Chromatin state transition underlies the temporal changes in gene expression during cardiomyocyte maturation

Congenital heart disease (CHD) is often rooted in aberrant gene expression during heart development. As cells commit to a specific lineage during development, chromatin dynamics and developmental plasticity generally become more limited. However, it remains unclear how differentiated cardiomyocytes (CMs) undergo morphological and functional adaptations to the postnatal environment during the process of CM maturation. We sought to investigate the regulatory mechanisms that control postnatal cardiac gene networks. A time-series transcriptomic analysis of postnatal hearts revealed an integrated, time-ordered transcriptional network that regulates CM maturation. Remarkably, depletion of histone H2B ubiquitin ligase RNF20 after formation of the four-chamber heart disrupted these highly coordinated gene networks. As such, its ablation caused early-onset cardiomyopathy, a phenotype reminiscent of CHD. Furthermore, the dynamic modulation of chromatin accessibility by RNF20 during CM maturation was necessary for the operative binding of cardiac transcription factors that drive transcriptional gene networks. Together, our results reveal how epigenetic-mediated chromatin state transitions modulate time-ordered gene expression for CM maturation.

Towards restorative spaces for postnatal recovery in urban tertiary hospitals

<p>Modern living and globalisation are increasingly contributing to access to and utilisation of modern healthcare services in both developed and developing countries; from diagnosis, treatments, and even to birth in a specialised healthcare environment. In many resource-rich countries, birth is one of the main reasons for women’s hospitalisation. Research suggests that physical environments of healthcare impact on patient/users’ health outcomes. Yet decisions about healthcare facilities’ design and programming are often made without input from users. A key challenge for patient-centred care in the maternity field is the assumption that healthcare spaces and facilities created for the general “unwell” hospital population can support the emotional, physiological and psychological needs of healthy women who give birth in hospitals. Previous research into the childbirth environment has focused on physical environments and satisfaction with the labour and birth process. But studies examining the impacts of physical environments on women’s postnatal recovery experience and wellbeing have been limited. The aim of this thesis is to determine the design factors that influence women’s recovery experiences and wellbeing with a view to proposing design guidelines for optimal postnatal environment in large, tertiary hospitals. A two phase sequential explanatory mixed methods approach was taken to the research which combined a quantitative method (online survey questionnaires) with a qualitative approach (focus group discussions – FGDs). Research was conducted with two user groups, comprising postnatal women and midwives, to examine perceptions of physical environment factors that influence women’s recovery experiences and wellbeing in New Zealand hospitals. The results of the questionnaire surveys were followed up in phase two FGDs to provide explanations and descriptions of architectural factors and design features that impacted on women’s recovery experiences and psychological wellbeing. The results were compared, synthesised and interpreted to inform the outcomes of this thesis. The research found several physical environment factors and design features which were significant and a number which were non-significant among the two user groups in all four categories investigated: perception of postnatal room features; interior environment; sensory comfort environment and social comfort environment. The research found factors related to maintenance (e.g. cleanliness), environmental design (e.g. noise/quiet in rooms, and daylighting), and interior spatial characteristics (e.g. view to nature, combined home-like and clinical features and privacy) are more important in fostering wellbeing. Strong evidence was found on how building spaces impact on postnatal recovery experience, especially regarding single-bed rooms for emotional support and psychosocial support environments such as communal spaces and outdoor environments. The original contribution of this thesis is an identification of the environments which have the potential for enhanced recovery experience of women during the postnatal period. This understanding of the architectural design factors and building spaces could help architects, healthcare designers and hospital care providers in applying and promoting restorativeness in large, tertiary hospitals to better help in providing quality postnatal care for women whose hospital stays are crucial to their wellbeing and health prior to going home with their new baby.</p>

Towards restorative spaces for postnatal recovery in urban tertiary hospitals

<p>Modern living and globalisation are increasingly contributing to access to and utilisation of modern healthcare services in both developed and developing countries; from diagnosis, treatments, and even to birth in a specialised healthcare environment. In many resource-rich countries, birth is one of the main reasons for women’s hospitalisation. Research suggests that physical environments of healthcare impact on patient/users’ health outcomes. Yet decisions about healthcare facilities’ design and programming are often made without input from users. A key challenge for patient-centred care in the maternity field is the assumption that healthcare spaces and facilities created for the general “unwell” hospital population can support the emotional, physiological and psychological needs of healthy women who give birth in hospitals. Previous research into the childbirth environment has focused on physical environments and satisfaction with the labour and birth process. But studies examining the impacts of physical environments on women’s postnatal recovery experience and wellbeing have been limited. The aim of this thesis is to determine the design factors that influence women’s recovery experiences and wellbeing with a view to proposing design guidelines for optimal postnatal environment in large, tertiary hospitals. A two phase sequential explanatory mixed methods approach was taken to the research which combined a quantitative method (online survey questionnaires) with a qualitative approach (focus group discussions – FGDs). Research was conducted with two user groups, comprising postnatal women and midwives, to examine perceptions of physical environment factors that influence women’s recovery experiences and wellbeing in New Zealand hospitals. The results of the questionnaire surveys were followed up in phase two FGDs to provide explanations and descriptions of architectural factors and design features that impacted on women’s recovery experiences and psychological wellbeing. The results were compared, synthesised and interpreted to inform the outcomes of this thesis. The research found several physical environment factors and design features which were significant and a number which were non-significant among the two user groups in all four categories investigated: perception of postnatal room features; interior environment; sensory comfort environment and social comfort environment. The research found factors related to maintenance (e.g. cleanliness), environmental design (e.g. noise/quiet in rooms, and daylighting), and interior spatial characteristics (e.g. view to nature, combined home-like and clinical features and privacy) are more important in fostering wellbeing. Strong evidence was found on how building spaces impact on postnatal recovery experience, especially regarding single-bed rooms for emotional support and psychosocial support environments such as communal spaces and outdoor environments. The original contribution of this thesis is an identification of the environments which have the potential for enhanced recovery experience of women during the postnatal period. This understanding of the architectural design factors and building spaces could help architects, healthcare designers and hospital care providers in applying and promoting restorativeness in large, tertiary hospitals to better help in providing quality postnatal care for women whose hospital stays are crucial to their wellbeing and health prior to going home with their new baby.</p>

The Interplay Between Prenatal Adversity, Offspring Dopaminergic Genes, and Early Parenting on Toddler Attentional Function

Background: Few studies have explored the complex gene-by-prenatal environment-by-early postnatal environment interactions that underlie the development of attentional competence. Here, we examined if variation in dopamine-related genes interacts with prenatal adversity to influence toddler attentional competence and whether this influence is buffered by early positive maternal behavior.Methods: From the Maternal Adversity, Vulnerability and Neurodevelopment cohort, 134 participants (197 when imputing missing data) had information on prenatal adversity (prenatal stressful life events, prenatal maternal depressive symptoms, and birth weight), five dopamine-related genes (DAT1, DRD4, DRD2, COMT, BDNF), observed maternal parenting behavior at 6 months and parent-rated toddler attentional competence at 18 and 24 months. The Latent Environmental and Genetic Interaction (LEGIT) approach was used to examine genes-by-prenatal environment-by-postnatal environment interactions while controlling for sociodemographic factors and postnatal depression.Results: Our hypothesis of a three-way interaction between prenatal adversity, dopamine-related genes, and early maternal parenting behavior was not confirmed. However, consistent two-way interactions emerged between prenatal adversity and dopamine-related genes; prenatal adversity and maternal parenting behavior, and dopamine-related genes and maternal parenting behavior in relation to toddler attentional competence. Significant interaction effects were driven by the DAT1, COMT, and BDNF genotypes; prenatal stressful life events; maternal sensitivity, tactile stimulation, vocalization, and infant-related activities.Conclusions: Multiple dopamine-related genes affected toddler attentional competence and they did so in interaction with prenatal adversity and the early rearing environment, separately. Effects were already visible in young children. Several aspects of early maternal parenting have been identified as potential targets for intervention.

High Choline During Pregnancy Reduces Characteristics of the Metabolic Syndrome in Male Wistar Rat Offspring Fed a High Fat Post-Weaning Diet

Objectives The prenatal period is a critical time for fetal development, programming the offspring's later-life health in response to the postnatal environment. We have shown that a high maternal choline diet programs long-term energy regulation leading to higher food intake and weight-gain in mature rat offspring fed a normal fat diet. However, the offspring's response to an obesogenic post-weaning diet has not been described. We aim to elucidate the interaction between the choline content of the gestational diet (GD) and fat content of the post-weaning diet (PWD) on male Wistar rat offspring's long-term metabolic phenotype. Methods Pregnant Wistar rats were fed an AIN-93G diet with either recommended choline (RC, 1g/kg diet choline bitartrate) or high choline (HC, 2.5-fold). Male pups were weaned to either a normal (10%) fat (RC-NF and HC-NF) or a high (45%) fat (RC-HF and HC-HF) diet for 17 weeks. Dependent measures were body weight, food intake, visceral adiposity, plasma glucoregulatory hormones and triglycerides, and plasma and hepatic free fatty acids (FFAs). Data were analyzed with 2-way ANOVA for main effects of GD and PWD and their interaction. Measures with significant interaction effects were followed by a Student's T-test comparing groups stratified by PWD. Results HC-HF offspring had lower body weight (7%, P &lt; 0.05), and visceral adiposity (15%, P &lt; 0.05), but no difference in food intake compared to RC-HF. HC-HF offspring had lower insulin (18%, P &lt; 0.05), HOMA-IR (24%, P &lt; 0.01), and plasma triglycerides (30%, P &lt; 0.05) but no difference in leptin. Total hepatic ω-3 FFAs (30%, P &lt; 0.05) were higher and ω-6/ω-3 (P &lt; 0.01) was lower in HC-HF compared to RC-HF, indicating an ameliorated metabolic phenotype in HC-HF offspring. In contrast, HC-NF offspring had higher food intake (8%, P &lt; 0.01) and body weight (6%, P &lt; 0.05) and no difference in adiposity compared to RC-NF. They also had higher plasma leptin adjusted for adiposity (22%, P &lt; 0.05) but not insulin or HOMA-IR compared to RC-NF. Hepatic C16:1n-7/C16:0 ratio was higher in HC-NF compared to RC-NF, suggestive of dysregulated lipid metabolism. Conclusions Gestational choline supplementation is associated with improved long-term metabolic regulation in male Wistar rat offspring fed a high fat post-weaning diet. Funding Sources CIHR-Institute of Nutrition, Metabolism, and Diabetes.

Phenotypic diversity and sensitivity to injury of the pulmonary endothelium during a period of rapid postnatal growth

BackgroundEndothelial cells (EC) sit at the forefront of dramatic physiologic changes occurring in the pulmonary circulation during late embryonic and early postnatal life. First, as the lung moves from the hypoxic fetal environment to oxygen-rich postnatal environment, marked changes in pulmonary EC structure and function facilitate a marked increase in blood flow from the placenta to the lungs. Subsequently, pulmonary angiogenesis expands the microvasculature to drive exponential distal lung growth during early postnatal life. Yet, how these marked physiologic changes alter distinct EC subtypes to facilitate the transition of the pulmonary circulation and regulate vascular growth and remodeling remains incompletely understood.MethodsIn this report, we employed single cell RNA-transcriptomics and in situ RNA imaging to profile pulmonary EC in the developing mouse lung from just before birth through this period of rapid postnatal growth.ResultsMultiple, transcriptionally distinct macro- and microvascular EC were identified in the late embryonic and early postnatal lung, with gene expression profiles distinct from their adult EC counterparts. A novel arterial subtype, unique to the developing lung localized to the distal parenchyma and expressed genes that regulate vascular growth and patterning. Birth particularly heightened microvascular diversity, inducing dramatic shifts in the transcriptome of distinct microvascular subtypes in pathways related to proliferation, migration and antigen presentation. Two distinct waves of EC proliferation were identified, including one just prior to birth, and a second during early alveolarization, a time of exponential pulmonary angiogenesis. Chronic hyperoxia, an injury that impairs parenchymal and vascular growth, induced a common gene signature among all pulmonary EC, unique alterations to distinct microvascular EC subtypes, and disrupted EC-EC and EC-immune cell cross talk.ConclusionsTaken together, these data reveal tremendous diversity of pulmonary EC during a critical window of postnatal vascular growth, and provide a detailed molecular map that can be used to inform both normal vascular development and alterations in EC diversity upon injury. These data have important implications for lung diseases marked by dysregulated angiogenesis and pathologic pulmonary vascular remodeling.

Prenatal Immunity and Influences on Necrotizing Enterocolitis and Associated Neonatal Disorders

Prior to birth, the neonate has limited exposure to pathogens. The transition from the intra-uterine to the postnatal environment initiates a series of complex interactions between the newborn host and a variety of potential pathogens that persist over the first few weeks of life. This transition is particularly complex in the case of the premature and very low birth weight infant, who may be susceptible to many disorders as a result of an immature and underdeveloped immune system. Chief amongst these disorders is necrotizing enterocolitis (NEC), an acute inflammatory disorder that leads to necrosis of the intestine, and which can affect multiple systems and have the potential to result in long term effects if the infant is to survive. Here, we examine what is known about the interplay of the immune system with the maternal uterine environment, microbes, nutritional and other factors in the pathogenesis of neonatal pathologies such as NEC, while also taking into consideration the effects on the long-term health of affected children.

Skeletal Muscle Development in Postnatal Beef Cattle Resulting from Maternal Protein Restriction during Mid-Gestation

We aimed to investigate the effects of maternal protein restriction during mid-gestation on the skeletal muscle composition of the offspring. In the restriction treatment (RES, n = 9), cows were fed a basal diet, while in the control (CON, n = 9) group cows received the same RES diet plus the protein supplement during mid-gestation (100–200d). Samples of Longissimus dorsi muscle were collected from the offspring at 30d and 450d postnatal. Muscle fiber number was found to be decreased as a result of maternal protein restriction and persisted throughout the offspring’s life (p < 0.01). The collagen content was enhanced (p < 0.05) due to maternal protein restriction at 30d. MHC2X mRNA expression tended to be higher (p = 0.08) in RES 30d offspring, however, no difference (p > 0.05) was found among treatments at 450d. Taken together, our results suggest that maternal protein restriction during mid-gestation has major and persistent effects by reducing muscle fiber formation and may slightly increase collagen accumulation in the skeletal muscle of the offspring. Although maternal protein restriction may alter the muscle fiber metabolism by favoring the establishment of a predominant glycolytic metabolism, the postnatal environment may be a determinant factor that establishes the different proportion of muscle fiber types.

PENGARUH PERSIAPAN PRANIKAH, LINGKUNGAN PRE DAN POSTNATAL TERHADAP PERTUMBUHAN DAN PERKEMBANGAN BALITA DI KABUPATEN SOLOK

Introduction: The first five years of a child's life (toddler) is the fastest growing and developing period in the human brain, this period is a very sensitive but also critical period for the child's brain in receiving various inputs / learning / influences from the surrounding environment, and nutritional intake. It is at this time that children have the opportunity to develop aspects in themselves, both physically, cognitively and socio-emotionally. The growth of toddlers is assessed from the anthropomentri of the toddler. The indicator that researchers use refers to regulation of the minister of health No.2 of 2020 on child anthropometric standards. The purpose of the study was to analyze the relationship of prenatal preparation, prenatal environment, delivery environment, and post-Christmas with the growth and development of children in mothers who have children under five in Kanagarian Taruang-taruang Working Area Lasi River Health Center Solok in 2020. Method: This research is a type of analytical research and has been conducted in The Kanagarian Taruang-taruang Working Area of Puskesmas Lasi Solok in July - September 2020. The population of this study was mothers who had children who were 5 years old and the sample was toddlers who came to posyandu and who were in the working area of Puskesmas Lasi and met the criteria of inclusion (consecutive sampling) of 45 people. Data processing through editing, coding, data entry, cleaning, and tabulating stages. The processed data is then analyzed using univariate and bivariate (chi square). Result: Out of 45 respondents, 18 toddlers (40%) were found who have nutritional status with abnormal weight/age indicator, 11 toddlers (24.2%) with abnormal nutritional status of height/age, weight/height 16 people (35.6%) abnormal, did not do pre-marital preparation 23 people (51.1%), did not get a good antenatal environment as many as 17 people (37.8%), did not get a good delivery environment as many as 17 people (37.8%), did not get a good postnatal environment as many as 22 people (48.9%), and the development of dubious toddlers according to the age of toddlers as much as 9 people (20%). Conclusion: There was a meaningful relationship between the postnatal environment and the growth of toddlers based on weight/age indicators, whereas, pre-marital preparation variables, antenatal environment, and delivery environment have no meaningful relationship with the growth and development of the child.