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Hintergrund: Postpartale Hämorrhagien (PPH) gehören zu den häufigsten Notfallsituationen im Gebärsaal. Sie zählen zu den Hauptursachen der Müttersterblichkeit. Zur Prävention der PPH wird hauptsächlich das aktive Management der Plazentarperiode angewandt. Diverse Studien zeigen mit Placental cord drainage (PCD) eine weitere Massnahme auf. Ziel: Das Ziel dieser Arbeit ist, die in der Literatur beschriebenen Effekte von PCD in der Plazentarperiode im Niedrig-Risiko-Kollektiv darzulegen. Es werden die Variablen Dauer und Blutverlust der Plazentarperiode, Hämoglobinwert sowie PPH-Inzidenz untersucht. Zudem soll eine Empfehlung für Fachpersonen abgegeben werden, um PCD im klinischen Alltag zu fördern. Methodik: Anhand definierter Ein- und Ausschlusskriterien wurde eine systematische Literaturrecherche durchgeführt. Dabei sind vier quantitative Studien ausgewählt und kritisch bewertet worden. Ergebnisse: Es zeigt sich die Tendenz, dass PCD zu einer kürzeren Dauer und zu einem geringeren Blutverlust der Plazentarperiode sowie zu einer tieferen PPH-Inzidenz führt. Die genauen Auswirkungen auf den postpartalen Hämoglobinwert bleiben unklar. Schlussfolgerung: PCD hat im Niedrig-Risiko-Kollektiv keine nachteilige Wirkung auf die diskutierten Resultate der Plazentarperiode und kann als ergänzende Massnahme zum aktiven Management angewendet werden. Weitere Forschung ist notwendig, um den tatsächlichen Nutzen von PCD in der Praxis zu bestätigen und eine allgemeine Empfehlung zur Anwendung bei allen Gebärenden abgeben zu können.

Aim/hypothesis This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes. Methods A combined Phase I/II trial, composed of a dose escalation followed by a randomised double-blind placebo-controlled study in parallel design, was performed in which treatment with allogeneic MSCs produced as an advanced therapy medicinal product (ProTrans) was compared with placebo in adults with newly diagnosed type 1 diabetes. Inclusion criteria were a diagnosis of type 1 diabetes <2 years before enrolment, age 18-40 years and a fasting plasma C-peptide concentration >0.12 nmol/l. Randomisation was performed with a web-based randomisation system, with a randomisation code created prior to the start of the study. The randomisation was made in blocks, with participants randomised to ProTrans or placebo treatment. Randomisation envelopes were kept at the clinic in a locked room, with study staff opening the envelopes at the baseline visits. All participants and study personnel were blinded to group assignment. The study was conducted at Karolinska University Hospital, Stockholm, Sweden. Results Three participants were included in each dose cohort during the first part of the study. Fifteen participants were randomised in the second part of the study, with ten participants assigned to ProTrans treatment and five to placebo. All participants were analysed for the primary and secondary outcomes. No serious adverse events related to treatment were observed and, overall, few adverse events (mainly mild upper respiratory tract infections) were reported in the active treatment and placebo arms. The primary efficacy endpoint was defined as Delta-change in C-peptide AUC for a mixed meal tolerance test at 1 year following ProTrans/placebo infusion compared with baseline performance prior to treatment. C-peptide levels in placebo-treated individuals declined by 47%, whereas tho

Aim/hypothesis This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes. Methods A combined Phase I/II trial, composed of a dose escalation followed by a randomised double-blind placebo-controlled study in parallel design, was performed in which treatment with allogeneic MSCs produced as an advanced therapy medicinal product (ProTrans) was compared with placebo in adults with newly diagnosed type 1 diabetes. Inclusion criteria were a diagnosis of type 1 diabetes <2 years before enrolment, age 18-40 years and a fasting plasma C-peptide concentration >0.12 nmol/l. Randomisation was performed with a web-based randomisation system, with a randomisation code created prior to the start of the study. The randomisation was made in blocks, with participants randomised to ProTrans or placebo treatment. Randomisation envelopes were kept at the clinic in a locked room, with study staff opening the envelopes at the baseline visits. All participants and study personnel were blinded to group assignment. The study was conducted at Karolinska University Hospital, Stockholm, Sweden. Results Three participants were included in each dose cohort during the first part of the study. Fifteen participants were randomised in the second part of the study, with ten participants assigned to ProTrans treatment and five to placebo. All participants were analysed for the primary and secondary outcomes. No serious adverse events related to treatment were observed and, overall, few adverse events (mainly mild upper respiratory tract infections) were reported in the active treatment and placebo arms. The primary efficacy endpoint was defined as Delta-change in C-peptide AUC for a mixed meal tolerance test at 1 year following ProTrans/placebo infusion compared with baseline performance prior to treatment. C-peptide levels in placebo-treated individuals declined by 47%, whereas tho

Aim/hypothesis This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes. Methods A combined Phase I/II trial, composed of a dose escalation followed by a randomised double-blind placebo-controlled study in parallel design, was performed in which treatment with allogeneic MSCs produced as an advanced therapy medicinal product (ProTrans) was compared with placebo in adults with newly diagnosed type 1 diabetes. Inclusion criteria were a diagnosis of type 1 diabetes <2 years before enrolment, age 18-40 years and a fasting plasma C-peptide concentration >0.12 nmol/l. Randomisation was performed with a web-based randomisation system, with a randomisation code created prior to the start of the study. The randomisation was made in blocks, with participants randomised to ProTrans or placebo treatment. Randomisation envelopes were kept at the clinic in a locked room, with study staff opening the envelopes at the baseline visits. All participants and study personnel were blinded to group assignment. The study was conducted at Karolinska University Hospital, Stockholm, Sweden. Results Three participants were included in each dose cohort during the first part of the study. Fifteen participants were randomised in the second part of the study, with ten participants assigned to ProTrans treatment and five to placebo. All participants were analysed for the primary and secondary outcomes. No serious adverse events related to treatment were observed and, overall, few adverse events (mainly mild upper respiratory tract infections) were reported in the active treatment and placebo arms. The primary efficacy endpoint was defined as Delta-change in C-peptide AUC for a mixed meal tolerance test at 1 year following ProTrans/placebo infusion compared with baseline performance prior to treatment. C-peptide levels in placebo-treated individuals declined by 47%, whereas tho

BackgroundCOVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology.ObjectiveThis study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes.Study designThis was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings.ResultsThis study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timi

Aim/hypothesis This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes. Methods A combined Phase I/II trial, composed of a dose escalation followed by a randomised double-blind placebo-controlled study in parallel design, was performed in which treatment with allogeneic MSCs produced as an advanced therapy medicinal product (ProTrans) was compared with placebo in adults with newly diagnosed type 1 diabetes. Inclusion criteria were a diagnosis of type 1 diabetes <2 years before enrolment, age 18-40 years and a fasting plasma C-peptide concentration >0.12 nmol/l. Randomisation was performed with a web-based randomisation system, with a randomisation code created prior to the start of the study. The randomisation was made in blocks, with participants randomised to ProTrans or placebo treatment. Randomisation envelopes were kept at the clinic in a locked room, with study staff opening the envelopes at the baseline visits. All participants and study personnel were blinded to group assignment. The study was conducted at Karolinska University Hospital, Stockholm, Sweden. Results Three participants were included in each dose cohort during the first part of the study. Fifteen participants were randomised in the second part of the study, with ten participants assigned to ProTrans treatment and five to placebo. All participants were analysed for the primary and secondary outcomes. No serious adverse events related to treatment were observed and, overall, few adverse events (mainly mild upper respiratory tract infections) were reported in the active treatment and placebo arms. The primary efficacy endpoint was defined as Delta-change in C-peptide AUC for a mixed meal tolerance test at 1 year following ProTrans/placebo infusion compared with baseline performance prior to treatment. C-peptide levels in placebo-treated individuals declined by 47%, whereas tho

A liquid-based perinatal life support system (PLS) for extremely premature infants (born before 28 week of gestational age) envisions a connection between the infant’s native umbilical cord and an artificial placenta system through cannulation. This system mimics a natural mothers’ womb to achieve better organ maturations. The objective of this study is to gain insight into the clinical focus points of umbilical cord cannulation and how cannulation should be addressed in extremely premature infants during the transfer from the uterus to an in-utero simulating liquid-based PLS system. We performed an explorative qualitative study. Twelve medical specialists with knowledge of vessel cannulation participated. We collected data through twelve interviews and two focus group discussions. Data were analyzed using inductive content and constant comparison analysis via open and axial coding. Results were derived on the following topics: (1) cannulation technique, (2) cannula fixation, (3) local and systemic anticoagulation, and (4) vasospasm. A side-entry technique is preferred as this may decrease wall damage, stabilizes the vessel better and ensures continuous blood flow. Sutures, especially via an automatic microsurgery instrument, are favored above glue, stents, or balloons as these may be firmer and faster. Medication possibilities for both vasospasm and anticoagulation should function locally since there were uncertainties regarding the systemic effects. According to the findings of this research, the needed umbilical cord cannulation method should include minimal wall damage, improved vascular stability, blood flow maintenance, a strong fixation connection, and local anticoagulation effect.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers worldwide. Treatment of PDAC remains a major challenge. This study aims to evaluate, in vitro, the use of human umbilical cord mesenchymal stromal cell (UC-MSC)-derived EVs to specifically target pancreatic cancer cells. EVs were isolated from the FBS-free supernatants of the cultured UC-MSCs by ultracentrifugation and characterized by several methods. EVs were loaded with scramble or KRASG12D-targeting siRNA by electroporation. The effects of control and loaded EVs on different cell types were evaluated by assessing cell proliferation, viability, apoptosis and migration. Later, the ability of EVs to function as a drug delivery system for doxorubicin (DOXO), a chemotherapeutic drug, was also evaluated. Loaded EVs exhibited different kinetic rates of uptake by three cell lines, namely, BxPC-3 cells (pancreatic cancer cell line expressing KRASwt), LS180 cells (colorectal cell line expressing KRASG12D) and PANC-1 cells (pancreatic cell line expressing KRASG12D). A significant decrease in the relative expression of the KRASG12D gene after incubation with KRAS siRNA EVs was observed by real-time PCR. KRASG12D siRNA EVs significantly reduced the proliferation, viability and migration of the KRASG12D cell lines compared to scramble siRNA EVs. An endogenous EV production method was applied to obtain DOXO-loaded EVs. Briefly, UC-MSCs were treated with DOXO. After 24 h, UC-MSCs released DOXO-loaded EVs. DOXO-loaded EVs were rapidly taken up by PANC-1 cells and induced apoptotic cell death more efficiently than free DOXO. In conclusion, the use of UC-MSC-derived EVs as a drug delivery system for siRNAs or drugs could be a promising approach for the targeted treatment of PDAC., SCOPUS: ar.j, info:eu-repo/semantics/published

Aim/hypothesis This study aimed to investigate the safety and efficacy of treatment with allogeneic Wharton's jelly-derived mesenchymal stromal cells (MSCs) in recent-onset type 1 diabetes. Methods A combined Phase I/II trial, composed of a dose escalation followed by a randomised double-blind placebo-controlled study in parallel design, was performed in which treatment with allogeneic MSCs produced as an advanced therapy medicinal product (ProTrans) was compared with placebo in adults with newly diagnosed type 1 diabetes. Inclusion criteria were a diagnosis of type 1 diabetes <2 years before enrolment, age 18-40 years and a fasting plasma C-peptide concentration >0.12 nmol/l. Randomisation was performed with a web-based randomisation system, with a randomisation code created prior to the start of the study. The randomisation was made in blocks, with participants randomised to ProTrans or placebo treatment. Randomisation envelopes were kept at the clinic in a locked room, with study staff opening the envelopes at the baseline visits. All participants and study personnel were blinded to group assignment. The study was conducted at Karolinska University Hospital, Stockholm, Sweden. Results Three participants were included in each dose cohort during the first part of the study. Fifteen participants were randomised in the second part of the study, with ten participants assigned to ProTrans treatment and five to placebo. All participants were analysed for the primary and secondary outcomes. No serious adverse events related to treatment were observed and, overall, few adverse events (mainly mild upper respiratory tract infections) were reported in the active treatment and placebo arms. The primary efficacy endpoint was defined as Delta-change in C-peptide AUC for a mixed meal tolerance test at 1 year following ProTrans/placebo infusion compared with baseline performance prior to treatment. C-peptide levels in placebo-treated individuals declined by 47%, whereas tho

BackgroundNeonatal Resuscitation Program does not recommend placental transfusion in depressed preterm neonates.MethodsOur objectives were to study the effect of delayed cord clamping (DCC) with ventilation for 5 min (DCCV, n-5), umbilical cord milking (UCM) without ventilation (n-6), UCM with ventilation (UCMV, n-6), early cord clamping followed by ventilation (ECCV, n-6) on red cell volume (RCV), and hemodynamic changes in asphyxiated preterm lambs. Twenty-three preterm lambs at 127-128 days gestation were randomized to DCCV, UCM, UCMV, and ECCV. We defined asphyxia as heart rate <100/min.ResultsThe UCMV had the highest neonatal RCV as a percentage of fetoplacental volume compared to the other groups (UCMV 85.5 ± 10%, UCM 72 ± 10%, ECCV 65 ± 14%, DCCV 61 ± 10%, p < 0.01). The DCCV led to better ventilation (66 ± 1 mmHg) and higher pulmonary blood flow (75 ± 24 ml/kg/min). The carotid flow was significantly higher in UCM without ventilation. The fluctuations in carotid flow with milking were 25 ± 6% higher from baseline during UCM, compared to 6 ± 3% in UCMV (p < 0.01).ConclusionsCord milking with ventilation led to higher RCV than other interventions. Ventilation during cord milking reduced fluctuation in carotid flow compared to UCM alone. DCCV led to better ventilation and pulmonary blood flow but did not increase RCV.ImpactThe best practice of placental transfusion in a depressed preterm neonate remains unknown. Ventilation with an intact cord improves gas exchange and hemodynamics in an asphyxiated preterm model. Cord milking without ventilation led to lower red cell volume but higher carotid blood flow fluctuations compared to milking with ventilation. Our data can be translated to bedside and could impact preterm resuscitation.

BackgroundIn prior work we observed differences in morphology features in placentas from an autism-enriched cohort as compared to those from a general population sample. Here we sought to examine whether these differences associate with ASD-related outcomes in the child.MethodsParticipants (n = 101) were drawn from the Early Autism Risk Longitudinal Investigation (EARLI), a cohort following younger siblings of children with autism spectrum disorder (ASD). ASD-related outcomes, including the Social Responsiveness Scale (SRS), Mullen Scales of Early Learning (MSEL) Early Learning Composite, and ASD diagnosis, were assessed at age 3. Crude and adjusted linear regression was used to examine associations between placental morphological features (parametrized continuously and in quartiles) and SRS and MSEL scores; comparisons by ASD case status were explored as secondary analyses due to the small number of cases (n = 20).ResultsIn adjusted analyses, we observed a modest positive association between umbilical cord eccentricity, defined as the ratio of the maximum:minimum radius from the cord insertion point, and SRS scores (Beta = 1.68, 95%CI = 0.45, 2.9). Positive associations were also suggested between placental maximum thickness and cord centrality and SRS scores, though these were estimated with little precision. Associations between other placental morphological features and outcomes were not observed.ConclusionsOur analyses suggested a potential association between umbilical cord features and ASD-related traits, of interest as non-central cord insertion may reflect reduced placenta efficiency. Future studies with larger sample sizes are needed to further examine these and other placental features in association with ASD-related outcomes.

Objectives To evaluate umbilical cord immune cells in pregnancies with autoimmune disorders (AID) and/or methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Methods Umbilical cords were obtained from seven AID women without MTHFR polymorphisms, eight with AID and MTHFR polymorphisms, nine with MTHFR polymorphisms, and eight with neither. Umbilical cords were assessed immunohistologcally by anti-CD4, anti-CD8, anti-CD14, anti-CD19, anti-CD21, and anti-CD56 antibodies in six umbilical cord zones: 1) arterial wall 2) periarterial zone 3) venous wall 4) perivenous zone 5) intervascular zone, and 6) subamniotic zone. Results AIDs and MTHFR polymorphisms had an effect on the number and composition of CD4+ cells in the venous wall. The presence of a MTHFR polymorphism may affect the number and morphology of CD4+ cells in the subamniotic zone. CD8+ cell distribution is substantially influenced by the presence of maternal risk factors. The co-existence of AID with MTHFR polymorphism has a prominent effect on the number and morphology of CD14+ cells, especially in the arterial wall. CD19+ cells were only observed in the control group in the venous wall, perivenous zone, and intervascular zone. CD21+ cells were only observed in the arterial wall of the control group and the intervascular zone of the AID group with different morphologic features. The number and morphology of CD56+ cells is prominently affected by the presence of maternal risk factors. Conclusions Umbilical cord stem cell and immune cell composition may be affected by the presence of risk factors like MTHFR polymorphisms and/or AID., Hacettepe University's scientific research fund [08 D07 101 014], This study was supported by Hacettepe University's scientific research fund (08 D07 101 014).

Objectives To evaluate umbilical cord immune cells in pregnancies with autoimmune disorders (AID) and/or methylenetetrahydrofolate reductase (MTHFR) polymorphisms. Methods Umbilical cords were obtained from seven AID women without MTHFR polymorphisms, eight with AID and MTHFR polymorphisms, nine with MTHFR polymorphisms, and eight with neither. Umbilical cords were assessed immunohistologcally by anti-CD4, anti-CD8, anti-CD14, anti-CD19, anti-CD21, and anti-CD56 antibodies in six umbilical cord zones: 1) arterial wall 2) periarterial zone 3) venous wall 4) perivenous zone 5) intervascular zone, and 6) subamniotic zone. Results AIDs and MTHFR polymorphisms had an effect on the number and composition of CD4+ cells in the venous wall. The presence of a MTHFR polymorphism may affect the number and morphology of CD4+ cells in the subamniotic zone. CD8+ cell distribution is substantially influenced by the presence of maternal risk factors. The co-existence of AID with MTHFR polymorphism has a prominent effect on the number and morphology of CD14+ cells, especially in the arterial wall. CD19+ cells were only observed in the control group in the venous wall, perivenous zone, and intervascular zone. CD21+ cells were only observed in the arterial wall of the control group and the intervascular zone of the AID group with different morphologic features. The number and morphology of CD56+ cells is prominently affected by the presence of maternal risk factors. Conclusions Umbilical cord stem cell and immune cell composition may be affected by the presence of risk factors like MTHFR polymorphisms and/or AID., Hacettepe University's scientific research fund [08 D07 101 014], This study was supported by Hacettepe University's scientific research fund (08 D07 101 014).

Introducción: el consumo de drogas en embarazadas sigue siendo un gran problema sanitario, por ser perjudicial tanto para la madre como para el feto, afectando no solo al embarazo, sino al posterior desarrollo del neonato. Existen numerosas pruebas para la detección de dicho consumo, basándose esta revisión en el pelo materno, el meconio, el cordón umbilical y la placenta, siendo importante no solo sus métodos de análisis, sino también el conocimiento de los metabolitos de cada droga en cada matriz, que permitan la realización de un estudio más dirigido. Objetivos: comparar el pelo materno, el meconio, el cordón umbilical y la placenta como muestras biológicas para la detección del consumo de drogas en embarazadas y valorar su uso como medio de cribado para tal fin. Metodología: se realizó una revisión sistemática de la literatura científica de los últimos 10 años, siguiendo el método PRISMA, en las bases de datos Medline, PubMed, Scopus y Web of Science, obteniéndose un total final de 22 artículos que cumplían los criterios de inclusión establecidos. Resultados y discusión: revisando los 22 artículos incluidos, se vio que el pelo materno es la matriz más usada, seguida del meconio. El meconio no sólo es una buena matriz para la detección del consumo materno de drogas, sino también para determinar la exposición fetal a estas, y su capacidad de detección es similar a la del pelo. El cordón umbilical y la placenta muestran, a partir de los resultados obtenidos, una sensibilidad semejante entre ellas, siendo en ambos casos menores que las del pelo materno y el meconio. Conclusiones: el pelo materno y el meconio son, hoy en día, las mejores matrices biológicas para la detección del consumo de drogas en mujeres embarazadas, lo que permite un mejor manejo clínico y social de dichas situaciones, siendo necesaria la realización de más estudios en relación con la placenta y el cordón umbilical, Introdución: o consumo de drogas nas mulleres embarazadas segue a ser un importante problema de saude, por ser prexudicial tanto para a nai como para o feto, afectando non so ao embarazo, senon tamen ao desenvolvemento posterior do recentemente nado. Existen numerosas probas para a deteccion do devandito consumo, baseandose esta revision en cabelo materno, meconio, cordon umbilical e placenta, sendo importantes non so os seus metodos de analise, senon tamen o conecemento dos metabolitos de cada farmaco en cada matriz, que permiten realizar un estudo mais orientado. Obxectivos: comparar o cabelo materno, o meconio, o cordon umbilical e a placenta como mostras bioloxicas para a deteccion do consumo de drogas en mulleres embarazadas e valorar o seu uso como medio de cribado para este fin. Metodoloxía: realizouse unha revision sistematica da literatura cientifica dos ultimos 10 anos, seguindo o metodo PRISMA, nas bases de datos Medline, PubMed, Scopus e Web of Science, obtendo un total final de 22 artigos que cumprian os criterios de inclusion establecidos. Resultados e discusión: revisando os 22 artigos incluidos, comprobouse que o cabelo materno e a matriz mais empregada, seguida do meconio. O meconio non so e unha boa matriz para detectar o consumo materno de drogas, senon tamen para determinar a exposicion fetal a estas, e a sua capacidade de deteccion e similar a do cabelo. O cordon umbilical e a placenta mostran, a partir dos resultados obtidos, unha sensibilidade similar entre eles, sendo en ambos casos menor que os do cabelo materno e do meconio. Conclusións: o cabelo materno e o meconio son, hoxe en dia, as mellores matrices bioloxicas para a deteccion do consumo de drogas en mulleres embarazadas, o cal permiten un mellor manexo clinico e social destas situacions, sendo necesaria a realizacion de mais estudos en relacion coa placenta e o cordon umbilical, Introduction: drug use in pregnant women continues to be a major health problem, being harmful to both the mother and the fetus, affecting not only the pregnancy, but also the subsequent development of the newborn. There are numerous tests for the detection of this consumption. This review focuses on maternal hair, meconium, umbilical cord and placenta. In order to carry out a more adjusted analysis, not only the analytical methods used but also the knowledge of the preferential presence of the metabolites of each drug in the matrices were considered important. Objectives: to compare maternal hair, meconium, umbilical cord and placenta as biological samples for the detection of drug use in pregnant women and to assess their use as a screening for this purpose. Methods: a systematic review of the scientific literature of the last 10 years was carried out following the PRISMA method, in Medline, PubMed, Scopus and Web of Science databases, obtaining a final total of 22 articles that met the inclusion criteria established. Results and discussion: from the review of the 22 articles included, it was seen that maternal hair is the most used matrix, followed by meconium. Meconium is not only a good matrix for detecting maternal drug use, but also for determining fetal exposure to drugs. The ability to detect drugs varies depending on the sample, with maternal hair and meconium again being the most sensitive. The umbilical cord and the placenta show, from the results obtained, a similar sensitivity between them, being in both cases less than those of the maternal hair and meconium. Conclusions: maternal hair and meconium are, today, the best biological matrices for detection of drug use in pregnant women, which allow a better clinical and social management of these situations. Further studies in relation to placenta and umbilical cord are needed

Background: Pregravid obesity and abnormal gestational weight gain added to the physiological stresses of pregnancy have been shown to be associated with increased risks of morbidity and mortality for both the infant and mother. However, their effects on placental health are still uncertain. The placenta and the umbilical cord facilitate the interchange of nutrients between the maternal-fetal dyad. Recent research suggests that the placenta influences the metabolic environment in utero, which can in turn affect birth outcomes. Therefore, understanding how obesity affects the health of the placenta is vital. Methods: This dissertation consists of three studies using data from the University of California San Diego Perinatal Biospecimen Repository Cohort. Study 1 evaluated the effect maternal BMI has on indicators of placental health and assessed GDM as a mediator within the casual pathway. Study 2 assessed the effect gestational weight gain has on indicators of placental health. Study 3 built upon results from the first study by stratifying analyses to determine if the effect of maternal BMI on indicators of placental health were modified by fetal sex. The attenuation of the effect of obese maternal BMI on placental outcomes in the presence of chronic villitis was also evaluated in Study 3. Results: We found that maternal obesity was significantly associated with increased risk of larger placentas, longer umbilical cords, and chronic villitis (Study 1). Women with excessive gestational weight gain were shown to have higher risks of longer umbilical cords, especially in pregnancies with male fetuses (Study 2). We found that in pregnancies with female fetuses, the risk of chronic villitis is increased in women with obesity while other measurements of abnormal placental health were not at an increased risk. This varied in pregnancies with male fetuses, where the risk of larger placentas and longer umbilical cords were increased in women with maternal obesity, but no inc

In our critique of a pay-to-participate study, we address how the failure to disclose study-related payments appears to have violated STEM CELLS Translational Medicine's editorial policies concerning conflict-of-interest and financial disclosure. Our analysis also identifies broader ethical issues and scientific concerns related to pay-to-participate studies conducted by businesses with a record of selling purported stem cell treatments before determining whether the products they sell are safe and efficacious. Authors of peer-reviewed articles have a responsibility to comply with journal policies and disclose financial conflicts of interest to editors, reviewers, and readers. Authors should also disclose when stem cell interventions being tested in clinical trials have already been sold on a direct-to-consumer basis as "stem cell treatments" by authors' affiliate institutions. Financial conflicts of interest and other forms of possible bias must be disclosed to put clinical studies in context and facilitate the critical assessment of research methods, findings, and conclusions. The apparent failure to comply with journal editorial policies and disclose such financial conflicts warrants careful investigation.

Background: Dopamine is frequently used as inotropic agent in preterm infants. Its cardiovascular actions, as well as effects on neurovascular interactions may be neuroprotective during hypoxic-ischaemic events. Using a preterm lamb model we aimed to test the impact of intravenous dopamine on hypoxic-ischaemic brain injury. Method(s): Nine fetal lambs (91-93d gestation) were instrumented with catheters in carotid artery and jugular vein, and an umbilical cord occluder. Four days after surgery, intravenous dopamine (DA, 10 mug/kg/ min, n = 5) (or saline, n = 4) was commenced. Then a hypoxic-ischaemic insult was induced with umbilical cord occlusion for 25 min. Infusions were continued for another 72 h before euthanasia. Fetal brains were collected for immunohistopathology. Result(s): Dopamine infusion increased fetal heart rate (184 +/- 1 to 203 +/- 1 bpm, P < 0.05) while arterial pressure was unchanged. Three animals in the DA group showed tachycardic response to cord occlusion, while the other two animals showed bradycardic response similar to the saline group. In the periventricular white matter, the saline group had higher number of microglia (lectin positive) than the DA group (10 +/- 3 vs. 6 +/- 2 per 0.04 mm2, P < 0.05). The saline group tended to have shorter myelinated fibre lengths (CNPase) compared with the DA group (15.0 +/- 2.0 vs. 18.4 +/- 5.7 mum respectively, P = ns). No histological differences were evident between DA animals exhibiting a tachycardic or bradycardic response during cord occlusion. Conclusion(s): Intravenous dopamine reduces hypoxic-ischaemic white matter injury in preterm lambs, independent of the cardiovascular response during the hypoxic-ischaemia., F.Y. Wong, Ritchie Centre, MIMR, Monash University, Melbourne, VIC, Australia. E-mail: flora.wong@med.monash.edu.au, CONFERENCE ABSTRACT

To date, 18 living recommendations for the clinical care of pregnant and postpartum women with COVID-19 have been issued by the National COVID-19 Clinical Evidence Taskforce. This includes recommendations on mode of birth, delayed umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, antenatal corticosteroids, angiotensin-converting enzyme inhibitors, disease-modifying treatments (including dexamethasone, remdesivir and hydroxychloroquine), venous thromboembolism prophylaxis and advanced respiratory support interventions (prone positioning and extracorporeal membrane oxygenation). Through continuous evidence surveillance, these living recommendations are updated in near real-time to ensure clinicians in Australia have reliable, evidence-based guidelines for clinical decision-making. Please visit https://covid19evidence.net.au/ for the latest recommendation updates.Copyright © 2020 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists

Multipotent mesenchymal stromal cells (MSCs) are currently the most extensively studied type of adult stem cells in advanced stages of development in the field of regenerative medicine. The biological properties of MSCs have generated great hope for their therapeutic use in degenerative and autoimmune conditions that, at present, lack effective treatment options. Over the last decades, MSCs have been typically obtained from adult bone marrow, but the extraction process is highly invasive and the quality and numbers of isolated cells is drastically influenced by patient age, medication and associated comorbidities. Therefore, there is currently an open discussion on the convenience of allogeneic over autologous treatments, despite potential disadvantages such as rejection by the host. This shift to the allogeneic setting entails the need for high production of MSCs to ensure availability of sufficient cell numbers for transplantation, and therefore making the search for alternative tissue sources of highly proliferative MSC cultures with low levels of senescence occurrence, which is one of the greatest current challenges in the scale up of therapeutic cell bioprocessing. Herein we (i) present the main isolation protocols of MSCs from bone marrow, adipose tissue and Wharton's jelly of the umbilical cord; and (ii) compare their qualities from a bioprocess standpoint, addressing both quality and regulatory aspects, in view of their anticipated clinical use.

To date, 18 living recommendations for the clinical care of pregnant and postpartum women with COVID-19 have been issued by the National COVID-19 Clinical Evidence Taskforce. This includes recommendations on mode of birth, delayed umbilical cord clamping, skin-to-skin contact, breastfeeding, rooming-in, antenatal corticosteroids, angiotensin-converting enzyme inhibitors, disease-modifying treatments (including dexamethasone, remdesivir and hydroxychloroquine), venous thromboembolism prophylaxis and advanced respiratory support interventions (prone positioning and extracorporeal membrane oxygenation). Through continuous evidence surveillance, these living recommendations are updated in near real-time to ensure clinicians in Australia have reliable, evidence-based guidelines for clinical decision-making. Please visit https://covid19evidence.net.au/ for the latest recommendation updates.Copyright © 2020 The Authors. Australian and New Zealand Journal of Obstetrics and Gynaecology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Obstetricians and Gynaecologists

Purpose: Delayed cord clamping for at least 60 s is recommended to improve neonatal outcomes. The aim of this study is to evaluate whether there are differences in cord BGA between samples collected after double clamping the cord or without clamping the cord, when blood collection occurs within 60 s from birth in both groups. Methods: A cross-sectional study was carried out, collecting data from 6884 high-risk women who were divided into two groups based on the method of cord sampling (clamped vs unclamped). Results: There were significant decrease in pH and BE values into unclamped group compared with the clamped group. This difference remained significant when considering pathological blood gas analysis parameters, with a higher percentage of pathological pH or BE values in the unclamped group. Conclusion: Samples from the unclamped cord alter the acid–base parameters compared to collection from the clamped cord; however, this difference does not appear to be of clinical relevance. Findings could be due to the large sample size, which allowed to achieve a high power and to investigate very small numerical changes between groups, leading to a statistically significant difference in pH and BE between samples even when we could not appreciate any clinical relevant difference of pH or BE between groups. When blood gas analysis is indicated, the priority should be given to the timing of blood collection to allow reliable results, to assess newborns status at birth and intervene when needed.

Introduction: Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal. Objective: The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years. Methods: In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment. Results: At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02. Conclusion: There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.

Background: Pregravid obesity and abnormal gestational weight gain added to the physiological stresses of pregnancy have been shown to be associated with increased risks of morbidity and mortality for both the infant and mother. However, their effects on placental health are still uncertain. The placenta and the umbilical cord facilitate the interchange of nutrients between the maternal-fetal dyad. Recent research suggests that the placenta influences the metabolic environment in utero, which can in turn affect birth outcomes. Therefore, understanding how obesity affects the health of the placenta is vital. Methods: This dissertation consists of three studies using data from the University of California San Diego Perinatal Biospecimen Repository Cohort. Study 1 evaluated the effect maternal BMI has on indicators of placental health and assessed GDM as a mediator within the casual pathway. Study 2 assessed the effect gestational weight gain has on indicators of placental health. Study 3 built upon results from the first study by stratifying analyses to determine if the effect of maternal BMI on indicators of placental health were modified by fetal sex. The attenuation of the effect of obese maternal BMI on placental outcomes in the presence of chronic villitis was also evaluated in Study 3. Results: We found that maternal obesity was significantly associated with increased risk of larger placentas, longer umbilical cords, and chronic villitis (Study 1). Women with excessive gestational weight gain were shown to have higher risks of longer umbilical cords, especially in pregnancies with male fetuses (Study 2). We found that in pregnancies with female fetuses, the risk of chronic villitis is increased in women with obesity while other measurements of abnormal placental health were not at an increased risk. This varied in pregnancies with male fetuses, where the risk of larger placentas and longer umbilical cords were increased in women with maternal obesity, but no inc

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder, affecting up to 10% of pregnancies worldwide. The primary etiology is considered to be abnormal development and function of placental cells called trophoblasts. We previously developed a two-step protocol for differentiation of human pluripotent stem cells, first into cytotrophoblast (CTB) progenitor-like cells, and then into both syncytiotrophoblast (STB)- and extravillous trophoblast (EVT)-like cells, and showed that it can model both normal and abnormal trophoblast differentiation. We have now applied this protocol to induced pluripotent stem cells (iPSC) derived from placentas of pregnancies with or without PE. While there were no differences in CTB induction or EVT formation, PE-iPSC-derived trophoblast showed a defect in syncytialization, as well as a blunted response to hypoxia. RNAseq analysis showed defects in STB formation and response to hypoxia; however, DNA methylation changes were minimal, corresponding only to changes in response to hypoxia. Overall, PE-iPSC recapitulated multiple defects associated with placental dysfunction, including a lack of response to decreased oxygen tension. This emphasizes the importance of the maternal microenvironment in normal placentation, and highlights potential pathways that can be targeted for diagnosis or therapy, while absence of marked DNA methylation changes suggests that other regulatory mechanisms mediate these alterations.

In our critique of a pay-to-participate study, we address how the failure to disclose study-related payments appears to have violated STEM CELLS Translational Medicine's editorial policies concerning conflict-of-interest and financial disclosure. Our analysis also identifies broader ethical issues and scientific concerns related to pay-to-participate studies conducted by businesses with a record of selling purported stem cell treatments before determining whether the products they sell are safe and efficacious. Authors of peer-reviewed articles have a responsibility to comply with journal policies and disclose financial conflicts of interest to editors, reviewers, and readers. Authors should also disclose when stem cell interventions being tested in clinical trials have already been sold on a direct-to-consumer basis as "stem cell treatments" by authors' affiliate institutions. Financial conflicts of interest and other forms of possible bias must be disclosed to put clinical studies in context and facilitate the critical assessment of research methods, findings, and conclusions. The apparent failure to comply with journal editorial policies and disclose such financial conflicts warrants careful investigation.

Aim: It has been suggested that intact cord resuscitation can reduce the risk of brain damage. We investigated the effects on neurodevelopment at two years of age. Methods: This study was performed in Kathmandu, Nepal. In 2016, 231 late preterm and term infants born vaginally and not breathing were randomised to resuscitation with an intact cord or the standard practice of early cord clamping (CC). At two years of age, the World Health Organization's Infant and Young Child Development tool was used to assess the child's neurodevelopment, during telephone interviews with caregivers. Results: We followed up 138 infants (59.7%) at a mean age of 24.8 ± 0.8 months. A significant difference was seen in the development for age Z-score, between the group resuscitated with an intact umbilical cord and the group resuscitated with early CC. The median (range) scores were 1.0 (0.1-2.1) vs 0.9 (-2.0 to 1.8), respectively (P = .04). There was no difference in the motor, language-cognitive and socio-emotional domains. Conclusion: Neurodevelopment improvements were observed at two years of age in infants resuscitated with an intact rather than early clamped umbilical cord. No definitive conclusions could be drawn due to protocol violations and a low follow-up rate. More research is needed.

Aim: It has been suggested that intact cord resuscitation can reduce the risk of brain damage. We investigated the effects on neurodevelopment at two years of age. Methods: This study was performed in Kathmandu, Nepal. In 2016, 231 late preterm and term infants born vaginally and not breathing were randomised to resuscitation with an intact cord or the standard practice of early cord clamping (CC). At two years of age, the World Health Organization's Infant and Young Child Development tool was used to assess the child's neurodevelopment, during telephone interviews with caregivers. Results: We followed up 138 infants (59.7%) at a mean age of 24.8 ± 0.8 months. A significant difference was seen in the development for age Z-score, between the group resuscitated with an intact umbilical cord and the group resuscitated with early CC. The median (range) scores were 1.0 (0.1-2.1) vs 0.9 (-2.0 to 1.8), respectively (P = .04). There was no difference in the motor, language-cognitive and socio-emotional domains. Conclusion: Neurodevelopment improvements were observed at two years of age in infants resuscitated with an intact rather than early clamped umbilical cord. No definitive conclusions could be drawn due to protocol violations and a low follow-up rate. More research is needed.

Introduction: Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal. Objective: The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years. Methods: In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment. Results: At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02. Conclusion: There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.

Aim: It has been suggested that intact cord resuscitation can reduce the risk of brain damage. We investigated the effects on neurodevelopment at two years of age. Methods: This study was performed in Kathmandu, Nepal. In 2016, 231 late preterm and term infants born vaginally and not breathing were randomised to resuscitation with an intact cord or the standard practice of early cord clamping (CC). At two years of age, the World Health Organization's Infant and Young Child Development tool was used to assess the child's neurodevelopment, during telephone interviews with caregivers. Results: We followed up 138 infants (59.7%) at a mean age of 24.8 ± 0.8 months. A significant difference was seen in the development for age Z-score, between the group resuscitated with an intact umbilical cord and the group resuscitated with early CC. The median (range) scores were 1.0 (0.1-2.1) vs 0.9 (-2.0 to 1.8), respectively (P = .04). There was no difference in the motor, language-cognitive and socio-emotional domains. Conclusion: Neurodevelopment improvements were observed at two years of age in infants resuscitated with an intact rather than early clamped umbilical cord. No definitive conclusions could be drawn due to protocol violations and a low follow-up rate. More research is needed.

Introduction: Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal. Objective: The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years. Methods: In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment. Results: At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02. Conclusion: There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.

Aim: It has been suggested that intact cord resuscitation can reduce the risk of brain damage. We investigated the effects on neurodevelopment at two years of age. Methods: This study was performed in Kathmandu, Nepal. In 2016, 231 late preterm and term infants born vaginally and not breathing were randomised to resuscitation with an intact cord or the standard practice of early cord clamping (CC). At two years of age, the World Health Organization's Infant and Young Child Development tool was used to assess the child's neurodevelopment, during telephone interviews with caregivers. Results: We followed up 138 infants (59.7%) at a mean age of 24.8 ± 0.8 months. A significant difference was seen in the development for age Z-score, between the group resuscitated with an intact umbilical cord and the group resuscitated with early CC. The median (range) scores were 1.0 (0.1-2.1) vs 0.9 (-2.0 to 1.8), respectively (P = .04). There was no difference in the motor, language-cognitive and socio-emotional domains. Conclusion: Neurodevelopment improvements were observed at two years of age in infants resuscitated with an intact rather than early clamped umbilical cord. No definitive conclusions could be drawn due to protocol violations and a low follow-up rate. More research is needed.

Introduction: Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal. Objective: The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years. Methods: In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment. Results: At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02. Conclusion: There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.

ObjectiveTo compare short-term outcomes after placental transfusion (delayed cord clamping (DCC) or umbilical cord milking (UCM)) versus immediate cord clamping among extremely preterm infants.DesignRetrospective study.SettingThe Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network registry.PatientsInfants born <29 weeks' gestation in 2016 or 2017 without congenital anomalies who received active treatment after delivery.Intervention/exposureDCC or UCM.Main outcome measuresPrimary outcomes: (1) composite of mortality or major morbidity by 36 weeks' postmenstrual age (PMA); (2) mortality by 36 weeks PMA and (3) composite of major morbidities by 36 weeks' PMA. Secondary composite outcomes: (1) any grade intraventricular haemorrhage or mortality by 36 weeks' PMA and (2) hypotension treatment in the first 24 postnatal hours or mortality in the first 12 postnatal hours. Outcomes were assessed using multivariable regression, adjusting for mortality risk factors identified a priori, significant confounders and centre as a random effect.ResultsAmong 3116 infants, 40% were exposed to placental transfusion, which was not associated with the primary composite outcome of mortality or major morbidity by 36 weeks' PMA (adjusted OR (aOR) 1.26, 95% CI 0.95 to 1.66). However, exposure was associated with decreased mortality by 36 weeks' PMA (aOR 0.71, 95% CI 0.55 to 0.92) and decreased hypotension treatment in first 24 postnatal hours (aOR 0.66, 95% CI 0.53 to 0.82).ConclusionIn this extremely preterm infant cohort, exposure to placental transfusion was not associated with the composite outcome of mortality or major morbidity, though there was a reduction in mortality by 36 weeks' PMA.Trial registration numberNCT00063063.

ObjectiveTo compare in-hospital outcomes after umbilical cord milking vs delayed cord clamping among infants <29 weeks of gestation.Study designMulticenter retrospective study of infants born <29 weeks of gestation from 2016 to 2018 without congenital anomalies who received active treatment at delivery and were exposed to umbilical cord milking or delayed cord clamping. The primary outcome was mortality or severe (grade III or IV) intraventricular hemorrhage (IVH) by 36 weeks of postmenstrual age (PMA). Secondary outcomes assessed at 36 weeks of PMA were mortality, severe IVH, any IVH or mortality, and a composite of mortality or major morbidity. Outcomes were assessed using multivariable regression, incorporating mortality risk factors identified a priori, confounders, and center. A prespecified, exploratory analysis evaluated severe IVH in 2 gestational age strata, 22-246/7 and 25-286/7 weeks.ResultsAmong 1834 infants, 23.6% were exposed to umbilical cord milking and 76.4% to delayed cord clamping. The primary outcome, mortality or severe IVH, occurred in 21.1% of infants: 28.3% exposed to umbilical cord milking and 19.1% exposed to delayed cord clamping, with an aOR that was similar between groups (aOR 1.45, 95% CI 0.93, 2.26). Infants exposed to umbilical cord milking had higher odds of severe IVH (19.8% umbilical cord milking vs 11.8% delayed cord clamping, aOR 1.70 95% CI 1.20, 2.43), as did the 25-286/7 week stratum (14.8% umbilical cord milking vs 7.4% delayed cord clamping, aOR 1.89 95% CI 1.22, 2.95). Other secondary outcomes were similar between groups.ConclusionsThis analysis of extremely preterm infants suggests that delayed cord clamping is the preferred practice for placental transfusion, as umbilical cord milking exposure was associated with an increase in the adverse outcome of severe IVH.Trial registrationClinicalTrials.gov: NCT00063063.

Aim: It has been suggested that intact cord resuscitation can reduce the risk of brain damage. We investigated the effects on neurodevelopment at two years of age. Methods: This study was performed in Kathmandu, Nepal. In 2016, 231 late preterm and term infants born vaginally and not breathing were randomised to resuscitation with an intact cord or the standard practice of early cord clamping (CC). At two years of age, the World Health Organization's Infant and Young Child Development tool was used to assess the child's neurodevelopment, during telephone interviews with caregivers. Results: We followed up 138 infants (59.7%) at a mean age of 24.8 ± 0.8 months. A significant difference was seen in the development for age Z-score, between the group resuscitated with an intact umbilical cord and the group resuscitated with early CC. The median (range) scores were 1.0 (0.1-2.1) vs 0.9 (-2.0 to 1.8), respectively (P = .04). There was no difference in the motor, language-cognitive and socio-emotional domains. Conclusion: Neurodevelopment improvements were observed at two years of age in infants resuscitated with an intact rather than early clamped umbilical cord. No definitive conclusions could be drawn due to protocol violations and a low follow-up rate. More research is needed.

Introduction: Iron deficiency (ID) is associated with poor neurodevelopment. We have previously shown that delayed umbilical cord clamping (CC) improves iron stores at 8 months and neurodevelopment at 1 year in term, healthy infants in Nepal. Objective: The aim of this study was to assess the effects of delayed CC (≥180 s) compared to early CC (≤60 s) on neurodevelopment using the Ages and Stages Questionnaire (ASQ) at age 3 years. Methods: In 2014, 540 healthy Nepalese infants born at term were randomized in a 1:1 ratio to delayed or early CC. At 3 years of age, ASQ assessment was performed by phone interviews with parents. A score >1 standard deviation below the mean was defined as "at risk" for developmental impairment. Results: At 3 years of age, 350 children were followed up, 170 (63.0%) in the early CC group and 180 (66.7%) in the delayed CC group. No significant differences in ASQ scores in any domains between groups were found. However, more girls were "at risk" for affected gross motor development in the early CC group: 14 (18.9%) versus 6 (6.3%), p = 0.02. Conclusion: There were no significant differences in ASQ scores in any domains between groups. In the subgroup analysis, fewer girls who underwent delayed CC were "at risk" for delayed gross motor development. Due to the pronounced difference in iron stores at 8 months postpartum in this cohort, follow-up studies at an older age are motivated since neurodevelopmental impairment after early ID may be more detectable with increasing age.

The question arises regarding the Public Health Services, if they should collaborate, at the time of the child's birth, with private companies so that the conservation of the umbilical cord blood is feasible, even if the custody centers are located located abroad. The ownership of the blood and tissues of the umbilical cord, the duties of the parents and also of the Administration in these circumstances are reasoned., Se plantea la cuestión respecto de los Servicios públicos de Sanidad, si éstos deben colaborar, en el momento del nacimiento del niño, con las empresas privadas para que sea factible la conservación de la sangre del cordón umbilical, incluso aunque se encuentren los centros de custodia situados en el extranjero. Se razona sobre la titularidad de la sangre y tejidos del cordón umbilical, sobre los deberes de los padres y también de la Administración en estas circunstancias.

Purpose: Delayed cord clamping for at least 60 s is recommended to improve neonatal outcomes. The aim of this study is to evaluate whether there are differences in cord BGA between samples collected after double clamping the cord or without clamping the cord, when blood collection occurs within 60 s from birth in both groups. Methods: A cross-sectional study was carried out, collecting data from 6884 high-risk women who were divided into two groups based on the method of cord sampling (clamped vs unclamped). Results: There were significant decrease in pH and BE values into unclamped group compared with the clamped group. This difference remained significant when considering pathological blood gas analysis parameters, with a higher percentage of pathological pH or BE values in the unclamped group. Conclusion: Samples from the unclamped cord alter the acid–base parameters compared to collection from the clamped cord; however, this difference does not appear to be of clinical relevance. Findings could be due to the large sample size, which allowed to achieve a high power and to investigate very small numerical changes between groups, leading to a statistically significant difference in pH and BE between samples even when we could not appreciate any clinical relevant difference of pH or BE between groups. When blood gas analysis is indicated, the priority should be given to the timing of blood collection to allow reliable results, to assess newborns status at birth and intervene when needed.

The pathophysiology of preeclampsia (PE) is poorly understood; however, there is a large body of evidence that suggests a role of immune cells in the development of PE. Amongst these, B cells are a dominant element in the pathogenesis of PE, and they have been shown to play an important role in various immune-mediated diseases, both as pro-inflammatory and regulatory cells. Perinatal cells are defined as cells from birth-associated tissues isolated from term placentas and fetal annexes and more specifically from the amniotic membrane, chorionic membrane, chorionic villi, umbilical cord (including Wharton’s jelly), the basal plate, and the amniotic fluid. They have drawn particular attention in recent years due to their ability to modulate several aspects of immunity, making them promising candidates for the prevention and treatment of various immune-mediated diseases. In this review we describe main findings regarding the multifaceted in vitro and in vivo immunomodulatory properties of perinatal cells, with a focus on B lymphocytes. Indeed, we discuss evidence on the ability of perinatal cells to inhibit B cell proliferation, impair B cell differentiation, and promote regulatory B cell formation. Therefore, the findings discussed herein unveil the possibility to modulate B cell activation and function by exploiting perinatal immunomodulatory properties, thus possibly representing a novel therapeutic strategy in PE.

Rheumatoid arthritis (RA) is an inflammatory disease of the joints, which causes severe pain and excessive systemic circulation of harmful inflammatory cytokines. Current treatments are limited, with some patients not responding well, and some experiencing severe and detrimental side effects. Mesenchymal stem cells (MSC) are cell-based therapeutics being evaluated as potent immunomodulators in RA and may provide relief to patients not responding well to drug-based treatments. We evaluated the safety and efficacy of BX-U001 human umbilical cord tissue-derived mesenchymal stem cells (hUC-MSC) to treat RA, in support of a successful investigational new drug application. A collagen-induced arthritis (CIA) mouse model of RA was established in DBA/1 J mice. Mice from the treatment assessment group were given a tail vein infusion of hUC-MSC 24 days after primary RA induction, while control assessment (CA) group mice were given cell-free carrier solution. All animals were evaluated daily for RA symptoms via clinical scoring, blood was taken periodically for cytokine analysis, and mice were dissected at end point for histological analysis. A linear mixed model was used to compare the rate of change among groups. The clinical scores of TA group were significantly reduced compared with CA group (P < 0.01), indicating therapeutic effects. The histological scores of the joints in TA group were significantly lower than those in the CA group (P < 0.05), but had no significant difference compared with Healthy groups (P > 0.05). The concentration of (interleukin) IL-6 in TA group was significantly reduced by 80.0% (P < 0.0001) 2 days after treatment and by 93.4% at the experimental endpoint compared with levels prior to hUC-MSC injection. A single intravenous infusion of hUC-MSC (2 × 106 cells/mouse), to CIA-induced DBA/1 J mice, resulted in significant alleviation of RA symptoms and may provide significant therapeutic benefits in humans.

Cell therapy manufacturing is limited by lack of online tools capable of realtime in-process monitoring, particularly of simultaneous changes in multiple orthogonal (mutually independent) parameters. Here, we studied changes in CD36 expression, number density and size (area) of erythroblasts through different stages of erythropoiesis in vitro using a quartz crystal resonator (QCR), integrated with a microscope, and flow cytometry in parallel. An analytical model was developed extending the Kanazawa-Gordon theory. Based on this model, independent correlations were established between changes in each QCR parameter, dissipation (ΔΓ) and resonance frequency (−Δf0), and CD36 expression (from flow cytometry) and cell area (from microscope). The correlation functions were used to derive an acoustic signature (−ΔΓ/Δf0) of the differentiation process that uniquely mapped the relative changes in CD36 expression and late-stage enucleation-related deviations. A method to quantify relative changes in cell area purely from the acoustic parameters was also proposed. This work demonstrated for the first time the potential of an electromechanical tool for online monitoring of concurrently varying orthogonal phenotypic parameters in cell therapy manufacturing. © 2020 The Authors, QC 20210907

Dopamine is often used to treat hypotension in preterm infants who are at risk of hypoxic-ischemic (HI) brain injury due to cerebral hypoperfusion and impaired autoregulation. There is evidence that systemically administered dopamine crosses the preterm blood-brain barrier. However, the effects of exogenous dopamine and cerebral HI on dopaminergic signaling in the immature brain are unknown. We determined the effect of HI and dopamine on D1 and D2 receptor binding and expressions of dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum of the preterm fetal sheep. Fetal sheep (99 days of gestation, term=147days) were unoperated controls (n = 6) or exposed to severe HI using umbilical cord occlusion and saline infusion (UCO + saline, n = 8) or to HI with dopamine infusion (UCO + dopamine, 10 microg/kg/min, n = 7) for 74 h. D1 and D2 receptor densities were measured by autoradiography in vitro. DAT, TH, and cell death were measured using immunohistochemistry. HI resulted in cell death in the caudate nucleus and putamen, and dopamine infusion started before HI did not exacerbate or ameliorate these effects. HI led to reduced D1 and D2 receptor densities in the caudate nucleus and reduction in DAT protein expression in the caudate and putamen. Fetal brains exposed to dopamine in addition to HI were not different from those exposed to HI alone in these changes in dopaminergic parameters. We conclude that dopamine infusion does not alter the striatal cell death or the reductions in D1 and D2 receptor densities and DAT protein expression induced by HI in the preterm brain.NEW & NOTEWORTHY This is the first study on the effects of hypoxia-ischemia and dopamine treatment on the dopaminergic pathway in the preterm brain. In the striatum of fetal sheep (equivalent to ~26-28 wk of human gestation), we demonstrate that hypoxia-ischemia leads to cell death, reduces D1 and D2 receptors, and reduces dopamine transporter. Intravenous dopamine infusion at clinical d

Dopamine is often used to treat hypotension in preterm infants who are at risk of hypoxic-ischemic (HI) brain injury due to cerebral hypoperfusion and impaired autoregulation. There is evidence that systemically administered dopamine crosses the preterm blood-brain barrier. However, the effects of exogenous dopamine and cerebral HI on dopaminergic signaling in the immature brain are unknown. We determined the effect of HI and dopamine on D1 and D2 receptor binding and expressions of dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum of the preterm fetal sheep. Fetal sheep (99 days of gestation, term=147days) were unoperated controls (n = 6) or exposed to severe HI using umbilical cord occlusion and saline infusion (UCO + saline, n = 8) or to HI with dopamine infusion (UCO + dopamine, 10 microg/kg/min, n = 7) for 74 h. D1 and D2 receptor densities were measured by autoradiography in vitro. DAT, TH, and cell death were measured using immunohistochemistry. HI resulted in cell death in the caudate nucleus and putamen, and dopamine infusion started before HI did not exacerbate or ameliorate these effects. HI led to reduced D1 and D2 receptor densities in the caudate nucleus and reduction in DAT protein expression in the caudate and putamen. Fetal brains exposed to dopamine in addition to HI were not different from those exposed to HI alone in these changes in dopaminergic parameters. We conclude that dopamine infusion does not alter the striatal cell death or the reductions in D1 and D2 receptor densities and DAT protein expression induced by HI in the preterm brain.NEW & NOTEWORTHY This is the first study on the effects of hypoxia-ischemia and dopamine treatment on the dopaminergic pathway in the preterm brain. In the striatum of fetal sheep (equivalent to ~26-28 wk of human gestation), we demonstrate that hypoxia-ischemia leads to cell death, reduces D1 and D2 receptors, and reduces dopamine transporter. Intravenous dopamine infusion at clinical d

Blood drawing of newborn piglets is necessary for physio-metabolic profiles assessment, and to determine gas change levels in it, what is used in various phenomena diagnosis, such as, intrapartum asphyxia a non-infectious condition that causes a high rate of neonatal mortality in pigs. This study aimed to test three of the most common blood sampling sites used in piglets: umbilical cord (UC), retroorbital sinus (ROS), and cava vein (VC), besides determining the differences among them, concerning to physio-metabolic variables and the acid-base balance. Thirty-two healthy non asphyxiated piglets were randomly selected, coming from nine eutocic farrowing to carry out the three sampling sites. All of the physio-metabolic concentrations determined showed basal values within normal fetal ranges corresponding to the sampling site. However, UC values were more suitable for gas exchange diagnosis in asphyxia due to their similarity with physiological parameters of a normal newborn (pCO2= 36.10 ± 2.03, pO2= 32.68 ± 3.03), whereas for the metabolic profile (glucose and lactate) ROS values were more accurate for measuring a common lactate and glycaemia profile than the other sites. Therefore, when a physio-metabolic profile is required, the methodological approach of the blood sampling site should be adequate to obtain the data needed for research following planned objectives and subsequent interpretation, La extracción sanguínea en los lechones neonatos es necesaria para la evaluación fisiometabólica y para determinar alteraciones gaseosas útiles en el diagnóstico de varios fenómenos como la asfixia intraparto; siendo la causa principal no infecciosa que origina una alta tasa de mortalidad neonatal en cerdos. Nuestro objetivo fue evaluar tres de los sitios más comunes de muestreo sanguíneo usados en lechones: cordón umbilical (UC), seno retro orbital (ROS) y vena cava (VC); así como determinar las diferencias entre ellos con respecto a las variables fisiometabólicas y el equilibrio ácido-base. Treinta y dos lechones sanos provenientes de nueve partos eutócicos fueron aleatoriamente seleccionados para los tres sitios de muestreo. Todas las concentraciones fisiometabólicas mostraron valores basales de los parámetros fisiológicos fetales correspondientes al sitio de muestreo. Sin embargo, los valores de UC resultaron más confiables para el diagnóstico del intercambio gaseoso durante la asfixia, debido a su similitud con los parámetros fisiológicos de un neonato sano (pCO2= 36.10 ± 2.03, pO2= 32.68 ± 3.03); mientras que para el perfil metabólico (glucosa y lactato) los valores de ROS fueron más precisos en determinar la glicemia y el lactato, comparados con los demás sitios. Por consiguiente, cuando el perfil fisiometabólico neonatal es requerido, el abordaje metodológico en el sitio de muestreo tiene que ser específico, de acuerdo a los objetivos planteados y a su subsecuente interpretación

Rheumatoid arthritis (RA) is an inflammatory disease of the joints, which causes severe pain and excessive systemic circulation of harmful inflammatory cytokines. Current treatments are limited, with some patients not responding well, and some experiencing severe and detrimental side effects. Mesenchymal stem cells (MSC) are cell-based therapeutics being evaluated as potent immunomodulators in RA and may provide relief to patients not responding well to drug-based treatments. We evaluated the safety and efficacy of BX-U001 human umbilical cord tissue-derived mesenchymal stem cells (hUC-MSC) to treat RA, in support of a successful investigational new drug application. A collagen-induced arthritis (CIA) mouse model of RA was established in DBA/1 J mice. Mice from the treatment assessment group were given a tail vein infusion of hUC-MSC 24 days after primary RA induction, while control assessment (CA) group mice were given cell-free carrier solution. All animals were evaluated daily for RA symptoms via clinical scoring, blood was taken periodically for cytokine analysis, and mice were dissected at end point for histological analysis. A linear mixed model was used to compare the rate of change among groups. The clinical scores of TA group were significantly reduced compared with CA group (P < 0.01), indicating therapeutic effects. The histological scores of the joints in TA group were significantly lower than those in the CA group (P < 0.05), but had no significant difference compared with Healthy groups (P > 0.05). The concentration of (interleukin) IL-6 in TA group was significantly reduced by 80.0% (P < 0.0001) 2 days after treatment and by 93.4% at the experimental endpoint compared with levels prior to hUC-MSC injection. A single intravenous infusion of hUC-MSC (2 × 106 cells/mouse), to CIA-induced DBA/1 J mice, resulted in significant alleviation of RA symptoms and may provide significant therapeutic benefits in humans.

ObjectiveCurrent data on the role of the umbilical cord in pregnancy complications are conflicting; estimates of the proportion of stillbirths due to cord problems range from 3.4 to 26.7%. A systematic review and meta-analysis were undertaken to determine which umbilical cord abnormalities are associated with stillbirth and related adverse pregnancy outcomes.MethodsMEDLINE, EMBASE, CINAHL and Google Scholar were searched from 1960 to present day. Reference lists of included studies and grey literature were also searched. Cohort, cross-sectional, or case-control studies of singleton pregnancies after 20 weeks' gestation that reported the frequency of umbilical cord characteristics or cord abnormalities and their relationship to stillbirth or other adverse outcomes were included. Quality of included studies was assessed using NIH quality assessment tools. Analyses were performed in STATA.ResultsThis review included 145 studies. Nuchal cords were present in 22% of births (95% CI 19, 25); multiple loops of cord were present in 4% (95% CI 3, 5) and true knots of the cord in 1% (95% CI 0, 1) of births. There was no evidence for an association between stillbirth and any nuchal cord (OR 1.11, 95% CI 0.62, 1.98). Comparing multiple loops of nuchal cord to single loops or no loop gave an OR of 2.36 (95% CI 0.99, 5.62). We were not able to look at the effect of tight or loose nuchal loops. The likelihood of stillbirth was significantly higher with a true cord knot (OR 4.65, 95% CI 2.09, 10.37).ConclusionsTrue umbilical cord knots are associated with increased risk of stillbirth; the incidence of stillbirth is higher with multiple nuchal loops compared to single nuchal cords. No studies reported the combined effects of multiple umbilical cord abnormalities. Our analyses suggest specific avenues for future research.

Blood drawing of newborn piglets is necessary for physio-metabolic profiles assessment, and to determine gas change levels in it, what is used in various phenomena diagnosis, such as, intrapartum asphyxia a non-infectious condition that causes a high rate of neonatal mortality in pigs. This study aimed to test three of the most common blood sampling sites used in piglets: umbilical cord (UC), retroorbital sinus (ROS), and cava vein (VC), besides determining the differences among them, concerning to physio-metabolic variables and the acid-base balance. Thirty-two healthy non asphyxiated piglets were randomly selected, coming from nine eutocic farrowing to carry out the three sampling sites. All of the physio-metabolic concentrations determined showed basal values within normal fetal ranges corresponding to the sampling site. However, UC values were more suitable for gas exchange diagnosis in asphyxia due to their similarity with physiological parameters of a normal newborn (pCO2= 36.10 ± 2.03, pO2= 32.68 ± 3.03), whereas for the metabolic profile (glucose and lactate) ROS values were more accurate for measuring a common lactate and glycaemia profile than the other sites. Therefore, when a physio-metabolic profile is required, the methodological approach of the blood sampling site should be adequate to obtain the data needed for research following planned objectives and subsequent interpretation, La extracción sanguínea en los lechones neonatos es necesaria para la evaluación fisiometabólica y para determinar alteraciones gaseosas útiles en el diagnóstico de varios fenómenos como la asfixia intraparto; siendo la causa principal no infecciosa que origina una alta tasa de mortalidad neonatal en cerdos. Nuestro objetivo fue evaluar tres de los sitios más comunes de muestreo sanguíneo usados en lechones: cordón umbilical (UC), seno retro orbital (ROS) y vena cava (VC); así como determinar las diferencias entre ellos con respecto a las variables fisiometabólicas y el equilibrio ácido-base. Treinta y dos lechones sanos provenientes de nueve partos eutócicos fueron aleatoriamente seleccionados para los tres sitios de muestreo. Todas las concentraciones fisiometabólicas mostraron valores basales de los parámetros fisiológicos fetales correspondientes al sitio de muestreo. Sin embargo, los valores de UC resultaron más confiables para el diagnóstico del intercambio gaseoso durante la asfixia, debido a su similitud con los parámetros fisiológicos de un neonato sano (pCO2= 36.10 ± 2.03, pO2= 32.68 ± 3.03); mientras que para el perfil metabólico (glucosa y lactato) los valores de ROS fueron más precisos en determinar la glicemia y el lactato, comparados con los demás sitios. Por consiguiente, cuando el perfil fisiometabólico neonatal es requerido, el abordaje metodológico en el sitio de muestreo tiene que ser específico, de acuerdo a los objetivos planteados y a su subsecuente interpretación

Blood drawing of newborn piglets is necessary for physio-metabolic profiles assessment, and to determine gas change levels in it, what is used in various phenomena diagnosis, such as, intrapartum asphyxia a non-infectious condition that causes a high rate of neonatal mortality in pigs. This study aimed to test three of the most common blood sampling sites used in piglets: umbilical cord (UC), retroorbital sinus (ROS), and cava vein (VC), besides determining the differences among them, concerning to physio-metabolic variables and the acid-base balance. Thirty-two healthy non asphyxiated piglets were randomly selected, coming from nine eutocic farrowing to carry out the three sampling sites. All of the physio-metabolic concentrations determined showed basal values within normal fetal ranges corresponding to the sampling site. However, UC values were more suitable for gas exchange diagnosis in asphyxia due to their similarity with physiological parameters of a normal newborn (pCO2= 36.10 ± 2.03, pO2= 32.68 ± 3.03), whereas for the metabolic profile (glucose and lactate) ROS values were more accurate for measuring a common lactate and glycaemia profile than the other sites. Therefore, when a physio-metabolic profile is required, the methodological approach of the blood sampling site should be adequate to obtain the data needed for research following planned objectives and subsequent interpretation, La extracción sanguínea en los lechones neonatos es necesaria para la evaluación fisiometabólica y para determinar alteraciones gaseosas útiles en el diagnóstico de varios fenómenos como la asfixia intraparto; siendo la causa principal no infecciosa que origina una alta tasa de mortalidad neonatal en cerdos. Nuestro objetivo fue evaluar tres de los sitios más comunes de muestreo sanguíneo usados en lechones: cordón umbilical (UC), seno retro orbital (ROS) y vena cava (VC); así como determinar las diferencias entre ellos con respecto a las variables fisiometabólicas y el equilibrio ácido-base. Treinta y dos lechones sanos provenientes de nueve partos eutócicos fueron aleatoriamente seleccionados para los tres sitios de muestreo. Todas las concentraciones fisiometabólicas mostraron valores basales de los parámetros fisiológicos fetales correspondientes al sitio de muestreo. Sin embargo, los valores de UC resultaron más confiables para el diagnóstico del intercambio gaseoso durante la asfixia, debido a su similitud con los parámetros fisiológicos de un neonato sano (pCO2= 36.10 ± 2.03, pO2= 32.68 ± 3.03); mientras que para el perfil metabólico (glucosa y lactato) los valores de ROS fueron más precisos en determinar la glicemia y el lactato, comparados con los demás sitios. Por consiguiente, cuando el perfil fisiometabólico neonatal es requerido, el abordaje metodológico en el sitio de muestreo tiene que ser específico, de acuerdo a los objetivos planteados y a su subsecuente interpretación

Mezenhimske matične ćelije (MMĆ) deo su populacije multipotentnih matičnih ćelija prisutnih u mnogim adultnim tkivima gde učestvuju u održavanju homeostaze. Zahvaljujući sposobnosti samoobnove, potencijalu diferenciranja u specijalizovane ćelije mezodermskog porekla i imunomodultatornim svojstvima, ove nediferencirane ćelije karakteriše širok opseg potencijalne terapijske primene. Regenerativnom kapacitetu MMĆ doprinosi i sposobnost migracije do oštećenih tkiva gde učestvuju u njihovom obnavlјanju što ove ćelije čini pogodnim za ćelijsku terapiju. Mezenhimske MĆ su do sada izolovane iz velikog broja adultnih tkiva i mnoge studije potvrdile su da njihov regenerativni potencijal u velikoj meri zavisi od izvora iz kojeg potiču. Prvobitno su izolovane iz kostne srži koja je do sada najčešće korišćen izvor MMĆ, međutim zbog invazivnih metoda izolacije i malog prinosa MMĆ, stvorena je potreba za alternativnim izvorima. Činjenica da su MMĆ izolovane i iz periferne krvi jedno je od značajnih otkrića iz ove oblasti i smatra se da ove ćelije najverovatnije vode poreklo iz kostne srži, međutim nije dovoljno poznato na koji način migriraju i bivaju privučene u oštećena tkiva. Poslednjih godina se kao povolјan izvor MMĆ sa potencijalnom primenom u regenerativnoj medicini sve češće pominju i perinatalna tkiva (pupčanik i placenta). Prednost pupčanika kao izvora MMĆ ogleda se u lakoj dostupnosti tkiva koje se smatra medicinskim otpadom, neinvazivnoj izolaciji ćelija i činjenici da su izolovane MMĆ po kapacitetu samoobnove i većoj ekspresiji markera pluripotentnost slične embrionalnim MĆ. Iako se već nekoliko decenija MMĆ intenzivno istražuju, uprkos velikom doprinosu nauci i medicini, o njihovom upkupnom terapijskom potencijalu se još uvek nedovoljno zna. Trenutno nije poznat univerzalan mehanizam terapijskog delovanja MMĆ, a mnogobrojni nalazi sve više u poslednje vreme upućuju da ponašanje i uloge MMĆ zavise od konteksta mikrosredine u kojoj obitavaju i/ili deluju, kao mestu int, present in many adult tissues where they participate in maintaining of homeostasis. Due to their self-renewal capacity, differentiation potential into specialized cells of mesodermal origin and immunomodulatory features, these undifferentiated cells are characterized with wide range of potential therapeutic applications. Their ability to migrate towards damaged tissues where they participate in tissue repair, also contributes to their regenerative potential which makes them suitable for cell therapy. MSCs have so far been isolated from various adult tissues and many studies confirmed that MSCs’ regenerative potential depends largely on the suorce which they originate from. They were originaly isolated from bone marrow which has been the most commonly used source of MSCs so far, however due to invasive methods of isolation and low MSCs yield, there is a need for alternative sources of MSCs. The fact that these cells were isolated from peripheral blood is one of the significant discoveries in this area and it is believed that these MSCs are most likely to originate from bone marrow, but how they migrate and home to damaged tissues has not yet been elucidated completely. Perinatal tissues (umbilical cord and placenta) have been recently increasingly suggested as favourable sources of MSCs with potential applications in regenerative medicine. The advantage of umbilical cord as a source of MSCs is reflected in easy availability of tissue considered as medical waste, non-invasive cell isolation methods, and the fact that MSCs isolated from umbilical cord are similar to embryonic stem cells in the terms of self-renewal capacity and pluripotency markers’ expression. Eventhough MSCs have been extensively investigated for several decades, and despite their great contribution to science and medicine, their overall therapeutic potential is still poorly understood. Currently, there is no universal mechanism of MSCs’ therapeutic action known, and many findings have recently sugge

Background: Experiments have shown improved cardiovascular stability in lambs if umbilical cord clamping is postponed until positive pressure ventilation is started. Studies on intact cord resuscitation on human term infants are sparse. The purpose of this study was to evaluate differences in clinical outcomes in non-breathing infants between groups, one where resuscitation is initiated with an intact umbilical cord (intervention group) and one group where cord clamping occurred prior to resuscitation (control group). Methods: Randomized controlled trial, inclusion period April to August 2016 performed at a tertiary hospital in Kathmandu, Nepal. Late preterm and term infants born vaginally, non-breathing and in need of resuscitation according to the 'Helping Babies Breathe' algorithm were randomized to intact cord resuscitation or early cord clamping before resuscitation. Main outcome measures were saturation by pulse oximetry (SpO2), heart rate and Apgar at 1, 5 and 10 minutes after birth. Results: At 10 minutes after birth, SpO2 (SD) was significantly higher in the intact cord group compared to the early cord clamping group, 90.4 (8.1) vs 85.4 (2.7) %, P < .001). In the intact cord group, 57 (44%) had SpO2 < 90% after 10 minutes, compared to 93 (100%) in the early cord clamping group, P < 0.001. SpO2 was also significantly higher in the intervention (intact cord) group at one and five minutes after birth. Heart rate was lower in the intervention (intact cord) group at one and five minutes and slightly higher at ten minutes, all significant findings. Apgar score was significantly higher at one, five and ten minutes. At 5 minutes, 23 (17%) had Apgar score < 7 in the intervention (intact cord) group compared to 26 (27%) in the early cord clamping group, P < .07. Newborn infants in the intervention (intact cord) group started to breathe and establish regular breathing earlier than in the early cord clamping group. Conclusions: This study provides new an