Forward-Looking Ultrasound Wearable Scanner System for Estimation of Urinary Bladder Volume.

Accurate measurement of bladder volume is an important tool for evaluating bladder function. In this study, we propose a wearable bladder scanner system that can continuously measure bladder volume in daily life for urinary patients who need urodynamic studies. The system consisted of a 2-D array, which included integrated forward-looking piezoelectric transducers with thin substrates. This study aims to estimate the volume of the bladder using a small number of piezoelectric transducers. A least-squares method was implemented to optimize an ellipsoid in a quadratic surface equation for bladder volume estimation. Ex-vivo experiments of a pig bladder were conducted to validate the proposed system. This work presents the potential of the approach for wearable bladder monitoring, which has similar measurement accuracy compared to the commercial bladder imaging system. The wearable bladder scanner can be improved further as electronic voiding diaries by adding a few more features to the current function.

Effect of Stem Cell Treatment on Acute Liver Failure Model Using Scaffold.

BACKGROUND: Injecting MSCs via blood vessel is most commonly used method, which has a major drawback of safety. The aim of our study was to evaluate efficacy using scaffold-loaded MSCs in acute liver failure model. METHOD: Acute liver failure was induced in mice using thioacetamide (TAA) (200 mg/kg, i.p) once a day for two consecutive days. The animals were divided in four acute liver failure groups: (1) TAA; (2) empty scaffold; (3) MSCs injected through tail vein; (4) MSC + Scaffold, scaffold loaded with MSCs, to evaluate the mortality and changes in liver function. Polylactic-co-glycolic acid scaffold alone and loaded with human MSCs was implanted on mice dorsum. RESULTS: TAA dose was titrated until one-third mortality rate was achieved. TAA (200 mg/kg) once daily for two consecutive days was injected to establish the acute liver failure model. The mortality of TAA and scaffold groups was 55.9% and 63.2%, respectively. Although, mortality of MSC-TV group decreased 14.7% as compared to TAA group (p = 0.200), MSC + Scaffold group had the lowest mortality (31.4%) (p = 0.013). Cells implanted in PLGA biomaterial were survived until 3 weeks, and their function was increased. Area of hepatic inflammation and necrosis was significantly reduced in MSC-TV and MSC + Scaffold groups; but there was no difference between the two groups. Gene expressions related to inflammation were significantly decreased in MSC-TV and MSC + Scaffold groups compared to TAA group. In MSC + Scaffold group, no migration of stem cells to liver tissue was observed. Although, not all cells in scaffold were stained, some of them were differentiated into hepatocyte-like cells which stained positive for PAS and CYP2E1 antibody. CONCLUSION: Scaffold loaded with MSCs showed protective effects via paracrine signaling on acute liver failure model.

Positive Effect of Baby-Friendly Hospital Initiatives on Improving Mothers' Intention for Successful Breastfeeding in Korea.

BACKGROUND: In Korea, the breastfeeding (BF) rate of infants aged 6 months or more is drastically decreasing, and this phenomenon is particularly worrisome for the future health of the population. The present study aimed to identify an antenatal strategy for initiation and continuation of human BF, and to identify how Baby-Friendly Hospitals (BFHs) may positively influence the intention to breastfeed. METHODS: A total of 414 pregnant Korean antenatal women were surveyed using questionnaires to determine current knowledge of the benefits of human breast milk, whether they planned to breastfeed after delivery, to continue BF after reinstatement in the workforce, are willing to abide by rooming-in care for infants, and plan to give birth at BFHs. RESULTS: We found that planning room-in care, greater awareness of BF benefits for infant and mother, participation in antenatal education programs, and provision of BF facilities in the workplace were positively associated with plans for exclusive breastfeeding (EBF) and longer BF duration. The mothers who planned to give birth at BFHs also desired to breastfeed immediately after birth, implement in-room care, continue BF at their workplace, participate in antenatal BF educational programs, and were more aware of the benefits of BF. CONCLUSION: If the beneficial effects of BFHs were well known to individuals, these would enhance the success rate of BF in Korea. Antenatal education and consequent acquisition of better knowledge of the benefits of BF are important for increasing the rate of BF practices.

Complex and irregular heart rate dynamics in fetuses compromised by maternal anemia as a high-risk pregnancy.

AIM: To examine how complex and irregular fetal heart rate (FHR) dynamics differ between fetuses of normal pregnancies and those of pregnancies complicated by maternal anemia (MA), and to place this in the context of high-risk pregnancies. METHODS: Our study population consisted of 97 pregnant women affected by MA, 118 affected by pregnancy-induced hypertension (PIH), 88 affected by gestational diabetes mellitus (GDM), 53 with preterm premature rupture of membranes (pPROM), and 356 normal pregnancies as controls. We calculated approximate entropy (ApEn), sample entropy (SampEn), and correlation dimension (CD) to quantify irregularity and the chaotic dynamics of each FHR time series. RESULTS: The ApEn in the fetuses of the MA and PIH groups was significantly lower than that of the normal controls (P<0.05). The SampEn was significantly lower in the high-risk groups, except for the pPROM group, than in the normal controls (P<0.05). The CD in the PIH and severe MA groups was significantly lower than that of the normal controls (P<0.05, respectively). In the MA group, the dynamic indices showed a highly significant positive correlation with hemoglobin (Hb) levels (P<0.0001). CONCLUSION: The decreased complexity and/or irregularity in the FHR from pregnancies with MA may reflect abnormalities in the complex, integrated cardiovascular control. The irregularity and complexity of the FHR increased together with Hb levels in pregnancies with MA. Our data suggest that the integrity of the nervous system in the fetuses compromised by severe MA might result directly in adverse outcomes.

The RNA in reticulocytes is not just debris: it is necessary for the final stages of erythrocyte formation.

Reticulocytes contain both RNA and micro-organelles and represent the last stage of erythropoiesis before full maturation to red blood cells (RBCs). Even though there is continuing synthesis of hemoglobin and membrane-bound proteins in reticulocytes, the small amount of RNA that they contain has been regarded as non-functional residual material. Here we show that this residual RNA is both functional and essential for further reticulocyte maturation. Reticulocytes from which the remnant RNA had been removed by exposure to RNase did not survive or mature into RBCs in either humans or mice. Conversely, reticulocytes treated with an RNase Inhibitor were able to form normal biconcave cells. Similarly, poor survival was also seen in reticulocytes in which protein synthesis had been blocked. To identify the signaling pathways involved we isolated RNAs in reticulocytes versus those present in fully matured erythroblasts cultured from hematopoietic stem cells. RNAs found in erythroblasts were related to exocytosis, metabolism, and signal transduction all of which are critical for maturation through reticulocyte and into a fully mature, biconcave erythrocyte. Our results suggest that the mRNA in reticulocytes has to be translated into novel proteins that act to preserve mitochondria and maintain cell membrane integrity as reticulocytes mature. These results enhance our understanding of the final stage of erythropoiesis and may clarify why in vitro-generated reticulocytes for transfusion purposes survive poorly.

Maternal pre-pregnancy obesity affects the uncinate fasciculus white matter tract in preterm infants.

Background: A growing body of evidence suggests an association between a higher maternal pre-pregnancy body mass index (BMI) and adverse long-term neurodevelopmental outcomes for their offspring. Despite recent attention to the effects of maternal obesity on fetal and neonatal brain development, changes in the brain microstructure of preterm infants born to mothers with pre-pregnancy obesity are still not well understood. This study aimed to detect the changes in the brain microstructure of obese mothers in pre-pregnancy and their offspring born as preterm infants using diffusion tensor imaging (DTI). Methods: A total of 32 preterm infants (born to 16 mothers with normal BMI and 16 mothers with a high BMI) at <32 weeks of gestation without brain injury underwent brain magnetic resonance imaging at term-equivalent age (TEA). The BMI of all pregnant women was measured within approximately 12 weeks before pregnancy or the first 2 weeks of gestation. We analyzed the brain volume using a morphologically adaptive neonatal tissue segmentation toolbox and calculated the major white matter (WM) tracts using probabilistic maps of the Johns Hopkins University neonatal atlas. We investigated the differences in brain volume and WM microstructure between preterm infants of mothers with normal and high BMI. The DTI parameters were compared among groups using analysis of covariance adjusted for postmenstrual age at scan and multiple comparisons. Results: Preterm infants born to mothers with a high BMI showed significantly increased cortical gray matter volume (p = 0.001) and decreased WM volume (p = 0.003) after controlling for postmenstrual age and multiple comparisons. We found a significantly lower axial diffusivity in the uncinate fasciculus (UNC) in mothers with high BMI than that in mothers with normal BMI (1.690 ± 0.066 vs. 1.762 ± 0.101, respectively; p = 0.005). Conclusion: Our study is the first to demonstrate that maternal obesity impacts perinatal brain development patterns in preterm infants at TEA, even in the absence of apparent brain injury. These findings provide evidence for the detrimental effects of maternal obesity on brain developmental trajectories in offspring and suggest potential neurodevelopmental outcomes based on an altered UNC WM microstructure, which is known to be critical for language and social-emotional functions.

Gut microbiome profiling of neonates using Nanopore MinION and Illumina MiSeq sequencing.

This study aimed to evaluate the difference in gut microbiomes between preterm and term infants using third-generation long-read sequencing (Oxford Nanopore Technologies, ONT) compared with an established gold standard, Illumina (second-generation short-read sequencing). A total of 69 fecal samples from 51 term (T) and preterm (P) infants were collected at 7 and 28 days of life. Gut colonization profiling was performed by 16S rRNA gene sequencing using ONT. We used Illumina to validate and compare the patterns in 13 neonates. Using bioinformatic analysis, we identified features that differed between P and T. Both T1 and P1 microbiomes were dominated by Firmicutes (Staphylococcus and Enterococcus), whereas sequentially showed dominant transitions to Lactobacillus (p < 0.001) and Streptococcus in T2 (p = 0.001), and pathogenic bacteria (Klebsiella) in P2 (p = 0.001). The abundance of beneficial bacteria (Bifidobacterium and Lactobacillus) increased in T2 (p = 0.026 and p < 0.001, respectively). These assignments were correlated with the abundance at the species-level. Bacterial α-diversity increased in T (p = 0.005) but not in P (p = 0.156), and P2 showed distinct ß-diversity clustering than T2 (p = 0.001). The ONT reliably identified pathogenic bacteria at the genus level, and taxonomic profiles were comparable to those identified by Illumina at the genus level. This study shows that ONT and Illumina are highly correlated. P and T had different microbiome profiles, and the α- and ß-diversity varied. ONT sequencing has potential for pathogen detection in neonates in clinical settings.

Dissemination of sulfonamide resistance genes in digester microbiome during anaerobic digestion of food waste leachate.

The preeminence of sulfonamide drug resistance genes in food waste (FW) and the increased utilization of high-strength organic FW in anaerobic digestion (AD) to enhance methane production have raised severe public health concerns in wastewater treatment plants worldwide. In this regard, the dissemination patterns of different sulfonamide resistance genes (sul1 and sul2) and their impact on the digester core microbiota during AD of FW leachate (FWL) were evaluated. The presence of various sulfonamide antibiotics (SAs) in FWL digesters improved the final methane yield by 37 % during AD compared with FWL digesters without SAs. Microbial population shifts towards hydrolytic, acidogenic, and acetogenic bacteria in the phyla Actinobacteriota, Bacteroidota, Chloroflexi, Firmicutes, Proteobacteria, and Synergistota occurred due to SA induced substrate digestion and absorption through active transport; butanoate, propanoate, and pyruvate metabolism; glycolysis; gluconeogenesis; the citrate cycle; and pentose phosphate pathway. The initial dominance of Methanosaeta (89-96 %) declined to 47-53 % as AD progressed and shifted towards Methanosarcina (40 %) in digesters with the highest SA concentrations at the end of AD. Dissemination of sul1 depended on class 1 integron gene (intl1)-based horizontal gene transfer to pathogenic members of Chloroflexi, Firmicutes, and Patescibacteria, whereas sul2 was transmitted to Synergistota independent of intl1. Low susceptibility and ability to utilize SAs during methanogenesis shielded methanogenic archaea against selection pressure, thus preventing them from interacting with sul or intl1 genes, thereby minimizing the risk of antibiotic resistance development. The observed emergence of cationic antimicrobial peptide, vancomycin, and ß-lactam resistance in the core microbiota during AD of FWL in the presence of SAs suggests that multidrug resistance caused by bacterial transformation could lead to an increase in the environmental resistome through wastewater sludge treatment.

Fetal heart rate regresses toward the mean in the third trimester.

The purpose of this study was to investigate the feasibility of different fetal heart rate (FHR) ranges in the nonstress test (NST) and to better understand the meaning of mild bradycardia and/or tachycardia without non-reassuring patterns. We employed the heredity to show that mild bradycardia (100-119 beats per minute, bpm) and mild tachycardia (161-180 bpm) regressed to the normal FHR range (120-160 bpm). We used linear regression to analyze FHR data from FHR tracings recorded 10 min before (NST, as the predictor) and 10 min after vibroacoustic stimulation testing (as the dependent variable). Acceleration for 15 bpm-15 seconds (Acc1515) and deceleration for 15 bpm-15 seconds (Dec1515) in the NST were also analyzed for each group. The slope of the best-fit line was the largest in the mild bradycardia group and the smallest in the normal range group. Dec1515 was most prominent in mild tachycardia and both the mild bradycardia and tachycardia groups regressed towards the mean FHR range. Therefore, we propose that both mild bradycardia and tachycardia of FHR in non-acute situations (range between 100 and 180 bpm) are not regarded a pathologic signal for clinical use.

Fetal heart rate parameters and perinatal outcomes in fetuses with nuchal cords.

AIM: The purpose of the present study was to compare and analyze differences in antepartal fetal heart rate (FHR) parameters during pregnancy and pregnancy outcomes in normal fetuses and fetuses with nuchal cord (NC). MATERIAL AND METHODS: We surveyed all non-stress test (NST) data acquired using a computerized FHR analysis system at Hanyang University Hospital between 2005 and 2008, and selected 150 cases that had NC. NSTs were performed between 37 and 42 weeks of gestation. Subjects were divided into three groups by the number of NCs: no NC and normal (n = 300), single (n = 124) and multiple NCs (n = 26). Neonatal outcomes were compared, and FHR parameters analyzed using computerized fetal monitoring system. RESULTS: FHR variability, with respect to amplitude (AMP) and mean minute range (MMR), was lower in the multiple NCs group than in the normal group (18.04 ± 0.38 vs 14.54 ± 1.10 bpm, P = 0.0207; 55.69 ± 1.22 vs 44.35 ± 3.41 ms, P = 0.0145, respectively). There were no other statistically significant differences of FHR parameters between the three groups. Baby weight was significantly lower in the multiple NCs group than in the normal group (3317 ± 24 vs 3054 ± 55; P = 0.0008), and there were no other significant differences between the groups. CONCLUSION: Computerized analysis of FHR would be helpful to assess fetal status, especially in cases of multiple NCs. Multiple NCs may be a subliminal risk factor for the babies even though they present no complications at delivery.

Fetal heart rate parameters of anencephalic fetuses according to gestational age.

OBJECTIVE: To evaluate various fetal heart rate (FHR) parameters of anencephalic fetuses and to assess the effect of the fetal nervous system on FHR according to gestational age. STUDY DESIGN: The antepartum nonstress test was performed in 25 anencephalic fetuses. Each FHR parameter was analyzed using a computerized FHR analysis system for various gestational groups, and the results were compared with results from a normal control group (N = 25). RESULTS: The mean baseline FHR of anencephalic fetuses decreased with increasing gestational age, as in normal fetuses. FHR variability increased with increasing gestational age, as in normal fetuses. CONCLUSION: In anencephalic fetuses, baseline FHR and FHR variability changed significantly with gestational age. These results suggest that the autonomic nervous system is more likely to be preserved than the central nervous system in anencephalic fetuses in spite of malformed or insufficient central nervous system.

Translocation of a cerclage band into the endocervical canal after preconception transabdominal cervico-isthmic cerclage.

A 34-year-old woman, who had a history of five spontaneous losses and failures of two McDonald purse-string cerclages, underwent a transabdominal cervico-isthmic cerclage (TCC). She became pregnant 17 months after TCC. At 35 weeks of gestation, she was admitted to our hospital due to preterm labor and delivered a healthy female baby (2270 g) by cesarean section. After delivery of the newborn infant, we found a migration of about one third of the cerclage band into the endocervical canal. Two years later, she had one further pregnancy, reached 33 weeks of gestation, and delivered a 1450 g male baby by cesarean section due to a preterm labor without any signs of infection. Although it could have been a case of pure coincidence, we take a chance to speculate that the migration of the cerclage band into the endocervical canal might have been the reason for the preterm labor, and it must have been removed at her first cesarean section and replaced by a new cerclage band for her next pregnancy.

Difference of fetal heart rate accelerations based on 10 and 15 beats per minute.

AIM: To evaluate the correlation of 10 b.p.m.-10 s and 15 b.p.m.-15 s fetal heart rate (FHR) accelerations in gestations before or after 32 weeks using computerized analysis. METHODS: A combination of amplitude and duration of FHR accelerations, 10 b.p.m.-10 s (Acc10-10) and 15 b.p.m.-15 s (Acc15-15), was analyzed according to gestational weeks between January 1999 and December 2005 in 2358 normal pregnant women who received a non-stress test at 30-42 gestational weeks. A linear regression model between Acc10-10 and Acc15-15 was estimated, and the duration difference between 10 b.p.m. and 15 b.p.m. was converted into seconds. RESULTS: Before 32 weeks of gestation, the mean number of FHR accelerations based on 15 b.p.m. was below 2.00 (mean + or - standard error, 1.58 + or - 0.19). The correlation between Acc10-10 and Acc15-15 was Acc15-15 + 2.8 = Acc10-10 (r(2) = 0.94, P = 0.0013). The mean duration difference between 10 b.p.m. and 15 b.p.m. was 36.8 s (range, 4-227 s). CONCLUSIONS: Our study verified the difference of Acc10-10 and Acc15-15 using computerized analysis as the base of visual interpretation of the definition of FHR acceleration. Acc15-15 did not occur often enough to be relevant to the definition of FHR acceleration before 32 weeks' gestation. The difference between the mean number of FHR accelerations based on 10 b.p.m. and 15 b.p.m. within a 20-min window was 2.8.

Conventional linear criteria with sample entropy in the interpretation of reactive antepartum fetal heart rate tracings.

OBJECTIVE: To compare the test duration times and rate of nonreactive results between the conventional linear reactive criteria (CLRC) and the modified nonlinear reactive criteria (MNRC) in electronic fetal heart rate (FHR) monitoring. The MNRC are the CLRC with the addition of approximate entropy or sample entropy. METHODS: One thousand women with singleton pregnancies between 30 and 37 weeks' gestation were selected. They visited Hanyang University Hospital for non-stress tests (NSTs). In these patients, FHR tracings were recorded for 50 min including the first and second 20 min of NST and 10 min of vibroacoustic stimulation test. All patients had a reactive NST with CLRC in these antepartum FHR tests. The rate of nonreactive tests and test duration times of these linear and nonlinear criteria were calculated and compared. RESULTS: The rate of nonreactive tests within a 20- and 40-min period with the MNRC (6.8 and 1.2%) was significantly lower than with the CLRC (35.2 and 10.5%, respectively; p < 0.001). To meet the reactive criteria, the mean durations of the MNRC and the CLRC were 11.47 (95% CI, 11.11-11.84) and 18.45 (95% CI, 17.79-19.12) min, respectively (p < 0.001). The MNRC led to a significant reduction in testing time of 37.8% compared to the CLRC. The rate of reactive tests using only sample entropy (0.20), calculated over 5-min segments of FHR tracings, was 88.3% (95% CI, 88.0-88.7). It was close to the results using the MNRC (93.2%) in the 20-min time window. CONCLUSION: The use of the MNRC significantly reduced the test duration times and decreased the rate of nonreactive tests when compared to the CLRC. It may be useful in providing more rapid and accurate assessment of the fetus in electronic FHR monitoring.

Immediate laparoscopic nontransvesical repair without omental interposition for vesicovaginal fistula developing after total abdominal hysterectomy.

BACKGROUND AND OBJECTIVE: We conducted this study to evaluate the feasibility and efficacy of immediate laparoscopic nontransvesical repair without omental interposition for vesicovaginal fistula (VVF) developing after total abdominal hysterectomy (TAH), which causes not only social and economic misery for the patient but also considerable stress to the physicians who perform the surgery. METHODS: We performed a retrospective review of 5 women who underwent immediate laparoscopic nontransvesical repair without omental interposition for VVFs, developing after TAH from October 2007 to March 2009. In terms of laparoscopic procedure, cystoscopy was performed to confirm the location of fistula and ureteral openings, initially. Without opening the bladder, the fistula tract was identified, and the bladder was dissected from the vagina. The bladder defect was closed by using intracorporeal, continuous, and double-layer suturing, laparoscopically. The vaginal defect was closed using interrupted and single-layer suturing, vaginally. A Foley catheter was inserted for 2 weeks and removed after bladder integrity was confirmed with a retrograde cystogram. RESULTS: The median age and body mass index of the patients were 47 years and 22.3 kg/m², respectively. Operating time, hemoglobin change, and hospital stay were 95 minutes, 1.1 g/dL, and 5 days, respectively. There were no complications or laparoconversions. During follow-up (median 56.1 weeks; range 26.6 to 74.0), there was no evidence of recurrence. CONCLUSIONS: Immediate laparoscopic nontransvesical repair without omental interposition might be an effective, feasible alternative to the traditional methods in select patients with small sized (<1 cm) VVF developing after TAH.

Increased amounts and stability of telomeric repeat-containing RNA (TERRA) following DNA damage induced by etoposide.

Telomeric repeat-containing RNAs (TERRAs) are long noncoding RNAs transcribed from subtelomeres toward telomeric repeat tracts, which have been implicated in telomere protection and heterochromatin formation. Genotoxic stress leads to upregulation of TERRAs. However, the mechanism of DNA damage-mediated TERRA induction remains elusive. Here, we treated HeLa cells with etoposide, a DNA double-strand break-generating agent, for various times and monitored the levels of TERRAs. Etoposide treatment led to a gradual time-dependent increase in TERRAs. Etoposide-mediated induction was evident in many TERRAs arising from various chromosome loci, including 20q and XpYp. Chromatin immunoprecipitation assays revealed no significant changes in the occupancy of RNA polymerase II at telomeres upon etoposide treatment. Interestingly, TERRAs arising from 20q, XpYp, 10q, and 13q degraded at slower rates in cells treated with etoposide, while degradation rates of TERRAs from many loci tested were nearly identical in both etoposide- and mock-treated cells. Telomere damage occurred from early time points of etoposide treatment, but telomere lengths and abundance of telomeric repeat-binding factor 2 (TRF2) at telomeres remained unchanged. In summary, etoposide treatment led to telomere damage and TERRA accumulation, but telomere lengths and TRF2-mediated telomere integrity were maintained. Etoposide-mediated TERRA accumulation could be attributed partly to RNA stabilization. These findings may provide insight into the post-transcriptional regulation of TERRAs in response to DNA damage.

Maternal outcomes and follow-up of preterm and term neonates born to mothers with systemic lupus erythematosus.

OBJECTIVE: There is little follow-up data in preterm infants from mothers with systemic lupus erythematosus (SLE). The aim of this study was to determine maternal outcomes and compare neonatal outcomes in preterm and term infants born to mothers with SLE. METHODS: This study is a prospective study in a tertiary medical care center and clinical research center for rheumatoid arthritis. Demographic data, clinical features, laboratory findings, treatment and complications in 77 pregnant SLE patients were prospectively evaluated from 2007 to 2013. RESULTS: Ninety-two infants (44 males and 48 females including four sets of twins) from 77 mothers with SLE were enrolled. Multivariate logistic analysis indicated that flares were significantly associated with antiphospholipid antibodies of lupus anticoagulant during pregnancy (p = 0.009) and preterm birth (p = 0.017). Compared with term infants, preterm infants had significantly higher antinuclear antibodies (ANA) positivity (p = 0.001) at 12 months of age in multivariate logistic analysis. CONCLUSION: Preterm birth is associated with maternal flares and persistent ANA positivity at 12 months of life in infants born to mothers with SLE.

Sex-related differences in the development of fetal heart rate dynamics.

BACKGROUND: Despite previous efforts to explain the general advantages of female fetuses over males regarding health, sex-related differences in the dynamics or complexity of fetal heart rate (FHR) variability and FHR maturation patterns have not yet been identified. AIM: To make linear and nonlinear comparisons of antepartum FHR indices, dynamics, complexity, and reactivity to the non-stress test (NST) and vibroacoustic-stimulation test (VAST) in male and female fetuses. STUDY DESIGN: A total of 3835 singleton term deliveries without maternal and fetal complications were divided into female (n=1849) and male (n=1986) groups, and subjected to comparison and analyses. SUBJECTS: Linear FHR indices, approximate entropy (ApEn), sample entropy (SampEn), short-term/long-term exponents (α1/α2), correlation dimension (CD), NST and VAST criteria, and modified nonlinear reactive criteria (MNRC) were used to evaluate outcomes. RESULTS: ApEn was consistently higher in female fetuses than in male ones. ApEn in female fetuses was maximal at 29-30 gestational weeks, while the increase in ApEn was delayed in male fetuses but more rapid, reaching its peak at 31-32 gestational weeks. In both sexes, CD increased up to term, and α2 rapidly decreased up to 31-32weeks in an analogous manner. The two sexes differed significantly in response to VAST at <31 gestational weeks and there was a structural difference in reactive patterns under MNRC. CONCLUSIONS: Female fetuses exhibit greater heart rate dynamics in early gestational periods, suggesting that their cardiovascular system matures earlier than that of males. Male fetuses undergo a compensatory period of rapid change to catch up with females at term.

Nonlinear analysis of fetal heart rate dynamics in fetuses compromised by asymptomatic partial placental abruption.

INTRODUCTION: We analyzed fetal heart rate (FHR) parameters, dynamics, and outcomes in pregnancies with asymptomatic partial placental abruption (PPA) compared with those in normal pregnancies. METHODS: We examined nonstress test (NST) data acquired from 2003 to 2012 at our institution. Normal pregnancies (N = 170) and PPA cases (N = 17) were matched for gestational age, fetal sex, and mean FHR. NSTs were performed at 33-42 weeks of gestation. FHR parameters obtained from the NST and perinatal outcomes were analyzed using linear methods. Nonlinear indices, including approximate entropy (ApEn), sample entropy (SampEn), short-term and long-term scaling exponents (α1 and α2), and correlation dimension (CD), were used to interpret FHR dynamics and system complexity. The area under a receiver operating characteristic curve (AUC) was used to evaluate the nonlinear indices. RESULTS: There were no significant differences in general characteristics and FHR parameters between the PPA and control groups. However, gestational age at delivery, birth weight, 5-min Apgar scores, ApEn, SampEn, and CD were significantly lower in the PPA group than in the control group (P < 0.05). The long-term scaling exponent (α2) and crossover index (α2/α1) of the PPA fetuses were significantly higher than those of the controls (P < 0.01). A multiple regression model showed better performance in predicting PPA (AUC, 0.92; sensitivity 82.35%; specificity, 94.12%). DISCUSSION: Nonlinear dynamic indices of FHR in asymptomatic PPA were qualitatively different from those in normal pregnancies, whereas the conventional FHR parameters were not significantly different.

Noggin Over-Expressing Mouse Embryonic Fibroblasts and MS5 Stromal Cells Enhance Directed Differentiation of Dopaminergic Neurons from Human Embryonic Stem Cells.

Directed methods for differentiating human embryonic stem cells (hESCs) into dopaminergic (DA) precursor cells using stromal cells co-culture systems are already well established. However, not all of the hESCs differentiate into DA precursors using these methods. HSF6, H1, H7, and H9 cells differentiate well into DA precursors, but CHA13 and CHA15 cells hardly differentiate. To overcome this problem, we modified the differentiation system to include a co-culturing step that exposes the cells to noggin early in the differentiation process. This was done using γ-irradiated noggin-overexpressing CF1-mouse embryonic fibroblasts (MEF-noggin) and MS5 stromal cells (MS5-noggin and MS5-sonic hedgehog). After directed differentiation, RT-PCR analyses revealed that engrailed-1 (En-1), Lmx1b, and Nurr1, which are midbrain DA markers, were expressed regardless of differentiation stage. Moreover, tyrosine hydroxylase (Th) and an A9 midbrain-specific DA marker (Girk2) were expressed during differentiation, whereas levels of Oct3/4, an undifferentiated marker, decreased. Immunocytochemical analyses revealed that protein levels of the neuronal markers TH and TuJ1 increased during the final differentiation stage. These results demonstrate that early noggin exposure may play a specific role in the directed differentiation of DA cells from human embryonic stem cells.