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BackgroundAn operational definition of organ dysfunction applicable to neonates that predicts mortality in the setting of infection is lacking. We determined the utility of an objective, electronic health record (EHR)-automated, neonatal sequential organ failure assessment (nSOFA) score to predict mortality from late-onset sepsis (LOS) in premature, very low birth weight (VLBW) infants.MethodsRetrospective, single-center study of bacteremic preterm VLBW newborns admitted between 2012 and 2016. nSOFA scores were derived for patients with LOS at multiple time points surrounding the sepsis evaluation.ResultsnSOFA scores at evaluation and at all points measured after evaluation were different between survivors and non-survivors. Among patients with an nSOFA score of >4, mortality was higher at evaluation (13% vs 67%, p < 0.001), +6 h (15% vs 64%, p = 0.002), and +12 h (7% vs 71%, p < 0.001) as compared to patients with a score of ≤4. Receiver operating characteristics area under the curve was 0.77 at evaluation (95% CI 0.62–0.92; p = 0.001), 0.78 at +6 h (0.66–0.92; p < 0.001), and 0.93 at +12 h (0.86–0.997; p < 0.001).ConclusionsThe nSOFA scoring system predicted mortality in VLBW infants with LOS and this automated system was integrated into our EHR. Prediction of LOS mortality is a critical step toward improvements in neonatal sepsis outcomes.

BACKGROUNDThe effects of antibiotics on infant gut microbiota are unclear. We hypothesized that the use of common antibiotics results in long-term aberration in gut microbiota.METHODSAntibiotic-naive infants were prospectively recruited when hospitalized because of a respiratory syncytial virus infection. Composition of fecal microbiota was compared between those receiving antibiotics during follow-up (prescribed at clinicians’ discretion because of complications such as otitis media) and those with no antibiotic exposure. Fecal sampling started on day 1, then continued at 2-day intervals during the hospital stay, and at 1, 3 and 6 months at home.RESULTSOne hundred and sixty-three fecal samples from 40 patients (median age 2.3 months at baseline; 22 exposed to antibiotics) were available for microbiota analyses. A single course of amoxicillin or macrolide resulted in aberration of infant microbiota characterized by variation in the abundance of bifidobacteria, enterobacteria and clostridia, lasting for several months. Recovery from the antibiotics was associated with an increase in clostridia. Occasionally, antibiotic use resulted in microbiota profiles associated with inflammatory conditions.CONCLUSIONSAntibiotic use in infants modifies especially bifidobacterial levels. Further studies are warranted whether administration of bifidobacteria will provide health benefits by normalizing the microbiota in infants receiving antibiotics.

Background Early detection of cognitive disability is challenging. We assessed the domain-specific, concurrent validity of the ages and stages questionnaire (ASQ-3) and the Bayley Scales of Infant and Toddler Development (BSID-III), and their ability to predict cognitive delay at school age. Methods Within a longitudinal birth cohort study, a nested cohort of children was assessed using ASQ-3 and BSID-III at 24 months, and at 5 years using the Kaufmann brief IQ test (KBIT). Results 278 children were assessed using BSID-III and ASQ-3 at 24-months; mean(SD) BW = 3445(506) grams, M:F ratio=52:48. ASQ-3 had reasonable predictive ability (AUROC, p value, sensitivity:specificity) of same domain delay for motor (0.630, p  = 0.008, 50%:76.1%) and language (0.623, p  = 0.010, 25%:99.5%) at 2 years, but poor ability to detect cognitive delay compared to BSID-III (0.587, p  = 0.124, 20.7%/96.8%;). 204/278 children were assessed at 5 years. BSID-III language and cognition domains showed better correlation with verbal and nonverbal IQ (R = 0.435, p  < 0.001 and 0.388, p  < 0.001 respectively). Both assessments showed high specificity and low sensitivity for predicting delay at 5 years. Conclusions The ASQ-3 cognitive domain showed poor concurrent validity with BSID-III cognitive score. Both ASQ-3 and BSID-III at 2 years poorly predict cognitive delay at 5 years. Impact The ASQ-3 does not adequately detect cognitive delay or predict cognitive delay at 5 years, particularly for children with mild to moderate delay. The ASQ-3 shows reasonable concurrent validity with the motor and language subscales of the BSID-III. Neither early screening nor formal developmental testing demonstrated significant predictive validity to screen for cognitive delay at school age. This article highlights the need to analyse our existing model of using the ASQ-3 to screen for cognitive delay in children aged 2 years.

Plant cells are totipotent and competent to regenerate from differentiated organs. It has been known for six decades that cytokinin-rich medium induces shoot regeneration from callus cells. However, the underlying molecular mechanism remains elusive. The homeodomain transcription factor WUSCHEL (WUS) is essential for de novo establishment of the shoot stem cell niche in Arabidopsis thaliana. We found that WUS-positive (WUS+) cells mark the shoot progenitor region during regeneration. A cytokinin-rich environment initially promotes the removal of the repressive histone mark H3K27me3 at the WUS locus in a cell cycle-dependent manner. Subsequently, the B-type ARABIDOPSIS RESPONSE REGULATORs (ARRs) ARR1, ARR2, ARR10, and ARR12, which function as transcriptional activators in the cytokinin signaling pathway, spatially activate WUS expression through binding with microRNA165/6-targeted HD-ZIP III transcription factors. Thus, our results provide important insights into the molecular framework for cytokinin-directed shoot regeneration and reveal a two-step mechanism for de novo activation of WUS.

Background Therapeutic hypothermia (TH) is the gold-standard treatment for moderate and severe neonatal encephalopathy (NE). Care during TH has implications for long-term outcomes. Outcome variability exists among neonatal intensive care units (NICUs) in Canada, but care variations are not understood well. This study examines variations in care practices for neonates with NE treated with TH in NICUs across Canada. Methods A non-anonymous, web-based questionnaire was emailed to tertiary NICUs in Canada providing TH for NE to assess care practices during the first days of life and neurodevelopmental follow-up. Results Ninety-two percent (24/26) responded. Centres followed national guidelines regarding the use of the modified Sarnat score to assess the initial severity of NE, the need to initiate TH within the first 6 h of birth, and the importance of follow-up. However, other practices varied, including ventilation mode, definition/treatment of hypotension, routine echocardiography, use of sedation, use of electroencephalogram (EEG), MRI timing, placental analysis, and follow-up duration. Conclusions NICUs across Canada follow available national guidelines, but variations exist in practices for managing NE during TH. Development and implementation of a consensus-based care bundle for neonates during TH may reduce practice variability and improve outcomes. Impact This survey describes the current HIE care practices and variation among tertiary centres in Canada. Variations exist in the care of neonates with NE treated with TH in NICUs across Canada. This paper Identifies areas of variation that are not discussed in detail in the national guidelines and will help to set up quality improvement initiatives. Elucidating the variation in care practices calls for the creation and implementation of a national, consensus-based care bundle, with the objective to improve the outcomes of these critically ill neonates.

Background Music for neonatal pain has not been exclusively studied in term neonates in a well-designed trial compared to the standard of care. This study aims to assess the effectiveness of music intervention as an adjuvant in relieving acute pain in term newborns undergoing minor painful procedures. Methods This randomized, controlled, blinded trial included any term neonate undergoing heel prick. Both control and intervention groups received oral sucrose 2 min before heel prick. Intervention group was exposed to ‘Bedtime Mozart’ lullaby recorded music via bedside speakers. Pain was measured using Neonatal Infant Pain Scale (NIPS) at 1-min intervals. Investigators were blinded using noise-canceling headphones that played random music. Results A total of 100 neonates were enrolled. Mean gestational age was 39.2 weeks, and mean duration of the procedure was 113 s. Music group was found to have significantly lower pain scores [OR = 0.42 (0.31, 0.56), p  < 0.001]. Baseline NIPS scores were similar across groups and there was no interaction effect between groups and time. When NIPS were categorized as pain and no pain, there continued to be statistically significant lower NIPS scores in the music group ( p  < 0.001). Conclusion Recorded music, in addition to sucrose, is efficacious in reducing pain, encouraging its use in term neonates. Impact Recorded music effectively reduces pain induced by minor procedures in term neonates. Clinical studies have shown that live and recorded music induces changes in vital signs and pain scores in the NICU’s predominantly preterm population. Most of these studies were also conducted in the white ethnic population. Our study objectively proves reduction in pain scores by using recorded music in a randomized, controlled, blinded study of predominantly non-white, term neonates. Recorded music is effective in reducing acute pain in term neonates and can be widely used even in low-resource nurseries.

BackgroundAssociations between screen media and child cognition are complex. This study aimed to examine whether age of onset of media exposure, cumulative effect of high media exposure, and verbal interaction during screen time in the first 2 years of life were associated with 4-year-old cognition by including parenting behaviors into the final construct.MethodsThere were 274 healthy participants who were followed up until age 4 years. Screen media data were collected at age 6, 12, 18 months, and 2 years. Cognition or early learning composite (ELC) was evaluated at age 2, 3, and 4 years, where the latter variable was the primary outcome. Positive parenting was obtained by Parenting Styles and Dimensions Questionnaire.ResultsELC at age 2 years was associated with later age of onset of media exposure (β = 0.113, p < 0.05), fewer months of high media exposure above the upper quartile (β = 0.282, p < 0.001), and more months of verbal interaction during screen time (β = 0.261, p < 0.001). ELC at age 4 years was associated with ELC and positive parenting at earlier ages.ConclusionDelayed introduction of screen media, appropriate screen time, and increased verbal interaction during media use in the first 2 years of life were associated with better cognitive development in preschoolers.ImpactAssociations between screen media exposure and children’s cognitive development in existing literature mainly focused on duration of screen media viewing or the content of electronic media in which other factors are rarely explored.Earlier age of onset of media exposure, more months of excessive screen media exposure (>6.5 h/day), and fewer months of verbal interaction with children during media use in the first 2 years of life had associations with decreased preschool cognition.To mitigate undesirable effects of inappropriate screen media use on cognition, delayed introduction of screen media, appropriate electronic media exposure, and increased verbal interaction during media use with children should be recommended at health supervision visits.Lower positive parenting was a mediator for the relationship between cumulative months of high screen media exposure and decreased child cognition.

This article reports the first attempt to test the relevance of buoyancy—the capacity to overcome the setbacks, challenges, and pressures that are part of the ordinary course of school life—for instructed second language (L2) learning. Questionnaire data from 787 college-level L2 learners in South Korea assessed their academic buoyancy and a set of six hypothesized predictors. A two-step cluster analysis of the data identified five prominent L2 learner archetypes, providing evidence for the existence of L2 domain-specific buoyancy profiles. Using structural equation modeling, we examined links among the six predictor variables, buoyancy, and L2 achievement and grade point average (GPA). The results showed that buoyancy significantly predicted both L2 achievement and GPA and mediated the effect of the predictors on these two outcome variables. Buoyancy, thus, captures a dimension of L2 motivation that is conceptually and empirically distinct from existing constructs, and represents an essential yet underexplored capacity for success in language learning.

The Aptian Crato Konservat-Lagerstätte is renowned for its exceptionally preserved fossils in lacustrine laminated limestones. Although previous works on this site include numerous taxonomic studies, its taphonomy remains a subject of debate. Herein, we present new data on the taphonomy of decapod crustaceans preserved in wrinkle laminites, highlighting the role of microbial mats in enhancing fossil preservation. Our results suggest that benthic microorganisms may have promoted protection and organic mineralization of some of the allochthonous to parautochthonous organic remains within the microbial laminites of the Crato lake. Overall, this work provides the first empirical evidence that the preservational pathways of the fossils in the Crato Konservat-Lagerstätte involved microbial mats.

BackgroundThe impact of degree of prematurity at birth on premature infant gut microbiota has not been extensively studied in comparison to term infants in large cohorts.MethodsTo determine the effect of gestational age at birth and postnatal exposures on gut bacterial colonization in infants, we analyzed 65 stool samples from 17 premature infants in the neonatal intensive care unit, as well as 13 samples from 13 mostly moderate-to-late premature infants and 189 samples from 176 term infants in the New Hampshire Birth Cohort Study. Gut colonization patterns were determined with 16S rDNA microbiome profiling.ResultsGut bacterial alpha-diversity differed between premature and term infants at 6 weeks of age, after adjusting for exposures (p = 0.027). Alpha-diversity varied between extremely premature (<28 weeks gestation) and very premature infants (≥28 but <32 weeks, p = 0.011), as well as between extremely and moderate-to-late premature infants (≥32 and <37 weeks, p = 0.004). Newborn antibiotic use among premature infants was associated with lower Bifidobacterium and Bacteroides abundance (p = 0.015 and p = 0.041).ConclusionGestational age at birth and early antibiotic exposure have significant effects on the premature infant gut microbiota.