Building Blocks-A Block-by-Block Approach to Better Emergency Care in Children.

OBJECTIVE: We describe a case series of regional nerve blocks, which comprise an adapted framework for the pediatric emergency setting and were performed by pediatric emergency medicine physicians. METHODS: A case series of 8 different ultrasound-guided nerve blocks and 1 anatomical block, performed in 11 pediatric patients, aged 7 weeks to 17 years. RESULTS: All blocks resulted in adequate analgesia. No procedural complications were observed. CONCLUSION: We describe a set of nerve blocks performed by emergency medicine physicians in the pediatric population in an ED setting. In suitable settings, this is a safe and effective tool for procedural analgesia or for pain management. In such cases, performing an ultrasound-guided nerve block in the ED is a viable alternative for repeated doses of opiates, deep procedural sedation, or the operating theater. We propose this set of regional anesthesia procedures as a pediatric-adapted toolkit for the emergency physician to be performed in children in the ED setting. Adopting this set of procedures ensures better and safer care for children and provides a training framework for pediatric ED physicians.

Ultrasound-Guided Supraclavicular Brachial Plexus Blocks Performed by Pediatric Emergency Medicine Physicians for Painful Orthopedic Procedures in a Pediatric Emergency Department-A Case Series.

OBJECTIVE: The aim of this study was to describe our experience with ultrasound-guided supraclavicular brachial plexus blocks performed by pediatric emergency physicians for the purpose of forearm fracture reductions in the emergency department. METHODS: We present a case series of 15 pediatric patients aged 7 to 17 years undergoing ultrasound-guided supraclavicular blocks. RESULTS: All blocks resulted in adequate analgesia. No procedural complications were observed. CONCLUSIONS: We conclude that in select pediatric cases ultrasound-guided brachial plexus blocks can be a safe, swift, and efficient means of pain management and procedural analgesia. This approach obviates the need for sedation, thus shortening the time lag between presentation and the reduction procedure, as well as overall length of stay.

Dynamics of the cell-cycle network under genome-rewiring perturbations.

The cell-cycle progression is regulated by a specific network enabling its ordered dynamics. Recent experiments supported by computational models have shown that a core of genes ensures this robust cycle dynamics. However, much less is known about the direct interaction of the cell-cycle regulators with genes outside of the cell-cycle network, in particular those of the metabolic system. Following our recent experimental work, we present here a model focusing on the dynamics of the cell-cycle core network under rewiring perturbations. Rewiring is achieved by placing an essential metabolic gene exclusively under the regulation of a cell-cycle's promoter, forcing the cell-cycle network to function under a multitasking challenging condition; operating in parallel the cell-cycle progression and a metabolic essential gene. Our model relies on simple rate equations that capture the dynamics of the relevant protein-DNA and protein-protein interactions, while making a clear distinction between these two different types of processes. In particular, we treat the cell-cycle transcription factors as limited 'resources' and focus on the redistribution of resources in the network during its dynamics. This elucidates the sensitivity of its various nodes to rewiring interactions. The basic model produces the correct cycle dynamics for a wide range of parameters. The simplicity of the model enables us to study the interface between the cell-cycle regulation and other cellular processes. Rewiring a promoter of the network to regulate a foreign gene, forces a multitasking regulatory load. The higher the load on the promoter, the longer is the cell-cycle period. Moreover, in agreement with our experimental results, the model shows that different nodes of the network exhibit variable susceptibilities to the rewiring perturbations. Our model suggests that the topology of the cell-cycle core network ensures its plasticity and flexible interface with other cellular processes, without a need for an optimal setting of the kinetic parameters.

Cellular plasticity enables adaptation to unforeseen cell-cycle rewiring challenges.

The fundamental dynamics of the cell cycle, underlying cell growth and reproduction, were previously found to be robust under a wide range of environmental and internal perturbations. This property was commonly attributed to its network structure, which enables the coordinated interactions among hundreds of proteins. Despite significant advances in deciphering the components and autonomous interactions of this network, understanding the interfaces of the cell cycle with other major cellular processes is still lacking. To gain insight into these interfaces, we used the process of genome-rewiring in yeast by placing an essential metabolic gene HIS3 from the histidine biosynthesis pathway, under the exclusive regulation of different cell-cycle promoters. In a medium lacking histidine and under partial inhibition of the HIS3p, the rewired cells encountered an unforeseen multitasking challenge; the cell-cycle regulatory genes were required to regulate the essential histidine-pathway gene in concert with the other metabolic demands, while simultaneously driving the cell cycle through its proper temporal phases. We show here that chemostat cell populations with rewired cell-cycle promoters adapted within a short time to accommodate the inhibition of HIS3p and stabilized a new phenotypic state. Furthermore, a significant fraction of the population was able to adapt and grow into mature colonies on plates under such inhibiting conditions. The adapted state was shown to be stably inherited across generations. These adaptation dynamics were accompanied by a non-specific and irreproducible genome-wide transcriptional response. Adaptation of the cell-cycle attests to its multitasking capabilities and flexible interface with cellular metabolic processes and requirements. Similar adaptation features were found in our previous work when rewiring HIS3 to the GAL system and switching cells from galactose to glucose. Thus, at the basis of cellular plasticity is the emergence of a yet-unknown general, non-specific mechanism allowing fast inherited adaptation to unforeseen challenges.