Exposure to the parents' speech is positively associated with preterm infant's face preference.

BACKGROUND: The parents' presence and involvement in neonatal care is a promising approach to improve preterm infants' neurodevelopmental outcomes. We examined whether exposure to the parents' speech is associated with the preterm infant's social-cognitive development. METHODS: The study included infants born before 32 gestational weeks in two neonatal units. Each infant's language environment was assessed from 16-hour recordings using Language Environment Analysis (LENA®). Parental presence was assessed with Closeness Diary for 14 days during the hospital stay. Attention to faces and non-face patterns was measured at the corrected age of seven months using an eye-tracking disengagement test. RESULTS: A total of 63 preterm infants were included. Infants were less likely to disengage their attention from faces (M = 0.55, SD = 0.26) than non-face patterns (M = 0.24, SD = 0.22), p < 0.001, d = 0.84. Exposure to the parents' speech during the neonatal period was positively correlated with the preference for faces over non-face patterns (rs = 0.34, p = 0.009) and with the preference for parents over unfamiliar faces (rs = 0.28, p = 0.034). CONCLUSION: The exposure to the parents' speech during neonatal hospital care is a potential early marker for later social development in preterm infants. IMPACT: The exposure to the parents' speech during neonatal intensive care is a potential early marker for optimal social-cognitive development in preterm infants. This is the first study to show an association between parental vocal contact during neonatal intensive care and early social development (i.e., face preference), measured at seven months of corrected age. Our findings suggest that we should pay attention to the parents' vocal contact with their child in the neonatal intensive care unit and identify need for tailored support for face-to-face and vocal contact.

Altering distribution profile of palbociclib by its prodrugs.

Palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, is currently used clinically for treating hormone receptor-positive and human epidermal growth factor receptor 2 negative breast cancer. Additionally, it has the potential to be utilized in the treatment of various tumors, including malignant glioblastoma. Previous research has indicated that palbociclib is a substrate for two efflux transporters, P-glycoprotein (P-gp; MDR1) and breast cancer-resistant protein (BCRP), which restrict the brain exposure of palbociclib. In the present study, our objective was to alter the brain distribution pattern of palbociclib by creating and assessing two novel prodrugs through in vitro, in situ, and in vivo evaluations. To this end, we synthesized two prodrugs of palbociclib by attaching it to the tyrosine promoiety at the para- (PD1) and meta-(PD2) position via a carbamate bond. We hypothesized that the prodrugs could bypass efflux transporter-mediated drug resistance by leveraging the l-type amino acid transporter (LAT1) to facilitate their transport across the blood-brain barrier (BBB) and into cancer cells, such as glioma cells that express LAT1. The compounds PD1 and PD2 did not show selective binding and had limited inhibitory effects on LAT1 in three cell lines (MCF-7, U87-MG, HEK-hLAT1). However, PD1 and PD2 demonstrated the ability to evade efflux mechanisms, and their in vitro uptake profiles were comparable to that of palbociclib, indicating their potential for effective cellular transport. In in situ and in vivo studies, brain uptake was not significantly improved compared to palbociclib, but the pharmacokinetic profiles showed encouraging enhancements. PD1 exhibited a higher AUCbrain/plasma ratio, suggesting safer dosing, while PD2 showed favorable long-acting pharmacokinetics. Although our prodrug design did not significantly improve palbociclib brain delivery due to the potential size limitation of the prodrugs, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.

Evaluation of a community health worker home visit intervention to improve child development in South Africa: A cluster-randomized controlled trial.

BACKGROUND: Effective integration of home visit interventions focused on early childhood development into existing service platforms is important for expanding access in low- and middle-income countries (LMICs). We designed and evaluated a home visit intervention integrated into community health worker (CHW) operations in South Africa. METHODS AND FINDINGS: We conducted a cluster-randomized controlled trial in Limpopo Province, South Africa. CHWs operating in ward-based outreach teams (WBOTs; clusters) and caregiver-child dyads they served were randomized to the intervention or control group. Group assignment was masked from all data collectors. Dyads were eligible if they resided within a participating CHW catchment area, the caregiver was at least 18 years old, and the child was born after December 15, 2017. Intervention CHWs were trained on a job aid that included content on child health, nutrition, developmental milestones, and encouragement to engage in developmentally appropriate play-based activities, for use during regular monthly home visits with caregivers of children under 2 years of age. Control CHWs provided the local standard of care. Household surveys were administered to the full study sample at baseline and endline. Data were collected on household demographics and assets; caregiver engagement; and child diet, anthropometry, and development scores. In a subsample of children, electroencephalography (EEG) and eye-tracking measures of neural function were assessed at a lab concurrent with endline and at 2 interim time points. Primary outcomes were as follows: height-for-age z-scores (HAZs) and stunting; child development scores measured using the Malawi Developmental Assessment Tool (MDAT); EEG absolute gamma and total power; relative EEG gamma power; and saccadic reaction time (SRT)-an eye-tracking measure of visual processing speed. In the main analysis, unadjusted and adjusted impacts were estimated using intention-to-treat analysis. Adjusted models included a set of demographic covariates measured at baseline. On September 1, 2017, we randomly assigned 51 clusters to intervention (26 clusters, 607 caregiver-child dyads) or control (25 clusters, 488 caregiver-child dyads). At endline (last assessment June 11, 2021), 432 dyads (71%) in 26 clusters remained in the intervention group, and 332 dyads (68%) in 25 clusters remained in the control group. In total, 316 dyads attended the first lab visit, 316 dyads the second lab visit, and 284 dyads the third lab visit. In adjusted models, the intervention had no significant impact on HAZ (adjusted mean difference (aMD) 0.11 [95% confidence interval (CI): -0.07, 0.30]; p = 0.220) or stunting (adjusted odds ratio (aOR) 0.63 [0.32, 1.25]; p = 0.184), nor did the intervention significantly impact gross motor skills (aMD 0.04 [-0.15, 0.24]; p = 0.656), fine motor skills (aMD -0.04 [-0.19, 0.11]; p = 0.610), language skills (aMD -0.02 [-0.18, 0.14]; p = 0.820), or social-emotional skills (aMD -0.02 [-0.20, 0.16]; p = 0.816). In the lab subsample, the intervention had a significant impact on SRT (aMD -7.13 [-12.69, -1.58]; p = 0.012), absolute EEG gamma power (aMD -0.14 [-0.24, -0.04]; p = 0.005), and total EEG power (aMD -0.15 [-0.23, -0.08]; p < 0.001), and no significant impact on relative gamma power (aMD 0.02 [-0.78, 0.83]; p = 0.959). While the effect on SRT was observed at the first 2 lab visits, it was no longer present at the third visit, which coincided with the overall endline assessment. At the end of the first year of the intervention period, 43% of CHWs adhered to monthly home visits. Due to the COVID-19 pandemic, we were not able to assess outcomes until 1 year after the end of the intervention period. CONCLUSIONS: While the home visit intervention did not significantly impact linear growth or skills, we found significant improvement in SRT. This study contributes to a growing literature documenting the positive effects of home visit interventions on child development in LMICs. This study also demonstrates the feasibility of collecting markers of neural function like EEG power and SRT in low-resource settings. TRIAL REGISTRATION: PACTR 201710002683810; https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=2683; South African Clinical Trials Registry, SANCTR 4407.

Eye tracking: empirical foundations for a minimal reporting guideline.

In this paper, we present a review of how the various aspects of any study using an eye tracker (such as the instrument, methodology, environment, participant, etc.) affect the quality of the recorded eye-tracking data and the obtained eye-movement and gaze measures. We take this review to represent the empirical foundation for reporting guidelines of any study involving an eye tracker. We compare this empirical foundation to five existing reporting guidelines and to a database of 207 published eye-tracking studies. We find that reporting guidelines vary substantially and do not match with actual reporting practices. We end by deriving a minimal, flexible reporting guideline based on empirical research (Section "An empirically based minimal reporting guideline").

Maternal stress and development of infant attention to threat-related facial expressions.

Attentional biases to threat-related stimuli, such as fearful and angry facial expressions, are important to survival and emerge early in development. Infants demonstrate an attentional bias to fearful facial expressions by 5-7 months of age and an attentional bias toward anger by 3 years of age that are modulated by experiential factors. In a longitudinal study of 87 mother-infant dyads from families predominantly experiencing low income, we examined whether maternal stress and depressive symptoms were associated with trajectories of attentional biases to threat, assessed during an attention disengagement eye-tracking task when infants were 6-, 9-, and 12-month old. By 9 months, infants demonstrated a generalized bias toward threat (both fearful and angry facial expressions). Maternal perceived stress was associated with the trajectory of the bias toward angry facial expressions between 6 and 12 months. Specifically, infants of mothers with higher perceived stress exhibited a greater bias toward angry facial expressions at 6 months that decreased across the next 6 months, compared to infants of mothers with lower perceived stress who displayed an increased bias to angry facial expressions over this age range. Maternal depressive symptoms and stressful life events were not associated with trajectories of infant attentional bias to anger or fear. These findings highlight the role of maternal perceptions of stress in shaping developmental trajectories of threat-alerting systems.

The stability of early developing attentional bias for faces and fear from 8 to 30 and 60 months in the FinnBrain Birth Cohort Study.

Most infants exhibit an attentional bias for faces and fearful facial expressions. These biases reduce toward the third year of life, but little is known about the development of the biases beyond early childhood. We used the same methodology longitudinally to assess attention disengagement patterns from nonface control pictures and faces (neutral, happy, and fearful expressions) in a large sample of children at 8, 30, and 60 months (N = 389/393/492, respectively; N = 72 for data in all three assessment; girls > 45.3% in each assessment). "Face bias" was measured as a difference in disengagement probability (DP) from faces (neutral/happy) versus nonface patterns. "Fear bias" was calculated as a difference in DP for fearful versus happy/neutral faces. At group level, DPs followed a nonlinear longitudinal trajectory in all face conditions, being lowest at 8 months, highest at 30 months, and intermediate at 60 months. Face bias declined between 8 and 30 months, but did not change between 30 and 60 months. Fear bias declined linearly from 8 to 60 months. Individual differences in disengagement were generally not stable across age, but weak correlations were found in face bias between 8- and 60-month, and in DPs between 30- and 60-month (rs = .22-.41). The results suggest that prioritized attention to faces-that is, a hallmark of infant cognition and a key aspect of human social behavior-follows a nonlinear trajectory in early childhood and may have only weak continuity from infancy to mid childhood. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Eye tracking based assessment of lexical processing and early lexical development in very preterm children.

BACKGROUND: Associations between lexical processing and lexical development during the second year of life have been little studied in preterm children. AIMS: To evaluate associations between lexical processing at 18 months and lexical development between 12 and 18 months in very preterm children. STUDY DESIGN: Correlational study. SUBJECTS: 25 Finnish-speaking children born <32 gestational weeks. OUTCOME MEASURES: Lexical processing (reaction time RT; correct looking time CLT) was measured with an eye tracking technology-based task at 18 months' corrected age. Lexical development was measured longitudinally at 12-, 15- and 18-months' corrected age using the following screening instruments: the short form version of the MacArthur Communicative Development Inventories and the Communication and Symbolic Behavior Scale: Infant-Toddler Checklist. RESULTS: The longer the RT of the child, the weaker expressive skills the child had at 12 and 15 months (correlations coefficient values -0.45 to -0.51). The more the child looked at the target image compared to the distractor (CLT), the stronger expressive skills the child had at 18 months (r = 0.45-0.52). A linear regression model with RT and gender as independent variables explained 33 % of the variance in lexical skills at 18 months. A model with CLT explained 40 % of expressive skills at 18 months. CONCLUSIONS: Lexical processing at 18 months was associated with expressive lexical development in very preterm children. The results suggest eye tracking technology based methods may have utility in the assessment of early lexical growth in preterm children, although further research is needed to assess psychometric properties and predictive value of the method.

Assessing infant cognition in field settings using eye-tracking: a pilot cohort trial in Sierra Leone.

OBJECTIVES: To investigate the feasibility of eye-tracking-based testing of the speed of visual orienting in malnourished young children at rural clinics in Sierra Leone. DESIGN: Prospective dual cohort study nested in a cluster-randomised trial. SETTING: 8 sites participating in a cluster-randomised trial of supplementary feeding for moderate acute malnutrition (MAM). PARTICIPANTS: For the MAM cohort, all infants aged 7-11 months at the eight sites were enrolled, 138 altogether. For controls, a convenience sample of all non-malnourished infants aged 7-11 months at the same sites were eligible, 60 altogether. A sample of 30 adults at the sites also underwent eye-tracking tests as a further control. INTERVENTIONS: Infants with MAM were provided with supplementary feeding. OUTCOME MEASURES: The primary outcomes were feasibility and reliability of eye-tracking-based testing of saccadic reaction time (SRT). Feasibility was assessed by the percent of successful tests in the infants. Reliability was measured with intraclass correlation coefficients (ICCs). Secondary outcomes were mean SRT based on nutritional state as well as and changes in mean SRT after supplementary feeding of MAM children. RESULTS: Infants exhibited consistent orienting to targets on a computer screen (>95% of valid trials). Mean SRTs had moderate stability within visits (ICCs 0.60-0.69) and across the 4-week test-retest interval (0.53) in infants; the adult control group had greater SRT stability (within visit ICC=0.92). MAM infants had a trend toward higher adjusted SRT at baseline (difference=12.4 ms, 95% CI -2 to 26.9, p=0.09) and improvement in SRT 4 weeks thereafter (difference=-14 ms, 95% CI -26.2 to -1.7, p=0.025) compared with age-matched controls. CONCLUSIONS: The results demonstrate the feasibility of eye-tracking-based testing in a resource-poor field setting and suggest eye-tracking measures have utility in the detection of group level effects of supplementary feeding.

Maternal Shared Pleasure, Infant Withdrawal, and Developmental Outcomes in a High Risk Setting in South Africa.

Background: Infants in lower middle income countries are often exposed to early adversities which may lead to suboptimal caregiving environments and place them at risk of not achieving their developmental potential. Synchrony and positive engagement in the mother-infant relationship plays a critical role in buffering the impact of early adversity. Shared Pleasure (SP) is considered a marker of high intensity positive interaction and may hold a promise of improving developmental outcomes. Methods: This study was part of a prospective observational study of mothers with and without mental illness in South Africa. Dyadic videos were assessed for SP and infant withdrawal (using the Alarm Distress Baby Scale) at 6 months. Infant developmental outcomes were assessed using the Bayley's Scales for Infant and Toddler Development, third edition at 18 months. Results: Ninety-one dyads were assessed for SP. The occurrence of SP was low (20%). There was no significant association with an EPDS measure of maternal depression (p = 0.571) and SP moments. Infant withdrawal was high (72%) and associated with male infant gender (p = 0.025). There was a significant association between the occurrence of SP and a lower score of infant withdrawal (estimate = -1.29; SE = 0.4; p = 0.0002). The number of SP moments at 6 months was significantly associated with motor (estimate = 2.4; SE = 0.9; p = 0.007) and marginally significant with cognitive scores (estimate = 1.9; SE = 1.0; p = 0.052) at 18 months. Regression modelling differential outcomes showed a greater improvement in cognitive scores at 18 months in infants with an SP moment compared to those without an SP moment [SP average difference (AD) = 7.4 (2.4), no SP AD = 10.4 (1.2); p = 0.012]. Infants without an SP moment experienced a larger decrease in motor scores at 18 months compared to those with an SP moment [SP AD = -3 (3.0); no SP AD = -10.6 (1.5), p = 0.027]. Conclusion: While the occurrence of SP in this sample was low and the rates of infant withdrawal were high, there were promising results suggesting early positive SP interactions may contribute to improvements in subsequent developmental outcomes.

Signaled night awakening and its association with social information processing and socio-emotional development across the first two years.

STUDY OBJECTIVES: Night awakening is common in infancy, and some infants continue to have signaled night awakenings throughout early childhood. However, the influence of signaled night awakening on children's social development is less explored. In the present study, longitudinal associations between signaled night awakening, social information processing, and socio-emotional development were measured within the CHILD-SLEEP birth cohort in two groups formed based on parent-reported night awakenings. METHODS: At 8 months, there were 77 infants in the waking group (≥3 awakenings) and 69 infants in the nonwaking group (≤1 awakening). At 8 and 24 months, social information processing was measured as children's attention to neutral and emotional faces, and at 24 months, parent-reported socio-emotional behavior was measured with the Brief Infant-Toddler Social and Emotional Assessment (BITSEA) questionnaire. RESULTS: The two groups showed different patterns of attention to emotional faces. The waking group had a more pronounced attentional bias to fearful versus happy faces, whereas in the nonwaking group, attention to fearful and happy faces did not differ. In addition, at 24 months, the waking group had more dysregulation problems and lower social competence than the nonwaking group, but no clear differences in internalizing or externalizing problems were found. CONCLUSIONS: Our results contribute to the literature by showing that during the first 2 years of life, signaled night awakening is associated with social information processing and socio-emotional behavior.

Converging neural and behavioral evidence for a rapid, generalized response to threat-related facial expressions in 3-year-old children.

Electrophysiological studies on adults suggest that humans are efficient at detecting threat from facial information and tend to grant these signals a priority in access to attention, awareness, and action. The developmental origins of this bias are poorly understood, partly because few studies have examined the emergence of a generalized neural and behavioral response to distinct categories of threat in early childhood. We used event-related potential (ERP) and eye-tracking measures to examine children's early visual responses and overt attentional biases towards multiple exemplars of angry and fearful vs. other (e.g., happy and neutral) faces. A large group of children was assessed longitudinally in infancy (5, 7, or 12 months) and at 3 years of age. The final ERP dataset included 148 infants and 132 3-year-old children; and the final eye-tracking dataset included 272 infants and 334 3-year-olds. We demonstrate that 1) neural and behavioral responses to facial expressions converge on an enhanced response to fearful and angry faces at 3 years of age, with no differentiation between or bias towards one or the other of these expressions, and 2) a support vector machine learning model using data on the early-stage neural responses to threat reliably predicts the duration of overt attentional dwell time for threat-related faces at 3 years. However, we found little within-subject correlation between threat-bias attention in infancy and at 3 years of age. These results provide unique evidence for the early development of a rapid, unified response to two distinct categories of facial expressions with different physical characteristics, but shared threat-related meaning.

Pupillary and Attentional Responses to Infant Facial Expressions in Mothers Across Socioeconomic Variations.

Maternal responses to infant facial expressions were examined in two socioeconomically diverse samples of South African mothers (Study I, N = 111; and Study II, N = 214; age: 17-44 years) using pupil and gaze tracking. Study I showed increased pupil response to infant distress expressions in groups recruited from private as compared to public maternity clinics, possibly reflecting underlying differences in socioeconomic status (SES) across the groups. Study II, sampling uniformly low-SES neighborhoods, found increased pupil dilation and faster orientation to expressions of infant distress, but only in the highest income group. These results are consistent with maternal physiological and attentional sensitivity to infant distress cues but challenge the universality of this sensitivity across socioeconomic diversity.

Associations between individual variations in visual attention at 9 months and behavioral competencies at 18 months in rural Malawi.

Theoretical and empirical considerations suggest that individual differences in infant visual attention correlate with variations in cognitive skills later in childhood. Here we tested this hypothesis in infants from rural Malawi (n = 198-377, depending on analysis), who were assessed with eye tracking tests of visual orienting, anticipatory looks, and attention to faces at 9 months, and more conventional tests of cognitive control (A-not-B), motor, language, and socioemotional development at 18 months. The results showed no associations between measures of infant attention at 9 months and cognitive skills at 18 months, either in analyses linking infant visual orienting with broad cognitive outcomes or analyses linking specific constructs between the two time points (i.e., switching of anticipatory looks and manual reaching responses), as correlations varied between -0.08 and 0.14. Measures of physical growth, and family socioeconomic characteristics were also not correlated with cognitive outcomes at 18 months in the current sample (correlations between -0.10 and 0.19). The results do not support the use of the current tests of infant visual attention as a predictive tool for 18-month-old infants' cognitive skills in the Malawian setting. The results are discussed in light of the potential limitations of the employed infant tests as well as potentially unique characteristics of early cognitive development in low-resource settings.

Associations Between Neonatal Cry Acoustics and Visual Attention During the First Year.

It has been suggested that early cry parameters are connected to later cognitive abilities. The present study is the first to investigate whether the acoustic features of infant cry are associated with cognitive development already during the first year, as measured by oculomotor orienting and attention disengagement. Cry sounds for acoustic analyses (fundamental frequency; F0) were recorded in two neonatal cohorts at the age of 0-8 days (Tampere, Finland) or at 6 weeks (Cape Town, South Africa). Eye tracking was used to measure oculomotor orienting to peripheral visual stimuli and attention disengagement from central stimuli at 8 months (Tampere) or at 6 months (Cape Town) of age. Only a marginal positive correlation between fundamental frequency of cry (F0) and visual attention disengagement was observed in the Tampere cohort, but not in the Cape Town cohort. This correlation indicated that infants from the Tampere cohort with a higher neonatal F0 were marginally slower to shift their gaze away from the central stimulus to the peripheral stimulus. No associations between F0 and oculomotor orienting were observed in either cohort. We discuss possible factors influencing the current pattern of results suggesting a lack of replicable associations between neonatal cry and visual attention and suggest directions for future research investigating the potential of early cry analysis in predicting later cognitive development.

Tailored Synthesis of PEGylated Bismuth Nanoparticles for X-ray Computed Tomography and Photothermal Therapy: One-Pot, Targeted Pyrolysis, and Self-Promotion.

Complex experimental design is a common problem in the preparation of theranostic nanoparticles, resulting in poor reaction control, expensive production cost, and low experiment success rate. The present study aims to develop PEGylated bismuth (PEG-Bi) nanoparticles with a precisely controlled one-pot approach, which contains only methoxy[(poly(ethylene glycol)]trimethoxy-silane (PEG-silane) and bismuth oxide (Bi2O3). A targeted pyrolysis of PEG-silane was achieved to realize its roles as both the reduction and PEGylation agents. The unwanted methoxy groups of PEG-silane were selectively pyrolyzed to form reductive agents, while the useful PEG-chain was fully preserved to enhance the biocompatibility of Bi nanoparticles. Moreover, Bi2O3 not only acted as the raw material of the Bi source but also presented a self-promotion in the production of Bi nanoparticles via catalyzing the pyrolysis of PEG-silane. The reaction mechanism was systematically validated with different methods such as nuclear magnetic resonance spectroscopy. The PEG-Bi nanoparticles showed better compatibility and photothermal conversion than those prepared by the complex multiple step approaches in literature studies. In addition, the PEG-Bi nanoparticles possessed prominent performance in X-ray computed tomography imaging and photothermal cancer therapy in vivo. The present study highlights the art of precise reaction control in the synthesis of PEGylated nanoparticles for biomedical applications.

Newborn left amygdala volume associates with attention disengagement from fearful faces at eight months.

After 5 months of age, infants begin to prioritize attention to fearful over other facial expressions. One key proposition is that amygdala and related early-maturing subcortical network, is important for emergence of this attentional bias - however, empirical data to support these assertions are lacking. In this prospective longitudinal study, we measured amygdala volumes from MR images in 65 healthy neonates at 2-5 weeks of gestation corrected age and attention disengagement from fearful vs. non-fearful facial expressions at 8 months with eye tracking. Overall, infants were less likely to disengage from fearful than happy/neutral faces, demonstrating an age-typical bias for fear. Left, but not right, amygdala volume (corrected for intracranial volume) was positively associated with the likelihood of disengaging attention from fearful faces to a salient lateral distractor (r = .302, p = .014). No association was observed with the disengagement from neutral or happy faces in equivalent conditions (r = .166 and .125, p = .186 and .320, respectively). These results are the first to link the amygdala volume with the emerging perceptual vigilance for fearful faces during infancy. They suggest a link from the prenatally defined variability in the amygdala size to early postnatal emotional and social traits.

The role of TPH2 variant rs4570625 in shaping infant attention to social signals.

TPH2, the rate-limiting enzyme in the synthesis of serotonin, has been connected to several psychiatric outcomes. Its allelic variant, rs4570625, has been found to relate to individual differences in cognitive and emotion regulation during infancy with T-carriers of rs4570625 showing a relatively heightened attention bias for fearful faces. A significant gene-environment interaction was also reported with the T-carriers of mothers with depressive symptoms showing the highest fear bias. We investigated these associations in a sample of 8-month old infants (N = 330), whose mothers were prescreened for low/high levels of prenatal depressive and/or anxiety symptoms. Attention disengagement from emotional faces (neutral, happy, fearful, and phase-scrambled control faces) to distractors was assessed with eye tracking and an overlap paradigm. Maternal depressive symptoms were assessed at several time points during pregnancy and postpartum. The mean levels of symptoms at six months postpartum and the trajectories of symptoms from early pregnancy until six months postpartum were used in the analyses (N = 274). No main effect of the rs4570625 genotype on attention disengagement was found. The difference in fear bias between the genotypes was significant but in an opposite direction compared to a previous study. The results regarding the interaction of the genotype and maternal depression were not in accordance with the previous studies. These results show inconsistencies in the effects of the rs4570625 genotype on attention biases in separate samples of infants from the same population with only slight differences in age.

Emerging Opportunities Provided by Technology to Advance Research in Child Health Globally.

Current approaches to longitudinal assessment of children's developmental and psychological well-being, as mandated in the United Nations Sustainable Development Goals, are expensive and time consuming. Substantive understanding of global progress toward these goals will require a suite of new robust, cost-effective research tools designed to assess key developmental processes in diverse settings. While first steps have been taken toward this end through efforts such as the National Institutes of Health's Toolbox, experience-near approaches including naturalistic observation have remained too costly and time consuming to scale to the population level. This perspective presents 4 emerging technologies with high potential for advancing the field of child health and development research, namely (1) affective computing, (2) ubiquitous computing, (3) eye tracking, and (4) machine learning. By drawing attention of scientists, policy makers, investors/funders, and the media to the applications and potential risks of these emerging opportunities, we hope to inspire a fresh wave of innovation and new solutions to the global challenges faced by children and their families.

Prodrug Approach for Posterior Eye Drug Delivery: Synthesis of Novel Ganciclovir Prodrugs and in Vitro Screening with Cassette Dosing.

Because of poor ocular drug bioavailability, intravitreal injections have become the gold standard for drug delivery to the posterior eye. The prodrug approach can be used for optimizing the biopharmaceutical properties of intravitreal drugs. The preclinical screening of prodrugs' properties, such as hydrolysis and bioconversion, should be conducted in a resource-efficient way for an extensive set of synthesized compounds with validated methods. Our objective was to explore cassette dosing in in vitro prodrug hydrolysis and bioconversion studies in buffer, vitreous, and retinal pigment epithelium (RPE) homogenate for rapid medium-throughput screening. Moreover, our aim was to correlate the prodrug structure with hydrolytic behavior. We synthesized 18 novel ganciclovir prodrugs and first studied their hydrolysis in aqueous buffer and porcine vitreous in vitro with cassette dosing for 35 h. A method for vitreous homogenate pH equilibration to a physiological level by using buffer and incubation under 5% carbon dioxide was validated. The hydrolysis of the prodrugs was evaluated in porcine RPE homogenate in vitro with cassette dosing, and five prodrugs were assayed individually to examine their bioconversion into ganciclovir in RPE after 2 h. Lastly, the prodrugs' binding to melanin was studied in vitro. The prodrugs showed a wide spectrum of hydrolysis rates, ranging from a few percentages to 100% in the vitreous and RPE; in general, hydrolysis in RPE was faster than in vitreous. Prodrugs with long carbon chains and disubstitution showed lability in the tissue homogenates, whereas prodrugs with branched carbon chains and aromatic groups were stable. All five prodrugs chosen for the bioconversion study in RPE were hydrolyzed into ganciclovir, and their hydrolytic behavior matched results from the cassette mix experiment, supporting the cassette mix approach for hydrolysis and bioconversion studies. None of the prodrugs bound highly to melanin (<50% bound). In conclusion, cassette dosing proved useful for the rapid screening of prodrug hydrolysis and bioconversion properties. Analyzing several compounds simultaneously can complicate the analytics, and thus, choosing the compounds of the cassette mix should be done carefully to avoid mutual interference of the compounds with the results. The methodology and results of the work are applicable in ocular drug research and prodrug design.