The importance of mother-child interaction on smart device usage and behavior outcomes among toddlers: a longitudinal study.

BACKGROUND: In recent years, smart devices have become an integral part of daily life. However, longitudinal studies, particularly those regarding the relationship between toddlers' smart device usage and behavioral outcomes, are limited. Understanding the impact of parent-child interactions on this relationship is crucial for enhancing toddlers' developmental outcomes. Accordingly, this study examined the influence of early screen time and media content exposure on toddlers' behaviors, as well as the positive effects of mother-child interactions on this influence. METHODS: We used relevant data related to 277 children born between November 2016 and July 2020 and who were part of an ongoing prospective follow-up study conducted across five hospitals in Taipei City, Taiwan. We analyzed (1) data from maternal reports regarding children's behavior by using the Child Behavior Checklist (for ages 11/2-5 years), (2) assessments of mother-child interactions by using the Brigance Parent-Child Interactions Scale, and (3) self-reported parental data covering the first 3 postpartum years. Statistical analyses involved group-based trajectory modeling and multiple linear regression. RESULTS: A considerable increase in screen time between the ages of 1 and 3 years was associated with less favorable behavioral outcomes at age 3. These outcomes included somatic complaints [adjusted beta coefficient (aß) = 2.17, 95% confidence interval (CI) = 0.39-3.95, p-value = 0.01], withdrawal (aß = 2.42, 95% CI = 0.15-4.69, p-value = 0.04), and aggressive behavior (aß = 6.53, 95% CI = 0.25-12.81, p-value = 0.04). This association was particularly evident among children with lower levels of mother-child interaction. Nevertheless, positive mother-child interactions mitigated most of the adverse effects. Additionally, increased exposure to games and cartoons was associated with poorer behavioral outcomes in all children except for those experiencing positive mother-child interactions. CONCLUSION: Early mother-child interactions play a crucial role in mitigating the risk of behavioral problems in toddlers who spend prolonged periods looking at screens and who are frequently exposed to game and cartoon content.

Clinical factors associated with subsequent surgical intervention in women undergoing early medical termination of viable or non-viable pregnancies.

Introduction: Mifepristone-misoprostol treatment for medical abortion and miscarriage are safe and effective. This study aimed to assess clinical factors associated with subsequent surgical intervention after medical termination of early viable or non-viable pregnancy. Methods: This retrospective, single-center study included women who underwent medical abortion at Taipei Medical University between January 2010 and December 2019. A total of 1,561 subjects, with 1,080 viable and 481 non-viable pregnancies, who were treated with oral mifepristone 600 mg followed by misoprostol 600 mg 48 h later were included. Data of all pregnancies and medical termination of pregnancy were evaluated using regression analysis. The main outcome was successful termination of pregnancy. Results: The success rate of medical abortion was comparable in women with viable and non-viable (92.13% vs. 92.93%) pregnancies. Besides retained tissue, more existing pregnancies with ultrasonographic findings were found in the non-viable pregnancy group than in the viable pregnancy group (29.4% vs. 14.1%, p = 0.011). Multivariate analysis showed that previous delivery was an independent risk factor for failed medical abortion among all included cases. In women with viable pregnancy, longer gestational age [adjusted odds ratio (aOR): 1.483, 95% confidence interval (CI): 1.224-1.797, p < 0.001] and previous Cesarean delivery (aOR: 2.177, 95% CI: 1.167-40.62, p = 0.014) were independent risk factors for failed medical abortion. Number of Cesarean deliveries (aOR: 1.448, 95% CI: 1.029-2.039, p = 0.034) was an independent risk factor for failed medication abortion in women with non-viable pregnancies. Conclusion: This is the first cohort study to identify risk factors for subsequent surgical intervention in women with viable or non-viable pregnancies who had undergone early medically induced abortions. The success rate of medical abortion is comparable in women with viable and non-viable pregnancies. Previous delivery is an independent risk factor for failed medical abortion. Clinical follow-up may be necessary for women who are at risk of subsequent surgical intervention.

Impact of miscarriage and termination of pregnancy on subsequent pregnancies: A longitudinal study of maternal and paternal depression, anxiety and eudaimonia.

BACKGROUND: Although miscarriage and termination of pregnancy affect maternal mental illnesses on subsequent pregnancies, their effects on the positive mental health (e.g., eudaimonia) of both first-time and multi-time parents have received minimal attention, especially for fathers. This longitudinal study examines the effects of experiences of miscarriage and termination on parental well-being in subsequent pregnancies from prenatal to postpartum years, while simultaneously considering parity. METHODS: Pregnant women and their partners were recruited during early prenatal visits in Taiwan from 2011 to 2022 and were followed up from mid-pregnancy to 1 year postpartum. Six waves of self-reported assessments were employed. RESULTS: Of 1813 women, 11.3 % and 14.7 % had experiences of miscarriage and termination, respectively. Compared with the group without experiences of miscarriage or termination, experiences of miscarriage were associated with increased risks of paternal depression (adjusted odds ratio = 1.6, 95 % confidence interval [CI] = 1.13-2.27), higher levels of anxiety (adjusted ß = 1.83, 95 % CI = 0.21-3.46), and lower eudaimonia scores (adjusted ß = -1.09, 95 % CI = -1.99 to -0.19) from the prenatal to postpartum years, particularly among multiparous individuals. Additionally, experiences of termination were associated with increased risks of depression in their partner. LIMITATIONS: The experiences of miscarriage and TOP were self-reported and limited in acquiring more detailed information through questioning. CONCLUSIONS: These findings highlight the decreased well-being of men whose partners have undergone termination of pregnancy or experienced miscarriage, and stress the importance of interventions aimed at preventing adverse consequences among these individuals.

Effects of mobile device use on emotional and behavioral problems in the CBCL among preschoolers: Do shared reading and maternal depression matter?

INTRODUCTION: Although mobile devices are used ubiquitously, studies on their detrimental effects on preschoolers are limited. Furthermore, no study has considered shared reading and mobile device usage simultaneously. Therefore, this study examined the effects of mobile devices and shared reading on preschoolers' development along with the effects of maternal depression on this association. MATERIALS AND METHODS: Mothers of 202 children aged 2-5 years were recruited in Taiwan. Maternal self-reported questionnaires on mobile device usage, shared reading, and child's emotional and behavioral development were collected. Multiple linear regression models were used for analyses. RESULTS: Mothers' higher usage time on mobile devices and an education level of college or less were significantly associated with the child's exceeding recommended use of mobile devices. Particularly among depressed mothers, preschoolers' exceeding recommended use of mobile devices was associated with more sleep (ß = 9.87, 95% confidence interval [CI] = 1.34, 18.40) and attention (ß = 7.20, 95% CI = 1.50, 12.91) problems, whereas shared reading was associated with less somatic complaints (ß = -16.19, 95% CI = -32.22, -0.15) and withdrawn (ß = -21.50, 95% CI = -40.52, -2.47), compared with their respective counterparts. CONCLUSION: Our study suggested the beneficial effects of shared reading. Moreover, we highlighted the adverse effects of preschoolers' exceeding recommended use of mobile device on sleep and attention problems, especially for children of mothers with depression.

Adverse effects of inadequate sleep duration patterns during pregnancy on toddlers suspected developmental delay: A longitudinal study.

BACKGROUND: Although studies have reported the effects of inadequate sleep on maternal health, few have examined the relationships of maternal sleep patterns with fetal health and early childhood development. This study investigated maternal sleep duration patterns from early pregnancy to 3-years postpartum and their effects on birth outcomes and child development. METHODS: This study recruited pregnant women and their partners during prenatal visits at five selected hospitals in the Taipei area; follow-up lasted from July 2011 to April 2021. A total of 1178 parents completed self-reported assessments from early pregnancy until childbirth and 544 completed eight assessments up to 3-years postpartum. Generalized estimated equation models were used for analyses. RESULTS: Group-based trajectory modeling was used to identify four trajectories of sleep duration patterns. Although maternal sleep duration was not associated with birth outcomes, maternal "short decreasing" and "stably short" sleep patterns were associated with a higher risk of suspected overall developmental delay and language developmental delay, respectively. Furthermore, an "extremely long decreasing" pattern was associated with a higher risk of suspected overall developmental delay, [adjusted odds ratio (aOR) = 2.97, 95% confidence interval (CI):1.39-6.36)], gross motor delay, (aOR = 3.14, 95% CI: 1.42-6.99) and language developmental delay (aOR = 4.59, 95% CI:1.62-13.00). The results were significant for the children of multiparous women. CONCLUSIONS: We identified a U-shaped distribution of risk between offspring developmental delay and maternal prenatal sleep duration, with the highest risk levels on both ends of the maternal prenatal sleep duration pattern. Interventions for maternal sleep are relatively straightforward to implement and should thus be a key part of standard prenatal care.

Aspartame Consumption, Mitochondrial Disorder-Induced Impaired Ovarian Function, and Infertility Risk.

Frequent consumption of diet drinks was associated with oocyte dysmorphism, decreased embryo quality, and an adverse effect on pregnancy rate. We investigated the harmful effects of aspartame and potential mechanisms through which it increases infertility risk through clinical observations and in vivo and in vitro studies. Methods: We established a cohort of 840 pregnant women and retrospectively determined their time to conceive. We assessed the estrus cycle, the anti-Mullerian hormone level, ovarian oxidative stress, and ovarian mitochondrial function in an animal study. We also evaluated mitochondria function, mitochondrial biogenesis, and progesterone release with in vitro studies. Aspartame consumption was associated with increased infertility risk in the younger women (Odds ratio: 1.79, 95% confidence interval: 1.00, 3.22). The results of the in vivo study revealed that aspartame disrupted the estrus cycle and reduced the anti-Mullerian hormone level. Aspartame treatment also suppressed antioxidative activities and resulted in higher oxidative stress in the ovaries and granulosa cells. This phenomenon is caused by an aspartame-induced decline in mitochondrial function (maximal respiration, spare respiratory capacity, and ATP production capacity) and triggered mitochondrial biogenesis (assessed by examining the energy depletion signaling-related factors sirtuin-1, phosphorylated adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator-1α, and nuclear respiratory factor 1 expression levels). Aspartame may alter fertility by reserving fewer follicles in the ovary and disrupting steroidogenesis in granulosa cells. Hence, women preparing for pregnancy are suggested to reduce aspartame consumption and avoid oxidative stressors of the ovaries.

Effects of prenatal subjective well-being on birth outcomes and child development: A longitudinal study.

BACKGROUND: Although maternal mental illnesses have been found to influence child health and development, little is known about the impact of maternal positive well-being on child health and development. Therefore, this longitudinal study investigated the effects of prenatal subjective well-being on birth outcomes and child development by considering the potential modifier effect of parity. METHODS: Pregnant women in early stages of pregnancy were recruited at five selected hospitals in Taipei, Taiwan, during their prenatal appointments since 2011. Self-reported evaluations were conducted at seven time points up to 2 years postpartum. Linear regression and generalized estimating equation models were used for examination. RESULTS: Higher prenatal eudaimonic well-being was associated with longer gestational length (adjusted beta [aß] = 0.36, 95% confidence interval [CI] = 0.03, 0.68) and higher birth weight (aß = 124.71, 95% CI = 35.75, 213.66). Higher positive and negative affect were associated with longer gestational length (aß = 0.38, 95% CI = 0.06, 0.70) and smaller birth weight (aß = -93.51, 95% CI = -178.35, -8.67), respectively. For child's outcomes, we found an association between higher prenatal eudaimonic well-being and decreased risks of suspected developmental delay, particularly for children of multiparous mothers (adjusted odds ratio = 0.18, 95% CI = 0.05, 0.70). Higher levels of prenatal depression and anxiety were significantly associated with increased risks of suspected developmental delay for children of primiparous mothers. CONCLUSIONS: Positive prenatal maternal mental health may benefit birth outcomes and child development, particularly for children of multiparous mothers. Interventions for improving prenatal mental health may be beneficial for child development.

Effects of an integrated childbirth education program to reduce fear of childbirth, anxiety, and depression, and improve dispositional mindfulness: A single-blind randomised controlled trial.

OBJECTIVE: To evaluate the effects of an integrated childbirth education intervention on reducing childbirth fear, anxiety, and depression, and improving dispositional mindfulness. DESIGN: A two-arm parallel, single-blind randomised controlled trial. SETTING: A teaching hospital in Northern Taiwan. PARTICIPANTS: Pregnant women ≥ 20 years of age with a singleton pregnancy (12-24 weeks gestation) and their support partners were recruited. All women included in the study had a score of ≥ 7 points on a fear of childbirth visual analogue scale. INTERVENTIONS: The intervention group (n = 53) received an 8-week course in a childbirth education programme, which included (1) childbirth education using simulation-based learning that highlighted coping with labour pain and (2) instruction in mindfulness breathing, body scans, stretching, sitting meditation, and mindfulness walking. Support partners were invited to participate. The control group (n = 53) received the usual standard prenatal care. MEASUREMENTS: The primary outcome of fear of childbirth was assessed using the Wijma Delivery Expectancy/Experience Questionnaire. The secondary outcomes of anxiety, depression, and dispositional mindfulness were assessed with the Edinburgh Postpartum Depression Scale, State-Trait Anxiety Inventory Scale, and the Mindful Attention Awareness Scale, respectively. Repeated data were collected at baseline, 36 weeks gestation, and 1 week postpartum. FINDINGS: Ninety-one mothers completed the study, with a mean age of 33.9 years (SD = 4.4), and most were primipara (n = 83). The baseline measurements did not differ between the groups. Compared with the control group, there were significant differences in all measures from baseline for the intervention group: the scores were significantly lower for fear of childbirth (mean difference (MD) =-14.8 ∼ -23.7, p < .01), symptoms of anxiety (MD =-7.4 ∼ -6.4, p < .01), and depression (MD =-3.7 ∼ -3.5, p < .01); the levels of dispositional mindfulness were significantly higher (MD =4.9 ∼ 5.7, p < .01) at 36 weeks gestation, and 1 week postpartum. CONCLUSION AND IMPLICATIONS FOR PRACTICE: The 8-week integrated childbirth education intervention was effective in reducing the fear of childbirth in pregnant women. The mindfulness techniques were easily learnt and applied by the participants. Using these techniques during pregnancy and labour enhanced participants' mental health and coping. The integrated childbirth education which includes pregnant women and their support partners could be easily taught by midwives in other contexts.

Association between intracytoplasmic sperm injection and neurodevelopmental outcomes among offspring.

PURPOSE: To compare the risk of neurodevelopmental disorders in children conceived via intracytoplasmic sperm injection (ICSI) and those conceived naturally. MATERIALS AND METHODS: A population-based cohort study using data retrieved from the Taipei Medical University Research Database (TMURD) from January, 2004 to August, 2016. The data included maternal pregnancy history, perinatal history and developmental follow up of their babies up to 5 years of age. The study included 23885 children, of whom 23148 were naturally conceived and 737 were conceived via ICSI. Neurodevelopmental disorders defined by 21 ICD-9-CM codes. RESULTS: Of the 23885 children enrolled for analysis, 2778 children were included for further subgrouping analysis after propensity matching to reduce bias from maternal factors. The single-birth group included 1752 naturally conceived (NC) children and 438 ICSI children. The multiple-birth group included 294 NC and 294 ICSI children. The risk of neurodevelopmental disorders was not increased for ICSI children in both groups (single birth: adjusted hazard ratio aHR = 0.70, 95% CI = 0.39-1.27, p = 0.243; multiple-birth group aHR = 0.77, 95% CI = 0.43-1.35, p = 0.853). In the single-birth group, multivariate analyses showed that male sex (aHR = 1.81, 95% CI = 1.29-2.54, p < 0.001), and intensive care unit (ICU) admission (aHR = 3.10, 95% CI = 1.64-5.86, p < 0.001) were risk factors for neurodevelopmental disorders. In the multiple-birth group, multivariate analyses demonstrated that ICU admission (aHR = 3.58, 95% CI = 1.82-7.04, p < 0.001), was risk factor for neurodevelopmental disorders. CONCLUSION: Our study indicated that the use of ICSI does not associated with higher risk of neurodevelopmental disorders in the offspring. But male sex, and ICU admission do have increased risk of neurodevelopmental disorders. However, long term follow up of this cohort on health outcomes in adolescence and adulthood will strengthen the conclusions that ICSI is safe regarding offspring long term outcome.

Niche Laminin and IGF-1 Additively Coordinate the Maintenance of Oct-4 Through CD49f/IGF-1R-Hif-2α Feedforward Loop in Mouse Germline Stem Cells.

The mechanism on how extracellular matrix (ECM) cooperates with niche growth factors and oxygen tension to regulate the self-renewal of embryonic germline stem cells (GSCs) still remains unclear. Lacking of an appropriate in vitro cell model dramatically hinders the progress. Herein, using a serum-free culture system, we demonstrated that ECM laminin cooperated with hypoxia and insulin-like growth factor 1 receptor (IGF-1R) to additively maintain AP activity and Oct-4 expression of AP+GSCs. We found the laminin receptor CD49f expression in d2 testicular GSCs that were surrounded by laminin. Laminin and hypoxia significantly increased the GSC stemness-related genes, including Hif-2α, Oct-4, IGF-1R, and CD49f. Cotreatment of IGF-1 and laminin additively increased the expression of IGF-IR, CD49f, Hif-2α, and Oct-4. Conversely, silencing IGF-1R and/or CD49f decreased the expression of Hif-2α and Oct-4. The underlying mechanism involved CD49f/IGF1R-(PI3K/AKT)-Hif-2α signaling loop, which in turn maintains Oct-4 expression, symmetric self-renewal, and cell migration. These findings reveal the additive niche laminin/IGF-IR network during early GSC development.

Effectiveness of an integrated breastfeeding education program to improve self-efficacy and exclusive breastfeeding rate: A single-blind, randomised controlled study.

BACKGROUND: Low self-efficacy affects new mothers' ability to sustain breastfeeding. Interventions that increase self-efficacy could improve sustained breastfeeding. OBJECTIVES: To develop an integrated breastfeeding education program based on self-efficacy theory, and evaluate the effect of the intervention on first-time mothers' breastfeeding self-efficacy and attitudes. DESIGN: A single-blind, randomised controlled trial. SETTING: A prenatal clinic of a teaching hospital. PARTICIPANTS: First-time mothers with a singleton pregnancy (12-32 weeks' gestation) and their support partners were selected by convenience sampling (N = 104) and allocated by block-randomization to an intervention or control group. METHODS: A 3-week breastfeeding intervention program was developed based on self-efficacy theory. The intervention group received the breastfeeding program; the control group received standard care. Data between groups were compared for scores on breastfeeding self-efficacy, infant feeding attitude, and breastfeeding practice, which were assessed using the Breastfeeding Self-Efficacy Scale-Short Form, the Iowa Infant Feeding Attitude Scale, and a structured questionnaire, respectively. Repeated data measurements were collected at baseline, 36-weeks' gestation, and postpartum at 1-week, and 1-, 3-, and 6-months. RESULTS: Ninety-three mothers completed the study. Data were compared for the self-efficacy intervention group (n = 50) with the control group (n = 43). Baseline measures did not differ between groups. The intervention group had significantly higher breastfeeding self-efficacy at 36 weeks' gestation (mean difference (MD): 7.3, p < .001), and postpartum at 1-week (p < .001), 1-month (p < .001) and 3-months (p < .01) with MD: 6.7, 7.9, and 8.1, respectively; differences in scores from baseline were also significantly greater from 36 weeks' gestation to 3-months (MD from 9.1~9.9, p < .001) and 6-months postpartum (MD: 7.0, p < .05). Infant feeding attitude scores significantly improved from 36 weeks' gestation to 6-months postpartum for the intervention group (MD from 3.5~7.4, p < .05). Rates for exclusive and predominant breastfeeding postpartum were significantly higher for the intervention group vs control (p < .02) at 1-week (98% vs. 86%), 1-month (100% vs. 90.7%), and 3-months (94% vs. 76.7%). Odds ratio (OR) postpartum for exclusive and predominant breastfeeding was greater for the intervention group at 3-months (OR = 4.7, 95% Confidence interval (CI), 1.2 -18.6; p = .05) and for exclusive breastfeeding at 6-months (OR: 2.82, 95% CI 1.0-8.1; p = .05). CONCLUSIONS: The breastfeeding education intervention improved breastfeeding self-efficacy, infant feeding attitudes, and exclusive breastfeeding rates. The breastfeeding education program could be effective for sustaining breastfeeding in new mothers. TRIAL REGISTRATION: Registered with www.clinicaltrials.gov (NCT03807726).

Paternal influences from early pregnancy to postpartum years on child development: A longitudinal study.

INTRODUCTION: Although an array of maternal and child-centered risks have been researched, considerably less is known about the effects of paternal influences on child's birth outcomes and early development. This longitudinal study thus examined the effects of paternal influences (parental stress, partner support, childcare and nursing, and father-child interaction) from early pregnancy to 2 years postpartum on pregnancy outcomes and toddlerhood development, with a simultaneous consideration of maternal depression. METHODS: Pregnant women together with their partners were recruited from 2011 to 2016 at five selected hospitals in Taipei, Taiwan. In total, 440 families completed seven assessments from early pregnancy to 2 years postpartum. Self-reported data were analyzed using logistic regression and generalized estimating equation models. RESULTS: The increment in parental stress from early to late pregnancy was independently and significantly associated with higher risks of low birthweight (adjusted odds ratio [aOR] = 5.3, 95% confidence interval [CI] = 1.0-27.7). In the postpartum years, paternal poorer childcare and nursing (aOR = 1.7, 95% CI = 1.0-3.0) and father-child interaction (aOR = 1.8, 95% CI = 1.2-2.9) were significantly associated with increased risks of child's suspected developmental delay up to 2 years postpartum, particularly among children of nondepressed mothers' children. LIMITATIONS: Selecting both parents in metropolitan areas with higher socioeconomic status may compromise the generalizability of the study. CONCLUSIONS: We suggested the essential role of longitudinal paternal influences from early pregnancy on birth outcomes and child's development during infancy and toddlerhood. Maternal depression remains critical to concern.

High risk of depression, anxiety, and poor quality of life among experienced fathers, but not mothers: A prospective longitudinal study.

BACKGROUND: Mental distress patterns in first-time or experienced mothers and fathers during the transition to parenthood have been inadequately studied. This longitudinal study thus investigated changes in depression, anxiety, and health-related quality of life in both parents from early pregnancy until 1 year postpartum. Parity effects were specifically examined. METHODS: In total, 531 pregnant women and their partners were recruited in Taiwan during early prenatal visits from 2011 to 2015, with five follow-ups from midpregnancy to 1 year postpartum. The participants' self-reported data were collected and analyzed using generalized estimating equation models. RESULTS: Maternal mental distress levels were highest at 1 month postpartum. During postpartum periods, depression scores increased and social relations domain scores decreased in men. Although mental distress levels were higher in mothers than in fathers, parity evidently affected men. Experienced fathers were independently associated with a 70% higher risk of perinatal depression (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.2-2.3) and anxiety (OR = 1.7, 95% CI = 1.2-2.6). Experienced fathers also exhibited significantly lower perinatal scores than first-time fathers in the physical health and social relations domains. LIMITATIONS: Selection of both parents in metropolitan areas with higher socioeconomic status may restrict the generalizability of our findings. CONCLUSIONS: In addition to maternal mental distress during the transition to parenthood, we highlighted experienced fathers' psychological difficulties throughout perinatal periods. Such trends may indicate unsatisfied needs and could guide timely intervention to prevent adverse consequences.

Chronic Niche Inflammation in Endometriosis-Associated Infertility: Current Understanding and Future Therapeutic Strategies.

Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects. This review will survey the latest evidence on the role of inflammatory niche in the peritoneal cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment strategies that target these inflammation processes are also included. Furthermore, mesenchymal stem cell-based therapies are highlighted for potential endometriosis treatment because of their immunomodulatory effects and tropism toward inflamed lesion foci. Potential applications of stem cell therapy in treatment of endometriosis-associated infertility in particular for safety and efficacy are discussed.

IGF-1R Promotes Symmetric Self-Renewal and Migration of Alkaline Phosphatase+ Germ Stem Cells through HIF-2α-OCT4/CXCR4 Loop under Hypoxia.

Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs). However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated that hypoxia significantly induced the GSC mesenchymal transition, increased the expression levels of the pluripotent transcription factor OCT4 and migration-associated proteins (SDF-1, CXCR4, IGF-1, and IGF-1R), and activated the cellular expression and translocalization of the CXCR4-downstream proteins ARP3/pFAK. The underlying mechanism involved significant IGF-1/IGF-1R activation of OCT4/CXCR4 expression through HIF-2α regulation. Picropodophyllin-induced inhibition of IGF-1R phosphorylation significantly suppressed hypoxia-induced SDF-1/CXCR4 expression and cell migration. Furthermore, transactivation between IGF-1R and CXCR4 was involved. In summary, we demonstrated that niche hypoxia synergistically cooperates with its associated IGF-1R signaling to regulate the symmetric division (self-renewal proliferation) and cell migration of alkaline phosphatase-positive GSCs through HIF-2α-OCT4/CXCR4 during embryogenesis.

Effects of smoking on perinatal depression and anxiety in mothers and fathers: A prospective cohort study.

INTRODUCTION: Considerable concern persists on tobacco use during perinatal periods. No study has simultaneously investigated the longitudinal association of paternal smoking with maternal and paternal depressive and anxiety symptoms during perinatal periods. METHODS: In this prospective study, 533 couples (pregnant women and their husbands) completed 5 self-report instruments from early pregnancy until 6 months postpartum. Generalized estimating equations were used for the analyses. RESULTS: We found that fathers who smoked in the mother's presence had higher depressive (regression coefficient=1.0, 95% confidence interval (CI) 0.3-1.8) and anxiety symptoms (3.0, 95% CI=1.2-4.7) during perinatal periods compared with nonsmoking fathers. Paternal smoking in the mother's presence also increased maternal disturbances, especially for depression during pregnancy (1.2, 95% CI=0.1-2.3) and anxiety during the postpartum period (3.4, 95% CI=0.6-6.3). No significant association was found between paternal smoking but not in the mother's presence and maternal emotional disturbances. Paternal smoking but not in the mother's presence affected only paternal anxiety, especially in the postpartum period (regression coefficient 2.7, 95% CI 0.7-4.7) compared with nonsmokers. LIMITATIONS: Self-report measures were used. The effects of maternal smoking could not be estimated because of the small sample of pregnant women who disclosed their smoking status. CONCLUSIONS: These findings imply a necessity to combine strategies for smoking cessation with interventions for affective disturbances in fathers. We also stress the importance of at least restricting the father's smoking in the presence of the pregnant wife during perinatal periods if smoking cessation is tentatively unattainable.

TGF-ßI Regulates Cell Migration through Pluripotent Transcription Factor OCT4 in Endometriosis.

Transforming growth factor (TGF-ß)/TGF-ß receptor signal is known to promote cell migration. Up-regulation of TGF-ß in serum/peritoneal fluid and increased levels of pluripotent transcription factor OCT4 in endometriotic tissues are frequently observed in patients with endometriosis. However, the mechanisms underlying how TGF-ß/TGF-ß receptor and OCT4 affect endometriotic cell migration still remain largely unknown. Therefore, endometriotic tissue with high cell migratory capacity were collected from patients with adenomyotic myometrium (n = 23) and chocolate cyst (n = 24); and endometrial tissue with low cell migratory capacity in normal endometrium or hyperplastic endometrium (n = 8) were collected as the controls. We found the mRNA levels of TGF-ß receptor I (TGF-ß RI) and OCT4 were significantly higher in the high-migratory ectopic endometriotic tissues than those of the low-migratory normal or hyperplastic endometrium. Positive correlations between TGF-ß RI and OCT4, and either TGF-ß RI or OCT4 with migration-related genes (SNAIL, SLUG and TWIST) regarding the mRNA levels were observed in human endometriotic tissues. TGF-ßI dose-dependently increased the gene and protein levels of OCT4, SNAIL and N-Cadherin (N-CAD) and silencing of endogenous OCT4 significantly suppressed the TGF-ßI-induced expressions of N-CAD and SNAIL in primary human endometriotic stromal cells and human endometrial carcinoma cell lines RL95-2 and HEC1A. Furthermore, TGF-ßI significantly increased the migration ability of endometriotic cells and silencing of OCT4 dramatically suppressed the TGF-ßI-induced cell migration activity evidenced by wound-closure assay, transwell assay, and confocal image of F-actin cellular distribution. In conclusion, the present findings demonstrate that the niche TGF-ß plays a critical role in initiating expressions of pluripotent transcription factor OCT4 which may contribute to the ectopic endometrial growth by stimulating endometrial cell migration. These findings would be useful for developing therapeutic strategies targeting TGF-ß-OCT4 signaling to prevent endometriosis in the future.

The efficacy of cold-gel packing for relieving episiotomy pain - a quasi-randomised control trial.

PURPOSES: This study evaluated the effectiveness of cold-gel packing on episiotomy pain among postpartum women who had normal spontaneous deliveries. METHODS: A quasi-randomised control trial was conducted in a maternity ward of a regional teaching hospital in northern Taiwan. Seventy postpartum women were recruited, choosing to be in either the experimental or control group (35 women per group). Subjects in the experimental group received at least six interventions of cold-gel packing applied to the perineal wound and were provided oral analgesics routinely. The subjects in the control group received oral analgesics routinely. FINDINGS: Pain intensity, pain interference on daily activities and satisfaction levels with pain management were assessed using Brief Pain Inventory (BPI) and pain management questionnaire, respectively. The results showed that women in the experimental group reported significantly lower mean pain intensity score, pain interference on daily activities scores at 48 hours post-delivery, and higher level of satisfaction with pain management at 24 and 48 hours post-delivery than the control group after adjusting for demographic and obstetric data. CONCLUSIONS: Cold-gel packing on the perineum is a cost-effective, convenient, easy-to-deploy and non-pharmacologic approach to pain reduction, with an overall positive impact on postpartum recovery for parturients.

Sonographic patterns of the endometrium in assessment of medical abortion outcomes.

BACKGROUND: We aimed to define endometrial pattern and endometrial thickness in predicting the outcome of early medical abortion. STUDY DESIGN: While blinded to outcomes of abortion, we retrospectively reviewed the ultrasound scan performed 14-21 days after medical abortion. We assessed the endometrial pattern and endometrial thickness. A total of 943 women at or before 56 days of gestation who underwent medical abortions were included. Abortion was induced with mifepristone (600 mg) orally followed 48 h later with oral misoprostol (600 mcg). A successful medical abortion was defined as complete abortion without surgical intervention. Three sonographic patterns (homogenous, heterogeneous and multilayered) were devised to correlate with the outcome. RESULTS: Of the 940 women, 92 (9.8%) had failed medical abortions. Eighty-seven (94.6%) patients with failed treatment outcomes had a heterogeneous pattern, while no patients with failed treatments had a multilayered pattern. Based on multivariable logistic regression, women who had an endometrial thickness in the range of 10-15 or >15 mm were more likely to have failed outcomes than those with a thickness <10 mm, with ORs of 3.69 (p=.001) and 8.82 (p<.001). Compared to those with a homogenous pattern, women with a heterogeneous endometrial pattern were more likely to have failed outcomes (OR 4.5, p=.003). In addition, an endometrial thickness >10 mm in combination with a heterogeneous pattern had the highest balanced accuracy in the prediction of failed outcome (81.9%; 95% CI, 77.6-86.3). CONCLUSION: Women with a multilayered pattern could be reassured that they have successful medical abortion, while those with a heterogeneous pattern and/or endometrium >10 mm may need follow-up. Sonographic endometrial pattern and endometrial thickness may serve as objective criteria in the management of early medical abortions.