TOLLIP and MUC5B modulate the effect of ambient NO2 on respiratory symptoms in infancy.

BACKGROUND: Current knowledge suggests that the gene region containing MUC5B and TOLLIP plays a role in airway defence and airway inflammation, and hence respiratory disease. It is also known that exposure to air pollution increases susceptibility to respiratory disease. We aimed to study whether the effect of air pollutants on the immune response and respiratory symptoms in infants may be modified by polymorphisms in MUC5B and TOLLIP genes. METHODS: 359 healthy term infants from the prospective Basel-Bern Infant Lung Development (BILD) birth cohort were included in the study. The main outcome was the score of weekly assessed respiratory symptoms in the first year of life. Using the candidate gene approach, we selected 10 single nucleotide polymorphisms (SNPs) from the MUC5B and TOLLIP regions. Nitrogen dioxide (NO2) and particulate matter ≤10µm in aerodynamic diameter (PM10) exposure was estimated on a weekly basis. We used generalised additive mixed models adjusted for known covariates. To validate our results in vitro, cells from a lung epithelial cell line were downregulated in TOLLIP expression and exposed to diesel particulate matter (DPM) and polyinosinic-polycytidylic acid. RESULTS: Significant interaction was observed between modelled air pollution (weekly NO2 exposure) and 5 SNPs within MUC5B and TOLLIP genes regarding respiratory symptoms as outcome: E.g., infants carrying minor alleles of rs5744034, rs3793965 and rs3750920 (all TOLLIP) had an increased risk of respiratory symptoms with increasing NO2 exposure. In vitro experiments showed that cells downregulated for TOLLIP react differently to environmental pollutant exposure with DPM and viral stimulation. CONCLUSION: Our findings suggest that the effect of air pollution on respiratory symptoms in infancy may be influenced by the genotype of specific SNPs from the MUC5B and TOLLIP regions. For validation of the findings, we provided in vitro evidence for the interaction of TOLLIP with air pollution.

The Effect of Prenatal Docosahexaenoic Acid Supplementation on Offspring Fat Mass and Distribution at 24 Months Old.

Background: Excessive gestational weight gain (GWG) is related to increased offspring fat accrual, and increased fat mass (FM) is related to obesity development. Prenatal DHA supplementation has been linked to lower levels of offspring FM; however, conflicting data exist. Objectives: This study aimed to determine if there is a protective effect of prenatal DHA supplementation on offspring fat accrual and adipose tissue deposition at 24 mo in offspring born to females who gain excessive weight compared with nonexcessive weight during pregnancy. We also explored if the effect of DHA dose on FM differed by offspring sex. Methods: Infants born to females who participated in the Assessment of DHA on Reducing Early Preterm Birth randomized controlled trial (ADORE) were recruited. In ADORE, females were randomly assigned to either a high or low prenatal DHA supplement. Offspring body composition and adipose tissue distribution were measured using dual-energy x-ray absorptiometry (DXA). GWG was categorized as excessive or not excessive based on clinical guidelines. Results: For total FM, there was a significant main effect for the DHA dose (P = 0.03); however, the dose by GWG status was nonsignificant (P = 0.44). Therefore, a higher prenatal DHA dose was related to greater offspring FM (622.9 g greater) and unrelated to GWG status. When investigating a DHA dose by sex effect, a significant main effect for DHA dose (P = 0.01) was detected for central FM. However, no interaction was detected (P = 0.98), meaning that both boys and girls had greater central FM if their mother was assigned to the higher DHA dose. Conclusions: Greater prenatal DHA supplementation was associated with greater offspring FM and adipose tissue distribution at 24 mo. It will be important to understand if these effects persist into childhood.This trial was registered at clinicaltrials.gov as NCT03310983.

Causes and Risk Factors of Vitamin B12 Deficiency at the Bookends of Life, From Infancy to Old Age.

The causes and risk factors of vitamin B12 deficiency are many and varied. Importantly, they vary considerably across the lifespan, from infancy to old age. The complexity of the physiology of vitamin B12 bespeaks the myriad of possible causes of deficiency and possible disruptions of its functional integrity. These lead ultimately to the pathobiological effects witnessed in deficiency of this fascinating micronutrient. This brief overview of the multiplicity of mechanisms that can result in vitamin B12 deficiency, and the panoply of its manifestations explores the underlying reasons for the protean presentations of the disease. As the human organism progresses through the chronology and milestones of age, various susceptibility factors arise resulting from the interplay of environmental and genetic factors. Acting independently and in concert, these factors produce the common denominator of vitamin B12 deficiency. However, the rate at which such deficiency develops and the way in which it presents clinically vary widely, subject to such influences as genetic variability, end-organ susceptibility, and concomitant micronutrient status. Some examples of unusual cases of vitamin B12 deficiency are described. Much has been learned about the last of the numbered vitamins in almost a century. Much yet remains to be discovered.

Improving Parental Health Literacy in Primary Caregivers of 0- to 3-Year-Old Children Through a WeChat Official Account: Cluster Randomized Controlled Trial.

Background: Parental health literacy is important to children's health and development, especially in the first 3 years. However, few studies have explored effective intervention strategies to improve parental literacy. Objective: This study aimed to determine the effects of a WeChat official account (WOA)-based intervention on parental health literacy of primary caregivers of children aged 0-3 years. Methods: This cluster randomized controlled trial enrolled 1332 caregiver-child dyads from all 13 community health centers (CHCs) in Minhang District, Shanghai, China, between April 2020 and April 2021. Participants in intervention CHCs received purposefully designed videos via a WOA, which automatically recorded the times of watching for each participant, supplemented with reading materials from other trusted web-based sources. The contents of the videos were constructed in accordance with the comprehensive parental health literacy model of WHO (World Health Organization)/Europe (WHO/Europe). Participants in control CHCs received printed materials similar to the intervention group. All the participants were followed up for 9 months. Both groups could access routine child health services as usual during follow-up. The primary outcome was parental health literacy measured by a validated instrument, the Chinese Parental Health Literacy Questionnaire (CPHLQ) of children aged 0-3 years. Secondary outcomes included parenting behaviors and children's health outcomes. We used the generalized linear mixed model (GLMM) for data analyses and performed different subgroup analyses. The ß coefficient, risk ratio (RR), and their 95% CI were used to assess the intervention's effect. Results: After the 9-month intervention, 69.4% (518/746) of caregivers had watched at least 1 video. Participants in the intervention group had higher CPHLQ total scores (ß=2.51, 95% CI 0.12-4.91) and higher psychological scores (ß=1.63, 95% CI 0.16-3.10) than those in the control group. The intervention group also reported a higher rate of exclusive breastfeeding (EBF) at 6 months (38.9% vs 23.44%; RR 1.90, 95% CI 1.07-3.38) and a higher awareness rate of vitamin D supplementation for infants younger than 6 months (76.7% vs 70.5%; RR 1.39, 95% CI 1.06-1.82). No significant effects were detected for the physical score on the CPHLQ, breastfeeding rate, routine checkup rate, and children's health outcomes. Furthermore, despite slight subgroup differences in the intervention's effects on the total CPHLQ score and EBF rate, no interaction effect was observed between these subgroup factors and intervention factors. Conclusions: Using a WHO literacy model-based health intervention through a WOA has the potential of improving parental health literacy and EBF rates at 6 months. However, innovative strategies and evidence-based content are required to engage more participants and achieve better intervention outcomes.

Exploring the Relationship between Co-Sleeping, Maternal Mental Health and Expression of Complaints during Infancy, and Breastfeeding.

BACKGROUND: This study explores whether the implementation of co-sleeping in infants aged 6-12 months (a) is associated with maternal complaints and mothers' difficulties regarding their infant's sleep, (b) is associated with maternal mental health, (c) affects infant sleep characteristics and maternal sleep quality, and (d) is associated with breastfeeding. METHODS: This study is a cross-sectional study conducted from July to November 2021. A total of 151 new mothers of infants aged 6-12 months participated. All participants were divided into two different groups, the group of mothers who adopted the co-sleeping method from birth up to the time of the survey and the group of those who did not adopt co-sleeping at that time. The Brief Infant Sleep Questionnaire-Revised Short Form (BISQ-R SF), the Edinburgh Postnatal Depression Scale (EPDS), the State-Trait Anxiety Inventory (STAI), and a questionnaire on mothers' demographics were administered. RESULTS: Regarding the mothers' complaints, mothers who co-sleep with their children have lower sleep quality than those who do not co-sleep. In respect of the mothers' mental health, there did not seem to be a statistically significant difference in the two groups. Regarding the difficulties during the sleep process, children who sleep with their parents seem to have more difficulties compared to the others (p = 0.008). It was also shown that co-sleeping children seem to have more disturbed sleep compared to those who sleep alone (p = 0.018), and a general trend obtained of a significantly higher number of awakenings for co-sleeping children (p < 0.001). Finally, breastfeeding appeared to be more related to the children of the present sample sleeping with their parents (p < 0.001). CONCLUSIONS: This study showed that co-sleeping is associated with more difficulties in infant and maternal sleep, but no direct correlation with maternal mental health was found. In addition, it showed a positive correlation of co-sleeping with breastfeeding.

Early-emerging combinatorial thought: Human infants flexibly combine kind and quantity concepts.

Combinatorial thought, or the ability to combine a finite set of concepts into a myriad of complex ideas and knowledge structures, is the key to the productivity of the human mind and underlies communication, science, technology, and art. Despite the importance of combinatorial thought for human cognition and culture, its developmental origins remain unknown. To address this, we tested whether 12-mo-old infants (N = 60), who cannot yet speak and only understand a handful of words, can combine quantity and kind concepts activated by verbal input. We proceeded in two steps: first, we taught infants two novel labels denoting quantity (e.g., "mize" for 1 item; "padu" for 2 items, Experiment 1). Then, we assessed whether they could combine quantity and kind concepts upon hearing complex expressions comprising their labels (e.g., "padu duck", Experiments 2-3). At test, infants viewed four different sets of objects (e.g., 1 duck, 2 ducks, 1 ball, 2 balls) while being presented with the target phrase (e.g., "padu duck") naming one of them (e.g., 2 ducks). They successfully retrieved and combined on-line the labeled concepts, as evidenced by increased looking to the named sets but not to distractor sets. Our results suggest that combinatorial processes for building complex representations are available by the end of the first year of life. The infant mind seems geared to integrate concepts in novel productive ways. This ability may be a precondition for deciphering the ambient language(s) and building abstract models of experience that enable fast and flexible learning.

Spindle Cell Lesions with Oncogenic EGFR Kinase Domain Aberrations: Expanding the Spectrum of Protein Kinase-Related Mesenchymal Tumors.

EGFR aberrations are reported in a subset of myofibroblastic lesions with kinase domain duplication (EGFR-KDD) and exon 20 mutations being assigned to infantile fibrosarcomas (IFS), mesoblastic nephroma, and fibrous hamartoma of infancy (FHI), respectively. In this retrospective study, we correlated molecular findings with the histomorphology of 14 myofibroblastic lesions harboring such genetic changes identified by NGS. We additionally performed DNA methylation profiling (DNAmp) and immunohistochemistry. Lesions were from 10 males and 4 females with a mean age of 3 years (range, 0.3-14) and occurred subcutaneously in the upper limbs (n = 5), lower limbs (n = 3), back/thorax (n = 5), and the nasal cavity (n = 1). Eleven were cured by surgery, including 1 relapsed case. Two patients were lost to follow-up. One case was very recent, and the patient was biopsied. Histologically, the lesions showed a wide spectrum varying from classic FHI (n = 9) to IFS (n = 1) or lipofibromatosis-like tumors (LFT-like) (n = 2) or dermatofibrosarcoma protuberans-like (DFSP-like) (n = 1) to a predominantly myxoid spindle cell lesion (n = 1). Immunohistochemically, all neoplasms stained with CD34, whereas S100 was positive in 2/14. EGFR expression was observed in 9/10 cases. Molecularly, the IFS and 1 LFT-like harbored EGFR-KDD, whereas an exon 20 mutation was identified in all FHI, 1 LFT-like, the DFSP-like, and in predominant myxoid spindle cell lesion. By DNAmp, all but 2 cases formed a well-defined cluster, demonstrating that these lesions are also epigenetically related. In conclusion, EGFR kinase domain aberrations found in FHI, IFS, LFT-like, DFSP-like, and a spindle cell lesion with a predominant myxoid stroma of children and adolescents showed that these neoplasms with a broad morphologic spectrum belong to the group of protein kinase-related lesions with a distinct epigenetic signature. Molecular analyses, including DNAmp, help to identify and characterize this emerging category and become mandatory when targeted treatment is considered.

Role of High Flow Nasal Cannula as a Novel Therapy for Treatment of Severe Obstructive Sleep Apnea in a Child With Neuroendocrine Hyperplasia of Infancy: A Case Report and Review of Literature.

Neuroendocrine hyperplasia of infancy is a rare form of pediatric interstitial lung disease presenting with hypoxemia, tachypnea, retractions, and persistent pulmonary crackles in the first year of life. As these children frequently require supplemental oxygen therapy and demonstrate nighttime hypoxemia, there is a concern for an increased prevalence of sleep-disordered breathing in this population, including obstructive sleep apnea. As untreated sleep-disordered breathing is associated with adverse developmental outcomes for children, it is essential to promptly diagnose and treat. However, treatment of obstructive sleep apnea is often challenging in children. In this report, we describe a case of a child diagnosed with neuroendocrine hyperplasia of infancy at 12 months of age who was subsequently found to have severe obstructive sleep apnea that persisted despite adenotonsillectomy. As continuous positive airway pressure was not well tolerated, the patient was initiated on a high-flow nasal cannula at nighttime, which resulted in improvement of his sleep apnea and daytime functioning with better adherence to treatment. Our case illustrates the importance of screening for sleep-disordered breathing in patients with neuroendocrine hyperplasia of infancy, as well as the utility of a high-flow nasal cannula as a novel, effective treatment for pediatric obstructive sleep apnea.

Reconsidering the nature of threat in infancy: Integrating animal and human studies on neurobiological effects of infant stress.

Early life stress has been associated with elevated risk for later psychopathology. One mechanism that may contribute to such long-term risk is alterations in amygdala development, a brain region critical to stress responsivity. Yet effects of stress on the amygdala during human infancy, a period of particularly rapid brain development, remain largely unstudied. In order to model how early stressors may affect infant amygdala development, several discrepancies across the existing literatures on early life stress among rodents and early threat versus deprivation among older human children and adults need to be reconciled. We briefly review the key findings of each of these literatures. We then consider them in light of emerging findings from studies of human infants regarding relations among maternal caregiving, infant cortisol response, and infant amygdala volume. Finally, we advance a developmental salience model of how early threat may impact the rapidly developing infant brain, a model with the potential to integrate across these divergent literatures. Future work to assess the value of this model is also proposed.

Neonatal Physical Growth Predicts Electroencephalography Power in Rural South African Children.

Anthropometric measures at birth, indexing prenatal growth, are associated with later cognitive development. Children in low- and middle-income countries (LMIC) are at elevated risk for impaired prenatal and early postnatal growth and enduring cognitive deficits. However, the associations of neonatal physical growth with neural activity are not well-characterized in LMIC contexts, given the dearth of early childhood neuroimaging research in these settings. The current study examined birth length, weight, and head circumference as predictors of EEG relative power over the first three years of life in rural Limpopo Province, South Africa, controlling for postnatal growth and socioeconomic status (SES). A larger head circumference at birth predicted lower relative gamma power, lower right hemisphere relative beta power, and higher relative alpha and theta power. A greater birth length also predicted lower relative gamma power. There were interactions with timepoints such that the associations of birth head circumference and length with EEG power were most pronounced at the 7-month assessment and were attenuated at the 17- and 36-month assessments. The results identify birth head circumference and length as specific predictors of infant neural activity within an under-resourced context.

Infant Care: Predictors of Outdoor Walking, Infant Carrying and Infant Outdoor Sleeping.

BACKGROUND: Although spending time outdoors is beneficial for development, little is known about outdoor time during infancy. The aim of this study was to assess frequencies and durations of (1a) outdoor walking and carrying in mother-infant dyads and (1b) infant outdoor sleeping in a stationary cot or pram. We furthermore aimed to identify associations of (2a) outdoor walking and carrying and (2b) infant outdoor sleeping, with infant, maternal and environmental sample characteristics. METHODS: An online survey was distributed among mothers of 0- to 12-month-old infants. Initially, 1453 mothers were recruited, of which 1275 were included in the analyses. With respect to (1a) the outcomes of interest were: mother-infant dyads' total weekly duration of walking in minutes, frequency of walking on weekdays, as well as weekends, and the frequency of using an infant carrier during walks, as well as the daily duration of carrying in hours (indoors and outdoors together). With respect to (1b) the outcome variables were: placing the infant outdoors to sleep (yes/no), the total weekly duration of outdoor sleeping and the weekly frequency of outdoor sleeping. For aim 2, associations of the outcome variables with infant (i.e., age), maternal (i.e., working status) and environmental (i.e., house type) sample characteristics were assessed. RESULTS: Mother-infant dyads engaged in walks for a total weekly duration of 201 min, for approximately one to three walks over weekdays (Monday through Friday), as well as one to three walks on the weekend. The infant carrier was used by 22% of mothers at least half of the time during outdoor walks, and 18% reported a daily duration of infant carrying of one hour or more. Among other associations, infant and maternal enjoyment of outdoor walking correlated positively with the duration as well as the frequency of walking during weekdays and during the weekend. Furthermore, employed mothers walked for a shorter duration and less frequently on weekdays as compared to mothers on maternity leave or mothers without a paid job. The availability of nearby recreational areas correlated positively with the weekly duration and frequency of walks. The infant carrier was used more frequently during outdoor walks if more than one child lived in the household. Infant carrying during outdoor walks was also related to infant behavior at night. Roughly a third of the mothers (29%) regularly had their infant sleep outdoors for a weekly duration of four hours and a weekly frequency of approximately one to two times. Younger infants, infants of mothers with higher education and infants living in detached houses were more likely to be placed outdoors to sleep. DISCUSSION: We identified associations of infant, maternal and environmental characteristics with outdoor time spent during infancy. These results lay the foundation for future research on the effects of the outdoors on child development as well as on facilitators and barriers for caregivers.

Association of early parent-child separation with depression, social and academic performance in adolescence and early adulthood: a prospective cohort study.

OBJECTIVE: The present study aimed to investigate the long-term effects of parent-child separation during infancy and early childhood on depression, social relationships including parent-child and peer relationships, and academic performance during adolescence and early adulthood. METHODS: Data from the China Family Panel Studies (CFPS) were analyzed, which included a sample of 3829 children aged 4-15 years from 25 provinces over a period of 8 years. The study examined the association between early parent-child separation and outcomes related to depression, social and academic performance, comparing outcomes between individuals with and without early separation experiences. A series of subgroup analyses were conducted to further explore these associations. RESULTS: Parent-child separation lasting 3 months or longer was found to be associated with moderate to severe levels of depression and impaired social relationships during adolescence and early adulthood, particularly among males, adolescents, urban dwellers, and those with less educated mothers. Children who experienced parent-child separation for 3 months or longer showed a positive correlation between separation duration and depression. Short-term separations under 3 months did not show this association. The duration of separation also had a negative correlation with parent-child and peer relationships, as well as academic performance. CONCLUSION: Early parent-child separation has significant adverse effects on the mental health, social and academic performance of adolescents and early adulthood, especially among males, adolescents, urban residents, and those with lower maternal education. The severity of depression was found to be related to the duration of separation, highlighting the importance of minimizing separation to less than 3 months for children under the age of 3. These findings underscore the critical role of early parental care and the need for targeted interventions for high-risk populations.

Urinary metabolite concentrations of phthalate and plasticizers in infancy and childhood in the UNC baby connectome project.

INTRODUCTION: Existing evidence suggests that exposure to phthalates is higher among younger age groups. However, limited knowledge exists on how phthalate exposure, as well as exposure to replacement plasticizers, di(isononyl) cyclohexane-1,2-dicarboxylate (DINCH) and di-2-ethylhexyl terephthalate (DEHTP), change from infancy through early childhood. METHODS: Urine samples were collected across the first 5 years of life from typically developing infants and young children enrolled between 2017 and 2020 in the longitudinal UNC Baby Connectome Project. From 438 urine samples among 187 participants, we quantified concentrations of monobutyl phthalate (MnBP), mono-3-carboxypropyl phthalate (MCPP), monoisobutyl phthalate (MiBP), monoethyl phthalate (MEP), monobenzyl phthalate (MBzP), and metabolites of di(2-ethylhexyl) phthalate (DEHP), diisonoyl phthalate (DiNP), DINCH and DEHTP. Specific gravity (SG) adjusted metabolite and molar sum concentrations were compared across age groups. Intraclass correlation coefficients (ICCs) were calculated among 122 participants with multiple urine specimens (373 samples). RESULTS: Most phthalate metabolites showed high detection frequencies (>80% of samples). Replacement plasticizers DINCH (58-60%) and DEHTP (>97%) were also commonly found. DiNP metabolites were less frequently detected (<10%). For some metabolites, SG-adjusted concentrations were inversely associated with age, with the highest concentrations found in the first year of life. ICCs revealed low to moderate reliability in metabolite measurements (ρ = 0.10-0.48) suggesting a high degree of within-individual variation in exposure among this age group. The first 6 months (compared to remaining age groups) showed an increased ratio of carboxylated metabolites of DEHP and DEHTP, compared to other common metabolites, but no clear age trends for DINCH metabolite ratios were observed. CONCLUSION: Metabolites of phthalates and replacements plasticizers were widely detected in infancy and early childhood, with the highest concentrations observed in the first year of life for several metabolites. Higher proportions of carboxylated metabolites of DEHP and DEHTP in younger age groups indicate potential differences in metabolism during infancy.

Serum biomarkers in neuroendocrine cell hyperplasia of infancy.

BACKGROUND: Neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease of unknown origin associated with hyperplasia of pulmonary neuroendocrine cells (PNECs). Diagnosis is based on the characteristic clinical picture and typical radiological imaging, and, in some cases, on lung biopsies. To date, no biochemical indicators of the disease have been identified. AIM: We aimed to determine biomarkers that could be useful in the management of children diagnosed with NEHI. METHODS: Patients with NEHI and healthy children were enrolled. Concentrations of serum biomarkers secreted by PNECs (calcitonin gene-related peptide and gastrin-releasing peptide) and biomarkers of the destruction of alveolar capillary membrane (surfactant proteins A and D [SP-A and SP-D]; glycoprotein Krebs von den Lungen-6 [KL-6]; metalloproteinases 7 and 9 [MMP-7 and MMP-9]; tissue inhibitor of metalloprotease 1) were measured. RESULTS: Fifty-two children with NEHI and 23 healthy children were included in the study. The median age of children with NEHI was 3.9 years. There were no differences in serum levels of biomarkers secreted by PNECs between groups. KL-6 levels were significantly higher in children with NEHI than in healthy ones (median 119.6 vs. 92.1 U/mL, p = 0.003); however, concentrations of KL-6 were low in both groups. No significant differences existed between groups for the remaining biomarkers associated with the destruction of the alveolar-capillary membrane. CONCLUSIONS: Measurement of serum biomarkers released by PNECs and those associated with the destruction of the alveolar-capillary membrane does not appear to be useful in the management of children with NEHI.

Prenatal family income, but not parental education, is associated with resting brain activity in 1-month-old infants.

Childhood socioeconomic disadvantage is associated with disparities in development and health, possibly through adaptations in children's brain function. However, it is not clear how early in development such neural adaptations might emerge. This study examined whether prenatal family socioeconomic status, operationalized as family income and average years of parental education, prospectively predicts individual differences in infant resting electroencephalography (EEG; theta, alpha, beta, and gamma power) at approximately 1 month of age (N = 160). Infants of mothers reporting lower family income showed more lower-frequency (theta) and less higher-frequency (beta and gamma) power. These associations held when adjusting for other prenatal and postnatal experiences, as well as infant demographic and health-related factors. In contrast, parental education was not significantly associated with infant EEG power in any frequency band. These data suggest that lower prenatal family income is associated with developmental differences in brain function that are detectable within the first month of life.

Development of nitroalkene-based inhibitors to target STING-dependent inflammation.

Stimulator of Interferon Genes (STING) is essential for the inflammatory response to cytosolic DNA. Despite that aberrant activation of STING is linked to an increasing number of inflammatory diseases, the development of inhibitors has been challenging, with no compounds in the pipeline beyond the preclinical stage. We previously identified endogenous nitrated fatty acids as novel reversible STING inhibitors. With the aim of improving the specificity and efficacy of these compounds, we developed and tested a library of nitroalkene-based compounds for in vitro and in vivo STING inhibition. The structure-activity relationship study revealed a robustly improved electrophilicity and reduced degrees of freedom of nitroalkenes by conjugation with an aromatic moiety. The lead compounds CP-36 and CP-45, featuring a ß-nitrostyrene moiety, potently inhibited STING activity in vitro and relieved STING-dependent inflammation in vivo. This validates the potential for nitroalkene compounds as drug candidates for STING modulation to treat STING-driven inflammatory diseases, providing new robust leads for preclinical development.

Learning phonetic categories in infancy: The role of word-context information.

Identifying the type of mechanisms at the core of phonetic categorization remains a central subject of research in infant language learning. Amongst different theories, one is that infants compute distributional information of phonemes based on their surrounding sounds (i.e., word context) such that phonemes that appear in different word contexts are more likely to be discriminated and categorized separately than phonemes that appear in similar word contexts. Following the procedure of Feldman et al. (2013a), we investigated the role of contextual information in the acquisition of phonetic categories in 8-month-old infants, using a non-native vowel contrast (English /ɒ/-/ʌ/). In Experiment 1, we established lack of discrimination of the non-native contrast without prior exposure to it. In Experiment 2, we manipulated the type of exposure prior to testing: half of the infants were exposed to minimal pair carriers (words that differ by one phoneme only; e.g., lituh and litoh), and the other half of the infants were exposed to non-minimal pair carriers (words formed by different phonemes; e.g., lituh and nutoh). All infants were tested for discrimination of the contrast (tuh vs. toh) presented as alternating (e.g., tuh-toh-tuh-toh) and non-alternating trials (e.g., tuh-tuh-tuh), as in Experiment 1. Infants in both conditions looked on average longer at alternating rather than non-alternating trials, suggesting that they discriminated the /ɒ/-/ʌ/ contrast after a brief exposure to the vowels embedded into words. Crucially, discrimination occurred regardless of whether words were minimal pair carriers or non-minimal pair carriers. A cross-experiment comparison revealed that infants showed different patterns of looking times based on whether they were exposed to the contrast before testing (Experiment 2) or not (Experiment 1). Our study shows that any type of word context helps infants to re-establish discrimination of non-native contrasts once sensitivity has been lost. These findings aid to better understand how the speech input modulates learning mechanisms during the establishment of phonetic categories in the first year of postnatal life.

Newborn auditory brainstem response and sudden infant death syndrome.

Sudden infant death syndrome (SIDS)-the sudden and unexplained death of a seemingly healthy infant, <1 year old-may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post-mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing-screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near-miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non-SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.