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DNA switches that can change conformation in response to certain wavelengths of light could enable rapid and noninvasive control of chemical processes for a wide range of applications. However, most current photoresponsive DNA switches are limited by either irreversible switching or reversible switching with impractically slow kinetics. Here, we report the design of an intramolecular triplex photoswitch (TPS) design based on single-stranded DNA that undergoes rapid and reversible photoswitching between folded and unfolded states through isomerization of internal azobenzene modifications. After optimizing the performance of our photoswitch design, we used molecular dynamics simulations to reveal how individual azobenzenes contribute to the stabilization or destabilization of the triplex depending on their photoisomerization state. By coupling our TPS to an existing aptamer, we can reversibly modulate its binding affinity with less than 15 s of UV light exposure. We further demonstrate reproducible shifting in affinity over multiple cycles of UV and blue light irradiation without substantial photobleaching.

BACKGROUND AND OBJECTIVE The Newborn Weight Tool (NEWT) can inform newborn feeding decisions and might reduce health care utilization by preventing excess weight loss. Clinical decision support (CDS) displaying NEWT might facilitate its use. Our study’s objective is to determine the effect of CDS displaying NEWT on feeding and health care utilization. METHODS At an hospital involved in NEWT development, we randomly assigned 2682 healthy infants born ≥36 weeks gestation in 2018–2019 either to CDS displaying NEWT with an electronic flag if most recent weight was ≥75th weight loss centile or to a control of usual care with NEWT accessed at clinician discretion. Our primary outcome was feeding type concordant with weight loss, defined as exclusive breastfeeding for those not flagged, exclusive breastfeeding or supplementation for those flagged once, and supplementation for those flagged more than once. Secondary outcomes included inpatient and outpatient utilization in the first 30 days. We used χ2 and Student’s t tests to compare intervention infants with control and to compare trial infants with those born in 2017. RESULTS Feeding was concordant with for 1854 (74.5%) trial infants and did not differ between randomized groups (P = .65); concordant feeding was higher for all trial infants than for infants born in 2017 (64.4%; P < .0005). Readmission occurred for 51 (3.8%) CDS infants and 45 (3.4%) control infants (P = .56). Among the 60% of trial infants with outpatient records available, there were 3.5 ± 1.7 visits with no differences between randomized groups (P = .10). CONCLUSIONS At an hospital involved in NEWT development, CDS displaying NEWT did not alter either feeding or health care utilization compared with discretionary NEWT access.

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Background Intervention Nurses Start Infants Growing on Healthy Trajectories tested an early life responsive parenting (RP) intervention designed for obesity prevention. Body mass index z-score at age 3 years was lower for the RP group versus controls with a larger effect for girls than boys. We sought to determine if child sex was associated with differing maternal feeding practices and whether sex moderated intervention effects on feeding. Design/Methods Mothers (N = 279) completed the Infant Feeding Styles Questionnaire (IFSQ) at 28 weeks, the Structure and Control in Parent Feeding (SCPF) at 1, 2, and 3 years, and the Child Feeding Questionnaire (CFQ) at 3 years. Study aims were tested using 2-way analysis of variance and repeated measures. Results Mothers reported greater restriction (limiting food quantity) for boys at 28 weeks (IFSQ: 3.0 ± 1.1 vs 2.8 ± 1.0, P = .07) and across annual measurements from age 1 to 3 years (SCPF: P = .04). At age 3, the intervention group effect on restriction differed by sex (CFQ: P = .047) such that higher restriction was reported by RP group mothers of boys versus girls (3.4 ± 0.7 vs 3.0 ± 0.9, P = .002) with no control group sex difference (3.4 ± 0.8 vs 3.3 ± 0.9, P = .79). There were no sex differences or sex by intervention group interactions in other reported feeding practices at any assessment (ie, structure-based feeding, pressure). Conclusions Mothers of boys used more restrictive feeding through age 3. These findings may be partially explained by previously reported better self-soothing and self-regulation abilities of participating girls.

A narrative review of randomized, blinded, controlled studies assessing the antipyretic effect of ibuprofen versus acetaminophen or combined or alternating treatment in children was conducted.Searches of the PubMed and Embase literature databases were conducted to identify relevant articles. Selected articles were limited to studies published in English that investigated OTC oral tablet and syrup formulations of acetaminophen and ibuprofen; there were no publication date limits. Open-label studies, nonrandomized studies, and those evaluating intravenous or suppository formulations of acetaminophen or ibuprofen were excluded. Variations in designs, endpoints, methods, and patient populations precluded our ability to conduct a formal systematic review.At physician-directed dosing (acetaminophen 15 mg/kg vs ibuprofen 10 mg/kg), no significant differences in antipyretic effects from 0‒6 h and between 0‒6, ‒12, ‒24, or ‒48 h, with single or multiple-doses, respectively, were observed. Tolerability profiles at physician dosing were similar. In 14 over-the-counter dose comparisons (acetaminophen, 10-15 mg/kg; ibuprofen, 2.5-10 mg/kg), antipyresis favored ibuprofen in 6, was similar between groups in 7, and favored acetaminophen (15 mg/kg vs ibuprofen 5 mg/kg) in 1 comparison. Both medications were well tolerated. Efficacy favored combination over individual components in 3 of 4 studies; alternating use results were mixed. All combination or alternating treatments were well tolerated.Antipyretic effects of ibuprofen and acetaminophen are similar at physician-directed doses; ibuprofen may be modestly superior at over-the-counter doses.

Newborns with neonatal abstinence syndrome (NAS) display symptoms related to neurologic excitability and autonomic dysfunction that result in increased metabolic demands. These infants also exhibit feeding difficulties and/or hyperphagia. Because the effects of these symptoms and behaviors on growth are unknown, we sought to measure serial body composition measurements over the first 4 months in infants with NAS requiring pharmacologic treatment using air displacement plethysmography. Fourteen infants of singleton birth with appropriate-for-gestational-age (AGA) weight and a gestational age of ≥35 weeks and N = 5) requiring multidrug therapy for symptom control had lower mean fat percent (−1.2%, CI: −5.2–2.1), fat mass (−60 g, CI: −25–13), and fat-free mass (−270 g, CI: −610–80) across time compared to infants requiring monotherapy. We are the first to report how body composition measures change over time in a small group of patients with NAS. Infants with NAS were smaller and leaner in the first several weeks compared to previously reported body composition measurements in term infants, but grew similarly to their healthy counterparts by 16 weeks. Infants with more severe NAS may be at risk for abnormalities in longer term growth.

Rapid infant growth increases the risk for adult obesity. The gut microbiome is associated with early weight status; however, no study has examined how interactions between microbial and host ribonucleic acid (RNA) expression influence infant growth. We hypothesized that dynamics in infant stool micro-ribonucleic acids (miRNAs) would be associated with both microbial activity and infant growth via putative metabolic targets. Stool was collected twice from 30 full-term infants, at 1 month and again between 6 and 12 months. Stool RNA were measured with high-throughput sequencing and aligned to human and microbial databases. Infant growth was measured by weight-for-length z-score at birth and 12 months. Increased RNA transcriptional activity of Clostridia (R = 0.55; Adj p = 3.7E-2) and Burkholderia (R = −0.820, Adj p = 2.62E-3) were associated with infant growth. Of the 25 human RNAs associated with growth, 16 were miRNAs. The miRNAs demonstrated significant target enrichment (Adj p < 0.05) for four metabolic pathways. There were four associations between growth-related miRNAs and growth-related phyla. We have shown that longitudinal trends in gut microbiota activity and human miRNA levels are associated with infant growth and the metabolic targets of miRNAs suggest these molecules may regulate the biosynthetic landscape of the gut and influence microbial activity.

BACKGROUND AND OBJECTIVES The Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) responsive parenting (RP) intervention for first-time mothers improved firstborn infant sleep compared with controls. The goals of this analysis were to test intervention spillover effects on secondborn siblings and examine birth order differences in infant sleep. METHODS Secondborns (n = 117) of INSIGHT mothers were enrolled in an observational cohort, SIBSIGHT. The Brief Infant Sleep Questionnaire was collected at 3, 16, and 52 weeks. Generalized linear mixed models assessed differences among secondborns by firstborn randomization, as well as birth order differences at 16 and 52 weeks. RESULTS The RP group secondborns slept 42 minutes longer at night (95% confidence interval [95% CI]: 19–64) and 53 minutes longer total (95% CI: 17–90) than control secondborns. RP secondborns were more likely to self-soothe to sleep (odds ratio [OR] = 2.0, 95% CI: 1.1–3.7) and less likely to be fed back to sleep after waking (OR = 0.5, 95% CI: 0.3–0.9) than secondborns of control mothers. RP secondborns were more likely to have a bedtime ≤8 pm at 3 (OR = 2.9, 95% CI: 1.1–7.7) and 16 weeks (OR = 4.7, 95% CI: 2.0–11.0). Few differences in sleep parenting practices were observed when comparing siblings within families. Secondborns slept 37 minutes longer than firstborns at 16 weeks (CI: 7–67, P = .03). CONCLUSIONS The INSIGHT RP intervention for first-time mothers had a spillover effect to secondborns, positively impacting sleep duration and behaviors. Intervening with first-time mothers benefits both firstborns and subsequent children.

Objectives Previous research has demonstrated that accidental unsupervised ingestions (AUIs) were responsible for the majority of cough and cold medication (CCM) ingestions leading to significant adverse events (AEs) in children. The objective of this analysis was to characterize the role of AUIs in the morbidity associated with CCM exposure in children. Methods This surveillance study collected data from 5 United States data sources from 2009 to 2016, in children younger than 6 years with an AE from an AUI involving at least 1 CCM over-the-counter pharmaceutical ingredient. An expert panel reviewed each case to determine causality. Results From 4756 total cases reviewed, 3134 (65.9%) had an AE from an AUI determined to be at least potentially related to a CCM ingredient. The majority (61.3%) of cases occurred in children aged 2 to younger than 4 years. Most exposures occurred in the child's own residence (94.9%), and 43.8% were admitted to a health care facility (22.0% to a critical care unit). Dextromethorphan and diphenhydramine, when packaged alone or in combination products, contributed to 96.0% of AUIs. The most common specific products involved were single-ingredient pediatric liquid diphenhydramine (30.1%) and single-ingredient pediatric liquid dextromethorphan (21.4%). There were 3 deaths from solid diphenhydramine formulations. Conclusions There continues to be opportunities for the implementation of interventions to prevent AUIs of CCM in children. Additional emphasis on engineering controls, such as flow restrictors for liquid formulations targeting diphenhydramine and dextromethorphan products, represent additional opportunities to further reduce AEs from AUIs of CCM.

Firstborn children are more likely to have obesity than secondborns, which may partially be explained by differential use of food to soothe (FTS) infant distress, which has been inked to higher weight status.To test associations between the birth order and maternal FTS and whether differences in sibling temperament and body mass index (BMI) z-scores were associated differences in maternal FTS.Random effect models assessed associations between birth order and FTS. Linear regressions examined associations between differences in maternal FTS and sibling differences in temperament at 16 weeks and BMI z-scores at 1 year.Mothers (n = 117) used contextual-based FTS more with firstborns than secondborns (2.70 vs. 2.38, p 0.0001). Sibling differences in negative affect were associated with differences in maternal contextual-based (RTo promote healthy child weight, mothers should learn to respond to each child's temperament and use alternatives to FTS infant distress.

Background Metabolomic analysis is commonly used to understand the biological underpinning of diseases such as obesity. However, our knowledge of gut metabolites related to weight outcomes in young children is currently limited. Objectives To (1) explore the relationships between metabolites and child weight outcomes, (2) determine the potential effect of covariates (e.g., child's diet, maternal health/habits during pregnancy, etc.) in the relationship between metabolites and child weight outcomes, and (3) explore the relationship between selected gut metabolites and gut microbiota abundance. Methods Using 1 H-NMR, we quantified 30 metabolites from stool samples of 170 two-year-old children. To identify metabolites and covariates associated with children's weight outcomes (BMI [weight/height2 ], BMI z-score [BMI adjusted for age and sex], and growth index [weight/height]), we analysed the 1 H-NMR data, along with 20 covariates recorded on children and mothers, using LASSO and best subset selection regression techniques. Previously characterized microbiota community information from the same stool samples was used to determine associations between selected gut metabolites and gut microbiota. Results At age 2 years, stool butyrate concentration had a significant positive association with child BMI (p-value = 3.58 × 10-4 ), BMI z-score (p-value = 3.47 × 10-4 ), and growth index (p-value = 7.73 × 10-4 ). Covariates such as maternal smoking during pregnancy are important to consider. Butyrate concentration was positively associated with the abundance of the bacterial genus Faecalibacterium (p-value = 9.61 × 10-3 ). Conclusions Stool butyrate concentration is positively associated with increased child weight outcomes and should be investigated further as a factor affecting childhood obesity.

Medication administration errors that take place in the home are common, especially when liquid preparations are used and complex medication schedules with multiple medications are involved; children with chronic conditions are disproportionately affected. Parents and other caregivers with low health literacy and/or limited English proficiency are at higher risk for making errors in administering medications to children in their care. Recommended strategies to reduce home medication errors relate to provider prescribing practices; health literacy–informed verbal counseling strategies (eg, teachback and showback) and written patient education materials (eg, pictographic information) for patients and/or caregivers across settings (inpatient, outpatient, emergency care, pharmacy); dosing-tool provision for liquid medication measurement; review of medication lists with patients and/or caregivers (medication reconciliation) that includes prescription and over-the-counter medications, as well as vitamins and supplements; leveraging the medical home; engaging adolescents and their adult caregivers; training of providers; safe disposal of medications; regulations related to medication dosing tools, labeling, packaging, and informational materials; use of electronic health records and other technologies; and research to identify novel ways to support safe home medication administration.

BACKGROUND AND OBJECTIVES In 2008, over-the-counter cough and cold medications (CCMs) underwent labeling changes in response to safety concerns, including fatalities, reported in children exposed to CCMs. The objective of this study is to describe fatalities associated with exposures to CCMs in children METHODS Fatalities in children RESULTS Of the 180 eligible fatalities captured during the study period, 40 were judged by the expert panel to be either related or potentially related to the CCM. Of these, the majority (n = 24; 60.0%) occurred in children CONCLUSIONS Pediatric fatalities associated with CCMs occurred primarily in young children after deliberate medication administration with nontherapeutic intent by a caregiver.

The aim of this study was to test whether the Intervention Nurses Start Infants Growing on Healthy Trajectories (INSIGHT) responsive parenting (RP) intervention, delivered to parents of firstborn children, is associated with the BMI of first- and second-born siblings during infancy.Participants included 117 firstborn infants enrolled in a randomized controlled trial and their second-born siblings enrolled in an observation-only ancillary study. The RP curriculum for firstborn children included guidance on feeding, sleep, interactive play, and emotion regulation. The control curriculum focused on safety. Anthropometrics were measured in both siblings at ages 3, 16, 28, and 52 weeks. Growth curve models for BMI by child age were fit.Second-born children were delivered 2.5 (SD 0.9) years after firstborns. Firstborn and second-born children whose parents received the RP intervention with their first child had BMI that was 0.44 kg/m2 (95% CI: -0.82 to 0.06) and 0.36 kg/m2 (95% CI: -0.75 to 0.03) lower than controls, respectively. Linear and quadratic growth rates for BMI for firstborn and second-born cohorts were similar, but second-born children had a greater average BMI at 1 year of age (difference = -0.33 [95% CI: -0.52 to -0.15]).A RP educational intervention for obesity prevention delivered to parents of firstborns appears to spill over to second-born siblings.

Significance Mitochondria frequently carry different DNA—a state called heteroplasmy. Heteroplasmic mutations can cause mitochondrial diseases and are involved in cancer and aging, but they are also common in healthy people. Here, we study heteroplasmy in 96 multigenerational healthy families. We show that mothers effectively transmit very few mitochondrial DNA to their offspring. Because of this bottleneck, which intensifies with increasing maternal age at childbirth, mutation frequencies can change dramatically between a mother and her child. Thus, a child might inherit a disease-causing mutation at high frequency from an asymptomatic carrier mother and might develop a disease. We also demonstrate that natural selection acts against disease-causing mutations during germline development. Our study has important implications for genetic counseling of mitochondrial diseases., Heteroplasmy—the presence of multiple mitochondrial DNA (mtDNA) haplotypes in an individual—can lead to numerous mitochondrial diseases. The presentation of such diseases depends on the frequency of the heteroplasmic variant in tissues, which, in turn, depends on the dynamics of mtDNA transmissions during germline and somatic development. Thus, understanding and predicting these dynamics between generations and within individuals is medically relevant. Here, we study patterns of heteroplasmy in 2 tissues from each of 345 humans in 96 multigenerational families, each with, at least, 2 siblings (a total of 249 mother–child transmissions). This experimental design has allowed us to estimate the timing of mtDNA mutations, drift, and selection with unprecedented precision. Our results are remarkably concordant between 2 complementary population-genetic approaches. We find evidence for a severe germline bottleneck (7–10 mtDNA segregating units) that occurs independently in different oocyte lineages from the same mother, while somatic bottlenecks are less severe. We demonstrate that divergence between mother and offspring increases with the mother’s age at childbirth, likely due to continued drift of heteroplasmy frequencies in oocytes under meiotic arrest. We show that this period is also accompanied by mutation accumulation leading to more de novo mutations in children born to older mothers. We show that heteroplasmic variants at intermediate frequencies can segregate for many generations in the human population, despite the strong germline bottleneck. We show that selection acts during germline development to keep the frequency of putatively deleterious variants from rising. Our findings have important applications for clinical genetics and genetic counseling.

Flow restrictors are child-resistant packaging innovations designed to limit the amount of liquid dispensed from a medication bottle. In 2011, flow restrictors were added to pediatric liquid single-ingredient acetaminophen formulations. The hypothesis of this study is that implementation would be associated with reduced volume and severity of pediatric acetaminophen exposures reported to the U.S. National Poison Data System.This study describes accidental unsupervised ingestions of acetaminophen in children aged6 years. Exposures were grouped into pre-implementation (pre-period; January 4, 2010-July 17, 2011); transition (July 18, 2011-July 15, 2012); and post-implementation (post-period; July 16, 2012-December 25, 2016) periods. Cumulative and annual rates of change per million units (i.e., bottles) sold were calculated for the pre- and post-periods for acetaminophen and pediatric liquid ibuprofen (comparator without flow restrictors). Pre- to post-period rate ratios were used to compare products and to estimate the potential effect on other over-the-counter medications. Analysis was conducted in 2017 and 2018.The pre- and post-period cumulative acetaminophen exposure rate was 507.2 (95% CI=481.1, 534.6) and 325.6 (95% CI=305.8, 346.7) per 1 million units sold, respectively. Declines in the pre- versus post-period rate ratios were seen for exposures with any effect (0.642, 95% CI=0.591, 0.696) and with clinically significant outcomes (0.728, 95% CI=0.581, 0.913). In the post-period, acetaminophen exposures decreased faster than ibuprofen with a rate of change ratio of 0.936 (95% CI=0.912, 0.960) for all exposures and 0.939 (95% CI=0.909, 0.970) for exposures with any effect.The addition of flow restrictors to pediatric liquid acetaminophen was associated with a reduction in the number and severity of exposures. Application of flow restrictors to other liquid medications should be considered.