Assessment of the proteome profile of decellularized human amniotic membrane and its biocompatibility with umbilical cord-derived mesenchymal stem cells.

Extracellular matrix-based bio-scaffolds are useful for tissue engineering as they retain the unique structural, mechanical, and physiological microenvironment of the tissue thus facilitating cellular attachment and matrix activities. However, considering its potential, a comprehensive understanding of the protein profile remains elusive. Herein, we evaluate the impact of decellularization on the human amniotic membrane (hAM) based on its proteome profile, physicochemical features, as well as the attachment, viability, and proliferation of umbilical cord-derived mesenchymal stem cells (hUC-MSC). Proteome profiles of decellularized hAM (D-hAM) were compared with hAM, and gene ontology (GO) enrichment analysis was performed. Proteomic data revealed that D-hAM retained a total of 249 proteins, predominantly comprised of extracellular matrix proteins including collagens (collagen I, collagen IV, collagen VI, collagen VII, and collagen XII), proteoglycans (biglycan, decorin, lumican, mimecan, and versican), glycoproteins (dermatopontin, fibrinogen, fibrillin, laminin, and vitronectin), and growth factors including transforming growth factor beta (TGF-ß) and fibroblast growth factor (FGF) while eliminated most of the intracellular proteins. Scanning electron microscopy was used to analyze the epithelial and basal surfaces of D-hAM. The D-hAM displayed variability in fibril morphology and porosity as compared with hAM, showing loosely packed collagen fibers and prominent large pore areas on the basal side of D-hAM. Both sides of D-hAM supported the growth and proliferation of hUC-MSC. Comparative investigations, however, demonstrated that the basal side of D-hAM displayed higher hUC-MSC proliferation than the epithelial side. These findings highlight the importance of understanding the micro-environmental differences between the two sides of D-hAM while optimizing cell-based therapeutic applications.

Quantitative assessment of umbilical cord care practices amongst mothers in Jos, Plateau State, Nigeria.

Introduction: A newly cut neonatal umbilical stump is a potential portal of pathogen entry leading to omphalitis. Neonatal sepsis can complicate omphalitis, but good cord care practices can reduce this risk. Objective: The objective of this study was to assess umbilical cord care practices in tertiary-, secondary- and primary-level healthcare facilities in Jos, Nigeria. Methods: A multi-centre, cross-sectional study of 284 mothers of infants aged 3-6 weeks old attending immunisation clinics in the three-level healthcare facilities using multistage sampling technique between April and September 2019. Data were analysed using SPSS version 23.0. Pearson's Chi-squared test was used to compare categorical variables. Adjusted odds ratios (AORs) and 95% confidence interval (CI) were used as point and interval estimates, respectively. P < 0.05 was adjudged to be statistically significant. Results: The mean age of the mothers and infants was 25 ± 6 years and 5 ± 1 week, respectively. Only 2.2% of mothers used chlorhexidine (CHX) gel for cord care. Mothers showed good knowledge but poor practice of cord care. A significant positive relationship was observed between quality of cord care practices and level of healthcare facility (χ2 = 15.213; df = 2; P < 0.001). Good cord care practices were predicted by mothers' age 30-46 (AOR = 3.6; CI: 1.4-9.1) and good knowledge of cord care (AOR = 4.7; 95% CI: 2.2-9.9). Conclusions: The study has highlighted the good knowledge but poor practices of cord care by mothers and the need to scale up the uptake of CHX gel in Jos. Mother's age and good knowledge of cord care are predictors of good cord care practices.

Primary hepatocyte urea assessment in the sodium-alginate patterned hydrogel by electrochemical procedure containing umbilical cord conditioned media.

Limitations in liver transplantation and advances in cell therapy methods motivated us to study primary hepatocytes. The main challenge in using primary hepatocytes for liver regeneration is that they lose their functionalities. We aimed to develop a controlled-shape hydrogel and apply the conditioned-media of mesenchymal stromal cells (CM-MSCs) to improve in vitro hepatocyte functions. In this experimental study, following rat hepatocyte isolation by collagenase perfusion and collection of human umbilical cord CM-MSCs, a simple and precise system called electrodeposition was used to produce the patterned alginate hydrogel. To reduce the cytopathic effects, we used an indirect electrodeposition method. For characterizing this structure, mechanical properties, Fourier-transform infrared spectroscopy (FTIR), water uptake, in-vitro degradation, and hydrogel stability were studied. Urea synthesis as a basic function of hepatocytes was assessed in five different groups. Scanning electron microscope (SEM) was utilized to evaluate the primary hepatocyte morphology and their dispersion in the fabricated structure. We observed a significant increase in urea synthesis in the presence of CM-MSCs in patterned hydrogel alginate compared to 2D culture on day 3 (p<0.05). However, there was no significant difference in simple and patterned hydrogel on day 2. We found that the electrodeposition method is appropriate for the rapid fabricating of hydrogel structures with arbitrary patterns for 3D cell culture.

The impact of ultrasound-based antenatal screening strategies to detect vasa praevia in the United Kingdom: An exploratory study using decision analytic modelling methods.

The objective of this exploratory modelling study was to estimate the effects of second-trimester, ultrasound-based antenatal detection strategies for vasa praevia (VP) in a hypothetical cohort of pregnant women. For this, a decision-analytic tree model was developed covering four discrete detection pathways/strategies: no screening; screening targeted at women undergoing in-vitro fertilisation (IVF); screening targeted at women with low-lying placentas (LLP); screening targeted at women with velamentous cord insertion (VCI) or a bilobed or succenturiate (BL/S) placenta. Main outcome measures were the number of referrals to transvaginal sonography (TVS), diagnosed and undiagnosed cases of VP, overdetected cases of VCI, and VP-associated perinatal mortality. The greatest number of referrals to TVS occurred in the LLP-based (2,083) and VCI-based screening (1,319) pathways. These two pathways also led to the highest proportions of pregnancies diagnosed with VP (VCI-based screening: 552 [78.9% of all pregnancies]; LLP-based: 371 [53.5%]) and the lowest proportions of VP leading to perinatal death (VCI-based screening: 100 [14.2%]; LLP-based: 196 [28.0%]). In contrast, the IVF-based pathway resulted in 66 TVS referrals, 50 VP diagnoses (7.1% of all VP pregnancies), and 368 (52.6%) VP-associated perinatal deaths which was comparable to the no screening pathway (380 [54.3%]). The VCI-based pathway resulted in the greatest detection of VCI (14,238 [99.1%]), followed by the IVF-based pathway (443 [3.1%]); no VCI detection occurred in the LLP-based or no screening pathways. In conclusion, the model results suggest that a targeted LLP-based approach could detect a substantial proportion of VP cases, while avoiding VCI overdetection and requiring minimal changes to current clinical practice. High-quality data is required to explore the clinical and cost-effectiveness of this and other detection strategies further. This is necessary to provide a robust basis for future discussion about routine screening for VP.

The association of umbilical coiling and angiogenesis markers: Impact assessment of gestational diabetes.

INTRODUCTION: The purpose of this study was to determine the association between the postnatal umbilical coiling index (pUCI) and vascular endothelial growth factor A (VEGFA) and its receptor (VEGFR2) in parturients with and without gestational diabetes mellitus (GDM). METHODS: Within 24 h following birth, the umbilical cord and pUCI of 29 newborns with GDM and 28 neonates with non-GDM parturients were prospectively examined. Real-time PCR tests were used to determine the expression levels of the VEGFA and VEGFR2 genes, measured from the umbilical cord. The Mann-Whitney and Chi-squared tests were used to compare continuous and discrete variables with and without GDM. RESULTS: The median (IQR) of maternal age was 30 (26-34) years. There were no differences in demographic features between GDM and non-GDM parturients. While there was a marginal difference in VEGFA expression levels between the GDM and non-GDM groups (P-values = 0.07), no difference was detected for VEGFR2 (P-values = 0.75). Comparing hyper- and hypocoiling cords revealed a small difference in VEGFA levels (P-values = 0.05), but no change in VEGFR2 (P-values = 0.50). Furthermore, in both GDM and non-GDM parturients, down-regulated VEGFA was the general rule among abnormal pUCIs. DISCUSSION: The GDM and coiling state both are associated with the amount of VEGFA expression, but neither is related to VEGFR2. Furthermore, regardless of whether the patient has GDM or not, the abnormal coiling pattern appears to be related to the VEGFA down-regulation.

Umbilical Cord Biometry and Fetal Abdominal Skinfold Assessment as Potential Biomarkers for Fetal Macrosomia in a Gestational Diabetes Romanian Cohort.

Backgroundand Objectives: Gestational diabetes mellitus (GDM) is a pregnancy-associated pathology commonly resulting in macrosomic fetuses, a known culprit of obstetric complications. We aimed to evaluate the potential of umbilical cord biometry and fetal abdominal skinfold assessment as screening tools for fetal macrosomia in gestational diabetes mellitus pregnant women. Materials and methods: This was a prospective case−control study conducted on pregnant patients presenting at 24−28 weeks of gestation in a tertiary-level maternity hospital in Northern Romania. Fetal biometry, fetal weight estimation, umbilical cord area and circumference, areas of the umbilical vein and arteries, Wharton jelly (WJ) area and abdominal fold thickness measurements were performed. Results: A total of 51 patients were enrolled in the study, 26 patients in the GDM group and 25 patients in the non-GDM group. There was no evidence in favor of umbilical cord area and WJ amount assessments as predictors of fetal macrosomia (p > 0.05). However, there was a statistically significant difference in the abdominal skinfold measurement during the second trimester between macrosomic and normal-weight newborns in the GDM patient group (p = 0.016). The second-trimester abdominal circumference was statistically significantly correlated with fetal macrosomia at term in the GDM patient group with a p value of 0.003, as well as when considering the global prevalence of macrosomia in the studied populations, 0.001, when considering both populations. Conclusions: The measurements of cord and WJ could not be established as predictors of fetal macrosomia in our study populations, nor differentiate between pregnancies with and without GDM. Abdominal skinfold measurement and abdominal circumference measured during the second trimester may be important markers of fetal metabolic status in pregnancies complicated by GDM.

The assessment of maternal and umbilical cord neudesin levels in pregnancies with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) occurs due to the inability to adapt to physiologically observed changes in carbohydrate metabolism during pregnancy. Neudesin is a multi-functional secreted protein suggested to have a crucial regulator role in energy and carbohydrate metabolism. This study aimed to evaluate maternal serum and umbilical cord neudesin levels in pregnancies with GDM. Twenty-four singleton pregnancies with GDM were compared with gestational age-matched 23 uncomplicated pregnancies in this cross-sectional study. In comparison to the control group, significantly higher maternal serum and umbilical cord neudesin levels were observed in pregnancies with GDM (p < .001). Maternal serum and umbilical cord neudesin levels were also significantly positively correlated with maternal serum insulin levels and HOMA-IR values in the study group (p < .001). Neudesin, with its regulator role in carbohydrate metabolism, may be a contributing factor in the pathophysiology of GDM and may be a target of strategies for the prevention and treatment of GDM.Impact statementWhat is already known on this subject? Progressive changes in carbohydrate metabolism occur in normal pregnancy to provide continuous nutritional supply to the developing foetus and pregnant woman. When these progressive metabolic changes cannot be compensated, gestational diabetes mellitus (GDM) occurs.What the results of this study add? This is the first study to provide information about maternal serum and umbilical cord neudesin levels in pregnancies with GDM. This study observed that the serum levels of neudesin, which is suggested to have a regulator role in carbohydrate metabolism, were increased in pregnant women with GDM.What the implications are of these findings for clinical practice and/or future research? Neudesin may contribute to impaired carbohydrate metabolism in pregnancies with GDM and can be the subject of further studies on the prevention and treatment of GDM.

Third trimester intrauterine fetal death: proposal for the assessment of the chronology of umbilical cord and placental thrombosis.

The timing of umbilical cord and placental thrombosis in the third trimester intrauterine fetal death (TT-IUFD) may be fundamental for medico-legal purposes, when it undergoes medical litigation due to the absence of risk factors. Authors apply to human TT-IUFD cases a protocol, which includes histochemistry and immunohistochemistry (IHC) for the assessment of thrombi's chronology. A total of 35 thrombi of umbilical cord and/or placenta were assessed: 2 in umbilical artery, 6 in umbilical vein, 15 in insertion, 10 in chorionic vessels, 1 in fetal renal vein, 1 in fetal brachiocephalic vein. Thrombi's features were evaluated with hematoxylin-eosin, Picro-Mallory, Von Kossa, Perls, and immunohistochemistry for CD15, CD68, CD31, CD61, and Smooth Muscle Actin. The estimation of the age of the thrombi was established by applying neutrophils/macrophages ratio taking into consideration, according to literature, the presence of hemosiderophagi, calcium deposition, and angiogenesis. To estimate an approximate age of fresh thrombi (< 1 day), a non-linear regression model was tested. Results were compared to maternal risk factors, fetal time of death estimated at autopsy, mechanism, and cause of death. Our study confirms that the maternal risk factors for fetal intrauterine death and the pathologies of the cord, followed by those of the placental parenchyma, are the conditions that are most frequently associated with the presence of thrombi. Results obtained with histological stainings document that the neutrophile/macrophage ratio is a useful tool for determining placental thrombi's age. Age estimation of thrombi on the first day is very challenging; therefore, the study presented suggests the N/M ratio as a parameter to be used, together with others, i.e., hemosiderophagi, calcium deposition, and angiogenesis, for thrombi's age determination, and hypothesizes that its usefulness regards particularly the first days when all other parameters are negative.

Cost and consequences of using 7.1 % chlorhexidine gel for newborn umbilical cord care in Kenya.

BACKGROUND: Omphalitis is an important contributor to neonatal mortality in Kenya. Chlorhexidine digluconate 7.1 % w/w (CHX; equivalent to 4 % w/w chlorhexidine) was identified as a life-saving commodity for newborn cord care by the United Nations and is included on World Health Organization and Kenyan Essential Medicines Lists. This pilot study assessed the potential resource savings and breakeven price of implementing CHX for neonatal umbilical cord care versus dry cord care (DCC) in Kenya. METHODS: We employed a cost-consequence model in a Kenyan birth cohort. Firstly, the number of omphalitis cases and cases avoided by healthcare sector were estimated. Incidence rates and treatment effect inputs were calculated from a Cochrane meta-analysis of randomised clinical trials (RCTs) (base case) and 2 other RCTs. Economic outcomes associated with omphalitis cases avoided were determined, including direct, indirect and total cost of care associated with omphalitis, resource use (outpatient visits and bed days) and societal impact (caregiver workdays lost). Costs and other inputs were sourced from literature and supplemented by expert clinical opinion/informed inputs, making necessary assumptions. RESULTS: The model estimated that, over 1 year, ~ 23,000 omphalitis cases per 500,000 births could be avoided through CHX application versus DCC, circumventing ~ 13,000 outpatient visits, ~ 43,000 bed days and preserving ~ 114,000 workdays. CHX was associated with annual direct cost savings of ~ 590,000 US dollars (USD) versus DCC (not including drug-acquisition cost), increasing to ~ 2.5 million USD after including indirect costs (productivity, notional salary loss). The most-influential model parameter was relative risk of omphalitis with CHX versus DCC. Breakeven analysis identified a budget-neutral price for CHX use of 1.18 USD/course when accounting for direct cost savings only, and 5.43 USD/course when including indirect cost savings. The estimated breakeven price was robust to parameter input changes. DCC does not necessarily represent standard of care in Kenya; other, potentially harmful, approaches may be used, meaning cost savings may be understated. CONCLUSIONS: Estimated healthcare cost savings and potential health benefits provide compelling evidence to implement CHX for umbilical cord care in Kenya. We encourage comprehensive data collection to make future models and estimates of impacts of upscaling CHX use more robust.

Assessment of Long-Term in vitro Multiplied Human Wharton's Jelly-Derived Mesenchymal Stem Cells prior to Their Use in Clinical Administration.

The quantity of mesenchymal stem/stromal cells (MSCs) required for a particular therapy demands their subsequent expansion through ex vivo culture. During in vitro multiplication, they undergo replicative senescence which may alter their genetic stability. Therefore, this study was aimed to analyze cellular, molecular, and chromosomal alterations in Wharton's jelly-derived MSCs (WJ-MSCs) during their in vitro sequential passages, where WJ-MSCs were sequentially passaged up to P14 and cells were evaluated at an interval of P2, P6, P10, and P14. They were examined for their morphology, tumorigenicity, surface markers, stemness markers, DNA damage, chromosomal aberration, and telomere length. We have processed five full-term delivered human umbilical cord samples to obtain WJ-MSCs. Morphological appearance observed at initial stages was small fine spindle-shaped WJ-MSCs which were transformed to flat, long, and broader cells in later passages. The cell proliferation rate was gradually decreased after the 10th passage. WJ-MSCs have expressed stemness markers OCT-4 and NANOG, while they showed high expression of positive surface markers CD90 and CD105 and lower expression of CD34 and CD45. They were non-tumorigenic with slow cellular aging during subsequent passages. There was no chromosomal abnormality up to the 14th passage, while increase in comet score and decrease in telomere length were observed in later passages. Hence, our study suggests that early and middle passaged (less than P10) WJ-MSCs are good candidates for clinical administration for treatment.

The Use of Atomic Force Microscopy in Comprehensive Assessment of the "Mother-Placenta-Fetus" System in Obstetric and Endocrine Pathology during Pregnancy.

Atomic force microscopy is not very popular in practical health care, therefore, its potential is not studied enough, for example, in obstetrics when studying the "mother-placenta-fetus" system. Our study summarizes the possibilities of using atomic force microscopy for detection of various circulatory disorders and vascular changes at the microscopic level in the uterus (endometrium and myometrium), placenta, and umbilical cord in the main variants of obstetric and endocrine pathology. For instance, in the case of endocrine pathologies, changes in the form of stasis, sludge, diapedesis, ischemia, destruction and separation of endotheliocytes in villous blood vessels were found in the mother. The oxygen content in erythrocytes also naturally decreased in pathologies; poikilo- and anisocytosis were observed.

ASSESSMENT OF CORRELATION BETWEEN MIRNAS-21-3P AND -210-3P EXPRESSION IN MATERNAL AND UMBILICAL CORD PLASMA AND FETAL WEIGHT AT BIRTH.

OBJECTIVE: The aim: To determine the degree of correlation of mass of the fetus and the level of mir-21, mir210 in maternal blood and umbilical cord blood of the fetus in uncomplicated gestation. PATIENTS AND METHODS: Materials and methods: 60 pregnant women with a single baby pregnancy in the third trimester (37-40 weeks) were examined. They all were given a general clinical, obstetric and the level of miRNA21-3р and miRNA210-3р were determined in the whole blood of pregnant women (before labor) and in fetal blood obtained from the umbilical artery at birth. The level of miRNAs was determined by the TaqMan method. RESULTS: Results: After examining maternal and fetal plasma samples, we were able to determine 49 samples of hsa-miR210-3p and hsa-miR21-3p from maternal plasma, 44 samples of hsa-miR210-3p and 37 samples of hsa-miR21-3p from the cord blood, which is a satisfactory result of more than 50%. Subsequently, between the results obtained and the birth weight of the fetus Pearson's correlation coefficient was studied. According to the results obtained, we found no correlation between fetal mass and hsa-miR210-3p level in maternal plasma (r-0,068674), low positive correlation of fetal mass with hsa-miR21-3p level in maternal plasma (r-0,212181 ), an average positive correlation with the level of hsa-miR21-3p in umbilical cord blood (r- 0.363374) and a high positive correlation with hsa-miR210-3p in umbilical cord blood (r-0.528616). CONCLUSION: Conclusions: Determination of the level of hypoxic miRNAs, in particular hsa-miR210-3p in the umbilical cord blood of the newborn may be a marker of the functional status of the placenta, which programs the normal development of the fetus.

Assessment of biological matrices for the detection of in utero cannabis exposure.

Cannabis consumption has been increasing worldwide among pregnant women. Due to the negative effects of prenatal cannabis exposure, it is necessary to develop an objective, sensitive, and specific method to determine cannabinoids use during pregnancy. In this study, we compared four different biological samples, maternal hair, meconium, umbilical cord, and placenta, for the detection of in utero cannabis exposure. The biological samples were collected from 627 mother-newborn dyads. All hair and meconium samples were analyzed, and umbilical cord and placenta if hair and/or meconium were positive for cannabinoids. Meconium and hair showed to complement each other, with an agreement between hair and meconium results of 96.7% but only 34.3% if just positive results were considered. Umbilical cord and placenta results showed a better agreement with meconium (91.3% and 92.6%, respectively) than with hair (39.1% and 34.6%, respectively). The predominant metabolites in meconium were 11-nor-carboxy-THC (THCCOOH) and 8,11-dihydroxy-THC (diOHTHC), and in umbilical cord and placenta was THCCOOH-glucuronide. Cannabidiol (CBD) and cannabinol (CBN) were detected in meconium but not in any umbilical cord or placenta. For the first time, prenatal marijuana exposure was analyzed and compared in paired hair, meconium, umbilical cord, and placental samples. Hair and meconium positivity rate was similar, but a more sensitive and specific analytical method for the hair may resolve discrepancies between the matrices. Umbilical cord and placenta may be considered suitable alternative matrices to meconium through the determination of THCCOOH-glucuronide as a biomarker of cannabis exposure.

Transperineal ultrasound assessment of fetal head elevation by maneuvers used for managing umbilical cord prolapse.

OBJECTIVE: To assess objectively the degree of fetal head elevation achieved by different maneuvers commonly used for managing umbilical cord prolapse. METHODS: This was a prospective observational study of pregnant women at term before elective Cesarean delivery. A baseline assessment of fetal head station was performed with the woman in the supine position, using transperineal ultrasound for measuring the parasagittal angle of progression (psAOP), head-symphysis distance (HSD) and head-perineum distance (HPD). The ultrasonographic measurements of fetal head station were repeated during different maneuvers, including elevation of the maternal buttocks using a wedge, knee-chest position, Trendelenburg position with a 15° tilt and filling the maternal urinary bladder with 100 mL, 300 mL and 500 mL of normal saline. The measurements obtained during the maneuvers were compared with the baseline measurements. RESULTS: Twenty pregnant women scheduled for elective Cesarean section at term were included in the study. When compared with baseline (median psAOP, 103.6°), the knee-chest position gave the strongest elevation effect, with the greatest reduction in psAOP (psAOP, 80.7°; P < 0.001), followed by filling the bladder with 500 mL (psAOP, 89.9°; P < 0.001) and 300 mL (psAOP, 94.4°; P < 0.001) of normal saline. Filling the maternal bladder with 100 mL of normal saline (psAOP, 96.1°; P = 0.001), the Trendelenburg position (psAOP, 96.8°; P = 0.014) and elevating the maternal buttocks (psAOP, 98.3°; P = 0.033) gave modest elevation effects. Similar findings were reported for HSD and HPD. The fetal head elevation effects of the knee-chest position, Trendelenburg position and elevation of the maternal buttocks were independent of the initial fetal head station, but that of bladder filling was greater when the initial head station was low. CONCLUSIONS: To elevate the fetal presenting part, the knee-chest position provides the best effect, followed by filling the maternal urinary bladder with 500 mL then 300 mL of fluid, respectively. Filling the bladder with 100 mL of fluid, the Trendelenburg position and elevation of the maternal buttocks have modest effects. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Harnessing the Secretome of Mesenchymal Stromal Cells for Traumatic Spinal Cord Injury: Multicell Comparison and Assessment of In Vivo Efficacy.

Cell therapy offers significant promise for traumatic spinal cord injury (SCI), which despite many medical advances, has limited treatment strategies. Able to address the multifactorial and dynamic pathophysiology of SCI, cells present various advantages over standard pharmacological approaches. However, the use of live cells is also severely hampered by logistical and practical considerations. These include specialized equipment and expertise, standardization of cell stocks, sustained cell viability post-thawing, and cryopreservation-induced delayed-onset cell death. For this reason, we suggest a novel and clinically translatable alternative to live-cell systemic infusion, which retains the efficacy of the latter while overcoming many of its limitations. This strategy involves the administration of concentrated cell secretome and exploits the trophic mechanism by which stromal cells function. In this study, we compare the efficacy of intravenously delivered concentrated conditioned media (CM) from human umbilical cord matrix cells (HUCMCs), bone marrow mesenchymal stromal cells, as well as newborn and adult fibroblasts in a rat model of moderately severe cervical clip compression/contusion injury (C7--T1, 35 g). This is further paired with a thorough profile of the CM cytokines, chemokines, and angiogenic factors. The HUCMC-derived CM was most effective at limiting acute (48 h post-SCI) vascular pathology, specifically lesion volume, and functional vascularity. Principle component analysis (PCA), hierarchical clustering, and interaction analysis of proteins highly expressed in the HUCMC secretome suggest involvement of the MAPK/ERK, JAK/STAT, and immune cell migratory pathways. This "secretotherapeutic" strategy represents a novel and minimally invasive method to target multiple organ systems and several pathologies shortly after traumatic SCI.

AI-PLAX: AI-based placental assessment and examination using photos.

Post-delivery analysis of the placenta is useful for evaluating health risks of both the mother and baby. In the U.S., however, only about 20% of placentas are assessed by pathology exams, and placental data is often missed in pregnancy research because of the additional time, cost, and expertise needed. A computer-based tool that can be used in any delivery setting at the time of birth to provide an immediate and comprehensive placental assessment would have the potential to not only to improve health care, but also to radically improve medical knowledge. In this paper, we tackle the problem of automatic placental assessment and examination using photos. More concretely, we first address morphological characterization, which includes the tasks of placental image segmentation, umbilical cord insertion point localization, and maternal/fetal side classification. We also tackle clinically meaningful feature analysis of placentas, which comprises detection of retained placenta (i.e., incomplete placenta), umbilical cord knot, meconium, abruption, chorioamnionitis, and hypercoiled cord, and categorization of umbilical cord insertion type. We curated a dataset consisting of approximately 1300 placenta images taken at Northwestern Memorial Hospital, with hand-labeled pixel-level segmentation map, cord insertion point and other information extracted from the associated pathology reports. We developed the AI-based Placental Assessment and Examination system (AI-PLAX), which is a novel two-stage photograph-based pipeline for fully automated analysis. In the first stage, we use three encoder-decoder convolutional neural networks with a shared encoder to address morphological characterization tasks by employing a transfer-learning training strategy. In the second stage, we employ distinct sub-models to solve different feature analysis tasks by using both the photograph and the output of the first stage. We evaluated the effectiveness of our pipeline by using the curated dataset as well as the pathology reports in the medical record. Through extensive experiments, we demonstrate our system is able to produce accurate morphological characterization and very promising performance on aforementioned feature analysis tasks, all of which may possess clinical impact and contribute to future pregnancy research. This work is the first for comprehensive, automated, computer-based placental analysis and will serve as a launchpad for potentially multiple future innovations.

Impact of umbilical cord length on fetal circulatory system by Doppler assessment.

INTRODUCTION: Numerous studies have revealed the impact of umbilical cord (UC) length on fetal perfusion; abundant data implicate abnormal UC length to neurological delay and subsequent poor prognoses for fetuses and newborns. Indeed, our group previously developed theoretical approximations that contributed to formulas capable of explaining the impact of UC length on cardiac output. METHODS: We performed an observational study that measured the pulsatility index and flow velocity in umbilical arteries. A special Doppler measured proximal and distal indexes in both arteries. After birth, medical staff measured complete UC length. We obtained maternal and neonatal outcomes from clinical records. RESULTS: Our study enrolled 20 pregnant mothers. We found that flow velocities in the two edges were different: fetal edges exhibited greater velocity in the majority of cases; but, when we compared pressure differentials (ΔP), the pulsatility index was significantly related to umbilical cord length. CONCLUSIONS: Fetal perfusion, welfare, and viability are related to UC function as the conveyor of all fetal volemia. Excessive UC length affects cardiac dynamics and increases peripheral vascular resistance. Further studies could validate routine use of the differential proximal and distal measurements proposed in this article, and their implications in in utero fetal heart function. We also hope that early diagnosis or UC alterations could alert neonatologists and obstetricians to clinical conditions of the fetus.

Umbilical Cord MSCs and Their Secretome in the Therapy of Arthritic Diseases: A Research and Industrial Perspective.

The prevalence of arthritic diseases is increasing in developed countries, but effective treatments are currently lacking. The injection of mesenchymal stem cells (MSCs) represents a promising approach to counteract the degenerative and inflammatory environment characterizing those pathologies, such as osteoarthritis (OA). However, the majority of clinical approaches based on MSCs are used within an autologous paradigm, with important limitations. For this reason, allogeneic MSCs isolated from cord blood (cbMSCs) and Wharton's jelly (wjMSCs) gained increasing interest, demonstrating promising results in this field. Moreover, recent evidences shows that MSCs beneficial effects can be related to their secretome rather than to the presence of cells themselves. Among the trophic factors secreted by MSCs, extracellular vesicles (EVs) are emerging as a promising candidate for the treatment of arthritic joints. In the present review, the application of umbilical cord MSCs and their secretome as innovative therapeutic approaches in the treatment of arthritic joints will be examined. With the prospective of routine clinical applications, umbilical cord MSCs and EVs will be discussed also within an industrial and regulatory perspective.

Cost-effective storage solution for delivering umbilical cord with efficient isolation of mesenchymal stem cells.

Mesenchymal stem cells (MSCs) represent a promising therapeutic candidate for treating many diseases. However, their proliferation and therapeutic abilities decline during the aging process and disease development. Therefore, fetal MSCs derived from the umbilical cord (UC) attract more attention. Storing and delivering the UC is one critical step for efficient MSC isolation. Although the culture medium-based solution is suitable for UC storage, it is not feasible for large-scale preparation because of its high price. Thus, we demonstrate here that a simple solution containing a pH buffering reagent, calcium, magnesium and glucose could be used as a cost-effective storage solution for UC delivery and efficient MSC isolation.

Rapid quantification of tenofovir in umbilical cord plasma and amniotic fluid in hepatitis B mono-infected pregnant women during labor by ultra-performance liquid chromatography/tandem mass spectrometry.

RATIONALE: Tenofovir (TFV) is a first-line antiviral agent against hepatitis B virus (HBV) and is recommended for the prevention of mother-to-infant transmission of HBV. To study the distribution of TFV in umbilical cord plasma and amniotic fluid of HBV-infected pregnant women, a rapid and sensitive method for TFV determination was developed and validated. METHODS: The quantification method was developed using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS). The analytes were separated on an Acquity UPLC HSS T3 column under gradient elution with methanol and 0.01% ammonia solution in 10 mM ammonium acetate/water. This is the first reported method for the determination of TFV using alkaline rather than acidic mobile phases. Linearity, accuracy, precision, limit of quantification, specificity and stability were assessed. RESULTS: Detection of TFV was achieved within 4 min. The calibration curves for TFV quantification showed excellent linearity in the range of 1-500 ng/mL. The intra- and interbatch precision and accuracy ranged from -4.35% to 6.92%. This method was successfully applied to determination of samples from 50 HBV mono-infected women undergoing tenofovir disoproxil fumarate therapy. The mean concentrations of TFV in the umbilical cord and amniotic fluid samples were 29.2 (4.6-86) and 470.9 (156-902) ng/mL, respectively, which showed a moderate positive correlation (r = 0.5299, P<0.001). CONCLUSIONS: A simple, rapid but sensitive bioanalytical method to determine TFV concentration in both umbilical cord plasma and amniotic fluid using LC/MS/MS was developed and applied to HBV-infected women during labor who were undergoing TDF therapy, which will help us understand the efficacy and safety of tenofovir during pregnancy.