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.

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.

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).

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.

Immune Escape After Adoptive T-cell Therapy for Malignant Gliomas.

PURPOSE: Immunotherapy has been demonstrably effective against multiple cancers, yet tumor escape is common. It remains unclear how brain tumors escape immunotherapy and how to overcome this immune escape. EXPERIMENTAL DESIGN: We studied KR158B-luc glioma-bearing mice during treatment with adoptive cellular therapy (ACT) with polyclonal tumor-specific T cells. We tested the immunogenicity of primary and escaped tumors using T-cell restimulation assays. We used flow cytometry and RNA profiling of whole tumors to further define escape mechanisms. To treat immune-escaped tumors, we generated escape variant-specific T cells through the use of escape variant total tumor RNA and administered these cells as ACT. In addition, programmed cell death protein-1 (PD-1) checkpoint blockade was studied in combination with ACT. RESULTS: Escape mechanisms included a shift in immunogenic tumor antigens, downregulation of MHC class I, and upregulation of checkpoint molecules. Polyclonal T cells specific for escape variants displayed greater recognition of escaped tumors than primary tumors. When administered as ACT, these T cells prolonged median survival of escape variant-bearing mice by 60%. The rational combination of ACT with PD-1 blockade prolonged median survival of escape variant glioma-bearing mice by 110% and was dependent upon natural killer cells and T cells. CONCLUSIONS: These findings suggest that the immune landscape of brain tumors are markedly different postimmunotherapy yet can still be targeted with immunotherapy.

Associations between prenatal sleep and psychological health: a systematic review.

STUDY OBJECTIVES: This systematic review aimed to examine the: (1) strength of associations between prenatal sleep (ie, duration, quality, and insomnia) and psychological health (ie, depression, anxiety, and stress); and (2) moderating influence of sociodemographic characteristics (ie, maternal age, gestational age/trimester, parity, marital and socioeconomic status [SES]), body mass index (BMI), and meeting sleep recommendations. METHODS: A systematic search was conducted using PubMed, PsycINFO, Web of Science, and CINHAL to identify studies with at least one sleep measure and a psychological health outcome. Effect sizes (ES) were calculated by associations between individual components of sleep and psychological health (eg, sleep quality-depression). RESULTS: Reviewed studies (n = 32) included 14,648 participants and yielded 219 ES. ES for anxiety/stress were combined due to insufficient data to analyze individually. Average strengths of associations for sleep duration-depression (ES = .52) and sleep duration-anxiety/stress (ES = .48), sleep quality-depression (ES = .55) and sleep quality-anxiety/stress (ES = .58), and insomnia-depression (ES = .67) ranged from medium to large. Marital status, parity, BMI, and meeting sleep recommendations moderated sleep duration-depression and sleep duration-anxiety/stress. SES, gestational age/trimester, parity, and BMI moderated sleep quality-depression and sleep quality-anxiety/stress associations. CONCLUSIONS: Poor sleep quality and depression are prevalent during pregnancy and may negatively impact maternal and fetal outcomes. Moderating effects suggest that pregnant women of different BMI status and gestational age differ in their sleep habits and depression and anxiety/stress levels. Findings highlight the need to better understand the impact of these associations on maternal-fetal outcomes to inform interventions to improve sleep and psychological health.

Quantitative characterization of 3D bioprinted structural elements under cell generated forces.

With improving biofabrication technology, 3D bioprinted constructs increasingly resemble real tissues. However, the fundamental principles describing how cell-generated forces within these constructs drive deformations, mechanical instabilities, and structural failures have not been established, even for basic biofabricated building blocks. Here we investigate mechanical behaviours of 3D printed microbeams made from living cells and extracellular matrix, bioprinting these simple structural elements into a 3D culture medium made from packed microgels, creating a mechanically controlled environment that allows the beams to evolve under cell-generated forces. By varying the properties of the beams and the surrounding microgel medium, we explore the mechanical behaviours exhibited by these structures. We observe buckling, axial contraction, failure, and total static stability, and we develop mechanical models of cell-ECM microbeam mechanics. We envision these models and their generalizations to other fundamental 3D shapes to facilitate the predictable design of biofabricated structures using simple building blocks in the future.

In sync: Physiological correlates of behavioral synchrony in infants and mothers.

Infant-mother behavioral synchrony is thought to scaffold the development of self-regulation in the first years of life. During this time, infants' and mothers' physiological regulation may contribute to dyadic synchrony and, in infants, dyadic synchrony may support infants' physiological regulation. Because the sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) serve different regulatory functions, the current study aimed to elucidate relations between infants' and mothers' SNS and PNS functioning and dyadic behavioral synchrony. Skin conductance (SC; SNS index), respiratory sinus arrhythmia (RSA; PNS index), heart period (HP; index of joint SNS and PNS arousal), and behavioral synchrony were assessed in 6-month-old infants (N = 140) and their mothers during a mild social stressor, the Face-to-Face Still-Face paradigm (Tronick, Als, Adamson, Wise, & Brazelton, 1978). Synchrony was related to infants' and mothers' PNS and to mothers' broad autonomic arousal but not to SNS-specific arousal. Higher levels of behavioral synchrony were associated with lower infant RSA but with higher mother HP and RSA at baseline and in each Face-to-Face Still-Face paradigm episode. Therefore, lower RSA infants may have required more synchronous engagement with mothers to support regulation, while higher RSA, less aroused mothers may have been particularly well-attuned to infants' emotions. Findings suggest that each individual's physiological state may contribute to the behavioral functioning of the dyad. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

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.

Lin-CCR2+ hematopoietic stem and progenitor cells overcome resistance to PD-1 blockade.

Immune checkpoint blockade using anti-PD-1 monoclonal antibodies has shown considerable promise in the treatment of solid tumors, but brain tumors remain notoriously refractory to treatment. In CNS malignancies that are completely resistant to PD-1 blockade, we found that bone marrow-derived, lineage-negative hematopoietic stem and progenitor cells (HSCs) that express C-C chemokine receptor type 2 (CCR2+) reverses treatment resistance and sensitizes mice to curative immunotherapy. HSC transfer with PD-1 blockade increases T-cell frequency and activation within tumors in preclinical models of glioblastoma and medulloblastoma. CCR2+HSCs preferentially migrate to intracranial brain tumors and differentiate into antigen-presenting cells within the tumor microenvironment and cross-present tumor-derived antigens to CD8+ T cells. HSC transfer also rescues tumor resistance to adoptive cellular therapy in medulloblastoma and glioblastoma. Our studies demonstrate a novel role for CCR2+HSCs in overcoming brain tumor resistance to PD-1 checkpoint blockade and adoptive cellular therapy in multiple invasive brain tumor models.

Developmental patterns of anger from infancy to middle childhood predict problem behaviors at age 8.

Anger is a central characteristic of negative affect and is relatively stable from infancy onward. Absolute levels of anger typically peak in early childhood and diminish as children become socialized and better able to regulate emotions. From infancy to school age, however, there are also individual differences in rank-order levels of anger. For example, although decreasing in absolute levels, some children may stay the same and others may increase in rank order relative to their peers. Although change in rank order of anger over time may provide unique insight into children's social development, little is known concerning variations in developmental patterns of anger from a rank-order perspective and how these patterns are related to children's behavioral adjustment. The current study (N = 361) used group-based trajectory analysis and identified 6 distinct patterns of parent-reported child anger by rank across 9 months to 7 years: low-stable rank, average-stable rank, average-decreasing rank, average-increasing rank, high-decreasing rank, and high-stable rank. Most children (65.1%) were in low- to average-rank groups. However, 28.2% and 6.7% of the children were in average-increasing and high-stable groups, respectively. Children in the high-stable group showed elevated levels of externalizing and internalizing problems at age 8 compared to children in the average-stable, average-decreasing, and high-decreasing groups. These findings help to clarify different patterns of anger development across childhood and how they may relate to later problem behaviors. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

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.

Opportunities and challenges in screening for childhood sexual abuse.

Retrospective studies suggest 1 in 4 girls and 1 in 6 boys will experience sexual abuse before 18 years of age, resulting in future morbidity. Successful interventions exist, however, victims are reluctant to disclose. Screening for childhood sexual abuse (CSA) may provide an opportunity to overcome this barrier, yet no current model for universal CSA screening exists. We sought to understand the perspective of key stakeholders on CSA screening through qualitative research. Eight focus groups of 7-10 participants each (n=62) were conducted from April-September 2016. Stakeholders included school nurses, school teachers, counselors and administrators, pediatric providers, and parents. The interview guide focused on reporting suspected CSA and impressions of a CSA screening tool. Sessions were audiotaped and transcribed. Researchers used qualitative content analysis to develop conceptual categories that related to CSA screening and reporting. Two research team members independently open-coded 20% of the data for interrater reliability (kappa=0.98) prior to completing the coding process. Three major categories emerged to inform CSA screening. First, early screening (e.g. kindergarten) was preferred. Confidentiality was a concern, specifically privacy in the school-setting. As CSA perpetrators are often known to the child, parental presence in the medical office was also a concern. Finally, refinement of the screening process was discussed starting with routine education on safe touch and defining "normal." Rather than direct questioning, consistent and repeated offering of opportunities to disclose CSA and identification of a trusted adult were suggested. Next steps should involve partnering with evidence-based CSA prevention programs to incorporate and evaluate the aforementioned elements.

Postpartum Mothers' Leisure-Time Exercise Behavior is Linked to Positive Emotion During Partner Discussions.

PURPOSE: Marital dissatisfaction and conflict often increase for couples after the birth of a child and are evident in fewer positive family interactions and more negative family interactions. Because exercise is known to increase positive emotions and decrease negative emotions, the current study examined the extent to which higher levels of mothers' exercise during the postpartum period were related to more positive and fewer negative emotion-expressive behaviors with their infants' fathers. METHOD: Mothers' (N = 46; M = 8 months postpartum) positive and negative expressive behaviors were coded during couples' discussions of current conflict and positive family experiences. Mothers self-reported their leisure-time exercise behavior. RESULTS: First-time mothers and mothers with higher levels of leisure-time exercise behavior displayed higher levels of positive expressive behaviors during couples' discussions. CONCLUSIONS: Exercise may be associated with increased positive emotion and, in turn, can have great potential to improve family relationships during the postpartum period when marital stress normatively increases, particularly for mothers with more than 1 child. Future longitudinal studies are needed to understand exercise patterns across the postpartum period to identify the most effective timing and optimal level of exercise that lead to more positive expressive behaviors.

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.

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.

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.

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.

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.