Publications by authors named "Daniel A Notterman"

Background: Childhood social determinants of adult cardiovascular health and potential mechanisms that link them are poorly understood. The FF-CHAYA (Future of Families-Cardiovascular Health Among Young Adults) study is designed to address these knowledge gaps.

Methods: The FF-CHAYA sample is a subcohort of the Future of Families and Child Wellbeing Study, which enrolled 4897 mother-baby dyads at delivery beginning in 1998 to 2000 and collected extensive data on neighborhood, family, school, and behavioral exposures at birth and offspring ages 1, 3, 5, 9, 15, and 22 years.

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Importance: Food insecurity is a social risk factor that may be associated with cardiovascular health across the life course.

Objective: To evaluate the association of food insecurity in early childhood with cardiovascular health (CVH) in young adulthood and whether associations are modified by participation during childhood in the Supplemental Nutrition Assistance Program (SNAP).

Design, Setting, And Participants: The Future of Families-Cardiovascular Health Among Young Adults cohort study was conducted in 20 US cities among 1071 individuals enrolled at birth (February 1998 to September 2000), evaluated in childhood (age, 3-5 years), and followed up to young adulthood (September 2021 to September 2023; mean [SD] participant age, 22.

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  • Viral lower respiratory tract infection (vLRTI) significantly impacts global child health, prompting research into the host immune responses using proteomics for better understanding and diagnosis.
  • The study analyzed 1,305 proteins from tracheal aspirate and plasma of 62 critically ill children, finding 200 differentially expressed proteins that reveal key immune responses, with a robust nine-protein TA classifier showing high diagnostic accuracy (AUC of 0.96).
  • It also highlighted the limited correlation between tracheal aspirate and plasma proteins and examined how viral load and bacterial co-infections influence immune signaling pathways.
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  • Viral lower respiratory tract infection (vLRTI) is a major cause of pediatric hospitalization and mortality globally, yet the immune responses involved are not well understood.
  • A study analyzed over 1,300 proteins in tracheal aspirate and plasma from critically ill children, identifying significant protein changes linked to vLRTI and developing a diagnostic tool with high accuracy.
  • Key findings included increased interferon and T cell responses in the lower airway, distinct protein profiles in plasma, and novel protein biomarkers that could enhance diagnostic approaches for severe vLRTI.
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Background: Sepsis-associated brain injury is associated with deterioration of mental status, persistent cognitive impairment, and morbidity. The SUR1/TRPM4 channel is a nonselective cation channel that is transcriptionally upregulated in the central nervous system with injury, allowing sodium influx, depolarization, cellular swelling, and secondary injury. We hypothesized that genetic variation in ABCC8 (SUR1 gene) and TRPM4 would associate with central nervous system dysfunction in severe pediatric sepsis.

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Telomere length (TL) serves as a biomarker of exposure to stressors, including material hardship. Data from the Future of Families and Child Wellbeing Study (1998-2015) were utilized to determine whether prior material hardship was associated with shorter salivary TL at years 9 and 15. 49% of the year 9 study population were female, 49% were Black, and 25% were Hispanic.

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Traumatic brain injury (TBI) is a major global health concern and is increasingly recognized as a risk factor for neurodegenerative diseases including Alzheimer's disease (AD) and chronic traumatic encephalopathy (CTE). Repetitive TBIs (rTBIs), commonly observed in contact sports, military service, and intimate partner violence (IPV), pose a significant risk for long-term sequelae. To study the long-term consequences of TBI and rTBI, researchers have typically used mammalian models to recapitulate brain injury and neurodegenerative phenotypes.

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Objectives: To describe family healthcare burden and health resource utilization in pediatric survivors of acute respiratory distress syndrome (ARDS) at 3 and 9 months.

Design: Secondary analysis of a prospective multisite cohort study.

Setting: Eight academic PICUs in the United States (2019-2020).

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In quantitative polymerase chain reaction (qPCR) experiments, primers containing mismatches with respect to the template are widely used in measuring repetitive DNA elements. Primer-template mismatches may lead to underestimation of the input sample quantity due to inefficient annealing and amplification. But how primer-template mismatches affect quantification accuracy has not been rigorously investigated.

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Objectives: Viral lower respiratory tract infection (vLRTI) contributes to substantial morbidity and mortality in children. Diagnosis is typically confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) of nasopharyngeal specimens in hospitalized patients; however, it is unknown whether nasopharyngeal detection accurately reflects presence of virus in the lower respiratory tract (LRT). This study evaluates agreement between viral detection from nasopharyngeal specimens by RT-PCR compared with metagenomic next-generation RNA sequencing (RNA-Seq) from tracheal aspirates (TAs).

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Importance: Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences.

Objective: To examine whether epigenetic measures of BMI developed in adults are valid biomarkers of childhood BMI and if they are sensitive to early life social determinants of health.

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Mathematical models have played a crucial role in exploring and guiding pandemic responses. University campuses present a particularly well-documented case for institutional outbreaks, thereby providing a unique opportunity to understand detailed patterns of pathogen spread. Here, we present descriptive and modeling analyses of SARS-CoV-2 transmission on the Princeton University (PU) campus-this model was used throughout the pandemic to inform policy decisions and operational guidelines for the university campus.

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Article Synopsis
  • Childhood adversity affects DNA methylation patterns, potentially changing health outcomes throughout development, particularly during sensitive periods.
  • The study looked at data from the Avon Longitudinal Study of Parents and Children, focusing on various types of childhood adversity and its impact on DNA methylation at age 15.
  • Using structured life course modeling, researchers evaluated how timing, accumulation, and recency of adversity influence adolescent DNA methylation and aimed to replicate findings with other studies.
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  • The study investigates the occurrence and contributing factors of acute disorders of consciousness (DoC) in children under 18 years old suffering from severe sepsis with organ failure, highlighting that 18% of cases exhibited signs of DoC.
  • The primary findings indicate that older children and those with multiple organ failure (MOF) are more likely to experience DoC, with increased mortality rates and associations with specific types of MOF, including nonphenotypeable and immunoparalysis-associated.
  • The research emphasizes the importance of recognizing DoC in pediatric sepsis cases as it correlates with worse outcomes and provides insight into factors that could inform clinical management.
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Article Synopsis
  • * Researchers analyzed saliva samples from 796 children at ages 9 and 15 and found 8,430 sites on autosomal chromosomes where DNA methylation levels differed by sex, with a significant 76.2% showing higher levels in females.
  • * The consistent results between ages 9 and 15 suggest that these sex-differential DNA methylation patterns are stable over time, contributing to our understanding of why some diseases show differing prevalence based on sex.
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Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences. Epigenetic mechanisms may regulate the influence of early life conditions on later life health.

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Objective: To examine the association between gestational age, telomere length (TL) and rate of shortening in newborns.

Study Design: Genomic DNA was isolated from buccal samples of 39 term infants at birth and one year and 32 preterm infants at birth, term-adjusted age (40 weeks post-conception) and age one-year corrected for gestational duration. Telomere length was measured by quantitative real-time PCR.

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Objectives: Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks.

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Prenatal maternal smoking is associated with low birthweight, neurological disorders, and asthma in exposed children. DNA methylation signatures can function as biomarkers of prenatal smoke exposure. However, the robustness of DNA methylation signatures across child ages, genetic ancestry groups, or tissues is not clear.

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Mechanical ventilators are safety-critical devices that help patients breathe, commonly found in hospital intensive care units (ICUs)-yet, the high costs and proprietary nature of commercial ventilators inhibit their use as an educational and research platform. We present a fully open ventilator device-The People's Ventilator: PVP1-with complete hardware and software documentation including detailed build instructions and a DIY cost of $1,700 USD. We validate PVP1 against both key performance criteria specified in the U.

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Background: Lower respiratory tract infections (LRTI) are a leading cause of critical illness and mortality in mechanically ventilated children; however, the pathogenic microbes frequently remain unknown. We combined traditional diagnostics with metagenomic next generation sequencing (mNGS) to evaluate the cause of LRTI in critically ill children.

Methods: We conducted a prospective, multicentre cohort study of critically ill children aged 31 days to 17 years with respiratory failure requiring mechanical ventilation (>72 h) in the USA.

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Background: Thrombotic microangiopathy-induced thrombocytopenia-associated multiple organ failure and hyperinflammatory macrophage activation syndrome are important causes of late pediatric sepsis mortality that are often missed or have delayed diagnosis. The National Institutes of General Medical Science sepsis research working group recommendations call for application of new research approaches in extant clinical data sets to improve efficiency of early trials of new sepsis therapies. Our objective is to apply machine learning approaches to derive computable 24-h sepsis phenotypes to facilitate personalized enrollment in early anti-inflammatory trials targeting these conditions.

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Objectives: To describe health-related quality of life (HRQL) and functional outcomes in pediatric acute respiratory distress syndrome (ARDS) and to determine risk factors associated with poor outcome defined as death or severe reduction in HRQL at 28 days or ICU discharge.

Design: Prospective multisite cohort-outcome study conducted between 2019 and 2020.

Setting: Eight academic PICUs in the United States.

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Objectives: Characterize the use of inhaled nitric oxide (iNO) for pediatric cardiac patients and assess the relationship between patient characteristics before iNO initiation and outcomes following cardiac surgery.

Design: Observational cohort study.

Setting: PICU and cardiac ICUs in seven Collaborative Pediatric Critical Care Research Network hospitals.

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