-
Nephrology, Dialysis, Transplantation :... Jun 2024Congenital anomalies of the kidney and the urinary tract (CAKUT), often discovered in utero, cover a wide spectrum of outcomes ranging from normal postnatal kidney...
BACKGROUND AND HYPOTHESIS
Congenital anomalies of the kidney and the urinary tract (CAKUT), often discovered in utero, cover a wide spectrum of outcomes ranging from normal postnatal kidney function to fetal death. The current ultrasound workup does not allow for an accurate assessment of the outcome. The present study aimed to significantly improve the ultrasound-based prediction of postnatal kidney survival in CAKUT.
METHODS
Histological analysis of kidneys of 15 CAKUT fetuses was performed to better standardize the ultrasound interpretation of dysplasia and cysts. Ultrasound images of 140 CAKUT fetuses with 2-year postnatal follow-up were annotated for amniotic fluid volume and kidney number, size, dysplasia and/or cysts using standardized ultrasound readout. Association of ultrasound features and clinical data (sex and age at diagnosis) with postnatal kidney function was studied using logistic regression. Amniotic fluid proteome associated to kidney dysplasia or cysts was characterized by mass spectrometry.
RESULTS
Histologically, poor ultrasound corticomedullary differentiation was associated to dysplastic lesions and ultrasound hyperechogenicity was associated to the presence of microcysts. Of all ultrasound and clinical parameters, reduced amniotic volume, dysplasia and cysts were the best predictors of poor outcome (Odd ratio = 57 [95%CI: 11-481], 20 [3-225] and 7 [1-100], respectively). Their combination into an algorithm improved prediction of postnatal kidney function compared to amniotic volume alone (area under the ROC curve = 0.92 [0.86-0.98] in a 10-fold cross validation). Dysplasia and cysts were correlated (Cramer's V coefficient = 0.44, p<0.0001), but amniotic fluid proteome analysis revealed that they had distinct molecular origin (extracellular matrix and cell contacts versus cellular death, respectively), probably explaining the additivity of their predictive performances.
CONCLUSION
Antenatal clinical advice for CAKUT pregnancies can be improved by a more standardized and combined interpretation of ultrasound data.
PubMed: 38908913
DOI: 10.1093/ndt/gfae145 -
American Family Physician Jun 2024Pregnancy dating is determined by the patient's last menstrual period or an ultrasound measurement. A full-term pregnancy is considered 37 weeks' gestation or more.... (Review)
Review
Pregnancy dating is determined by the patient's last menstrual period or an ultrasound measurement. A full-term pregnancy is considered 37 weeks' gestation or more. Spontaneous labor begins when regular painful uterine contractions result in a cervical change. Active labor begins at 6 cm dilation and is marked by more predictable, accelerated cervical change. In the absence of pregnancy complications, intermittent fetal auscultation may be considered as an alternative to continuous electronic fetal monitoring, which is associated with a high false-positive rate. Intravenous antibiotic prophylaxis is indicated in patients with group B streptococcus colonization or those at high risk to prevent newborn early-onset group B streptococcus. The likelihood of vaginal delivery is increased by providing continuous nonmedical support during labor, encouraging mobility, and using a peanut ball with epidural analgesia. Neuraxial analgesia is more effective for pain control than systemic opioids and is associated with fewer adverse effects. Delayed pushing during the second stage of labor has risks but does not affect the mode of delivery. Routine oropharyngeal suctioning of the newborn is not recommended, even with meconium-stained amniotic fluid. Delayed cord clamping reduces newborn anemia. Prevention of postpartum hemorrhage in patients at risk includes prophylactic uterotonic administration and controlled cord traction. Perineal lacerations that alter anatomy or are not hemostatic should be repaired. (Am Fam Physician. 2024;109(6):525-532.
Topics: Humans; Female; Pregnancy; Delivery, Obstetric; Infant, Newborn; Labor, Obstetric
PubMed: 38905550
DOI: No ID Found -
Redox Biology Jun 2024We previously demonstrated that the human amniotic fluid (hAF) from II trimester of gestation is a feasible source of stromal progenitors (human amniotic fluid stem...
BACKGROUND
We previously demonstrated that the human amniotic fluid (hAF) from II trimester of gestation is a feasible source of stromal progenitors (human amniotic fluid stem cells, hAFSC), with significant paracrine potential for regenerative medicine. Extracellular vesicles (EVs) separated and concentrated from hAFSC secretome can deliver pro-survival, proliferative, anti-fibrotic and cardioprotective effects in preclinical models of skeletal and cardiac muscle injury. While hAFSC-EVs isolation can be significantly influenced by in vitro cell culture, here we profiled EVs directly concentrated from hAF as an alternative option and investigated their paracrine potential against oxidative stress.
METHODS
II trimester hAF samples were obtained as leftover material from prenatal diagnostic amniocentesis following written informed consent. EVs were separated by size exclusion chromatography and concentrated by ultracentrifugation. hAF-EVs were assessed by nanoparticle tracking analysis, transmission electron microscopy, Western Blot, and flow cytometry; their metabolic activity was evaluated by oximetric and luminometric analyses and their cargo profiled by proteomics and RNA sequencing. hAF-EV paracrine potential was tested in preclinical in vitro models of oxidative stress and dysfunction on murine C2C12 cells and on 3D human cardiac microtissue.
RESULTS
Our protocol resulted in a yield of 6.31 ± 0.98 × 10 EVs particles per hAF milliliter showing round cup-shaped morphology and 209.63 ± 6.10 nm average size, with relevant expression of CD81, CD63 and CD9 tetraspanin markers. hAF-EVs were enriched in CD133/1, CD326, CD24, CD29, and SSEA4 and able to produce ATP by oxygen consumption. While oxidative stress significantly reduced C2C12 survival, hAF-EV priming resulted in significant rescue of cell viability, with notable recovery of ATP synthesis and concomitant reduction of cell damage and lipid peroxidation activity. 3D human cardiac microtissues treated with hAF-EVs and experiencing HO stress and TGFβ stimulation showed improved survival with a remarkable decrease in the onset of fibrosis.
CONCLUSIONS
Our results suggest that leftover samples of II trimester human amniotic fluid can represent a feasible source of EVs to counteract oxidative damage on target cells, thus offering a novel candidate therapeutic option to counteract skeletal and cardiac muscle injury.
PubMed: 38901103
DOI: 10.1016/j.redox.2024.103241 -
Frontiers in Immunology 2024IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL)....
INTRODUCTION
IL6 signaling plays an important role in triggering labor and IL6 is an established biomarker of intrauterine infection/inflammation (IUI) driven preterm labor (PTL). The biology of IL6 during IUI at the maternal-fetal interface was investigated in samples from human subjects and non-human primates (NHP).
METHODS
Pregnant women with histologic chorioamnionitis diagnosed by placenta histology were recruited (n=28 term, n=43 for preterm pregnancies from 26-36 completed weeks of gestation). IUI was induced in Rhesus macaque by intraamniotic injection of lipopolysachharide (LPS, n=23). IL1 signaling was blocked using Anakinra (human IL-1 receptor antagonist, n=13), and Tumor necrosis factor (TNF) signaling was blocked by anti TNF-antibody (Adalimumab n=14). The blockers were given before LPS. All animals including controls (intraamniotic injection of saline n=27), were delivered 16h after LPS/saline exposure at about 80% gestation.
RESULTS
IUI induced a robust expression of mRNAs in the fetal membranes (chorion-amnion-decidua tissue) both in humans (term and preterm) and NHP. The major sources of mRNA expression were the amnion mesenchymal cells (AMC) and decidua stroma cells. Additionally, during IUI in the NHP, (a protease that cleaves membrane bound IL6 receptor (IL6R) to release a soluble form) and mRNA increased in the fetal membranes, and the ratio of IL6 and soluble forms of IL6R, gp130 increased in the amniotic fluid signifying upregulation of IL6 trans-signaling. Both IL1 and TNF blockade suppressed LPS-induced mRNAs in the AMC and variably decreased elements of IL6 trans-signaling.
DISCUSSION
These data suggest that IL1 and TNF blockers may be useful anti-inflammatory agents via suppression of IL6 signaling at the maternal-fetal interface.
Topics: Female; Pregnancy; Humans; Animals; Interleukin-6; Signal Transduction; Macaca mulatta; Tumor Necrosis Factor-alpha; Chorioamnionitis; Lipopolysaccharides; Interleukin-1; Adult; Obstetric Labor, Premature; Inflammation; Interleukin 1 Receptor Antagonist Protein; Placenta
PubMed: 38895127
DOI: 10.3389/fimmu.2024.1416162 -
Journal of Animal Physiology and Animal... Jun 2024This investigation was directed to examine the influence of copper oxide nanoparticles (CuO-NPs) on the hatchability traits, and chick quality of newly hatched broiler...
Benefit and potential risk: Effects of in ovo copper oxide nanoparticles supplementation on hatchability traits, organ weights and histological features of newly hatched chicks.
This investigation was directed to examine the influence of copper oxide nanoparticles (CuO-NPs) on the hatchability traits, and chick quality of newly hatched broiler chicks. A total of 480 eggs were randomly divided into four treatment groups, each consisting of three duplicates. As a negative control (NC), the first group was not injected; the second group was injected with saline and served as a positive control (PC), the third and fourth groups were injected with 30 and 60 ppm of (CuO-NPs)/egg. Eggs were injected into the amniotic fluid on the eighteenth day of the incubation period. Results showed that the hatchability, chick yield %, yolk free-body mass (YFBM), chick length, shank length (SL), and relative weight of the heart, gizzard and intestine of day-old broiler chicks were all unaffected by the in ovo injection of CuO-NPs. The Pasgar Score was slightly improved compared to the NC and PC groups. Also, the in ovo administration of CuO-NPs (60 ppm/egg) significantly increased the intestine length. Both levels of CuO-NPs significantly increased the concentration of Cu ions in the hepatic tissue. Additionally, different levels of tissue damage were seen in the liver of the birds that were given low or high dosages of CuO-NPs. Conclusively, the in ovo injection of CuO-NPs has a good result on the appearance of the chicks (Pasgar score). However, negative effect of CuO-NPs on liver tissue may raise concerns about the potential risks of applying CuO-NPs in ovo administration.
PubMed: 38890818
DOI: 10.1111/jpn.14007 -
Bioelectrochemistry (Amsterdam,... Jun 2024Dravet syndrome is a rare form of epilepsy starting from infancy that can plaque the affected individuals all though his/her life with repeated seizures, and this...
Dravet syndrome is a rare form of epilepsy starting from infancy that can plaque the affected individuals all though his/her life with repeated seizures, and this condition is currently without a complete cure. So prenatal screening of molecular markers of this condition is urgently needed to help couples conceiving new lives to steer clear of this potential danger. And such an assay should ideally be of low cost and could be completed in a point-of-care fashion. This work reports an attempt to construct such an assay using simple peptides in the place of conventional biosensing macro-molecules such as antibodies and enzymes. Specifically, a marker protein of this syndrome can bring the two pieces of a self-splitting peptide "intein" together, which in turn facilitate the formation of metal ion coordination site, recruiting cupric ion to generate catalytically amplified signal readout. Using this method, disease marker protein Nav of this syndrome can be quantitatively detected directly in amniotic fluid samples, and samples associated with potential risk factors such as family history of this syndrome shows statistically evident decrease of this marker protein. These results may promise future application of the proposed method in clinical practice to reduce the social burden of Dravet syndrome by reducing its actual incident rate.
PubMed: 38889537
DOI: 10.1016/j.bioelechem.2024.108754 -
International Journal of Women's Health 2024To evaluate factors predictive of the success of a slow-release dinoprostone vaginal insert for cervical ripening.
OBJECTIVE
To evaluate factors predictive of the success of a slow-release dinoprostone vaginal insert for cervical ripening.
METHODS
This retrospective study included 187 women who received dinoprostone vaginal inserts for cervical ripening. The participants were divided into two groups: the transvaginal delivery group (n = 87) and cesarean section termination group (n = 100). The correlation between the parameters present before cervical ripening with dinoprostone slow release and its success, as well as complications and adverse outcomes, was analyzed. Cesarean section predictors and area under the curve (AUC) were compared between the two Groups.
RESULTS
There were statistical differences between the two groups in body mass index (BMI), height, cervical Bishop score, cephalic position, time of medication use, and fetal head position at the time of medication use (<0.05). The optimal thresholds for identifying cesarean section in dinoprostone vaginal insert for cervical ripening were 162.5 for height (AUC = 0.61), 10.65 cm for amniotic fluid index (AUC = 0.6), S-2.5 for cephalic position (AUC = 0.61), 5.5 for bishop score of cervix (AUC = 0.65). The height, amniotic fluid index, cephalic position, and Bishop score of the cervix were included in the same model. The AUC value of the combined model was higher than the AUC value of the single factor.
CONCLUSION
The combined model was a better predictor of cesarean section in dinoprostone vaginal inserts for cervical ripening and labor induction. The success of cervical ripening with a dinoprostone slow-release vaginal insert can be predicted by the factors that can be recognized at admission.
PubMed: 38887592
DOI: 10.2147/IJWH.S461094 -
Research Square Jun 2024Mesenchymal stem cells (MSCs) from gestational tissues represent promising strategies for treatment of congenital malformations, but plasticity and required high-risk...
BACKGROUND
Mesenchymal stem cells (MSCs) from gestational tissues represent promising strategies for treatment of congenital malformations, but plasticity and required high-risk surgical procedures limit their use. Here we propose natural exosomes (EXOs) isolated from amniotic fluid-MSCs (AF-MSCs), and their mimetic counterparts (MIMs), as valid, stable, and minimally invasive therapeutic alternatives.
METHODS
MIMs were generated from AF-MSCs by combining sequential filtration steps through filter membranes with different porosity and size exclusion chromatography columns. Physiochemical and molecular characterization was performed to compare them to EXOs released from the same number of cells. The possibility to exploit both formulations as mRNA-therapeutics was explored by evaluating cell uptake (using two different cell types, fibroblasts, and macrophages) and mRNA functionality overtime in an experimental setting as well as in an , whole embryo culture using pregnant C57BL6 dams.
RESULTS
Molecular and physiochemical characterization showed no differences between EXOs and MIMs, with MIMs determining a 3-fold greater yield. MIMs delivered a more intense and prolonged expression of mRNA encoding for green fluorescent protein (GFP) in macrophages and fibroblasts. An whole embryo culture demonstrated that MIMs mainly accumulate at the level of the yolk sac, while EXOs reach the embryo.
CONCLUSIONS
The present data confirms the potential application of EXOs for the prenatal repair of neural tube defects and proposes MIMs as prospective vehicles to prevent congenital malformations caused by exposure to drugs.
PubMed: 38883749
DOI: 10.21203/rs.3.rs-4325422/v1 -
International Journal of Gynaecology... Jun 2024To analyze the success rate of external cephalic version (ECV) in pregnant women with a history of previous cesarean section, as well as to describe the rate of...
OBJECTIVE
To analyze the success rate of external cephalic version (ECV) in pregnant women with a history of previous cesarean section, as well as to describe the rate of complications associated with the procedure.
METHODS
A retrospective cohort study of women who were offered an ECV at "Virgen de la Arrixaca" Clinic University Hospital (Murcia, Spain) between January 2014 and December 2023. We collected data for previous cesarean delivery, obstetric history, fetal presentation, amniotic fluid volume, ECV success rate, complications related to ECV, mode of delivery, and neonatal outcomes. The study confidently performed ECV under sedation with propofol and tocolysis with ritodrine. Univariate and multivariate analyses were conducted to compare the success rate of ECV, ECV complications, and mode of delivery between women with and without previous cesarean sections.
RESULTS
Of 1116 pregnant women who were offered ECV, 911 were included in the study, with 42 having a previous cesarean section. The success rate of ECV in pregnant women with a previous cesarean section was 78.6% (adjusted odds ratio 1.18; 95% confidence interval 0.49-2.86; P = 0.708), with a low complication rate of 9.5%, such as non-reassuring fetal heart rate (7.1%) or major vaginal bleeding (2.4%). Of the women who attempted a vaginal delivery after ECV, 80.8% were successful.
CONCLUSIONS
These findings support that ECV is a safe and effective option for women with a previous cesarean section, with success rates comparable to those in women without a previous cesarean section.
PubMed: 38881234
DOI: 10.1002/ijgo.15738 -
Stem Cells and Development Jun 2024Intrauterine Growth Restriction (IUGR) pathophysiology is driven by abnormal uterine natural killer cell (uNK) activity leading to placental dysfunction. Transamniotic...
Intrauterine Growth Restriction (IUGR) pathophysiology is driven by abnormal uterine natural killer cell (uNK) activity leading to placental dysfunction. Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can improve experimental IUGR by mechanisms not fully understood. We sought to examine TRASCET's effects in downstream products of uNKs in a model of IUGR. Fifteen Sprague-Dawley dams were exposed to alternating hypoxia (10.5% O2) from gestational-day 15 (E15) until term (E21). Their fetuses (n=189) were divided into 4 groups. One group remained untreated (n=52), while three groups received volume-matched intra-amniotic injections of either saline (sham, n=44), or a suspension of amniotic fluid-derived MSCs, either in their native state (TRASCET, n=50) or "primed" to an enhanced anti-inflammatory phenotype (TRASCET-Primed, n=43). Normal fetuses served as controls (n=33). At term, various analyses were performed, including ELISA for surrogates of placental inflammation and uNK activity. Statistical comparisons included Bonferroni-adjusted criterion. Overall survival from hypoxia was 74% (140/189). Placental efficiency was lower in untreated and sham but normalized in both TRASCET groups (p<0.001-0.469). Interleukin-17, a stimulator of uNK cells, was elevated from normal in all groups (p<0.001 for all). Interferon-gamma, released from activated uNK cells, was elevated in all groups except sham, but lower than the untreated in both TRASCET groups (p=<0.001-0.062). Tumor necrosis factor-alpha, also produced by uNKs, was elevated in untreated and sham (p<0.001 for both), but normalized by TRASCET (p=0.054) and even lowered from normal in TRASCET-Primed (p<0.001). Vascular endothelial growth factor, also released by uNKs, was elevated in untreated and sham but lower than normal in both TRASCET groups (p<0.001 for all). We conclude that TRASCET with MSCs modulates the activity of placental uNK cells in experimental IUGR, with distinct effects on their downstream products. This mechanistic insight may inform the development of novel strategies for the management of this disease.
PubMed: 38874223
DOI: 10.1089/scd.2023.0282