptor (TCR) is the receptor module that binds composite surfaces of peptide antigens embedded within MHCII molecules (pMHCII). It associates with three signaling modules (CD3γε, CD3δε, and CD3ζζ) to form TCR-CD3 complexes. CD4 is the coreceptor module. It reciprocally associates with TCR-CD3-pMHCII assemblies on the outside of a CD4+ T cells and with the Src kinase, LCK, on the inside. Previously, we reported that the CD4 transmembrane GGXXG and cytoplasmic juxtamembrane (C/F)CV+C motifs found in eutherian (placental mammal) CD4 have constituent residues that evolved under purifying selection (Lee et al., 2022). Expressing mutants of these motifs together in T cell hybridomas increased CD4-LCK association but reduced CD3ζ, ZAP70, and PLCγ1 phosphorylation levels, as well as IL-2 production, in response to agonist pMHCII. Because these mutants preferentially localized CD4-LCK pairs to non-raft membrane fractions, one explanation for our results was that they impaired proximal signaling by sequestering LCK away from TCR-CD3. An alternative hypothesis is that the mutations directly impacted signaling because the motifs normally play an LCK-independent role in signaling. The goal of this study was to discriminate between these possibilities. Using T cell hybridomas, our results indicate that: intracellular CD4-LCK interactions are not necessary for pMHCII-specific signal initiation; the GGXXG and (C/F)CV+C motifs are key determinants of CD4-mediated pMHCII-specific signal amplification; the GGXXG and (C/F)CV+C motifs exert their functions independently of direct CD4-LCK association. These data provide a mechanistic explanation for why residues within these motifs are under purifying selection in jawed vertebrates. The results are also important to consider for biomimetic engineering of synthetic receptors.

The relationship between cervical length and area measurements evaluated by MRI and the amount of hemorrhage in PAS cases.

BACKGROUND: Placenta accreta spectrum often leads to massive hemorrhage and even maternal shock and death. This study aims to identify whether cervical length and cervical area measured by magnetic resonance imaging correlate with massive hemorrhage in patients with placenta accreta spectrum. METHODS: The study was conducted at our hospital, and 158 placenta previa patients with placenta accreta spectrum underwent preoperative magnetic resonance imaging examination were included. The cervical length and cervical area were measured and evaluated their ability to identify massive hemorrhage in patients with placenta accreta spectrum. RESULTS: The cervical length and area in patients with massive hemorrhage were both significantly smaller than those in patients without massive hemorrhage. The results of multivariate analysis show that cervical length and cervical area were significantly associated with massive hemorrhage. In all patients, a negative linear was found between cervical length and amount of blood loss (r =-0.613), and between cervical area and amount of blood loss (r =-0.629). Combined with cervical length and cervical area, the sensitivity, specificity, and the area under the curve for the predictive massive hemorrhage were 88.618%, 90.209%, and 0.890, respectively. CONCLUSION: The cervical length and area might be used to recognize massive hemorrhage in placenta previa patients with placenta accreta spectrum.

Causal associations between Helicobacter pylori infection and pregnancy and neonatal outcomes: a two-sample Mendelian randomization study.

Background: Observational studies have reported that Helicobacter pylori (H. pylori) infection is associated with a series of pregnancy and neonatal outcomes. However, the results have been inconsistent, and the causal effect is unknown. Methods: A two-sample Mendelian randomization (MR) study was performed using summary-level statistics for anti-H. pylori IgG levels from the Avon Longitudinal Study of Parents and Children Cohort. Outcome data for pregnancy (miscarriage, preeclampsia-eclampsia, gestational diabetes mellitus, placental abruption, premature rupture of membranes, postpartum hemorrhage) and neonates (birthweight, gestational age, and preterm birth) were sourced from genome-wide association meta-analysis as well as the FinnGen and Early Growth Genetics Consortium. Causal estimates were calculated by five methods including inverse variance weighted (IVW). The heterogeneity of instrumental variables was quantified by Cochran's Q test, while sensitivity analyses were performed via MR-Egger, MR-PRESSO, and leave-one-out tests. Results: IVW estimates suggested that genetically predicted anti-H. pylori IgG levels were significantly associated with increased risks of preeclampsia-eclampsia (odds ratio [OR] = 1.12, 95% confidence interval [CI] 1.01-1.24, P = 0.026) and premature rupture of membranes (OR = 1.17, 95% CI 1.05-1.30, P = 0.004). Similar results were obtained for preeclampsia-eclampsia from the MR-Egger method (OR = 1.32, 95% CI 1.06-1.64, P = 0.027) and for premature rupture of membranes from the weighted median method (OR = 1.22, 95% CI 1.06-1.41, P = 0.006). No significant causal effects were found for other outcomes. There was no obvious heterogeneity and horizontal pleiotropy across the MR analysis. Conclusion: Our two-sample MR study demonstrated a causal relationship of H. pylori infection with preeclampsia-eclampsia and premature rupture of membranes. The findings confirm the epidemiological evidence on the adverse impact of H. pylori in pregnancy. Further studies are needed to elucidate the pathophysiological mechanisms and assess the effectiveness of pre-pregnancy screening and preventive eradication.

Topical Human Mesenchymal Stem Cell-Derived Exosomes for Acceleration of Wound Healing Following Tissue Trauma and Aesthetic Procedures: A Case Series.

BACKGROUND: In the aesthetics practice, measures to accelerate wound healing and minimize downtime following procedures have been largely restricted to topical serums and platelet-rich plasma (PRP), which can have varying levels of success. Here, the authors present a case series of patients treated in clinical practice with cell-free exosomes derived from human placental mesenchymal stem cells (Exovex, Exocelbio, Doylestown, PA). Topical administration of exosomes after either aesthetic treatment or traumatic injury (a dog bite) had a marked effect on healing. Effects were assessed visually, and case-study images are shared. Individuals demonstrated significantly accelerated recovery and wound healing within hours to days, depending on the procedure. Patients who had undergone the same aesthetic procedure prior without exosomes reported satisfaction with reductions in pain, swelling, redness, and post-procedure downtime. No adverse events were reported by patients after treatment. Together, these case series suggest that exosome treatment can accelerate wound healing safely and effectively and support topical use in an office-based setting. These findings also highlight the need for more formal evaluation of the effects of exosomes on wound healing in reducing aesthetic procedure recovery times for surgical and non-surgical interventions. Significant Finding: The case series presented here illustrates the potential for exosomes to be a versatile and important part of clinical care, especially in situations where expedited healing is central to patient safety and/or satisfaction. These results provide strong support for additional research.  Meaning: Topical administration of cell-free exosomes has the potential to improve patient care and satisfaction with aesthetic interventions. Early experience, illustrated by the presented case studies, has been remarkably positive and treatment has the potential to dramatically improve the standard of care.  Online ahead of print.

A rare case of adventitious placentation (diffuse semi-placenta) in a Jersey cow.

Placental abnormalities more frequently occur during pregnancy of somatic cell clones and may lead to pregnancy loss or dystocia. Adventitious placentation, or diffuse semi-placenta, is determined by the development of areas of accessory placentation between the cotyledons due to the abnormal growth of placentomes.After a full-term pregnancy, a 3-year-old Jersey heifer was referred for dystocia which resulted in the delivery of a dead calf. The cause of dystocia was found to be foetal malposition, while the placenta was physiologically expelled after dystocia resolution.Grossly, cotyledons appeared reduced in size and number in one placental horn, while the surface of the other horn was covered with microplacentomes. Numerous villous structures without trophoblastic coating were highlighted after histopathology. The dominant sign was an inflammatory reaction. The findings were consistent with inter-cotyledonal placentitis, which led to adventitial placentation.Diffuse semi-placenta compensates for the inadequate development of placentomes and may occur as a congenital or acquired defect. The outcome depends on its severity: in the worst scenario, pregnancy may not proceed beyond midterm and may be complicated by hydrallantois. In the case under examination, the dimensions of the cotyledons (from 2 to 10 cm) allowed for the natural course of pregnancy.

Smoking during pregnancy and its effect on placental weight: a Mendelian randomization study.

BACKGROUND: The causal relationship between maternal smoking in pregnancy and reduced offspring birth weight is well established and is likely due to impaired placental function. However, observational studies have given conflicting results on the association between smoking and placental weight. We aimed to estimate the causal effect of newly pregnant mothers quitting smoking on their placental weight at the time of delivery. METHODS: We used one-sample Mendelian randomization, drawing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) (N = 690 to 804) and the Norwegian Mother, Father and Child Cohort Study (MoBa) (N = 4267 to 4606). The sample size depends on the smoking definition used for different analyses. The analysis was performed in pre-pregnancy smokers only, due to the specific role of the single-nucleotide polymorphism (SNP) rs1051730 (CHRNA5 - CHRNA3 - CHRNB4) in affecting smoking cessation but not initiation. RESULTS: Fixed effect meta-analysis showed a 182 g [95%CI: 29,335] higher placental weight for pre-pregnancy smoking mothers who continued smoking at the beginning of pregnancy, compared with those who stopped smoking. Using the number of cigarettes smoked per day in the first trimester as the exposure, the causal effect on placental weight was 11 g [95%CI: 1,21] per cigarette per day. Similarly, smoking at the end of pregnancy was causally associated with higher placental weight. Using the residuals of birth weight regressed on placental weight as the outcome, we showed evidence of lower offspring birth weight relative to the placental weight, both for continuing smoking at the start of pregnancy as well as continuing smoking throughout pregnancy (change in z-score birth weight adjusted for z-score placental weight: -0.8 [95%CI: -1.6,-0.1]). CONCLUSION: Our results suggest that continued smoking during pregnancy causes higher placental weights.

Exploring the role of exosomal MicroRNAs as potential biomarkers in preeclampsia.

The complex pathogenesis of preeclampsia (PE), a significant contributor to maternal and neonatal mortality globally, is poorly understood despite substantial research. This review explores the involvement of exosomal microRNAs (exomiRs) in PE, focusing on their impact on the protein kinase B (AKT)/hypoxia-inducible factor 1-α (HIF1α)/vascular endothelial growth factor (VEGF) signaling pathway as well as endothelial cell proliferation and migration. Specifically, this article amalgamates existing evidence to reveal the pivotal role of exomiRs in regulating mesenchymal stem cell and trophoblast function, placental angiogenesis, the renin-angiotensin system, and nitric oxide production, which may contribute to PE etiology. This review emphasizes the limited knowledge regarding the role of exomiRs in PE while underscoring the potential of exomiRs as non-invasive biomarkers for PE diagnosis, prediction, and treatment. Further, it provides valuable insights into the mechanisms of PE, highlighting exomiRs as key players with clinical implications, warranting further exploration to enhance the current understanding and the development of novel therapeutic interventions.

The interplay of inflammation and placenta in maternal diabetes: insights into Hofbauer cell expression patterns.

Introduction: Inflammation of the placenta is harmful to both the fetus and the mother. Inflammation is strongly associated with diabetes, a common complication of pregnancy. Hofbauer cells (HBCs), unique immune system cells of fetal origin in the placenta, play complex roles, including growth of placental villi and their branching, stromal remodelling, and angiogenesis. Methods: Our study investigated the expression of IL-1ß, IL-10, CYP2C8, CYP2C9, CYP2J2 and sEH in HBCs from patients with type 1 diabetes mellitus (T1DM) and gestational diabetes mellitus (GDM) compared to healthy controls using immunohistochemistry. We also assessed the structure of the villus stroma using Masson´s trichrome. Results: In T1DM, HBCs showed inflammatory activation characterised by increased IL-1ß and decreased CYP epoxygenase expression compared to normal placentas. Conversely, significant inflammation in HBCs appeared less likely in GDM, as levels of IL-1ß and CYP epoxygenases remained stable compared to normal placentas. However, GDM showed a significant increase in sEH expression. Both types of diabetes showed delayed placental villous maturation and hypovascularisation, with GDM showing a more pronounced effect. Conclusion: The expression profiles of IL-1ß, CYP epoxygenases and sEH significantlly differ between controls and diabetic placentas and between T1DM and GDM. These facts suggest an association of the CYP epoxygenase-EETs-sEH axis with IL-1ß expression as well as villous stromal hypovascularisation. Given the stable high expression of IL-10 in both controls and both types of diabetes, it appears that immune tolerance is maintained in HBCs.

Efficacy and safety of prophylactic balloon occlusion in the management of placenta accreta spectrum disorder: a retrospective cohort study.

OBJECTIVE: Placenta accreta spectrum disorder (PAS) is a serious obstetric complication associated with significant maternal morbidity and mortality. Prophylactic balloon occlusion (PBO), as an intravascular interventional therapies, has emerged as a potential management strategy for controlling massive hemorrhage in patients with PAS. However, current evidence about the clinical application of PBO in PAS patients are still controversial. This study aimed to evaluate the effectiveness and safety of PBO in the management of PAS. METHODS: A retrospective cohort study including PAS patients underwent cesarean delivery was conducted in a tertiary hospital from January 2015 to March 2022. Included PAS patients were further divided into balloon and control groups by whether PBO was performed. Groups were compared for demographic characteristics, intraoperative and postoperative parameters, maternal and neonatal outcomes, PBO-related complication and follow up outcomes. Additionally, multivariate-logistic regression analysis was performed to determine the definitive associations between PBO and risk of massive hemorrhage and hysterectomy. RESULTS: A total of 285 PAS patients met the inclusion criteria were included, of which 57 PAS patients underwent PBO (PBO group) and 228 women performed cesarean section (CS) without PBO (control group). Irrespective of the differences of baseline characteristics between the two groups, PBO intervention did not reduce the blood loss, hysterectomy rate and postoperative hospital stay, but it prolonged the operation time and increased the cost of hospitalization (All P < 0.05) Additionally, there were no significant differences in postoperative complications, neonatal outcomes, and follow-up outcomes(All P > 0.05). In particular, patients undergoing PBO were more likely to develop the venous thrombosis postoperatively (P = 0.001). However, multivariate logistic regression analysis showed that PBO significantly decreased the risk of massive hemorrhage (OR 0.289, 95%CI:0.109-0.766, P = 0.013). The grade of PAS and MRI with S2 invasion were the significant risk factors affecting massive hemorrhage(OR:6.232 and OR:5.380, P<0.001). CONCLUSION: PBO has the potential to reduce massive hemorrhage in PAS patients undergoing CS. Obstetricians should, however, be aware of potential complications arising from the PBO. Additionally, MRI with S2 invasion and PAS grade will be useful to identify PAS patients who at high risk and may benefit from PBO. In brief, PBO seem to be a promising alternative for management of PAS, yet well-designed randomized controlled trials are needed to convincingly demonstrate its benefits and triage the necessity of PBO.

[Genetic origin analysis of regions of homozygosity in three cases].

OBJECTIVE: To explore the genetic characteristics of three fetuses with regions of homozygosity (ROH). METHODS: Three fetuses with ROH diagnosed at Nanjing Drum Tower Hospital on December 2, 2020, March 19, 2021, and May 27, 2022, respectively were selected as the study subjects. Clinical data of the fetuses were collected. Chromosomal microarray analysis (CMA) was used to detect the ROH, and tandem repeat sequences (STR)-based multiplex PCR assay was used to identify the mosaicism status in fetus 1. RESULTS: Partial maternal isodisomy (iUPD) (16) was found in fetus 1, for which trisomy rescue may be accountable. Meanwhile, the fetus also has confined placental mosaicism (CPM) but not true mosaicism. The formation mechanism of ROH for fetus 2 was identity by descent. Partial maternal iUPD (7) was found in fetus 3, which may be due to gametic recombination. CONCLUSION: The ROH of the three fetuses were inherited from both parents or the mother. Above findings suggested that it is justified to detect ROH on imprinting disorder-related chromosomes when potential uniparental disomy is suspected.

Evaluation of Lippia scaberrima Sond. and Aspalathus linearis (Burm.f.) R. Dahlgren extracts on human CYP enzymes and gold nanoparticle synthesis: implications for drug metabolism and cytotoxicity.

BACKGROUND: Metabolism is an important component of the kinetic characteristics of herbal constituents, and it often determines the internal dose and concentration of these effective constituents at the target site. The metabolic profile of plant extracts and pure compounds need to be determined for any possible herb-drug metabolic interactions that might occur. METHODS: Various concentrations of the essential oil of Lippia scaberrima, the ethanolic extract of Lippia scaberrima alone and their combinations with fermented and unfermented Aspalathus linearis extract were used to determine the inhibitory potential on placental, microsomal and recombinant human hepatic Cytochrome P450 enzymes. Furthermore, the study investigated the synthesis and characterization of gold nanoparticles from the ethanolic extract of Lippia scaberrima as a lead sample. Confirmation and characterization of the synthesized gold nanoparticles were conducted through various methods. Additionally, the cytotoxic properties of the ethanolic extract of Lippia scaberrima were compared with the gold nanoparticles synthesized from Lippia scaberrima using gum arabic as a capping agent. RESULTS: All the samples showed varying levels of CYP inhibition. The most potent inhibition took place for CYP2C19 and CYP1B1 with 50% inhibitory concentration (IC50) values of less than 0.05 µg/L for the essential oil tested and IC50-values between 0.05 µg/L-1 µg/L for all the other combinations and extracts tested, respectively. For both CYP1A2 and CYP2D6 the IC50-values for the essential oil, the extracts and combinations were found in the range of 1 - 10 µg/L. The majority of the IC50 values found were higher than 10 µg/L and, therefore, were found to have no inhibition against the CYP enzymes tested. CONCLUSION: Therefore, the essential oil of Lippia scaberrima, the ethanolic extract of Lippia scaberrima alone and their combinations with Aspalathus linearis do not possess any clinically significant CYP interaction potential and may be further investigated for their adjuvant potential for use in the tuberculosis treatment regimen. Furthermore, it was shown that the cytotoxic potential of the Lippia scaberrima gold nanoparticles was reduced by twofold when compared to the ethanolic extract of Lippia scaberrima.

Special Issue "Physiology and Pathophysiology of the Placenta".

The placenta is a transient but essential organ for normal in utero development, playing several essential functions in normal pregnancy [...].