Post-natal steroid exposure in very low birthweight neonates and associations with acute kidney injury.

OBJECTIVE: The relationship between adrenal insufficiency (AI), post-natal steroids (PNS) and neonatal acute kidney injury (AKI) remains understudied. We investigated associations between PNS and AKI in very low birthweight (VLBW) neonates, hypothesizing PNS is associated with reduced AKI. STUDY DESIGN: We conducted a single-center retrospective review of VLBW infants comparing those with and without PNS exposure. Associations between PNS exposure and AKI were evaluated using generalized linear mixed-modeling adjusted for confounders. RESULT: Of 567 neonates, 97 (17.1%) were exposed to PNS and 130 (22.9%) experienced AKI. Infants with PNS had lower gestational age, birthweight, Apgar scores, and experienced more AI versus those without PNS (all p < 0.05). PNS was associated with AKI (aRR 1.72, 95% CI 1.09-2.72) though hydrocortisone alone was not. CONCLUSION: PNS exposure, but not hydrocortisone alone, is associated with increased AKI in VLBW neonates. Further analysis is needed to investigate the role of AI and AKI.

Neonatal Acute Kidney Injury.

Acute kidney injury (AKI) is a common occurrence in the neonatal intensive care unit (NICU). In recent years, our knowledge of the incidence and impact of neonatal AKI on outcomes has expanded exponentially. Neonatal AKI has been shown to be associated with adverse outcomes including increased length of mechanical ventilation, prolonged length of stay, and rise in mortality. There has also been increasing work suggesting that neonates with AKI are at higher risk of chronic kidney disease (CKD). In the past, AKI had been defined multiple ways. The utilization of the neonatal modified Kidney Disease: Improving Global Outcomes (KDIGO) criteria as the standard definition for neonatal AKI in research and clinical care has driven the advances in our understanding of neonatal AKI over the last 10 years. This definition has allowed researchers and clinicians to better understand the incidence, risk factors, and outcomes associated with neonatal AKI across populations through a multitude of single-center studies and the seminal, multicenter Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates (AWAKEN) study. As the impacts of neonatal AKI have become clear, a shift in efforts toward identifying those at highest risk, protocolizing AKI surveillance, improving prevention and diagnosis, and expanding kidney support therapy (KST) for neonates has occurred. These efforts also include improving risk stratification (identifying high risk populations, including those with nephrotoxic medication exposure) and diagnostics (novel biomarkers and diagnostic tools). Recent work has also shown that the targeted use of methylxanthines may prevent AKI in a variety of high-risk populations. One of the most exciting developments in neonatal AKI is the advancement in technology to provide KST to neonates with severe AKI. In this comprehensive review we will provide an overview of recent work and advances in the field of neonatal AKI. This will include a detailed review of (1) the definition of neonatal AKI, (2) the epidemiology, risk factors, and outcomes associated with neonatal AKI, (3) improvements in risk stratification and diagnostics, (4) mitigation and treatment, (5) advancements in the provision of KST to neonates, and (6) the incidence and risk of subsequent CKD.

A comparison of Triple I classification with neonatal early-onset sepsis calculator recommendations in neonates born to mothers with clinical chorioamnionitis.

OBJECTIVE: To compare the early-onset sepsis (EOS) calculator recommendations for infants born to mothers with clinical chorioamnionitis with those made by the Triple I classification. STUDY DESIGN: Retrospective analysis of chorioamnionitis-exposed neonates ≥35 weeks. EOS risk was calculated with baseline risks of 0.5/1000 and 4/1000. Mothers were retrospectively categorized using the Triple I classification. Calculator recommendations were compared with the Triple I classification recommendations. RESULTS: We included 687 chorioamnionitis-exposed neonates. With a baseline risk of 0.5/1000, the calculator recommended no evaluation in 68.4% of infants of mothers with confirmed Triple I. With a baseline risk of 4/1000, 62.3% of infants of mothers with confirmed Triple I and 57.1% of infants born to mothers who did not meet fever criteria would have received evaluation. CONCLUSIONS: The EOS calculator with either baseline risk does not recommend evaluation in a large number of infants born to mothers with confirmed Triple I.

Use of a Modified Early-Onset Sepsis Risk Calculator for Neonates Exposed to Chorioamnionitis.

OBJECTIVE: To validate the recently modified Kaiser Permanente early-onset sepsis (EOS) calculator with a higher baseline incidence in chorioamnionitis exposed neonates. STUDY DESIGN: This is a retrospective study of chorioamnionitis-exposed neonates born at ≥35 weeks of gestation with a known EOS incidence of 4.3/1000. The risk and management categories were calculated using the calculator with an incidence of 4/1000. The results were compared with a previous analysis of the same cohort that used an EOS incidence of 0.5/1000. RESULTS: In our sample, the EOS calculator recommends at least a blood culture in 834 of 896 (93.1%) and empiric antibiotics in 533 of 896 (59.5%) chorioamnionitis-exposed neonates when using an EOS incidence of 4/1000. This captures 5 of 5 neonates (100%) with EOS. When using a baseline EOS incidence of 0.5/1000, the calculator recommends at least a blood culture in only 289 of 896 (32.2%) and empiric antibiotics in only 209 of 896 (23.3%) neonates, but fails to recommend empiric antibiotics in 2 of 5 neonates with EOS (40%). CONCLUSIONS: When using an EOS risk of 4 of 1000 in infants exposed to mothers with chorioamnionitis, the EOS calculator has the ability to capture an increased number of neonates with culture-positive EOS. However, this change also leads to nearly a 3-fold increase in the use of empiric antibiotics and an evaluation with blood culture in almost all infants born to mothers with chorioamnionitis.

Feasibility of Using a Commercial Fitness Tracker as an Adjunct to Family-Based Weight Management Treatment: Pilot Randomized Trial.

BACKGROUND: Fitness trackers can engage users through automated self-monitoring of physical activity. Studies evaluating the utility of fitness trackers are limited among adolescents, who are often difficult to engage in weight management treatment and are heavy technology users. OBJECTIVE: We conducted a pilot randomized trial to describe the impact of providing adolescents and caregivers with fitness trackers as an adjunct to treatment in a tertiary care weight management clinic on adolescent fitness tracker satisfaction, fitness tracker utilization patterns, and physical activity levels. METHODS: Adolescents were randomized to 1 of 2 groups (adolescent or dyad) at their initial weight management clinic visit. Adolescents received a fitness tracker and counseling around activity data in addition to standard treatment. A caregiver of adolescents in the dyad group also received a fitness tracker. Satisfaction with the fitness tracker, fitness tracker utilization patterns, and physical activity patterns were evaluated over 3 months. RESULTS: A total of 88 adolescents were enrolled, with 69% (61/88) being female, 36% (32/88) black, 23% (20/88) Hispanic, and 63% (55/88) with severe obesity. Most adolescents reported that the fitness tracker was helping them meet their healthy lifestyle goals (69%) and be more motivated to achieve a healthy weight (66%). Despite this, 68% discontinued use of the fitness tracker by the end of the study. There were no significant differences between the adolescent and the dyad group in outcomes, but adolescents in the dyad group were 12.2 times more likely to discontinue using their fitness tracker if their caregiver also discontinued use of their fitness tracker (95% CI 2.4-61.6). Compared with adolescents who discontinued use of the fitness tracker during the study, adolescents who continued to use the fitness tracker recorded a higher number of daily steps in months 2 and 3 of the study (mean 5760 vs 4148 in month 2, P=.005, and mean 5942 vs 3487 in month 3, P=.002). CONCLUSIONS: Despite high levels of satisfaction with the fitness trackers, fitness tracker discontinuation rates were high, especially among adolescents whose caregivers also discontinued use of their fitness tracker. More studies are needed to determine how to sustain the use of fitness trackers among adolescents with obesity and engage caregivers in adolescent weight management interventions.

Development of twitching in sleeping infant mice depends on sensory experience.

Myoclonic twitches are jerky movements that occur exclusively and abundantly during active (or REM) sleep in mammals, especially in early development [1-4]. In rat pups, limb twitches exhibit a complex spatiotemporal structure that changes across early development [5]. However, it is not known whether this developmental change is influenced by sensory experience, which is a prerequisite to the notion that sensory feedback from twitches not only activates sensorimotor circuits but modifies them [4]. Here, we investigated the contributions of proprioception to twitching in newborn ErbB2 conditional knockout mice that lack muscle spindles and grow up to exhibit dysfunctional proprioception [6-8]. High-speed videography of forelimb twitches unexpectedly revealed a category of reflex-like twitching-comprising an agonist twitch followed immediately by an antagonist twitch-that developed postnatally in wild-types/heterozygotes, but not in knockouts. Contrary to evidence from adults that spinal reflexes are inhibited during twitching [9-11], this finding suggests that twitches trigger the monosynaptic stretch reflex and, by doing so, contribute to its activity-dependent development [12-14]. Next, we assessed developmental changes in the frequency and organization (i.e., entropy) of more-complex, multi-joint patterns of twitching; again, wild-types/heterozygotes exhibited developmental changes in twitch patterning that were not seen in knockouts. Thus, targeted deletion of a peripheral sensor alters the normal development of local and global features of twitching, demonstrating that twitching is shaped by sensory experience. These results also highlight the potential use of twitching as a uniquely informative diagnostic tool for assessing the functional status of spinal and supraspinal circuits.

Very-long-range disynaptic V1 connections through layer 6 pyramidal neurons revealed by transneuronal tracing with rabies virus.

Neurons in primary visual cortex (V1) integrate across the representation of the visual field through networks of long-range projecting pyramidal neurons. These projections, which originate from within V1 and through feedback from higher visual areas, are likely to play a key role in such visual processes as low contrast facilitation and extraclassical surround suppression. The extent of the visual field representation covered by feedback is generally much larger than that covered through monosynaptic horizontal connections within V1, and, although it may be possible that multisynaptic horizontal connections across V1 could also lead to more widespread spatial integration, nothing is known regarding such circuits. In this study, we used injections of the CVS-11 strain of rabies virus to examine disynaptic long-range horizontal connections within macaque monkey V1. Injections were made around the representation of 5° eccentricity in the lower visual field. Along the opercular surface of V1, we found that the majority of connected neurons extended up to 8 mm in most layers, consistent with twice the typically reported distances of monosynaptic connections. In addition, mainly in layer 6, a steady presence of connected neurons within V1 was observed up to 16 mm away. A relatively high percentage of these connected neurons had large-diameter somata characteristic of Meynert cells, which are known to project as far as 8 mm individually. Several neurons, predominantly in layer 6, were also found deep within the calcarine sulcus, reaching as far as 20° of eccentricity, based on estimates, and extending well into the upper visual field representation. Thus, our anatomical results provide evidence for a wide-ranging disynaptic circuit within V1, mediated largely through layer 6, that accounts for integration across a large region of the visual field.

Designing facilities for the future, today.

Cassandra Coleman, business development manager at international healthcare consultancy, MJ Medical, discusses the challenges of designing healthcare facilities today that will cope well with, and adapt to, the changing clinical demands, patient care pathways, and advances in both diagnostics and treatment, that will inevitably characterise healthcare in the next 2-3 decades and beyond.

Spatiotemporal structure of REM sleep twitching reveals developmental origins of motor synergies.

BACKGROUND: During active (or REM) sleep, infant mammals exhibit myoclonic twitches of skeletal muscles throughout the body, generating jerky, discrete movements of the distal limbs. Hundreds of thousands of limb twitches are produced daily, and sensory feedback from these movements is a substantial driver of infant brain activity, suggesting that they contribute to motor learning and sensorimotor integration. It is not known whether the production of twitches is random or spatiotemporally structured, or whether the patterning of twitching changes with age; such information is critical for understanding how twitches contribute to development. RESULTS: We used high-speed videography and 3D motion tracking to assess the spatiotemporal structure of twitching at forelimb joints in 2- and 8-day-old rats. At both ages, twitches exhibited highly structured spatiotemporal properties at multiple timescales, including synergistic and multijoint movements within and across forelimbs. Hierarchical cluster analysis and latent class analysis revealed developmental changes in twitching quantity and patterning. Critically, we found evidence for a selectionist process whereby movement patterns at the early age compete for retention and expression over development. CONCLUSIONS: These findings indicate that twitches are not produced randomly but are highly structured at multiple timescales. This structure has important implications for understanding brain and spinal mechanisms that produce twitching, and the role that sensory feedback from twitching plays in sensorimotor system development. We propose that twitches represent a heretofore-overlooked form of motor exploration that helps animals probe the biomechanics of their limbs, build motor synergies, and lay a foundation for complex, automatic, and goal-directed wake movements.

The development of day-night differences in sleep and wakefulness in norway rats and the effect of bilateral enucleation.

The suprachiasmatic nucleus exhibits circadian rhythmicity in fetal and infant rats, but little is known about the consequences of this rhythmicity for infant behavior. Here, in experiment 1, the authors measured sleep and wakefulness in rats during the day and night in postnatal day (P)2, P8, P15, and P21 subjects. As early as P2, day-night differences in sleep-wake activity were detected. Nocturnal wakefulness began to emerge around P15 and was reliably expressed by P21. The authors hypothesized that the process of photic entrainment over the 1st postnatal week, which depends on the development of connectivity between the retinohypothalamic tract (RHT) and the SCN, influences the later emergence of nocturnal wakefulness. To test this hypothesis, in experiment 2 infant rats were enucleated bilaterally at P3 and P11, that is, before and after photic entrainment. Whereas pups enucleated at P11 and tested at P21 exhibited increased wakefulness at night, identical to sham controls, pups enucleated at P3 and tested at P21 exhibited the opposite pattern of increased wakefulness during the day. Pups tested at P28 and P35 exhibited this same pattern of increased daytime wakefulness. All together, these results suggest that prenatal and postnatal experience modulates the development of species-typical circadian sleep-wake patterns. Moreover, the authors suggest that visual system stimulation, via the RHT's connections with the SCN, exerts an organizational influence on the developing circadian system and, consequently, contributes to the emergence of nocturnality in this species.

Developmental divergence of sleep-wake patterns in orexin knockout and wild-type mice.

Narcolepsy, a disorder characterized by fragmented bouts of sleep and wakefulness during the day and night as well as cataplexy, has been linked in humans and nonhuman animals to the functional integrity of the orexinergic system. Adult orexin knockout mice and dogs with a mutation of the orexin receptor exhibit symptoms that mirror those seen in narcoleptic humans. As with narcolepsy, infant sleep-wake cycles in humans and rats are highly fragmented, with consolidated bouts of sleep and wakefulness developing gradually. Based on these common features of narcoleptics and infants, we hypothesized that the development of sleep-wake fragmentation in orexin knockout mice would be expressed as a developmental divergence between knockouts and wild-types, with the knockouts lagging behind the wild-types. We tested this hypothesis by recording the sleep-wake patterns of infant orexin knockout and wild-type mice across the first three postnatal weeks. Both knockouts and wild-types exhibited age-dependent, and therefore orexin-independent, quantitative and qualitative changes in sleep-wake patterning. At 3 weeks of age, however, by which time the sleep and wake bouts of the wild-types had consolidated further, the knockouts lagged behind the wild-types and exhibited significantly more bout fragmentation. These findings suggest the possibility that the fragmentation of behavioural states that characterizes narcolepsy in adults reflects reversion back toward the more fragmented sleep-wake patterns that characterize infancy.