Systematic review of the associations between prenatal sleep behaviours and components of energy balance for regulating weight gain.

This systematic review aimed to examine the magnitude and direction of the associations between prenatal sleep behaviours (i.e. nighttime sleep duration, sleep quality, night awakenings and daytime nap duration) and eating behaviours, physical activity and gestational weight gain. A systematic search was conducted using Medline/PubMed, PsychINFO, CINAHL Complete, ProQuest Dissertations and Thesis A&I, and Web of Science to identify studies with at least one sleep measure, and either eating behaviours, physical activity and/or gestational weight gain. In summary, 11 studies met the review criteria and generated 11 total effect size across 10,900 participants. The majority of the studies were conducted after 2010, which highlights the infancy of this research. Overall, the strengths of the effect size were small: sleep-gestational weight gain (effect size = 0.29), sleep-eating behaviours (effect size = 0.13) and sleep-physical activity (effect size = 0.13). The only effect size that emerged as significant was for the pooled sleep behaviours-physical activity association; good sleep behaviours were positively associated with higher levels of physical activity. These findings summarize and provide insight on how sleep behaviours are related to prenatal gestational weight gain, eating behaviours and physical activity by identifying the strength and direction of the associations that have been previously unknown. Results support the rationale for future longitudinal and randomized control trials to examine the effects of sleep behaviours on gestational weight gain, eating behaviours and physical activity over the course of pregnancy.

It Takes Two: An antenatal to postnatal RDoC framework for investigating the origins of maternal attachment and mother-infant social communication.

Transformation of the maternal-fetal relationship into the mother-infant relationship remains an enigmatic process. This progression is considered using an RDoC-informed approach centered on domains of Arousal/Regulation, Positive/Negative Valence, and Social Processes. 158 maternal-fetal dyads began participation during pregnancy, maternal-infant dyads were followed at 6-months postpartum. Women exhibited stability in feelings of attachment to the fetus and infant, and in positive/negative appraisal of pregnancy and motherhood. Elicited maternal physiological arousal to emotionally evocative videos generated fetal heart rate variability and motor activity responses. Parasympathetic (i.e., heart rate variability) suppression in the fetus was associated with more positive and regulated infant social communication in the Face-to-face Still Face protocol; suppression of maternal respiratory sinus arrhythmia was related to infant affect but in the opposite direction. Maternal ratings of infant temperament aligned with maternal antenatal affective valence. Attachment trajectories characterized by stability from antenatal to postnatal periods were most associated with maternal affective appraisal of pregnancy; shifts were influenced by infant characteristics and maternal sympathetic responsivity. Results illustrate how variation in arousal and regulatory systems of the pregnant woman and fetus operate within the context of maternal positive and negative valence systems to separately and jointly shape affiliation and temperament in early infancy.

Mothers' Physiological and Affective Responding to Infant Distress: Unique Antecedents of Avoidant and Resistant Attachments.

In a sample of 127 mother-infant dyads, this study examined the predictive significance of mothers' physiological and observed emotional responding within distressing and nondistressing caregiving contexts at 6 months for infant attachment assessed with Fraley and Spieker's (2003) dimensional approach and the categorical approach at 12 months. Findings revealed that a lesser degree of maternal respiratory sinus arrhythmia withdrawal and higher levels of maternal neutral (vs. positive) affect within distressing (vs. nondistressing) caregiving contexts were distinctive antecedents of avoidance versus resistance assessed dimensionally (but not categorically), independent of maternal sensitivity. Discussion focuses on the usefulness of examining mothers' physiological and affective responding, considering the caregiving context, and employing the dimensional approach to attachment in identifying unique antecedents of patterns of attachment insecurity.

Personalized Tumor RNA Loaded Lipid-Nanoparticles Prime the Systemic and Intratumoral Milieu for Response to Cancer Immunotherapy.

Translation of nanoparticles (NPs) into human clinical trials for patients with refractory cancers has lagged due to unknown biologic reactivities of novel NP designs. To overcome these limitations, simple well-characterized mRNA lipid-NPs have been developed as cancer immunotherapeutic vaccines. While the preponderance of RNA lipid-NPs encoding for tumor-associated antigens or neoepitopes have been designed to target lymphoid organs, they remain encumbered by the profound intratumoral and systemic immunosuppression that may stymie an activated T cell response. Herein, we show that systemic localization of untargeted tumor RNA (derived from whole transcriptome) encapsulated in lipid-NPs, with excess positive charge, primes the peripheral and intratumoral milieu for response to immunotherapy. In immunologically resistant tumor models, these RNA-NPs activate the preponderance of systemic and intratumoral myeloid cells (characterized by coexpression of PD-L1 and CD86). Addition of immune checkpoint inhibitors (ICIs) (to animals primed with RNA-NPs) augments peripheral/intratumoral PD-1+CD8+ cells and mediates synergistic antitumor efficacy in settings where ICIs alone do not confer therapeutic benefit. These synergistic effects are mediated by type I interferon released from plasmacytoid dendritic cells (pDCs). In translational studies, personalized mRNA-NPs were safe and active in a client-owned canine with a spontaneous malignant glioma. In summary, we demonstrate widespread immune activation from tumor loaded RNA-NPs concomitant with inducible PD-L1 expression that can be therapeutically exploited. While immunotherapy remains effective for only a subset of cancer patients, combination therapy with systemic immunomodulating RNA-NPs may broaden its therapeutic potency.

Vagal Regulation in Breastfeeding Infants and Their Mothers.

Consistent with the gustatory-vagal hypothesis, vagal stimulation during breastfeeding may contribute to infants' physiological regulatory development independent of caregiving effects. This study examined whether breastfeeding predicted 6-month-old infants' (N = 151) and their mothers' vagal regulation during the face-to-face still-face (FFSF). Although breastfed and nonbreastfed infants showed expected vagal withdrawal during the Still-Face episode, only breastfed infants showed continued withdrawal during the reunion episode, suggesting greater physiological mobilization to repair the interaction. Breastfeeding mothers showed higher vagal tone than nonbreastfeeding mothers at baseline, suggesting greater capacity for regulation, and throughout the FFSF, suggesting calmer states. Breastfeeding effects were independent of maternal sensitivity. Findings suggest that infants' and mothers' physiological regulation may be shaped by breastfeeding independently of associated social factors.

Dyadic flexibility mediates the relation between parent conflict and infants' vagal reactivity during the Face-to-Face Still-Face.

Parent conflict is related to attenuated infant vagal reactivity, suggesting less effective regulation. Because infants' self-regulation develops in the context of coregulation, the current study examined a novel measure, flexibility, purported to reflect dyadic reorganization in response to contextual demands. Flexibility was expected to mediate the relation between greater conflict and lesser vagal reactivity during the reunion episode of the Face-to-Face Still-Face (FFSF). Six-month-old infants' and their mothers' (N = 53) affective behaviors were observed during the FFSF and heart rate data were collected for infants. Flexibility was computed using state-space analysis of dyadic behaviors and measured variability in and movement among dyadic states. Conflict was related to lesser infant vagal reactivity in the reunion through lower flexibility, suggesting less effective recovery from social stress. Flexibility may capture aspects of coregulation affected by environmental stress and may be one mechanism by which conflict contributes to developing vagal regulation.

Physiological functioning moderates infants' sensory sensitivity in higher conflict families.

Children exposed to parent conflict may be at risk for emotional and behavioral disorders by becoming sensitized to conflict cues in their environments. This study explored possible precursors to negative child outcomes associated with parent conflict by examining the relation between parent conflict and infants' (N = 36; 23-42 weeks; 44% female) behavioral sensitivity to general sensory stimuli (e.g., loud noises, physical touch). To determine whether infants' characteristic autonomic arousal and regulation moderated this association, infant baseline skin conductance (SC) and respiratory sinus arrhythmia (RSA) were measured. Parents reported levels of parent conflict, and mothers reported infants' behavioral sensory sensitivity. The association between parent conflict and lower threshold for sensory sensitivity was strongest for infants with higher physiological arousal (higher SC) and lesser capacity for physiological regulation (lower RSA). Children may become more sensitive to environmental stimuli as a function of parent conflict during infancy, though this appears to depend on characteristic physiological arousal and regulation.

Infant respiratory sinus arrhythmia and maternal depressive symptoms predict toddler sleep problems.

This study examined the direct and interactive effects of infants' respiratory sinus arrhythmia (RSA) and maternal depressive symptoms (MDS) during the first 6 months of life in the prediction of children's sleep problems at age 18 months. Participants included 156 children and their mothers who were followed from 3 to 18 months of age. At ages 3 and 6 months, infants' cardiac activity was recorded at rest and during the still-face paradigm, a mother-child social challenge task, and estimates of infant baseline RSA (RSAB) and RSA withdrawal (RSAW) were calculated. Mothers reported about their depressive symptoms at 3, 6, and 18 months, and about infants' sleep problems at age 18 months. Less RSAW and higher levels of MDS predicted more sleep problems at age 18 months. Additionally, RSAB moderated the link between MDS and children's sleep problems such that MDS were related to more sleep problems only for infants with high levels of RSAB. Results illustrate the importance of RSA as both a direct predictor and a moderator of maternal influences in the prediction of early sleep problems.

The Interaction Between Child Respiratory Sinus Arrhythmia and Early Sensitive Parenting in the Prediction of Children's Executive Functions.

This study investigated the interaction between children's parasympathetic functioning and maternal sensitive parenting behaviors during infancy and toddlerhood in the prediction of children's executive functions (EF) at the age of 5 years. Participants included 137 children and their mothers who were followed from the age of 3 months to 5 years. Children's cardiac activity was recorded at rest at multiple times from ages 3 to 36 months, and estimates of respiratory sinus arrhythmia (RSA; a measure of parasympathetic functioning) were calculated. Sensitive parenting was assessed during a mother-child play task at ages 6, 12, 24, and 36 months, and 5 years. Children completed age appropriate EF tasks at the age of 5 years. The link between sensitive parenting during toddlerhood (ages 24 and 36 months) and children's later EF was moderated by children's RSA such that this positive link was evident only among children who had low levels of baseline RSA, and not among those who had high levels of baseline RSA. These findings were obtained while controlling for concurrent sensitive parenting and maternal and child verbal abilities. Results from this study provide evidence for the significant role of biopsychosocial processes in early childhood in the development of EF.

Angry responses to infant challenges: parent, marital, and child genetic factors associated with harsh parenting.

This study examined genetic and environmental influences on harsh parenting of adopted 9-month-olds (N = 503), with an emphasis on positive child-, parent-, and family-level characteristics. Evocative gene-environment correlation (rGE) was examined by testing the effect of both positive and negative indices of birth parent temperament on adoptive parents' harsh parenting. Adoptive fathers' harsh parenting was inversely related to birth mother positive temperament, indicating evocative rGE, as well as to marital quality. Adoptive parents' negative temperamental characteristics were related to hostile parenting for both fathers and mothers. Findings support the importance of enhancing positive family characteristics in addition to mitigating negative characteristics, as well as engaging multiple levels of the family system to prevent harsh parenting.

The Development of Early Profiles of Temperament: Characterization, Continuity, and Etiology.

This study used a data-driven, person-centered approach to examine the characterization, continuity, and etiology of child temperament from infancy to toddlerhood. Data from 561 families who participated in an ongoing prospective adoption study, the Early Growth and Development Study, were used to estimate latent profiles of temperament at 9, 18, and 27 months. Results indicated that four profiles of temperament best fit the data at all three points of assessment. The characterization of profiles was stable over time, while membership in profiles changed across age. Facets of adoptive parent and birth mother personality were predictive of children's profile membership at each age, providing preliminary evidence for specific environmental and genetic influences on patterns of temperament development from infancy to toddlerhood.

INFANT AVOIDANCE DURING A TACTILE TASK PREDICTS AUTISM SPECTRUM BEHAVIORS IN TODDLERHOOD.

The experience of touch is critical for early communication and social interaction; infants who show aversion to touch may be at risk for atypical development and behavior problems. The current study aimed to clarify predictive associations between infant responses to tactile stimuli and toddler autism spectrum, internalizing, and externalizing behaviors. This study measured 9-month-old infants' (N = 561; 58% male) avoidance and negative affect during a novel tactile task in which parents painted infants' hands and feet and pressed them to paper to make a picture. Parent reports on the Pervasive Developmental Problems (PDP), Internalizing, and Externalizing scales of the Child Behavior Checklist were used to measure toddler behaviors at 18 months. Infant observed avoidance and negative affect were significantly correlated; however, avoidance predicted subsequent PDP scores only, independent of negative affect, which did not predict any toddler behaviors. Findings suggest that incorporating measures of responses to touch in the study of early social interaction may provide an important and discriminating construct for identifying children at greater risk for social impairments related to autism spectrum behaviors.

Transactional Patterns of Maternal Depressive Symptoms and Mother-Child Mutual Negativity in an Adoption Sample.

Transactional models of analysis can examine both moment-to-moment interactions within a dyad and dyadic patterns of influence across time. This study used data from a prospective adoption study to test a transactional model of parental depressive symptoms and mutual negativity between mother and child over time, utilizing contingency analysis of second-by-second behavioral data. To consider both genetic and environmental influences on mutual negativity, depressive symptoms were examined in both adoptive and birth mothers. Adoptive mother depressive symptoms at 9 months increased the likelihood that, at 18 months, children reacted negatively to their mothers' negative behavior, which in turn predicted higher levels of adoptive mother depressive symptoms at 27 months, suggesting that over time, mothers' depressive symptoms influence and are influenced by moment-to-moment mutual negativity with their toddlers. Birth mother depressive symptoms moderated the association between mutual negativity at 18 months and adoptive mother depressive symptoms at 27 months, suggesting a child-driven contribution to maternal depressive symptoms that can be measured by a genetic sensitivity.

Parenting behaviors and vagal tone at six months predict attachment disorganization at twelve months.

The authors investigated the relationships among parenting behaviors, infant vagal tone, and subsequent attachment classification. Vagal tone was assessed among 6-month olds (n = 95) during the still-face paradigm (SFP) via respiratory sinus arrhythmia (RSA), while attachment security and disorganization were measured at 12 months during the strange situation procedure (SSP). Infants demonstrating higher levels of RSA during the normal interaction and reunion episodes of the SFP whose mothers were also rated as negative-intrusive exhibited higher levels of attachment disorganization at 12 months, while infants with lower RSA and mothers who were negative-intrusive did not exhibit higher levels of disorganization. These results suggest that high levels of RSA may not be adaptive within the context of negative-intrusive parenting.

mRNA-based precision targeting of neoantigens and tumor-associated antigens in malignant brain tumors.

BACKGROUND: Despite advancements in the successful use of immunotherapy in treating a variety of solid tumors, applications in treating brain tumors have lagged considerably. This is due, at least in part, to the lack of well-characterized antigens expressed within brain tumors that can mediate tumor rejection; the low mutational burden of these tumors that limits the abundance of targetable neoantigens; and the immunologically "cold" tumor microenvironment that hampers the generation of sustained and productive immunologic responses. The field of mRNA-based therapeutics has experienced a boon following the universal approval of COVID-19 mRNA vaccines. mRNA-based immunotherapeutics have also garnered widespread interest for their potential to revolutionize cancer treatment. In this study, we developed a novel and scalable approach for the production of personalized mRNA-based therapeutics that target multiple tumor rejection antigens in a single therapy for the treatment of refractory brain tumors. METHODS: Tumor-specific neoantigens and aberrantly overexpressed tumor-associated antigens were identified for glioblastoma and medulloblastoma tumors using our cancer immunogenomics pipeline called Open Reading Frame Antigen Network (O.R.A.N). Personalized tumor antigen-specific mRNA vaccine was developed for each individual tumor model using selective gene capture and enrichment strategy. The immunogenicity and efficacy of the personalized mRNA vaccines was evaluated in combination with anti-PD-1 immune checkpoint blockade therapy or adoptive cellular therapy with ex vivo expanded tumor antigen-specific lymphocytes in highly aggressive murine GBM models. RESULTS: Our results demonstrate the effectiveness of the antigen-specific mRNA vaccines in eliciting robust anti-tumor immune responses in GBM hosts. Our findings substantiate an increase in tumor-infiltrating lymphocytes characterized by enhanced effector function, both intratumorally and systemically, after antigen-specific mRNA-directed immunotherapy, resulting in a favorable shift in the tumor microenvironment from immunologically cold to hot. Capacity to generate personalized mRNA vaccines targeting human GBM antigens was also demonstrated. CONCLUSIONS: We have established a personalized and customizable mRNA-therapeutic approach that effectively targets a plurality of tumor antigens and demonstrated potent anti-tumor response in preclinical brain tumor models. This platform mRNA technology uniquely addresses the challenge of tumor heterogeneity and low antigen burden, two key deficiencies in targeting the classically immunotherapy-resistant CNS malignancies, and possibly other cold tumor types.

Immunotherapy reverses glioma-driven dysfunction of immune system homeostasis.

BACKGROUND: Glioma-induced immune dysregulation of the hematopoietic system has been described in a limited number of studies. In this study, our group further demonstrates that gliomas interrupt the cellular differentiation programming and outcomes of hematopoietic stem and progenitor cells (HSPCs) in the bone marrow. HSPCs from glioma-bearing mice are reprogrammed and driven towards expansion of myeloid lineage precursors and myeloid-derived suppressor cells (MDSCs) in secondary lymphoid organs. However, we found this expansion is reversed by immunotherapy. Adoptive cellular therapy (ACT) has been demonstrably efficacious in multiple preclinical models of central nervous system (CNS) malignancies, and here we describe how glioma-induced dysfunction is reversed by this immunotherapeutic platform. METHODS: The impact of orthotopic KR158B-luc glioma on HSPCs was evaluated in an unbiased fashion using single cell RNAseq (scRNAseq) of lineage- cells and phenotypically using flow cytometry. Mature myeloid cell frequencies and function were also evaluated using flow cytometry. Finally, ACT containing total body irradiation, tumor RNA-pulsed dendritic cells, tumor-reactive T cells and HSPCs isolated from glioma-bearing or non-tumor-bearing mice were used to evaluate cell fate differentiation and survival. RESULTS: Using scRNAseq, we observed an altered HSPC landscape in glioma-bearing versus non-tumor-bearing mice . In addition, an expansion of myeloid lineage subsets, including granulocyte macrophage precursors (GMPs) and MDSCs, were observed in glioma-bearing mice relative to non-tumor-bearing controls. Furthermore, MDSCs from glioma-bearing mice demonstrated increased suppressive capacity toward tumor-specific T cells as compared with MDSCs from non-tumor-bearing hosts. Interestingly, treatment with ACT overcame these suppressive properties. When HSPCs from glioma-bearing mice were transferred in the context of ACT, we observed significant survival benefit and long-term cures in orthotopic glioma models compared with mice treated with ACT using non-glioma-bearing HSPCs.

Let Me Go: The Influences of Crawling Experience and Temperament on the Development of Anger Expression.

Infants' emerging ability to move independently by crawling is associated with changes in multiple domains, including an increase in expressions of anger in situations that block infants' goals, but it is unknown whether increased anger is specifically because of experience with being able to move autonomously or simply related to age. To examine the influence of locomotion on developmental change in anger, infants' (N = 20) anger expressions during an arm restraint procedure were observed longitudinally at a precrawling baseline assessment and 2 and 6 weeks after the onset of crawling. Infant age at each crawling stage was unrelated to the frequency of anger expressed in response to arm restraint. At 6 weeks postcrawling onset, infants whose mothers rated them as temperamentally higher in distress to limitations, compared with those rated lower, showed a greater increase in the frequency of anger expressed during the arm restraint relative to earlier assessments and took longer to reduce the frequency of anger expressed when no longer restrained. Findings suggest that experience with autonomous crawling has an effect on anger expression, independent of age, and that a temperamental tendency to become distressed by limitations may exacerbate the effect of crawling on anger expression.

Maternal perinatal depression in the neonatal intensive care unit: the role of the neonatal nurse.

The onset of depressive symptoms during pregnancy or the first year postpartum, termed perinatal depression, occurs in approximately 15 percent of women. Perinatal depression can have a significant negative impact on health outcomes for the mother and her infant including maternal emotional distress and parenting difficulties and infant behavioral and developmental problems. Nurses caring for patients in the neonatal intensive care unit (NICU) are in a key position to affect positive change in the lives of families affected by perinatal depression. An overview of antepartum and postpartum depression is provided that has been tailored to the educational needs of the neonatal nurse. A discussion of the role of neonatal nurses in the identification and treatment of perinatal depression follows in order that neonatal nurses may improve both short- and long-term outcomes for mothers, infants, and families in the NICU affected by perinatal depression.

Examining Research Domain Criteria (RDoC) constructs for anger expression and regulation in toddlers.

The present study is focused on anger expression and regulation within the National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC) construct of Frustrative Nonreward. Although previous studies have examined associations between child anger regulation and expression, these studies do not directly address the dynamic processes involved in Frustrative Nonreward using microlongitudinal methods. The current study used data from 561 adopted children, their adoptive parents, and birth parents and aimed to address gaps in the literature by examining: (a) temporal associations between anger expression during a frustrating situation, and behaviors thought to regulate emotions (e.g., attempt-to-escape, support-seeking, distraction, and focus-on-restraint) on a microlongitudinal scale during an arm restraint task assessed at 27 months; (b) birth parent externalizing problems and overreactive parenting by adoptive parents as predictors of child anger expression and moderators of the moment-to-moment associations estimated in Step 1; and (c) longitudinal associations (linear vs. quadratic) between anger expressions and externalizing behaviors at 4.5 years. Findings indicated that children's attempt-to-escape and support-seeking predicted an increase in anger expression in the following 3-s interval, whereas distraction and focus-on-restraint were not associated with changes in anger expression. Furthermore, we found that birth parents' externalizing problems were significantly associated with child anger expression, suggesting heritable influences. Anger expression showed a U-shaped longitudinal association with paternal report of externalizing behaviors at 4.5 years. Taken together, the findings emphasize the significance of integrating microlongitudinal analysis approaches into the RDoC framework, helping to advance our understanding of dynamic processes underlying reactions to Frustrative Nonreward. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Parent conflict predicts infants' vagal regulation in social interaction.

Parent conflict during infancy may affect rapidly developing physiological regulation. To examine the association between parent conflict and infants' vagal tone functioning, mothers (N = 48) reported levels of parent conflict and their 6-month-old male and female infants' respiratory sinus arrhythmia (RSA) was measured in the still-face paradigm. Higher parent conflict was related to lower RSA at baseline and each episode of the still-face paradigm. Infants in relatively higher conflict families showed attenuated RSA withdrawal in response to mothers' disengagement and attenuated RSA activation when interacting with mothers. Findings suggest atypical RSA regulation and reliance on self-regulation for infants in families with moderate levels of parent conflict. Implications for later development and future research are discussed.