Longitudinal Change in Common Impairments in Children with Cerebral Palsy from age 1.5 to 11 years

Purpose: This project aimed to determine if change occurs over time for impairments of balance, range of motion (ROM), endurance, and strength of children with cerebral palsy (CP), by Gross Motor Function Classification System (GMFCS) levels. Methods: Measurements were completed in 77 children at two sessions (T1, T2) on average 5.8 years apart. Mean ages were 2.9 years (SD .9) and 8.7 years (SD 1.1) at T1 and T2, respectively. Results: Significant differences were noted from T1 to T2 for some children (GMFCS levels I, II, and III/IV: balance increased, GMFCS levels I and II: strength increased, and GMFCS levels III/IV and V: ROM decreased). Endurance scores were not different. Endurance scores did not change. Conclusions: Longitudinal changes in most impairments occurred in children with CP. Monitoring and targeted interventions should support each child’s development

Developmental Trajectories and Reference Percentiles for Range of Motion, Endurance, and Muscle Strength of Children With Cerebral Palsy.

BACKGROUND: Children with cerebral palsy (CP) frequently present with secondary impairments in spinal alignment and extremity range of motion, endurance for activity, and muscle strength. Creation of developmental trajectories for these impairments will help guide clinical decision-making. OBJECTIVE: For children in each level of the Gross Motor Function Classification System (GMFCS) this study aimed to: (1) create longitudinal developmental trajectories for range of motion (Spinal Alignment and Range of Motion Measures [SAROMM]), endurance (Early Activity Scale for Endurance [EASE]), and functional strength (Functional Strength Assessment [FSA]); and (2) develop age-specific reference percentiles and amount of change typical over 1 year for these outcomes. DESIGN: This study used a longitudinal cohort design. METHODS: Participants comprised 708 children with CP across GMFCS levels, aged 18 months up to the 12th birthday, and their families. In 2 to 5 assessments every 6 months over 2 years, trained therapists performed the SAROMM and FSA, and parents completed the EASE questionnaire. For children in each GMFCS level, longitudinal trajectories using linear and nonlinear mixed-effects models from all visits, and reference percentiles using quantile regression from the first, 12-month, and 24-month visits were created for each measure. RESULTS: Longitudinal trajectories and percentile graphs for SAROMM, FSA, and EASE were primarily linear, with different performance scores among GMFCS levels. There was much variability in both longitudinal trajectories and percentiles within GMFCS levels. LIMITATIONS: Limitations included a convenience sample and varying numbers of participants assessed at each visit. CONCLUSIONS: The longitudinal trajectories and percentile graphs have application for monitoring how children with CP are performing and changing over time compared with other children with CP. The resources presented allow therapists and families to collaboratively make decisions about intervention activities targeted to children\u27s unique needs

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Developmental Immaturity of Siglec Receptor Expression on Neonatal Alveolar Macrophages Predisposes to Severe Group B Streptococcal Infection.

Streptococcus agalactiae (Group B Streptococcus, GBS) is the most common neonatal pathogen. However, the cellular and molecular mechanisms for neonatal susceptibility to GBS pneumonia and sepsis are incompletely understood. Here we optimized a mouse model of GBS pneumonia to test the role of alveolar macrophage (ΑΜΦ) maturation in host vulnerability to disease. Compared with juvenile and adult mice, neonatal mice infected with GBS had increased mortality and persistence of lung injury. In addition, neonatal mice were defective in GBS phagocytosis and killing. ΑΜΦ depletion and disruption of ΑΜΦ differentiation in Csf2-/- mice both impaired GBS clearance. AMΦ engage the heavily sialylated GBS capsule via the cell surface Siglec receptors Sn and Siglec-E. Although both newborn and adult ΑΜΦ expressed Siglec-E, newborn ΑΜΦ expressed significantly lower levels of Sn. We propose that a developmental delay in Sn expression on ΑΜΦ may prevent effective killing and clearing of GBS from the newborn lung

Transcriptional profiling of lung macrophages identifies a predictive signature for inflammatory lung disease in preterm infants.

Lung macrophages mature after birth, placing newborn infants, particularly those born preterm, within a unique window of susceptibility to disease. We hypothesized that in preterm infants, lung macrophage immaturity contributes to the development of bronchopulmonary dysplasia (BPD), the most common serious complication of prematurity. By measuring changes in lung macrophage gene expression in preterm patients at risk of BPD, we show here that patients eventually developing BPD had higher inflammatory mediator expression even on the first day of life. Surprisingly, the ex vivo response to LPS was similar across all samples. Our analysis did however uncover macrophage signature genes whose expression increased in the first week of life specifically in patients resilient to disease. We propose that these changes describe the dynamics of human lung macrophage differentiation. Our study therefore provides new mechanistic insight into both neonatal lung disease and human developmental immunology

Transcriptional profiling of lung macrophages identifies a predictive signature for inflammatory lung disease in preterm infants.

Lung macrophages mature after birth, placing newborn infants, particularly those born preterm, within a unique window of susceptibility to disease. We hypothesized that in preterm infants, lung macrophage immaturity contributes to the development of bronchopulmonary dysplasia (BPD), the most common serious complication of prematurity. By measuring changes in lung macrophage gene expression in preterm patients at risk of BPD, we show here that patients eventually developing BPD had higher inflammatory mediator expression even on the first day of life. Surprisingly, the ex vivo response to LPS was similar across all samples. Our analysis did however uncover macrophage signature genes whose expression increased in the first week of life specifically in patients resilient to disease. We propose that these changes describe the dynamics of human lung macrophage differentiation. Our study therefore provides new mechanistic insight into both neonatal lung disease and human developmental immunology

New particle formation in the remote marine boundary layer

Marine low clouds play an important role in the climate system, and their properties are sensitive to cloud condensation nuclei concentrations. While new particle formation represents a major source of cloud condensation nuclei globally, the prevailing view is that new particle formation rarely occurs in remote marine boundary layer over open oceans. Here we present evidence of the regular and frequent occurrence of new particle formation in the upper part of remote marine boundary layer following cold front passages. The new particle formation is facilitated by a combination of efficient removal of existing particles by precipitation, cold air temperatures, vertical transport of reactive gases from the ocean surface, and high actinic fluxes in a broken cloud field. The newly formed particles subsequently grow and contribute substantially to cloud condensation nuclei in the remote marine boundary layer and thereby impact marine low clouds