The PCQLI has patient and parent-proxy forms, has wide age range, and discriminates between CHD subgroups. The ID and PI subscales of the PCQLI have excellent IC and correlate well with each other and the TS.

Typical neurons of the central nervous system (CNS) elaborate tens of thousands of membrane specializations at sites of synaptic contacts on their dendrites. To construct, maintain, and modify these specializations, neurons must produce and deliver the appropriate molecular constituents to particular synaptic sites. Previous studies have revealed that polyribosomes are selectively positioned beneath postsynaptic sites, suggesting that in neurons, as in other cell types, protein synthetic machinery is located at or near the sites where particular proteins are needed. The mechanisms that deliver ribosomes and messenger RNA to their specific destinations in cells are therefore of considerable interest. Here we describe a system for RNA transport in dendrites that could provide a mechanism for the delivery of ribosomes and mRNA to synaptic sites in dendrites. Hippocampal neurons grown in culture incorporate 3H-uridine in the nucleus, then selectively transport the newly synthesized RNA into dendrites at a rate of about 0.5 mm day-1. The transport is inhibited by metabolic poisons, suggesting that it is an active, energy-dependent process. The RNA may be transported in association with the cytoskeleton.

This study investigates the capacity of neuronal growth cones to synthesize protein locally and independently of their cell body. Isolated growth cones were prepared from cultures of neurons from the snail Helisoma by transecting neurites proximal to the growth cone. The capacity for protein synthesis was tested by radiolabeling cultures with 3H-leucine and analyzing the resultant autoradiograms. Isolated growth cones displayed incorporation of 3H-leucine that was inhibited by treatment with the protein synthesis inhibitors anisomycin and pactamycin, indicating that ribosomal-dependent translation occurs in growth cones. Ultrastructural analyses of growth cones demonstrated the presence of polyribosomes, the machinery for protein synthesis. The density of polyribosomes varied between growth cones, even between different growth cones on the same neuron, suggesting that growth cones express a range of protein synthetic capabilities. That different types of growth cones possess differing capabilities for protein synthesis is suggested in autoradiograms of 3H-leucine incorporation by the growth cones of axonal and nonaxonal neurites; incorporation was radically reduced in axonal growth cones in comparison with non-axonal growth cones. Finally, growth cones that were isolated for 2 d prior to radiolabeling incorporate 3H-leucine in a eukaryotic ribosomal-dependent manner, suggesting that the capacity for translation is long-lived in growth cones. Taken together, these studies reveal a capacity for protein synthesis confined totally to the neuronal growth cone proper. The synthesis of proteins in growth cones could afford a mechanism for the alteration of growth cone structure or function. This is in accord with the view that growth cones participate autonomously, to at least some extent, in the processes of synaptogenesis and the construction of neuronal architecture.

Humans are able to continuously monitor environmental situations and adjust their behavioral strategies to optimize performance. Here we investigate the behavioral and brain adjustments that occur when conflicting stimulus elements are, or are not, temporally predictable. Event-related potentials (ERPs) were collected while manual-response variants of the Stroop task were performed in which the stimulus onset asynchronies (SOAs) between the relevant-color and irrelevant-word stimulus components were either randomly intermixed, or held constant, within each experimental run. Results indicated that the size of both the neural and behavioral effects of stimulus incongruency varied with the temporal arrangement of the stimulus components, such that the random-SOA arrangements produced the greatest incongruency effects at the earliest irrelevant-first SOA (−200 ms) and the constant-SOA arrangements produced the greatest effects with simultaneous presentation. These differences in conflict processing were accompanied by rapid (~150 ms) modulations of the sensory ERPs to the irrelevant distracter components when they occurred consistently first. These effects suggest that individuals are able to strategically allocate attention in time to mitigate the influence of a temporally predictable distracter. As these adjustments are instantiated by the subjects without instruction, they reveal a form of rapid strategic learning for dealing with temporally predictable stimulus incongruency.

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The present study was undertaken to define the ultrastructure of synapses of the crossed temporodentate pathway after they had sprouted to reinnervate the dentate gyrus following the destruction of the normal ipsilateral temporodentate pathway. The synapses of the sprouted crossed temporodentate pathway were identified at the EM level by using autoradiographic techniques and by evaluating the degeneration of the pathway following secondary lesions. Both EM autoradiography and EM degeneration revealed that the terminals of the sprouted crossed temporodentate pathway formed asymmetric synapses on spines; individual terminals appeared to make more synaptic contacts per terminal (multiple synapses) than in the case of the normal crossed pathway. In the two lesioned animals exhibiting the best labeling, labeled terminals made an average of 3.0 ± 2.2 and 2.0 ± 1.3 contacts per terminal. In contrast, labeled terminals in normal animals exhibited only one contact per terminal. The terminals of the sprouted pathway were also larger than those of the normal crossed pathway. The synapses of the crossed temporodentate pathway that degenerated after a secondary lesion of the entorhinal cortex exhibited both electron‐lucent and electron‐dense forms of degeneration at 2 days postlesion. In two animals that were quantitatively analyzed, the density of degenerating synaptic terminals was 281 and 218/10,000 μm2 in the terminal field of the sprouted crossed pathway. These values are much higher than in normal animals, where the density of degenerating synaptic terminals was only 2.12/10,000 μm2 at 2 days postlesion. Because degenerating terminals were evident at 2 days postlesion, the sprouted crossed pathway does not appear to exhibit the very rapid degeneration that is characteristic of the normal crossed pathway. We conclude that sprouting in this pathway involves terminal proliferation (an increase in the number of presynaptic elements), and terminal hypertrophy (an increase in the size of presynaptic terminals, together with an increase in the number of synaptic contacts formed by individual terminals).

We performed a blinded, randomized pharmacokinetic study of milrinone in 16 neonates with hypoplastic left heart undergoing stage I reconstruction to determine the impact of cardiopulmonary bypass and modified ultrafiltration on drug disposition and to define the drug exposure during a continuous IV infusion of drug postoperatively. Neonates received an initial dose of either a 100 or 250 microg/kg of milrinone into the cardiopulmonary bypass circuit at the start of rewarming. Postoperatively, milrinone was infused to clinical needs. A mixed-effect modeling approach was used to characterize milrinone pharmacokinetics during cardiopulmonary bypass, modified ultrafiltration, and postoperatively using the NONMEM algorithm. All patients in this study demonstrated a modified ultrafiltration concentrating effect that occurred despite a modified ultrafiltration drug clearance of 3.3 mL x kg(-1) x min(-1). The infants in this study demonstrated an impaired renal clearance during the immediate postoperative period. A constant infusion of 0.5 microg x kg(-1) x min(-1) resulted in drug accumulation during the initial 12 h of drug administration. Postoperatively, milrinone clearance was significantly impaired (0.4 mL x kg(-1) x min(-1)), improved by the 12th postoperative hour, and approached steady-state clearance (2.6 mL x kg(-1) x min(-1)) by postoperative day 4. In the postoperative setting of markedly impaired renal function, an infusion rate of 0.2 microg x kg(-1) x min(-1) should be considered.