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Multipotent mesenchymal stromal cells (MSC) can be isolated from many tissues, including bone marrow (BM) and placenta (PL). Human placenta can be obtained readily without invasive procedures. There may be differences, however, in differentiation capacity and immunomodulation by MSC isolated from BM or PL. The early pregnancy factor (heat shock protein 10; EPF/Hsp10) is a small protein that exhibits immunomodulatory properties. We compared BM- and PL-MSC, and assessed their efficacy for suppressing T-cell proliferation in vitro and the role of EPF/Hsp10 in this process. PL-MSC were collected from whole placenta after removal of the amniotic and chorionic membranes followed by serial enzymatic digestions. The PL-MSC were compared to BM-MSC, obtained from healthy donors. Differentiation capacity, cytokine secretion, expression and secretion of immunomodulatory molecules, immunophenotype and real time proliferation were assessed using cytokine arrays, ELISA assays, flow cytometry, immunohistochemical staining and western blotting. Whereas BM-MSC consisted of a homogeneous cell population with strong expression of mesenchymal markers, PL-MSC consisted of a mixed population of cells with variable CD73, CD90 and CD105 expression. PL-MSC exhibited a significantly greater proliferation rate than BM-MSC. The presence of both stem cells and more mature cells in the PL-MSC cultures resulted in decreased differentiation capacity and reduced efficacy of immune suppression in co-cultures with T-cells. Although robust intracellular expression of EPF/Hsp10 in both BM- and PL-MSC was observed, secretion of the protein in response to immune activating stimuli remained below detectable levels. Secretion of pro-inflammatory cytokines was significantly greater in BM-MSC than PL-MSC, whereas no difference was observed in the secretion of hematopoiesis supporting growth factors. Development of culture methods for isolation of pure populations of PL-MSC may improve the quality of the product and reproducibility of results. [ABSTRACT FROM AUTHOR]

We assessed the neural injury markers (NIMs) in maternal and umbilical blood in preterm deliveries with and without intrauterine growth restriction (IUGR), and relationship between NIMs and neonatal complications. Deliveries between 24 and 34 weeks’ gestation with (study group) and without (control group) IUGR were included to the study. Three NIMs (s100B, neurone-specific enolase [NSE] and alpha-foetoprotein [AFP]) were investigated in umbilical arterial, umbilical venous and maternal venous serum. Thirty-two IUGR and twenty-nine non-IUGR pregnancies with preterm delivery were included. Maternal and umbilical arterial s100B levels were significantly higher in the study group, whereas there was no relationship among IUGR, AFP and NSE levels. In the study group, umbilical venous s100B and NSE levels were associated with perinatal mortality (p= 0.012, 0.005, respectively), necrotising enterocolitis (NEC) (p= 0.001, 0.04, respectively) and need for intubation (p= 0.001, 0.007, respectively). Negative predictive values for perinatal mortality and NEC were 100% and for need for intubation it was 92.8% when both s100B and NSE were below the cutoff line determined by the receiver-operating characteristic curves. Perinatal mortality, NEC and need for intubation can be predicted by assessment of umbilical venous s100B and NSE measurement during birth in IUGR newborns. [ABSTRACT FROM PUBLISHER]

Background: Several musculoskeletal changes occur in pregnancy, particularly in the abdominal region. The aim of this study was to search and compare the effects of long (LEP) and short exercise programs (SEP) in terms of the satisfaction of the needs of pregnant women., Methods: This study consisted of 2 groups: LEP (n=16) and SEP (n=16). Muscle thickness measurements determined by ultrasound, the 6 minute walk test, Pregnancy Physical Activity Questionnaire, Visual Analogue Scale, Oswestry Disability Index, and Short Form-36 Quality of Life Questionnaire were the study variables. Evaluations were done at the 16th (baseline), 24th, and 32nd gestational weeks. The LEP consisted of 20 and the SEP consisted of 9 exercises, which were applied for 16 weeks until the 32nd gestational week., Results: Emotional role limitation and pain scores of quality of life, 6 minute walk test, and occupational physical activity were found to be better in the LEP group at the 24th gestational week (p=0.043, p=0.049, p=0.049, p=0.026). At the 32nd gestational week, the 6 minute walk test and occupational physical activity were found to be higher in the LEP group (p=0.006, p=0.017). Additionally, rectus abdominis and bilateral diaphragm muscle thicknesses, "moderate intensity and sports physical activity" and "vitality and emotional well-being" were increased over time with the LEP (p+<+0.05 for all). On the other hand, unilateral diaphragm muscle thickness, sports physical activity level, and vitality were improved with the SEP (p+<+0.05 for all)., Conclusions: The SEP and LEP both have beneficial effects in pregnant women. However, the LEP increases physical activity level, functional capacity, and quality of life more than the SEP during the later stages of pregnancy., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

The placental cholinergic system; known as an important factor in intracellular metabolic activities, regulation of placental vascular tone, placental development, and neurotransmission; can be affected by persistent organic pesticides, particularly organochlorine pesticides(OCPs), which can influence various epigenetic regulations and molecular pathways. Although OCPs are legally prohibited, trace amounts of the persistent dichlorodiphenyltrichloroethane(DDT) are still found in the environment, making prenatal exposure inevitable. In this study, the effects of 2,4'-DDT and 4,4'-DDT; and its breakdown product 4,4'-DDE in the environment on placental cholinergic system were evaluated with regards to cholinergic genes. 40 human placentas were screened, where 42,50% (17 samples) were found to be positive for the tested compounds. Average concentrations were 10.44 μg/kg; 15.07 μg/kg and 189,42 μg/kg for 4,4'-DDE; 2,4'-DDT and 4,4'-DDT respectively. RNA-Seq results revealed 2396 differentially expressed genes in positive samples; while an increase in CHRM1,CHRNA1,CHRNG and CHRNA2 genes at 1.28, 1.49, 1.59 and 0.4 fold change were found(p<0028). The increase for CHRM1 was also confirmed in tissue samples with immunohistochemistry. In vitro assays using HTR8/SVneo cells; revealed an increase in mRNA expression of CHRM1, CHRM3 and CHRN1 in DDT and DDE treated groups; which was also confirmed through western blot assays. An increase in the expression of CHRM1,CHRNA1, CHRNG(p<0001) and CHRNA2(p<0,05) were found from the OCPs exposed and non exposed groups.The present study reveals that intrauterine exposure to DDT affects the placental cholinergic system mainly through increased expression of muscarinic receptors. This increase in receptor expression is expected to enhance the sensitivity of the placental cholinergic system to acetylcholine., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Begum Yurdakok Dikmen reports financial support was provided by Scientific and Technological Research Council of Turkey., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Glycine encephalopathy with normal serum glycine (MIM #617301), also known as GLYT1 encephalopathy, is an extremely rare disorder caused by biallelic variants in SLC6A9 and characterised by facial dysmorphic features, skeletal findings including contractures, knee hyperextension, and joint dislocations and seizures. To date, only ten patients from five families have been reported and only two of them could survive until childhood. In this study, we report on a consanguineous Turkish couple with a history of six pregnancies with three habitual abortions and three postpartum exitus. While in three pregnancies the babies were born prematurely at 32nd gestational week by emergency ceserean section due to hydrops and fetal distress, the other pregnancy was medically terminated at 16th gestational week due to absent fetal heart activity. The product of all these three pregnancies exhibited similar phenotype including short neck, thoracic kyphosis, hypertrichosis, joint contractures and dislocations, hypertonia, knee hyperextension and facial dysmorphic features. Trio exome sequencing was performed prenatally during the last pregnancy and a novel VUS variant in SLC6A9 and a likely pathogenic variant in MTOR gene were detected. DNA isolation was performed from frozen muscle and adrenal tissue of previously autopsied fetuses with similar clinical features, and the same variants were confirmed in both of them. Our data suggest that SLC6A9 and MTOR variants may be responsible for this extremely lethal phenotype in this family., Competing Interests: Declaration of competing interest All the authors declare they have no conflict of interest., (Published by Elsevier Masson SAS.)

Objective: To evaluate perinatal outcomes in human immunodeficiency virus (HIV) infected pregnant women in Turkey., Material and Methods: Maternal characteristics, pregnancy complications, laboratory findings including HIV load, CD4 cell count, CD4/CD8 ratio, neonatal features and final HIV status of the baby were retrospectively analyzed., Results: The sample included 26 singleton pregnancies, from 25 HIV-infected women. The ethnicities were Turkish (n=18), East European (n=4), Asian (n=2) and African (n=2). The majority (76.9%) was aware of their HIV status before becoming pregnant. Four cases (15.3%) were diagnosed during pregnancy and two (7.8%) at the onset of labor. The results for median HIV viral load, CD4 count, and CD4/CD8 ratio at birth were 20 copies/mL (0-34 587), 577/mm 3 (115-977), and 0.7 (0.1-1.9), respectively. The HIV viral load rate was 5.5% in eighteen women taking anti-retroviral treatment. The rates of gestational diabetes mellitus, gestational hypertension, intrauterine growth restriction, and preterm delivery were 3.8%, 3.8%, 7.6%, and 8% (numbers are 1;1;2;2), respectively. The mean gestational week at birth was 38 weeks and mean birthweight is 2972±329 g. Two babies were congenitally infected with HIV (infection rate of 8.3%). There was one needle-related accident during surgery., Conclusion: Timely diagnosis of HIV infection during pregnancy is important for preventing mother to child transmission. HIV infected women may give birth to HIV negative babies with the help of a multidisciplinary team, composed of perinatology, infectious diseases, and pediatrics specialists.

The newly developed 6-hydroxychromanol derivate SUL-109 was shown to provide protection during hypothermic storage of several cell lines, but has not been evaluated in hematopoietic stem cells (HSCs). Hypothermic preservation of HSCs would be preferred over short-term cryopreservation to prevent cell loss during freezing/thawing and would be particularly useful for short-term storage, such as during conditioning of patients or transport of HSC transplants. Here we cultured human CD34 + umbilical cord blood (UCB) cells and lineage-depleted (Lin - ) Balb/c bone marrow (BM) cells for up to 7 days in serum-free HSC expansion medium with hematopoietic growth factors. SUL-109-containing cultures were stored at 4°C for 3 to 14 days. The UCB cells were tested for viability, cell cycle, and reactive oxygen species (ROS). DMSO-cryopreserved Lin - BM cells or Lin - BM cells maintained for 14 days at 4°C were transplanted into RAG2 -/- Balb/c mice and engraftment was followed for 6 months. The addition of SUL-109 during the hypothermic storage of expanded CD34 + UCB cells provided a significant improvement in cell survival of the immature CD34 + /CD38 - fraction after 7 days of hypothermic storage through scavenging of hypothermia-induced ROS and was able to preserve the multilineage capacity of human CD34 + UCB cells for up to 14 days of cold storage. In addition, SUL-109 protected murine BM Lin - cells from 14 days of hypothermic preservation and maintained their engraftment potential after transplantation in immune-deficient RAG2 -/- mice. Our data indicate that SUL-109 is a promising novel chemical for use as a protective agent during cold storage of human and murine HSCs to prevent hypothermia-induced apoptosis and promote cell viability., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Differentiation, self-renewal and quiescence of Hematopoietic stem cells (HSCs) is tightly regulated in order to protect the HSCs from the strain of constant cell division and depletion of the stem cell pool. The neurotransmitter Neuropeptide Y (NPY) is released from sympathetic nerves in the bone marrow and has been shown to indirectly affect HSC function through effects on bone marrow (BM) multipotent Mesenchymal Stromal Cells (MSCs), osteoblasts (OBs) and macrophages. Although the absence of NPY has been shown to be accompanied by severe BM impairment and delayed engraftment of HSCs, the direct effects of NPY on HSCs have never been assessed. Here, we aimed to explore the effect of NPY on the regulation of HSCs. All NPY receptors Y1, Y2, Y4 and Y5 were found to be highly expressed on most HSCs and mature hematopoietic cell subsets. In culture, in particularly expression of the Y1 receptor was shown to decrease in time. Doses of 300 nM NPY suppressed HSC proliferation in cell cultures, as confirmed by an increase of HSCs in G 0 phase and an increase in the gene expression levels of FOXO3, DICER1, SMARCA2 and PDK1, which all have been shown to play an important role in the regulation of cell quiescence. These data support the idea that NPY may have a direct effect on the regulation of HSC fate by modulating cell quiescence., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Bisphenol A (BPA) and phthalates can adversely affect the fetal development. However, observational studies on the effects of these chemicals on fetal male reproductive system are still limited. A hundred of umbilical cord blood samples were analyzed for the levels of BPA, di-2-ethylhexyl phthalate (DEHP), mono-2-ethylhexyl phthalate (MEHP), and sex hormones. After birth, male newborns underwent physical examination that included measurements of anogenital distance, stretched penile length (SPL), and penile width. BPA, DEHP and MEHP levels were detectable in ≈99% of cord blood samples. In covariate-adjusted models, cord blood BPA levels were inversely associated with SPL of newborns and positively associated with cord blood estradiol levels. In addition, there was a significant inverse relationship between cord blood DEHP levels and anogenital distance index of newborn males. Our results suggest that in utero BPA and DEHP exposure exerted adverse effects on fetal male reproductive development and cord blood estradiol levels., (Copyright © 2019. Published by Elsevier Inc.)

Çelik HT, Korkmaz A, Özyüncü Ö, Yiğit Ş, Yurdakök M. Maternal adipose tissue, antenatal steroids, and Respiratory Distress syndrome: complex relations. Turk J Pediatr 2019; 61: 859-866. The incidences of maternal obesity and obesity-related maternal, fetal and neonatal complications have increased considerably. Obese people may have lower, normal or increased fat mass independent from their body mass index. We aimed to investigate the relationships between antenatal steroid therapy and maternal body fat ratio for the risk of Respiratory distress syndrome (RDS) in preterm infants. Pregnant women and their newborn infants between 24-34 weeks of gestation, who received a full course of antenatal steroid therapy were included in the study. Mother`s body weight, body mass ındex (BMI), and body compositions (muscle, fat, water) were calculated using the bioelectrical impedance method 5 days after giving birth. Neonatal characteristics and respiratory outcomes were noted. A total of 42 mothers and their single premature infants were included in the study. Nineteen (45.2%) infants developed RDS (Group 1) while 23 (54.8%) infants did not develop RDS (Group 2). The mean body fat mass (kg), fat ratio (%), truncal fat mass (kg), and truncal fat ratio (%) were statistically significantly higher in Group 1 than in Group 2. The incidence of RDS was significantly higher in the group of mothers with a body fat ratio > 30.0% (n=15/24, 62.5%) when compared with the group of mothers with a body fat ratio ≤ 30% (n=4/18, 22.2%) (p=0.013). Maternal adipose tissue plays an important role and should be taken into consideration especially in obese women, before giving antenatal steroids to achieve positive effects of the therapy in preterm infants.

Perivascular cells are known to be ancestors of mesenchymal stem cells (MSCs) and can be obtained from heart, skin, bone marrow, eye, placenta and umbilical cord (UC). However detailed characterization of perivascular cells around the human UC vein and comparative analysis of them with MSCs haven't been done yet. In this study, our aim is to isolate perivascular cells from human UC vein and characterize them versus UC blood MSCs (UCB-MSCs). For this purpose, perivascular cells around the UC vein were isolated enzymatically and then purified with magnetic activated cell sorting (MACS) method using CD146 Microbead Kit respectively. MSCs were isolated from UCB by Ficoll density gradient solution. Perivascular cells and UCB-MSCs were characterized by osteogenic and adipogenic differentiation procedures, flow cytometric analysis [CD146, CD105, CD31, CD34, CD45 and alpha-smooth muscle actin (α-SMA)], and immunofluorescent staining (MAP1B and Tenascin C). Alizarin red and Oil red O staining results showed that perivascular cells and MSCs had osteogenic and adipogenic differentiation capacity. However, osteogenic differentiation capacity of perivascular cells were found to be less than UCB-MSCs. According to flow cytometric analysis, CD146 expression of perivascular cells were appeared to be 4.8-fold higher than UCB-MSCs. Expression of α-SMA, MAP1B and Tenascin-C from perivascular cells was determined by flow cytometry analysis and immunfluorescent staining. The results appear to support the fact that perivascular cells are the ancestors of MSCs in vascular area. They may be used as alternative cells to MSCs in the field of vascular tissue engineering.

Objective: To determine the effects of fibroids on pregnancy and neonatal parameters., Study Design: A total of 12,855 consecutive pregnant women admitted to a tertiary care university hospital between January 2002 and December 2009 were retrospectively reviewed. Of those, 267 patients with fibroids and 267 age- and parity-matched controls were included. The Clavien-Dindo classification was used to grade postoperative complications., Results: Mean gestational age at delivery (p<0.001) and mean neonatal birthweight (p=0.034) were significantly different between the 2 groups. We recorded a higher rate of pain-related hospitalization in the large fibroid group (38.2% and 7.8%, p <0.001). Myomectomy was performed in 124 of 267 patients during cesarean section (C/S). The myomectomy group was associated with lower postoperative hemoglobin levels (p=0.01) and higher need for transfusion (p=0.009). When postpartum hemoglobin levels of the control group and fibroid group without myomectomy were compared, hemoglobin levels were higher in favor of the control group (p = 0.009)., Conclusion: Beyond lower gestational age and mean birthweight, perinatal complications did not increase with fibroids during pregnancy. Performing myomectomy increases the need for transfusion (Grade 2) without an increase in the risk of hysterectomy (Grade 3) and other life-threatening complications (Grade 4-5). Leaving fibroids in situ during C/S did not prevent a fall in post-partum hemoglobin levels.

Quantitative ultrasound (QUS) measurement of tibial speed of sound (SOS) can be used to determine bone strength. Children conceived with assisted reproduction treatments (ART) are taller than naturally conceived (NC) children, so we hypothesized that these infants would have higher SOS levels than NC infants. Thirty-seven ART (ART group) and 51 NC neonates (NC group) were included in the study. Tibial initial SOS (iSOS) was measured within 96 hours of birth using QUS. Measurements were performed weekly until the infant was discharged from the hospital. The iSOS levels of the ART group (2823.41±110.8 m/sec) were lower than those of the NC group (2917.14±145.6 m/sec) (p=0.001). A decrease in SOS levels was observed in 39 of 53 infants who had serial scans. The difference in SOS levels between the first and last scan was significant (p<0.02). In vitro manipulation during the periconceptual period can result in metabolic alterations in bone mineral content. Contrary to our null hypothesis, bone SOS of infants in the ART group was found to be lower than in the NC group. Moreover, bone SOS decreases in early postnatal life. This result emphasizes the fact that even with advances in nutritional care, the ex utero environment remains a poor substitute for in utero development.

Aim: The objective of this study was to determine the accuracy of ultrasonographic measurement of amniochorionic membrane thickness (AMT) in the prediction of preterm birth among an asymptomatic pregnant population., Methods: One hundred and ninety consecutive singleton pregnant women presenting for prenatal care between May 2010 and August 2011 were recruited for the study. AMT of the patients was measured once between 18 and 22 weeks of gestation and then again between 28 and 32 weeks of gestation with transabdominal ultrasound. The results of measurements were recorded and compared with the perinatal outcome related to prematurity., Results: Thirteen of the 190 births were preterm. The mean AMT of the pregnant women who delivered at term were 0.79 ± 0.23 mm in the second trimester and 0.88 ± 0.27 mm in the third trimester. The mean AMT of pregnant women who delivered preterm were 0.77 ± 0.27 mm in the second trimester and 0.91 ± 0.20 mm in the third trimester. There were no statistically significant differences between the second and third trimester AMT of the preterm delivery group and term delivery group (P = 0.542 and P = 0.448, respectively)., Conclusion: In this study, ultrasonographic measurement of fetal membranes was not found to be a useful marker for prediction of preterm birth. The findings of our study may help in understanding ultrasonographic changes in fetal membranes in normal pregnancies., (© 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.)

In this study, a simple, rapid, cost-effective, and sensitive reversed-phase high-performance liquid chromatographic method has been developed and validated for the analysis of moxifloxacin in plasma. The chromatographic separation was achieved on a Zorbax Eclipse XDB-C18 column (150 mm x 4.6 mm i.d.) connected to a Phenomenex C(18) column (4 mm x 3.0 mm i.d.) using a mixture of acetonitrile: 15 mM citrate buffer (pH 3) (23:77, v/v) as the mobile phase with isocratic system at a flow rate of 1 mL/min. Fluorescence detection was employed with excitation at 290 nm and emission at 500 nm. Lomefloxacin was used as internal standard. Plasma samples were prepared with addition of acetonitrile only. The method was fully validated according to the International Conference on Harmonization (ICH) guidelines. The results of the validation parameters were: linearity range, 3-6000 ng/mL (R(2) = 0.9994); mean recovery, 100.48 %; limit of quantification, 5 ng/mL; limit of detection, 1 ng/mL; and intra- and inter-day precision less than 3.2% and 5.1%, respectively. The robustness of the method was evaluated and confirmed with fractional factorial design. After validation studies, the method was applied in order to conclude the effects of pregnancy on postoperative pharmacokinetic profiles of moxifloxacin. For this aim, moxifloxacin was given to non-pregnant women (n=9) and caesarean-sectioned women (n=6) as a single intravenous dose (400 mg Avelox(R) infusion). Plasma samples were analyzed in order to compare pharmacokinetic profiles of pregnants and non-pregnants. Peak serum concentrations of non-pregnant and caesarean-sectioned women at the arterial port after the infusion were 4.95 +/- 1.50 and 1.56 +/- 0.16 microg/mL, respectively. The mean elimination half-life, volume of distribution and calculated area under the concentration-time curve (AUC)(0-infinity) were 5.54 +/- 0.73 h, 65.58 +/- 6.30 L and 49.95 +/- 6.30 microg.h/mL for non-pregnant women and 3.50 +/- 0.37 h, 215.85 +/- 24.87 L and 10.53 +/- 0.66 microg.h/mL for caesarean-sectioned women, respectively. These results indicated that pregnancy has a significant effect on the pharmacokinetics of moxifloxacin.