Potential for head injuries in infants from low-height falls: Laboratory investigation

Object. Falls are the most common accident scenario in young children as well as the most common history provided in child abuse cases. Understanding the biomechanics of falls provides clinicians with objective data to aid in their diagnosis of accidental or inflicted trauma. The objective of this study was to determine impact forces and angular accelerations associated with low-height falls in infants. Methods. An instrumented anthropomorphic infant surrogate was created to measure the forces and 3D angular accelerations associated with falls from low heights (0.3–0.9 m) onto a mattress, carpet pad, or concrete. Results. Although height significantly increased peak angular acceleration (αp), change in peak-to-peak angular velocity, time duration associated with the change in velocity, and peak impact force (Fp) for head-first drops onto a carpet pad or concrete, none of these variables were significantly affected by height when dropped onto a mattress. The αp was not significantly different for drops onto a carpet pad and concrete from 0.6 or 0.9 m due to compression of the carpet pad. Surprisingly, sagittal αp was equaled or surpassed by axial αp. Conclusions. These are the first 3D angular acceleration and impact force data available for head impact in infants from low-height falls. A future study involving a computational model of the infant head will use the loads measured in this study to predict the probability of occipital skull fracture on impact from head-first low-height falls. Together, these studies will provide data that will aid clinicians in the evaluation of accidental and inflicted head injuries, and will contribute to the design of safer environments for children. (DOI: 10.3171/PED.2008.2.11.321

Biomechanics of Toddler Head During Low-height Falls: An Anthorpomorphic Dummy Analysis

Object. Falls are the most common environmental setting for closed head injuries in children between 2 and 4 years of age. The authors previously found that toddlers had fewer skull fractures and scalp/facial soft-tissue injuries, and more frequent altered mental status than infants for the same low-height falls (≤ 3 ft). Methods. To identify potential age-dependent mechanical load factors that may be responsible for these clinical findings, the authors created an instrumented dummy representing an 18-month-old child using published toddler anthropometry and mechanical properties of the skull and neck, and they measured peak angular acceleration during low-height falls (1, 2, and 3 ft) onto carpet pad and concrete. They compared these results from occiput-first impacts to previously obtained values measured in a 6-week-old infant dummy. Results. Peak angular acceleration of the toddler dummy head was largest in the sagittal and horizontal directions and increased significantly (around 2-fold) with fall height between 1 and 2 ft. Impacts onto concrete produced larger peak angular accelerations and smaller impact durations than those onto carpet pad. When compared with previously measured infant drops, toddler head accelerations were more than double those of the infant from the same height onto the same surface, likely contributing to the higher incidence of loss of consciousness reported in toddlers. Furthermore, the toddler impact forces were larger than those in the infant, but because of the thicker toddler skull, the risk of skull fracture from low-height falls is likely lower in toddlers compared with infants. Conclusions. If similar fracture limits and brain tissue injury thresholds between infants and toddlers are assumed, it is expected that for impact events, the toddler is likely less vulnerable to skull fracture but more vulnerable to neurological impairment compared with the infant

Biomechanics of the Toddler Head During Low-height Falls: An Anthropomorphic Dummy Analysis Laboratory Investigation

OBJECT Falls are the most common environmental setting for closed head injuries in children between 2 and 4 years of age. The authors previously found that toddlers had fewer skull fractures and scalp/facial soft-tissue injuries, and more frequent altered mental status than infants for the same low-height falls (≤3 ft). METHODS To identify potential age-dependent mechanical load factors that may be responsible for these clinical findings, the authors created an instrumented dummy representing an 18-month-old child using published toddler anthropometry and mechanical properties of the skull and neck, and they measured peak angular acceleration during low-height falls (1, 2, and 3 ft) onto carpet pad and concrete. They compared these results from occiput-first impacts to previously obtained values measured in a 6-week-old infant dummy. RESULTS Peak angular acceleration of the toddler dummy head was largest in the sagittal and horizontal directions and increased significantly (around 2-fold) with fall height between 1 and 2 ft. Impacts onto concrete produced larger peak angular accelerations and smaller impact durations than those onto carpet pad. When compared with previously measured infant drops, toddler head accelerations were more than double those of the infant from the same height onto the same surface, likely contributing to the higher incidence of loss of consciousness reported in toddlers. Furthermore, the toddler impact forces were larger than those in the infant, but because of the thicker toddler skull, the risk of skull fracture from low-height falls is likely lower in toddlers compared with infants. CONCLUSIONS If similar fracture limits and brain tissue injury thresholds between infants and toddlers are assumed, it is expected that for impact events, the toddler is likely less vulnerable to skull fracture but more vulnerable to neurological impairment compared with the infant

Rho Kinase Signaling Pathways During Stretch in Primary Alveolar Epithelia

Alveolar epithelial cells (AECs) maintain integrity of the blood-gas barrier with actin-anchored intercellular tight junctions. Stretched type I-like AECs undergo magnitude- and frequency-dependent actin cytoskeletal remodeling into perijunctional actin rings. On the basis of published studies in human pulmonary artery endothelial cells (HPAECs), we hypothesize that RhoA activity, Rho kinase (ROCK) activity, and phosphorylation of myosin light chain II (MLC2) increase in stretched type I-like AECs in a manner that is dependent on stretch magnitude, and that RhoA, ROCK, or MLC2 activity inhibition will attenuate stretch-induced actin remodeling and preserve barrier properties. Primary type I-like AEC monolayers were stretched biaxially to create a change in surface area (ΔSA) of 12%, 25%, or 37% in a cyclic manner at 0.25 Hz for up to 60 min or left unstretched. Type I-like AECs were also treated with Rho pathway inhibitors (ML-7, Y-27632, or blebbistatin) and stained for F-actin or treated with the myosin phosphatase inhibitor calyculin-A and quantified for monolayer permeability. Counter to our hypothesis, ROCK activity and MLC2 phosphorylation decreased in type I-like AECs stretched to 25% and 37% ΔSA and did not change in monolayers stretched to 12% ΔSA. Furthermore, RhoA activity decreased in type I-like AECs stretched to 37% ΔSA. In contrast, MLC2 phosphorylation in HPAECs increased when HPAECs were stretched to 12% ΔSA but then decreased when they were stretched to 37% ΔSA, similar to type I-like AECs. Perijunctional actin rings were observed in unstretched type I-like AECs treated with the Rho pathway inhibitor blebbistatin. Myosin phosphatase inhibition increased MLC2 phosphorylation in stretched type I-like AECs but had no effect on monolayer permeability. In summary, stretch alters RhoA activity, ROCK activity, and MLC2 phosphorylation in a manner dependent on stretch magnitude and cell type

Uses of Remnant Human Lung Tissue for Mechanical Stretch Studies

Human lung tissue donated for research purposes is a precious resource which can enhance the exploration of mechanisms involved in ventilator-induced lung injury (VILI). The goal of this work was to establish methods and demonstrate the feasibility of obtaining viable primary human type I-like alveolar epithelial cells (AECs) from remnant tissue, even after a significant lapse in post-mortem time, as well as human precision-cut lung slices (PCLSs), and stretch them at magnitudes correlated with mechanical ventilation volumes. Although after 3 days in culture many of the isolated cells stained for the type II AEC marker pro-surfactant Protein C (pro-SPC), after 6 days in culture the monolayer stained only weakly and non-specifically for pro-SPC, and stained brightly for the type I AEC marker aquaporin-5. A strong zona-occludin 1 stain demonstrated the formation of tight junctions between the cells in the epithelial monolayer after only 3 days in culture. To demonstrate the utility of the preparations for the study of lung injury, we stretched the cells and the PCLSs cyclically, uniformly, and equibiaxially and quantified their viability. Our data show that the described methods allow the utilization of human tissue in in vitro stretch studies investigating VILI

Noninvasive Metrics for Identification of Brain Injury Deficits in Piglets

Balance and bispectral index metrics were evaluated in piglets following focal and diffuse brain injury. A significant decrease in bispectral index existed at 24 hours after diffuse brain injury, but not after focal injury. Postural sway increased at 1–6 hours after both focal and diffuse injuries

MicroRNA Modulate Alveolar Epithelial Response to Cyclic Stretch

Background MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression implicated in multiple cellular processes. Cyclic stretch of alveoli is characteristic of mechanical ventilation, and is postulated to be partly responsible for the lung injury and inflammation in ventilator-induced lung injury. We propose that miRNAs may regulate some of the stretch response, and therefore hypothesized that miRNAs would be differentially expressed between cyclically stretched and unstretched rat alveolar epithelial cells (RAECs). Results RAECs were isolated and cultured to express type I epithelial characteristics. They were then equibiaxially stretched to 25% change in surface area at 15 cycles/minute for 1 hour or 6 hours, or served as unstretched controls, and miRNAs were extracted. Expression profiling of the miRNAs with at least 1.5-fold change over controls revealed 42 miRNAs were regulated (34 up and 8 down) with stretch. We validated 6 of the miRNAs using real-time PCR. Using a parallel mRNA array under identical conditions and publicly available databases, target genes for these 42 differentially regulated miRNAs were identified. Many of these genes had significant up- or down-regulation under the same stretch conditions. There were 362 down-regulated genes associated with up-regulated miRNAs, and 101 up-regulated genes associated with down-regulated miRNAs. Specific inhibition of two selected miRNAs demonstrated a reduction of the increased epithelial permeability seen with cyclic stretch. Conclusions We conclude that miRNA expression is differentially expressed between cyclically stretched and unstretched alveolar epithelial cells, and may offer opportunities for therapeutic intervention to ameliorate stretch-associated alveolar epithelial cell dysfunction

Gr\"obner Bases and Nullstellens\"atze for Graph-Coloring Ideals

We revisit a well-known family of polynomial ideals encoding the problem of graph-$k$-colorability. Our paper describes how the inherent combinatorial structure of the ideals implies several interesting algebraic properties. Specifically, we provide lower bounds on the difficulty of computing Gr\"obner bases and Nullstellensatz certificates for the coloring ideals of general graphs. For chordal graphs, however, we explicitly describe a Gr\"obner basis for the coloring ideal, and provide a polynomial-time algorithm.Comment: 16 page

Stretch Increases Alveolar Epithelial Permeability to Uncharged Micromolecules

We measured stretch-induced changes in transepithelial permeability in vitro to uncharged tracers 1.5–5.5 Å in radius to identify a critical stretch threshold associated with failure of the alveolar epithelial transport barrier. Cultured alveolar epithelial cells were subjected to a uniform cyclic (0.25 Hz) biaxial 12, 25, or 37% change in surface area (ΔSA) for 1 h. Additional cells served as unstretched controls. Only 37% ΔSA (100% total lung capacity) produced a significant increase in transepithelial tracer permeability, with the largest increases for bigger tracers. Using the permeability data, we modeled the epithelial permeability in each group as a population of small pores punctuated by occasional large pores. After 37% ΔSA, increases in paracellular transport were correlated with increases in the radii of both pore populations. Inhibition of protein kinase C and tyrosine kinase activity during stretch did not affect the permeability of stretched cells. In contrast, chelating intracellular calcium and/or stabilizing F-actin during 37% ΔSA stretch reduced but did not eliminate the stretch-induced increase in paracellular permeability. These results provide the first in vitro evidence that large magnitudes of stretch increase paracellular transport of micromolecules across the alveolar epithelium, partially mediated by intracellular signaling pathways. Our monolayer data are supported by whole lung permeability results, which also show an increase in alveolar permeability at high inflation volumes (20 ml/kg) at the same rate for both healthy and septic lungs