Associations between early efficiency in language processing and language and cognitive outcomes in children born full term and preterm: similarities and differences.

Associations between children's early language processing efficiency and later verbal and non-verbal outcomes shed light on the extent to which early information processing skills support later learning across different domains of function. Examining whether the strengths of associations are similar in typically developing and at-risk populations provides an additional lens into the varying routes to learning that children may take across development. In this follow-up study, children born full-term (FT, n = 49) and preterm (PT, n = 45, ≤32 weeks gestational age, birth weight <1800 g) were assessed in the Looking While Listening (LWL) task at 18 months (corrected for degree of prematurity in PT group). This eye-tracking task assesses efficiency of real-time spoken language comprehension as accuracy and speed (RT) of processing. At 4 ½ years, children were assessed on standardized tests of receptive vocabulary, expressive language, and non-verbal IQ. Language processing efficiency was associated with both language outcomes (r2-change: 7.0-19.7%, p < 0.01), after covariates. Birth group did not moderate these effects, suggesting similar mechanisms of learning in these domains for PT and FT children. However, birth group moderated the association between speed and non-verbal IQ (r2-change: 4.5%, p < 0.05), such that an association was found in the PT but not the FT group. This finding suggests that information processing skills reflected in efficiency of real-time language processing may be recruited to support learning in a broader range of verbal and non-verbal domains in the PT compared to the FT group.

Trends in national and county-level Hispanic mortality in the United States, 2011-2020.

Hispanic populations generally experience more adverse socioeconomic conditions yet demonstrate lower mortality compared with Non-Hispanic White (NHW) populations in the US. This finding of a mortality advantage is well-described as the "Hispanic paradox." The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately affected Hispanic populations. To quantify these effects, we evaluated US national and county-level trends in Hispanic versus NHW mortality from 2011 through 2020. We found that a previously steady Hispanic mortality advantage significantly decreased in 2020, potentially driven by COVID-19-attributable Hispanic mortality. Nearly 16% of US counties experienced a reversal of their pre-pandemic Hispanic mortality advantage such that their Hispanic mortality exceeded NHW mortality in 2020. An additional 50% experienced a decrease in a pre-pandemic Hispanic mortality advantage. Our work provides a quantitative understanding of the disproportionate burden of the pandemic on Hispanic health and the Hispanic paradox and provides a renewed impetus to tackle the factors driving these concerning disparities.

Global, distinctive, and personal changes in molecular and microbial profiles by specific fibers in humans.

Dietary fibers act through the microbiome to improve cardiovascular health and prevent metabolic disorders and cancer. To understand the health benefits of dietary fiber supplementation, we investigated two popular purified fibers, arabinoxylan (AX) and long-chain inulin (LCI), and a mixture of five fibers. We present multiomic signatures of metabolomics, lipidomics, proteomics, metagenomics, a cytokine panel, and clinical measurements on healthy and insulin-resistant participants. Each fiber is associated with fiber-dependent biochemical and microbial responses. AX consumption associates with a significant reduction in LDL and an increase in bile acids, contributing to its observed cholesterol reduction. LCI is associated with an increase in Bifidobacterium. However, at the highest LCI dose, there is increased inflammation and elevation in the liver enzyme alanine aminotransferase. This study yields insights into the effects of fiber supplementation and the mechanisms behind fiber-induced cholesterol reduction, and it shows effects of individual, purified fibers on the microbiome.

N-Terminal Pro-B-Type Natriuretic Peptide as a Biomarker for the Severity and Outcomes With COVID-19 in a Nationwide Hospitalized Cohort.

Background Currently, there is limited research on the prognostic value of NT-proBNP (N-terminal pro-B-type natriuretic peptide) as a biomarker in COVID-19. We proposed the a priori hypothesis that an elevated NT-proBNP concentration at admission is associated with increased in-hospital mortality. Methods and Results In this prospective, observational cohort study of the American Heart Association's COVID-19 Cardiovascular Disease Registry, 4675 patients hospitalized with COVID-19 were divided into normal and elevated NT-proBNP cohorts by standard age-adjusted heart failure thresholds, as well as separated by quintiles. Patients with elevated NT-proBNP (n=1344; 28.7%) were older, with more cardiovascular risk factors, and had a significantly higher rate of in-hospital mortality (37% versus 16%; P<0.001) and shorter median time to death (7 versus 9 days; P<0.001) than those with normal values. Analysis by quintile of NT-proBNP revealed a steep graded relationship with mortality (7.1%-40.2%; P<0.001). NT-proBNP was also associated with major adverse cardiac events, intensive care unit admission, intubation, shock, and cardiac arrest (P<0.001 for each). In subgroup analyses, NT-proBNP, but not prior heart failure, was associated with increased risk of in-hospital mortality. Adjusting for cardiovascular risk factors with presenting vital signs, an elevated NT-proBNP was associated with 2-fold higher adjusted odds of death (adjusted odds ratio [OR], 2.23; 95% CI, 1.80-2.76), and the log-transformed NT-proBNP with other biomarkers projected a 21% increased risk of death for each 2-fold increase (adjusted OR, 1.21; 95% CI, 1.08-1.34). Conclusions Elevated NT-proBNP levels on admission for COVID-19 are associated with an increased risk of in-hospital mortality and other complications in patients with and without heart failure.

Molecular Choreography of Acute Exercise.

Acute physical activity leads to several changes in metabolic, cardiovascular, and immune pathways. Although studies have examined selected changes in these pathways, the system-wide molecular response to an acute bout of exercise has not been fully characterized. We performed longitudinal multi-omic profiling of plasma and peripheral blood mononuclear cells including metabolome, lipidome, immunome, proteome, and transcriptome from 36 well-characterized volunteers, before and after a controlled bout of symptom-limited exercise. Time-series analysis revealed thousands of molecular changes and an orchestrated choreography of biological processes involving energy metabolism, oxidative stress, inflammation, tissue repair, and growth factor response, as well as regulatory pathways. Most of these processes were dampened and some were reversed in insulin-resistant participants. Finally, we discovered biological pathways involved in cardiopulmonary exercise response and developed prediction models revealing potential resting blood-based biomarkers of peak oxygen consumption.

Personal aging markers and ageotypes revealed by deep longitudinal profiling.

The molecular changes that occur with aging are not well understood1-4. Here, we performed longitudinal and deep multiomics profiling of 106 healthy individuals from 29 to 75 years of age and examined how different types of 'omic' measurements, including transcripts, proteins, metabolites, cytokines, microbes and clinical laboratory values, correlate with age. We identified both known and new markers that associated with age, as well as distinct molecular patterns of aging in insulin-resistant as compared to insulin-sensitive individuals. In a longitudinal setting, we identified personal aging markers whose levels changed over a short time frame of 2-3 years. Further, we defined different types of aging patterns in different individuals, termed 'ageotypes', on the basis of the types of molecular pathways that changed over time in a given individual. Ageotypes may provide a molecular assessment of personal aging, reflective of personal lifestyle and medical history, that may ultimately be useful in monitoring and intervening in the aging process.

A longitudinal big data approach for precision health.

Precision health relies on the ability to assess disease risk at an individual level, detect early preclinical conditions and initiate preventive strategies. Recent technological advances in omics and wearable monitoring enable deep molecular and physiological profiling and may provide important tools for precision health. We explored the ability of deep longitudinal profiling to make health-related discoveries, identify clinically relevant molecular pathways and affect behavior in a prospective longitudinal cohort (n = 109) enriched for risk of type 2 diabetes mellitus. The cohort underwent integrative personalized omics profiling from samples collected quarterly for up to 8 years (median, 2.8 years) using clinical measures and emerging technologies including genome, immunome, transcriptome, proteome, metabolome, microbiome and wearable monitoring. We discovered more than 67 clinically actionable health discoveries and identified multiple molecular pathways associated with metabolic, cardiovascular and oncologic pathophysiology. We developed prediction models for insulin resistance by using omics measurements, illustrating their potential to replace burdensome tests. Finally, study participation led the majority of participants to implement diet and exercise changes. Altogether, we conclude that deep longitudinal profiling can lead to actionable health discoveries and provide relevant information for precision health.

Longitudinal multi-omics of host-microbe dynamics in prediabetes.

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host-microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.

Predictors of early vocabulary growth in children born preterm and full term: A study of processing speed and medical complications.

Delays in expressive vocabulary may be harbingers of long-term language difficulties. In toddlers born full term (FT), individual differences in language processing speed are associated with variation in expressive vocabulary growth. Children born preterm (PT) are at increased risk for persistent language deficits. Here, we evaluate predictors of early vocabulary growth in PT toddlers in relation to two sources of variability: language processing speed and medical complications of prematurity. Vocabulary growth from 16 to 30 months (adjusted for degree of prematurity) was modeled longitudinally using parent reports in English-speaking FT (n = 63; ≥37 weeks, ≥2495 g) and PT (n = 69; ≤32 weeks, <1800 g) children, matched on sex and socioeconomic status. Children were tested in the "looking-while-listening task" at 18 months to derive a measure of language processing speed. Each PT child was assessed for number of medical complications (13 maximum), based on medical chart reviews. PT and FT children displayed similar vocabulary trajectories; however, birth group disparities began to emerge by 30 months. PT children were slower in language processing speed than FT children. Critically, language processing speed predicted expressive vocabulary size at 30 months; interactions with birth group were not significant (all p > .20). In PT children, faster language processing speed predicted stronger outcomes regardless of number of medical complications; slower processing speed and more medical complications predicted poorer outcomes. Faster processing speed reflected favorable neuropsychological processes associated with faster expressive vocabulary growth that overrode the impact of medical complications on language outcomes in PT children.

Speed of Language Comprehension at 18 Months Old Predicts School-Relevant Outcomes at 54 Months Old in Children Born Preterm.

OBJECTIVE: Identifying which preterm (PT) children are at increased risk of language and learning differences increases opportunities for participation in interventions that improve outcomes. Speed in spoken language comprehension at early stages of language development requires information processing skills that may form the foundation for later language and school-relevant skills. In children born full-term, speed of comprehending words in an eye-tracking task at 2 years old predicted language and nonverbal cognition at 8 years old. Here, we explore the extent to which speed of language comprehension at 1.5 years old predicts both verbal and nonverbal outcomes at 4.5 years old in children born PT. METHOD: Participants were children born PT (n = 47; ≤32 weeks gestation). Children were tested in the "looking-while-listening" task at 18 months old, adjusted for prematurity, to generate a measure of speed of language comprehension. Parent report and direct assessments of language were also administered. Children were later retested on a test battery of school-relevant skills at 4.5 years old. RESULTS: Speed of language comprehension at 18 months old predicted significant unique variance (12%-31%) in receptive vocabulary, global language abilities, and nonverbal intelligence quotient (IQ) at 4.5 years, controlling for socioeconomic status, gestational age, and medical complications of PT birth. Speed of language comprehension remained uniquely predictive (5%-12%) when also controlling for children's language skills at 18 months old. CONCLUSION: Individual differences in speed of spoken language comprehension may serve as a marker for neuropsychological processes that are critical for the development of school-relevant linguistic skills and nonverbal IQ in children born PT.

Caregiver Talk and Medical Risk as Predictors of Language Outcomes in Full Term and Preterm Toddlers.

This study examined associations between caregiver talk and language skills in full term (FT) and preterm (PT) children (n = 97). All-day recordings of caregiver-child interactions revealed striking similarities in amount of caregiver talk heard by FT and PT children. Children who heard more caregiver talk at 16 months demonstrated better knowledge- and processing-based language skills at 18 months. The unique contributions of caregiver talk were tempered by medical risk in PT children, especially for processing speed. However, there was no evidence that birth status or medical risk moderated the effects of caregiver talk. These findings highlight the role of caregiver talk in shaping language outcomes in FT and PT children and offer insights into links between neurodevelopmental risk and caregiver-child engagement.

Quality of caregiver-child play interactions with toddlers born preterm and full term: Antecedents and language outcome.

BACKGROUND: Preterm birth may leave long-term effects on the interactions between caregivers and children. Language skills are sensitive to the quality of caregiver-child interactions. AIMS: Compare the quality of caregiver-child play interactions in toddlers born preterm (PT) and full term (FT) at age 22months (corrected for degree of prematurity) and evaluate the degree of association between caregiver-child interactions, antecedent demographic and language factors, and subsequent language skill. STUDY DESIGN: A longitudinal descriptive cohort study. SUBJECTS: 39 PT and 39 FT toddlers individually matched on sex and socioeconomic status (SES). OUTCOME MEASURES: The outcome measures were dimensions of caregiver-child interactions, rated from a videotaped play session at age 22months in relation to receptive language assessments at ages 18 and 36months. RESULTS: Caregiver intrusiveness was greater in the PT than FT group. A composite score of child interactional behaviors was associated with a composite score of caregiver interactional behaviors. The caregiver composite measure was associated with later receptive vocabulary at 36months. PT-FT group membership did not moderate the association between caregiver interactional behavior and later receptive vocabulary. CONCLUSIONS: The quality of caregiver interactional behavior had similar associations with concurrent child interactional behavior and subsequent language outcome in the PT and FT groups. Greater caregiver sensitivity/responsiveness, verbal elaboration, and less intrusiveness support receptive language development in typically developing toddlers and toddlers at risk for language difficulty.