Contributions of memory and brain development to the bioregulation of naps and nap transitions in early childhood.

The transition from multiple sleep bouts each day to a single overnight sleep bout (i.e., nap transition) is a universal process in human development. Naps are important during infancy and early childhood as they enhance learning through memory consolidation. However, a normal part of development is the transition out of naps. Understanding nap transitions is essential in order to maximize early learning and promote positive long-term cognitive outcomes. Here, we propose a novel hypothesis regarding the cognitive, physiological, and neural changes that accompany nap transitions. Specifically, we posit that maturation of the hippocampal-dependent memory network results in more efficient memory storage, which reduces the buildup of homeostatic sleep pressure across the cortex (as reflected by slow-wave activity), and eventually, contributes to nap transitions. This hypothesis synthesizes evidence of bioregulatory mechanisms underlying nap transitions and sheds new light on an important window of change in development. This framework can be used to evaluate multiple untested predictions from the field of sleep science and ultimately, yield science-based guidelines and policies regarding napping in childcare and early education settings.

Evaluating Accuracy in Five Commercial Sleep-Tracking Devices Compared to Research-Grade Actigraphy and Polysomnography.

The development of consumer sleep-tracking technologies has outpaced the scientific evaluation of their accuracy. In this study, five consumer sleep-tracking devices, research-grade actigraphy, and polysomnography were used simultaneously to monitor the overnight sleep of fifty-three young adults in the lab for one night. Biases and limits of agreement were assessed to determine how sleep stage estimates for each device and research-grade actigraphy differed from polysomnography-derived measures. Every device, except the Garmin Vivosmart, was able to estimate total sleep time comparably to research-grade actigraphy. All devices overestimated nights with shorter wake times and underestimated nights with longer wake times. For light sleep, absolute bias was low for the Fitbit Inspire and Fitbit Versa. The Withings Mat and Garmin Vivosmart overestimated shorter light sleep and underestimated longer light sleep. The Oura Ring underestimated light sleep of any duration. For deep sleep, bias was low for the Withings Mat and Garmin Vivosmart while other devices overestimated shorter and underestimated longer times. For REM sleep, bias was low for all devices. Taken together, these results suggest that proportional bias patterns in consumer sleep-tracking technologies are prevalent and could have important implications for their overall accuracy.

Emotional memory consolidation during sleep is associated with slow oscillation-spindle coupling strength in young and older adults.

Emotional memories are processed during sleep; however, the specific mechanisms are unclear. Understanding such mechanisms may provide critical insight into preventing and treating mood disorders. Consolidation of neutral memories is associated with the coupling of NREM sleep slow oscillations (SOs) and sleep spindles (SPs). Whether SO-SP coupling is likewise involved in emotional memory processing is unknown. Furthermore, there is an age-related emotional valence bias such that sleep consolidates and preserves reactivity to negative but not positive emotional memories in young adults and positive but not negative emotional memories in older adults. If SO-SP coupling contributes to the effect of sleep on emotional memory, then it may selectively support negative memory in young adults and positive memory in older adults. To address these questions, we examined whether emotional memory recognition and overnight change in emotional reactivity were associated with the strength of SO-SP coupling in young (n = 22) and older (n = 32) adults. In younger adults, coupling strength predicted negative but not positive emotional memory performance after sleep. In contrast, coupling strength predicted positive but not negative emotional memory performance after sleep in older adults. Coupling strength was not associated with emotional reactivity in either age group. Our findings suggest that SO-SP coupling may play a mechanistic role in sleep-dependent consolidation of emotional memories.

Extracellular vesicles as markers and mediators of pregnancy complications: gestational diabetes, pre-eclampsia, preterm birth and fetal growth restriction.

In high income countries, approximately 10% of pregnancies are complicated by pre-eclampsia (PE), preterm birth (PTB), fetal growth restriction (FGR) and/or macrosomia resulting from gestational diabetes (GDM). Despite the burden of disease this places on pregnant people and their newborns, there are still few, if any, effective ways of preventing or treating these conditions. There are also gaps in our understanding of the underlying pathophysiologies and our ability to predict which mothers will be affected. The placenta plays a crucial role in pregnancy, and alterations in placental structure and function have been implicated in all of these conditions. As extracellular vesicles (EVs) have emerged as important molecules in cell-to-cell communication in health and disease, recent research involving maternal- and placental-derived EV has demonstrated their potential as predictive and diagnostic biomarkers of obstetric disorders.  This review will consider how placental and maternal EVs have been investigated in pregnancies complicated by PE, PTB, FGR and GDM and aims to highlight areas where further research is required to enhance the management and eventual treatment of these pathologies.

Comparison of UK paediatric SARS-CoV-2 admissions across the first and second pandemic waves.

BACKGROUND: We hypothesised that the clinical characteristics of hospitalised children and young people (CYP) with SARS-CoV-2 in the UK second wave (W2) would differ from the first wave (W1) due to the alpha variant (B.1.1.7), school reopening and relaxation of shielding. METHODS: Prospective multicentre observational cohort study of patients <19 years hospitalised in the UK with SARS-CoV-2 between 17/01/20 and 31/01/21. Clinical characteristics were compared between W1 and W2 (W1 = 17/01/20-31/07/20,W2 = 01/08/20-31/01/21). RESULTS: 2044 CYP < 19 years from 187 hospitals. 427/2044 (20.6%) with asymptomatic/incidental SARS-CoV-2 were excluded from main analysis. 16.0% (248/1548) of symptomatic CYP were admitted to critical care and 0.8% (12/1504) died. 5.6% (91/1617) of symptomatic CYP had Multisystem Inflammatory Syndrome in Children (MIS-C). After excluding CYP with MIS-C, patients in W2 had lower Paediatric Early Warning Scores (PEWS, composite vital sign score), lower antibiotic use and less respiratory and cardiovascular support than W1. The proportion of CYP admitted to critical care was unchanged. 58.0% (938/1617) of symptomatic CYP had no reported comorbidity. Patients without co-morbidities were younger (42.4%, 398/938, <1 year), had lower PEWS, shorter length of stay and less respiratory support. CONCLUSIONS: We found no evidence of increased disease severity in W2 vs W1. A large proportion of hospitalised CYP had no comorbidity. IMPACT: No evidence of increased severity of COVID-19 admissions amongst children and young people (CYP) in the second vs first wave in the UK, despite changes in variant, relaxation of shielding and return to face-to-face schooling. CYP with no comorbidities made up a significant proportion of those admitted. However, they had shorter length of stays and lower treatment requirements than CYP with comorbidities once those with MIS-C were excluded. At least 20% of CYP admitted in this cohort had asymptomatic/incidental SARS-CoV-2 infection. This paper was presented to SAGE to inform CYP vaccination policy in the UK.

Early childhood naps initiate emotional memory processing in preparation for enhanced overnight consolidation.

Early childhood naps support emotional memory, but benefits are only observed after overnight sleep. Whether emotional memory consolidation occurs during naps, or whether napping only prepares memories for overnight consolidation is unknown. We investigated whether naps protect emotional memories from interference, indicating consolidation. Between 2018 and 2020, 63 children in western Massachusetts preschools (30 female, 33 male; 33-67 months; 23.8% Hispanic, 87.3% White) learned faces paired with negative or neutral descriptions, followed by nap or wake. Before delayed recognition, half completed an interference task. Without interference, napping benefited recognition. With interference, children recognized fewer negative faces post-nap (compared to wake), with overnight sleep attenuating this difference. Results suggest that naps initially destabilize emotional memories, possibly reflecting partial processing that promotes long-term consolidation.

Impact of an outdoor loose parts play intervention on Nova Scotian preschoolers' physical literacy: a mixed-methods randomized controlled trial.

BACKGROUND: Physical activity participation among preschoolers in childcare settings are low, and interventions to increase physical activity levels have produced mixed results. The Physical Literacy in the Early Years (PLEY) project implemented a six-month childcare-based outdoor loose parts play intervention in childcare centres in Nova Scotia, Canada. The purpose of this study was to examine the impact of the PLEY project on the development of domains of physical literacy (physical activity, physical competence, confidence and motivation, knowledge and understanding) in preschoolers attending childcare centres using mixed-methods. METHODS: Preschoolers (3-5 years) were recruited from 19 childcare centres in Nova Scotia and centres were randomized (parallel design) to the outdoor loose parts play intervention group (n = 11) or control (n = 8) group for 6 months. Participants, early childhood educators, and assessors were not blinded to group assignment. Quantitative and qualitative measures were used to comprehensively assess the impact of the PLEY project on all domains of physical literacy. At 3- and 6-months, early childhood educators participated in focus groups to assess how the intervention supported the development of 4 physical literacy domains: physical activity, physical competence, confidence and motivation, and knowledge and understanding. Physical activity and physical competence were also assessed with accelerometry and the Test of Gross Motor Development-3, respectively. RESULTS: Two hundred and nine preschoolers participated in the study (intervention group: n = 115; control group: n = 94). Accelerometer data showed that while baseline physical activity was similar between groups, children in the intervention group had higher physical activity at 3- (F(1,187) = 8.30, p = 0.004) and 6-months (F(1,187) = 9.90, p = 0.002) post-intervention. There was no intervention effect on physical competence scores. Thematic analysis of focus group data revealed that outdoor loose parts play contributed to development in all 4 physical literacy domains, including increased movement repertoires, social development, and enjoyment of physical activity. No adverse events or side effects of the intervention were reported. CONCLUSIONS: Participation in the PLEY project was associated with increased development of various domains of physical literacy and perceived physical literacy among preschoolers, and outdoor loose parts play may be encouraged as an effective strategy to increase physical literacy in early learning settings. TRIAL REGISTRATION: Biomed Central (ISRCTN14058106), 20/10/2017.

Fear of Cancer Recurrence and Sleep in Couples Coping With Early-Stage Breast Cancer.

BACKGROUND: Fear of cancer recurrence (FCR) and sleep disturbance are common in cancer survivors. Yet, little research has examined their relationship, and even less is known about what links may exist between these variables among the intimate partners of cancer survivors. PURPOSE: This study examines the relationship between FCR and sleep disturbance in breast cancer survivors and their partners. Using daily sleep data collected at two distinct periods early in survivorship-the completion of adjuvant treatment and the first post-treatment mammogram-higher survivor and partner FCR was hypothesized to predict greater sleep disturbance. METHODS: Breast cancer survivors and intimate partners (N = 76 couples; 152 individuals) each reported sleep duration, sleep quality, sleep onset latency, and wake after sleep onset each morning of two 21-day sleep diary bursts during the first year post-diagnosis. Three validated measures formed latent FCR factors for survivors and partners, which were used to predict average daily sleep. RESULTS: Across both sleep diary bursts, survivor FCR was associated with their own reduced sleep duration, reduced sleep quality, and greater sleep onset latency. Survivor FCR was also associated with their partners' reduced sleep quality and greater sleep onset latency. Partner FCR was associated with their own reduced sleep duration, reduced sleep quality, and greater sleep onset latency. Partner FCR was also associated with survivors' reduced sleep quality. CONCLUSIONS: Findings revealed intrapersonal and interpersonal associations between FCR and sleep disturbance, addressing gaps in knowledge on FCR and an outcome with known short- and long-term implications for health and mortality.

Foetal loss after chorionic villus sampling and amniocentesis in twin pregnancies: A multicentre retrospective cohort study.

OBJECTIVE: We aimed to determine foetal losses for DCDA and MCDA twins following transabdominal CVS or amniocentesis performed <22+0  weeks. METHODS: Retrospective cohort study conducted in the UK and Belgium 01/01/00-01/06/20. Cases with unknown chorionicity, monochorionic complications or complex procedures were excluded. Uncomplicated DCDA and MCDA twins without invasive procedures were identified as controls. We reported foetal losses <24+0  weeks and losses of genetically and structurally normal foetuses. RESULTS: Outcomes were compared for DCDA foetuses; 258 after CVS with 3406 controls, 406 after amniocentesis with 3390 controls plus MCDA foetuses, 98 after CVS with 1124 controls, and 160 after amniocentesis with 1122 controls. There were more losses <24+0  weeks with both procedures in DCDA (CVS RR 5.54 95% CI 3.38-9.08, amniocentesis RR 2.36 95% CI 1.22-4.56) and MCDA twins (CVS RR 5.14 95% CI 2.51-10.54, amniocentesis RR 7.01 95% CI 3.86-12.74). Losses of normal foetuses were comparable to controls (DCDA CVS RR 0.39 95% CI 0.05-2.83, DCDA amniocentesis RR 1.16 95% CI 0.42-3.22, MCDA CVS RR 2.3 95% CI 0.71-7.56, and MCDA amniocentesis RR 1.93 95% CI 0.59-6.38). CONCLUSIONS: This study indicates increased foetal losses for DCDA and MCDA twins following CVS and amniocentesis with uncertain risk to normal foetuses.

Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology.

OBJECTIVE: Adverse event (AE) monitoring is central to assessing therapeutic safety. The lack of a comprehensive framework to define and grade maternal and fetal AEs in pregnancy trials severely limits understanding risks in pregnant women. We created AE terminology to improve safety monitoring for developing pregnancy drugs, devices and interventions. METHOD: Existing severity grading for pregnant AEs and definitions/indicators of 'severe' and 'life-threatening' conditions relevant to maternal and fetal clinical trials were identified through a literature search. An international multidisciplinary group identified and filled gaps in definitions and severity grading using Medical Dictionary for Regulatory Activities (MedDRA) terms and severity grading criteria based on Common Terminology Criteria for Adverse Event (CTCAE) generic structure. The draft criteria underwent two rounds of a modified Delphi process with international fetal therapy, obstetric, neonatal, industry experts, patients and patient representatives. RESULTS: Fetal AEs were defined as being diagnosable in utero with potential to harm the fetus, and were integrated into MedDRA. AE severity was graded independently for the pregnant woman and her fetus. Maternal (n = 12) and fetal (n = 19) AE definitions and severity grading criteria were developed and ratified by consensus. CONCLUSIONS: This Maternal and Fetal AE Terminology version 1.0 allows systematic consistent AE assessment in pregnancy trials to improve safety.

The influence of vector-borne disease on human history: socio-ecological mechanisms.

Vector-borne diseases (VBDs) are embedded within complex socio-ecological systems. While research has traditionally focused on the direct effects of VBDs on human morbidity and mortality, it is increasingly clear that their impacts are much more pervasive. VBDs are dynamically linked to feedbacks between environmental conditions, vector ecology, disease burden, and societal responses that drive transmission. As a result, VBDs have had profound influence on human history. Mechanisms include: (1) killing or debilitating large numbers of people, with demographic and population-level impacts; (2) differentially affecting populations based on prior history of disease exposure, immunity, and resistance; (3) being weaponised to promote or justify hierarchies of power, colonialism, racism, classism and sexism; (4) catalysing changes in ideas, institutions, infrastructure, technologies and social practices in efforts to control disease outbreaks; and (5) changing human relationships with the land and environment. We use historical and archaeological evidence interpreted through an ecological lens to illustrate how VBDs have shaped society and culture, focusing on case studies from four pertinent VBDs: plague, malaria, yellow fever and trypanosomiasis. By comparing across diseases, time periods and geographies, we highlight the enormous scope and variety of mechanisms by which VBDs have influenced human history.

Ageing-related changes in nap neuroscillatory activity are mediated and moderated by grey matter volume.

Ageing-related changes in grey matter result in changes in the intensity and topography of sleep neural activity. However, it is unclear whether these findings can be explained by ageing-related differences in sleep pressure or circadian influence. The current study used high-density electroencephalography to assess how grey matter volume differences between young and older adults mediate and moderate neuroscillatory activity differences during a midday nap following a motor sequencing task. Delta, theta, and sigma amplitude were reduced in older relative to young adults, especially over frontocentral scalp, leading to increases in relative delta frontality and relative sigma lateral centroposteriority. Delta reductions in older adults were mediated by grey matter loss in frontal medial cortex, primary motor cortex, thalamus, caudate, putamen, and pallidum, and were moderated by putamen grey matter volume. Theta reductions were mediated by grey matter loss in primary motor cortex, thalamus, and caudate, and were moderated by putamen and pallidum grey matter volume. Sigma changes were moderated by putamen and pallidum grey matter volume. Moderation results suggested that across frequencies, young adults with more grey matter had increased activity, whereas older adults with more grey matter had unchanged or decreased activity. These results provide a critical extension of previous findings from overnight sleep in a midday nap, indicating that they are not driven by sleep pressure or circadian confounds. Moreover, these results suggest brain regions associated with motor sequence learning contribute to sleep neural activity following a motor sequencing task.

Encoding and consolidation of motor sequence learning in young and older adults.

Sleep benefits motor memory consolidation in young adults, but this benefit is reduced in older adults. Here we sought to understand whether differences in the neural bases of encoding between young and older adults contribute to aging-related differences in sleep-dependent consolidation of an explicit variant of the serial reaction time task (SRTT). Seventeen young and 18 older adults completed two sessions (nap, wake) one week apart. In the MRI, participants learned the SRTT. Following an afternoon interval either awake or with a nap (recorded with high-density polysomnography), performance on the SRTT was reassessed in the MRI. Imaging and behavioral results from SRTT performance showed clear sleep-dependent consolidation of motor sequence learning in older adults after a daytime nap, compared to an equal interval awake. Young adults, however, showed brain activity and behavior during encoding consistent with high SRTT performance prior to the sleep interval, and did not show further sleep-dependent performance improvements. Young adults did show reduced cortical activity following sleep, suggesting potential systems-level consolidation related to automatization. Sleep physiology data showed that sigma activity topography was affected by hippocampal and cortical activation prior to the nap in both age groups, and suggested a role of theta activity in sleep-dependent automatization in young adults. These results suggest that previously observed aging-related sleep-dependent consolidation deficits may be driven by aging-related deficiencies in fast learning processes. Here we demonstrate that when sufficient encoding strength is reached with additional training, older adults demonstrate intact sleep-dependent consolidation of motor sequence learning.

Placenta-specific Slc38a2/SNAT2 knockdown causes fetal growth restriction in mice.

Fetal growth restriction (FGR) is a complication of pregnancy that reduces birth weight, markedly increases infant mortality and morbidity and is associated with later-life cardiometabolic disease. No specific treatment is available for FGR. Placentas of human FGR infants have low abundance of sodium-coupled neutral amino acid transporter 2 (Slc38a2/SNAT2), which supplies the fetus with amino acids required for growth. We determined the mechanistic role of placental Slc38a2/SNAT2 deficiency in the development of restricted fetal growth, hypothesizing that placenta-specific Slc38a2 knockdown causes FGR in mice. Using lentiviral transduction of blastocysts with a small hairpin RNA (shRNA), we achieved 59% knockdown of placental Slc38a2, without altering fetal Slc38a2 expression. Placenta-specific Slc38a2 knockdown reduced near-term fetal and placental weight, fetal viability, trophoblast plasma membrane (TPM) SNAT2 protein abundance, and both absolute and weight-specific placental uptake of the amino acid transport System A tracer, 14C-methylaminoisobutyric acid (MeAIB). We also measured human placental SLC38A2 gene expression in a well-defined term clinical cohort and found that SLC38A2 expression was decreased in late-onset, but not early-onset FGR, compared with appropriate for gestational age (AGA) control placentas. The results demonstrate that low placental Slc38a2/SNAT2 causes FGR and could be a target for clinical therapies for late-onset FGR.

The Impact of a Randomized Controlled Trial of a Lifestyle Intervention on Sleep Among Latina Postpartum Women.

BACKGROUND: Poor sleep is associated with adverse outcomes among postpartum women. Exercise may improve sleep, but this has not been well examined in the postpartum period. PURPOSE: To examine the impact of a culturally modified, individually tailored lifestyle intervention on sleep outcomes among postpartum Latina women. METHODS: Estudio PARTO was a randomized controlled trial aimed at reducing Type 2 diabetes among Latina women with abnormal glucose tolerance in pregnancy. Participants were randomized to a lifestyle (i.e., diet and exercise; n = 70) or a health and wellness control intervention (n = 78) in late pregnancy (baseline). The Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality (PSQI score), onset latency (minutes per night), duration (hours per night), efficiency (percentage of the time in bed asleep), and daytime dysfunction at baseline, 6 weeks, 6 months, and 12 months postpartum. RESULTS: Mean PSQI score (6.56 ± 3.87), sleep duration (6.84 ± 1.75 hr/night), and sleep efficiency (79.70% ± 18.10%) did not differ between the arms at baseline. Mixed-effects models indicated a greater decrease of 1.29 in PSQI score (i.e., improved sleep quality) in the lifestyle versus health and wellness arm (95% confidence interval [CI] = -2.50 to -0.08, p = .04) over follow-up. There was the suggestion of a smaller decrease in sleep duration (mean = 0.48 hr/night, 95% CI = -0.10 to 1.06, p = .10) in the lifestyle versus health and wellness arm. There were no statistically significant differences in other sleep outcomes between arms. CONCLUSIONS: Findings suggest that lifestyle interventions improve sleep quality but not sleep duration, sleep onset latency, sleep efficiency, or daytime dysfunction in postpartum Latina women and, therefore, may hold promise for improving subsequent mental and physical health in this population. CLINICAL TRIALS REGISTRATION: NCT01679210.

Slow wave sleep in naps supports episodic memories in early childhood.

Naps have been shown to benefit visuospatial learning in early childhood. This benefit has been associated with sleep spindles during the nap. However, whether young children's naps and their accompanying physiology benefit other forms of declarative learning is unknown. Using a novel storybook task, we found performance in children (N = 22, mean age = 51.23 months) was better following a nap compared to performance following an equivalent interval spent awake. Moreover, performance remained better the following day if a nap followed learning. Change in post-nap performance was positively associated with the amount of time spent in slow wave sleep during the nap. This suggests that slow wave sleep in naps may support episodic memory consolidation in early childhood. Taken in conjunction with prior work, these results suggest that multiple features of brain physiology during naps may contribute to declarative memory processing in early childhood.

Parents' Nonstandard Work and Children's Sleep: The Mediating Role of Bedtime Routines.

OBJECTIVE: The present study examined if caregivers' long work hours or shift work are related to children's sleep duration through the disruption of bedtime routines. METHOD: Work hours and schedules, bedtime routines and sleep (actigraph assessments) were examined in a sample of 250 caregivers and their preschool children. RESULTS: Results revealed that consistent bedtime routines mediated the relationship between caregiver's work and children's sleep, such that longer hours and shift work predicted fewer routines that, in turn, predicted less child sleep. CONCLUSION: These results point to the crucial role of bedtime routines as a promising point of intervention for working parents. While caregivers may not be able to change their work hours or schedules, they can create more stable and consistent bedtime routines to mitigate the negative effects of their work on children's sleep.

A rapid review of Indigenous boys' and men's sexual health in Canada.

Indigenous boys and men in Canada face adverse social and structural circumstances that affect their ability to achieve and maintain sexual health. Research about Indigenous sexual health, however, is largely limited to matters relating to women and statistics on sexually transmitted infections. A rapid review of research was conducted to determine what is currently known about Indigenous boys' and men's sexual health in Canada. Given the prevalence of research documenting quantitative disparities, the current review included qualitative research only. Thirteen included studies explored a wide range of topics relating to sexual health and an overarching intersection between social conditions and individual health outcomes was observed. The results of this review reveal significant gaps in the literature relating to the holistic sexual health of Indigenous boys and men and highlight important domains of sexual health to consider in future research. Findings suggest that sexual health programmes that promote traditional Indigenous knowledge and intergenerational relationships may be effective for promoting sexual health among Indigenous boys and men.

Circulating mRNAs are differentially expressed in pregnancies with severe placental insufficiency and at high risk of stillbirth.

BACKGROUND: Fetuses affected by placental insufficiency do not receive adequate nutrients and oxygenation, become growth restricted and acidemic, and can demise. Preterm fetal growth restriction is a severe form of placental insufficiency with a high risk of stillbirth. We set out to identify maternal circulating mRNA transcripts that are differentially expressed in preterm pregnancies complicated by very severe placental insufficiency, in utero fetal acidemia, and are at very high risk of stillbirth. METHODS: We performed a cohort study across six hospitals in Australia and New Zealand, prospectively collecting blood from 128 pregnancies complicated by preterm fetal growth restriction (delivery < 34 weeks' gestation) and 42 controls. RNA-sequencing was done on all samples to discover circulating mRNAs associated with preterm fetal growth restriction and fetal acidemia in utero. We used RT-PCR to validate the associations between five lead candidate biomarkers of placental insufficiency in an independent cohort from Europe (46 with preterm fetal growth restriction) and in a third cohort of pregnancies ending in stillbirth. RESULTS: In the Australia and New Zealand cohort, we identified five mRNAs that were highly differentially expressed among pregnancies with preterm fetal growth restriction: NR4A2, EMP1, PGM5, SKIL, and UGT2B1. Combining three yielded an area under the receiver operative curve (AUC) of 0.95. Circulating NR4A2 and RCBTB2 in the maternal blood were dysregulated in the presence of fetal acidemia in utero. We validated the association between preterm fetal growth restriction and circulating EMP1, NR4A2, and PGM5 mRNA in a cohort from Europe. Combining EMP1 and PGM5 identified fetal growth restriction with an AUC of 0.92. Several of these genes were differentially expressed in the presence of ultrasound parameters that reflect placental insufficiency. Circulating NR4A2, EMP1, and RCBTB2 mRNA were differentially regulated in another cohort destined for stillbirth, compared to ongoing pregnancies. EMP1 mRNA appeared to have the most consistent association with placental insufficiency in all cohorts. CONCLUSIONS: Measuring circulating mRNA offers potential as a test to identify pregnancies with severe placental insufficiency and at very high risk of stillbirth. Circulating mRNA EMP1 may be promising as a biomarker of severe placental insufficiency.

Sleep preserves subjective and sympathetic emotional response of memories.

Sleep consolidates episodic content of emotional memories. Whether it likewise preserves or, to the contrary, depotentiates the emotional response associated with memory content is unclear, as there is conflicting evidence. In the current study, we investigated the influence of an afternoon nap (2-hr nap opportunity) on emotional responses of memories using multiple simultaneous measures. Young adults viewed 45 negative and 45 neutral pictures before taking a nap (measured with polysomnography) or remaining awake. Following the nap or wake period, participants viewed the same pictures intermixed with novel ones and indicated whether they remembered each picture. Emotional response to each picture was measured at both time points both subjectively, with valence and arousal ratings, and objectively, with recordings of electrodermal activity, electrocardiography, and corrugator supercilii electromyography. Compared to waking, a nap led to preserved subjective valence for negative pictures and preserved/increased skin conductance response in general. On the other hand, heart rate deceleration response decreased over the nap compared to wake interval, and this result was not influenced by picture type. These data suggest that sleep consolidates aspects of both subjective and physiological emotional response associated with episodic memory content. While sympathetic response appears to be preserved over sleep, parasympathetic response may be diminished.