An intravenous insulin protocol for strict glycemic control in acute ischaemic stroke.

BACKGROUND AND PURPOSE: There is a J-shaped association between admission glycemia and outcome. We designed an intravenous insulin protocol aiming at rapid and strict glucose control in hyperglycemic ischaemic stroke patients. Here, we describe the initial experience, safety, and efficacy of this protocol to achieve and maintain euglycemia in the first 48h. METHODS: The protocol is based on parallel scales for adjustment of insulin infusion rate according to current glycemia and the rate of change of glycemia, which was recommended in our stroke unit in 4/2007 in acute ischaemic stroke patients with glycemia >6mM. Data were registered in the Acute Stroke Registry and Analysis of Lausanne (ASTRAL). Capillary blood glycemia was measured hourly with fingerprick test at onset of treatment and after each scale change. Target glycemia was 4.0-6.0mM pre-prandially (5.5-8.0mM post-prandially). Hypokalemia was defined as serum potassium <3.5mM and measured every 12h. Specific algorithms were employed during meals and for patients leaving temporarily the stroke unit for diagnostic or therapeutic workup. RESULTS: In the 90 protocol patients, the first normoglycemia was achieved within 8h of treatment in 91.1% of patients (median interval 4h (interquartile range (IQR): 3-6). During the median treatment duration of 25.5h (IQR: 19.7-37.7), median glucose reduction was 2.5mM (IQR: 1.3-4.3mM). The overall rate of hypoglycemias was 4.5% and hypokalemias 18.5%. There was a significant increase in the proportion of hypokalemias on the first on-treatment measurement compared to admission (24.4% vs. 8.9%, P=0.002). CONCLUSIONS: The proposed intravenous insulin protocol controls acute post-stroke hyperglycemia but frequently leads to hypokalemia. This issue needs to be addressed for the protocol to be suitable for use in larger, randomized controlled trial to explore its clinical effect.

Nonregulated expression of TGBp3 of hordei-like viruses but not of potex-like viruses inhibits beet necrotic yellow vein virus cell-to-cell movement.

Plant viruses containing a Triple Gene Block (TGB) movement protein gene cassette fall into two classes. We have shown previously that the third TGB protein (TGBp3) of beet necrotic yellow vein virus (BNYVV; Class 1) and peanut clump virus (Class 1) inhibit BNYVV intercellular movement when expressed from a co-inoculated BNYVV RNA 3-based replicon. Here we show that autonomous expression of TGBp3's of four other Class 1 viruses of various genera also inhibits BNYVV movement. No such effect was observed for four Class 2 virus TGBp3's, suggesting that the roles of Class 1 and 2 TGBp3's in movement differ significantly.

Rapid screening for dominant negative mutations in the beet necrotic yellow vein virus triple gene block proteins P13 and P15 using a viral replicon.

Point mutations were introduced into the genes encoding the triple gene bock movement proteins P13 and P15 of beet necrotic yellow vein virus (BNYVV). Mutations which disabled viral cell-to-cell movement in Chenopodium quinoa were then tested for their ability to act as dominant negative inhibiters of movement of wild-type BNYVV when expressed from a co-inoculated BNYVV RNA 3-based replicon. For P13, three types of mutation inhibited the movement function: non-synomynous mutations in the N- and C-terminal hydrophobic domains, a mutation at the boundary between the N-terminal hydrophobic domain and the central hydrophilic domain (mutant P13-A12), and mutations in the conserved sequence motif in the central hydrophilic domain. However, only the 'boundary' mutant P13-A12 strongly inhibited movement of wild-type virus when expressed from the co-inoculated replicon. Similar experiments with P15 detected four movement-defective mutants which strongly inhibited cell-to-cell movement of wild-type BNYVV when the mutants were expressed from a co-inoculated replicon. Beta vulgaris transformed with two of these P15 mutants were highly resistant to fungus-mediated infection with BNYVV.

Virtually perfect time sharing in dual-task performance: uncorking the central cognitive bottleneck.

A fundamental issue for psychological science concerns the extent to which people can simultaneously perform two perceptual-motor tasks. Some theorists have hypothesized that such dual-task performance is severely and persistently constrained by a central cognitive "bottle-neck," whereas others have hypothesized that skilled procedural decision making and response selection for two or more tasks can proceed at the same time under adaptive executive control. The three experiments reported here support this latter hypothesis. Their results show that after relatively modest amounts of practice, at least some participants achieve virtually perfect time sharing in the dual-task performance of basic choice reaction tasks. The results also show that observed interference between tasks can be modulated by instructions about differential task priorities and personal preferences for daring (concurrent) or cautious (successive) scheduling of tasks. Given this outcome, future research should investigate exactly when and how such sophisticated skills in dual-task performance are acquired.

Aging and the psychological refractory period: task-coordination strategies in young and old adults.

The apparently deleterious effect of aging on dual-task performance is well established, but there is little agreement about the source of this effect. Studies of the psychological refractory period (PRP) indicate that young adults can flexibly control dual-task performance through task-coordination strategies. Thus, the performance of older adults might differ from young adults because older adults use different task-coordination strategies. To test this hypothesis, the executive-process interactive control (EPIC) architecture was applied to quantify the reaction time data from two PRP experiments conducted with young (age 18-26) and older (age 60-70) adults. The results show that participants' ability to coordinate the processing of two tasks did not decline with age. However, dual-task time costs were greater in the older adults. Three sources for this increase were found: generalized slowing, process-specific slowing, and the use of more cautious task-coordination strategies by the older adults.

Effects of structural modifications upon the accumulation in planta of replicons derived from beet necrotic yellow vein virus RNA 3.

Beet necrotic yellow vein virus (BNYVV) RNA 3 from which all but the 3' and 5' 'core' replication origins (promoters) have been deleted replicates when coinoculated to Chenopodium quinoa with viral RNAs 1 and 2. The resulting 'replicon' can be used to express inserted heterologous sequences in planta. The effects of alterations of replicon structure on its efficiency of accumulation in planta were examined. Inclusion of up to approximately 240 nucleotides of sequence from the region immediately upstream of the core 3'-promoter sequence increased replicon accumulation, suggesting that this region contains specific replication enhancer elements. Insertion of non-viral 'spacer' sequences between the core promoters also increased replicon accumulation, provided that no strong secondary structure was present. The highly homologous 3'-terminal core promoters of BNYVV RNAs 1, 2 and 4 could substitute for the RNA 3 core promoter but were generally somewhat less effective. Co-inoculation of full-length RNA 3 but not RNA 4 interfered with accumulation of the RNA 3-based replicons.

Cell-to-cell movement of beet necrotic yellow vein virus: I. Heterologous complementation experiments provide evidence for specific interactions among the triple gene block proteins.

Cell-to-cell movement of beet necrotic yellow vein virus (BNYVV) requires three proteins encoded by a triple gene block (TGB) on viral RNA 2. A BNYVV RNA 3-derived replicon was used to express movement proteins to functionally substitute for the BNYVV TGB proteins was tested by coinoculation of TGB-defective BNYVV with the various replicons to Chenopodium quinoa. Trans-heterocomplementation was successful with the movement protein (P30) of tobacco mosaic virus but not with the tubule-forming movement proteins of alfalfa mosaic virus and grapevine fanleaf virus. Trans-complementation of BNYVV movement was also observed when all three TGB proteins of the distantly related peanut clump virus were supplied together but not when they were substituted for their BNYVV counterparts one by one. When P30 was used to drive BNYVV movement in trans, accumulation of the first TGB protein of BNYVV was adversely affected by null mutations in the second and third TGB proteins. Taken together, these results suggest that highly specific interactions among cognate TGB proteins are important for their function and/or stability in planta.

Vascular movement of beet necrotic yellow vein virus in Beta macrocarpa is probably dependent on an RNA 3 sequence domain rather than a gene product.

RNAs 1 and 2 of beet necrotic yellow vein virus (BNYVV) carry the functions enabling viral RNA replication, cell-to-cell movement, virus assembly and vascular movement of the virus in the systemic host Spinacea oleracea. In Beta macrocarpa, on the other hand, BNYVV RNA 3 is required for vascular movement. Replication-competent RNA 3 transcripts carrying various point mutations and deletions were coinnoculated with RNAs 1 and 2 to young leaves of B. macrocarpa and the ability of the virus to multiply on the inoculated leaves and to invade the plant systemically was examined. None of the RNA 3 mutants tested interfered with virus multiplication in the inoculated leaves. Point mutations designed to specifically block or truncate translation of the ORFs of the two known RNA 3 gene products, P25 and N, did not interfere with vascular movement. Vascular movement was not inhibited by deletions eliminating the short 5'-proximal ORF on RNA 3 (ORF A) or by point mutations blocking putative translation of the short 5'-proximal ORF (ORF S) on RNA 3sub, a subgenomic RNA derived from RNA 3. On the other hand, deletions in a 'core region' encompassing nucleotides 1033-1257 of RNA 3 completely blocked vascular movement of the virus while removal of sequences flanking the core region lowered its efficiency. The observations suggest that some feature of the RNA 3 sequence rather than an RNA-3 coded protein is important for vascular movement of BNYVV in B. macrocarpa.

Isolation of specific interference processing in the Stroop task: PET activation studies.

The Stroop task, in which subjects must name the color of letters that spell color words different than the color-to-be-named, provides an important experimental paradigm for the study of selective attention. Cerebral blood flow activation studies have not always demonstrated consistent activation patterns; inconsistent results may reflect nonspecific responses, such as arousal or anticipation, rather than cerebral networks specific to Stroop interference processing. In order to identify regions consistently implicated in Stroop interference processing, we undertook two experiments with a Stroop interference paradigm and contrasting lexical and nonlexical control conditions. In our first experiment, standard Stroop stimuli, e.g., the word "RED" displayed in a green font, were contrasted with color naming of the font of noncolor words and color naming of a false font. In our second experiment, we compared Stroop stimuli with colored symbols and a control condition designed to elicit nonspecific interference-taboo words displayed in color fonts. Only two brain regions showed a consistent CBF change in both experiments. Activation in the left inferior frontal gyrus reflected processing more specific to the Stroop task, while deactivation in the right superior temporal gyrus occurred for the Stroop and the taboo conditions, consistent with more nonspecific processing. Activation in the anterior cingulate cortex occurred in only one comparison in one experiment and may not reflect functions central to overcoming Stroop interference.

Conformation of the 3'-end of beet necrotic yellow vein benevirus RNA 3 analysed by chemical and enzymatic probing and mutagenesis.

Secondary structure-sensitive chemical and enzymatic probes have been used to produce a model for the folding of the last 68 residues of the 3'-non-coding region of beet necrotic yellow vein benevirus RNA 3. The structure consists of two stem-loops separated by a single-stranded region. RNA 3-derived transcripts were produced containing mutations which either disrupted base pairing in the helices or maintained the helices but with alterations in the base pairing scheme. Other mutants contained substitutions in single-stranded regions (loops or bulged sequences). With a few exceptions all three types of mutation abolished RNA 3 replication in vivo, suggesting that both secondary structure and specific sequences are required for efficient recognition of the 3'-terminal region of RNA 3 by viral RNA-dependent RNA polymerase.

Verbal Working Memory Load Affects Regional Brain Activation as Measured by PET.

We report an experiment that assesses the effect of variations in memory load on brain activations that mediate verbal working memory. The paradigm that forms the basis of this experiment is the "n-back" task in which subjects must decide for each letter in a series whether it matches the one presented n items back in the series. This task is of interest because it recruits processes involved in both the storage and manipulation of information in working memory. Variations in task difficulty were accomplished by varying the value of n. As n increased, subjects showed poorer behavioral performance as well as monotonically increasing magnitudes of brain activation in a large number of sites that together have been identified with verbal working-memory processes. By contrast, there was no reliable increase in activation in sites that are unrelated to working memory. These results validate the use of parametric manipulation of task variables in neuroimaging research, and they converge with the subtraction paradigm used most often in neuroimaging. In addition, the data support a model of working memory that includes both storage and executive processes that recruit a network of brain areas, all of which are involved in task performance.

PET evidence for an amodal verbal working memory system.

Current models of verbal working memory assume that modality-specific representations are translated into phonological representations before entering the working memory system. We report an experiment that tests this assumption. Positron emission tomography measures were taken while subjects performed a verbal working memory task. Stimuli were presented either visually or aurally, and a visual or auditory search tasks, respectively, was used as a control. Results revealed an almost complete overlap between the active memory areas regardless of input modality. These areas included dorsolateral frontal, Broca's area, SMA, and premotor cortex in the left hemisphere; bilateral superior and posterior parietal cortices and anterior cingulate; and right cerebellum. These results correspond well with previous research and suggest that verbal working memory is modality independent and is mediated by a circuit involving frontal, parietal, and cerebellar mechanisms.

Conditional and unconditional automaticity: a dual-process model of effects of spatial stimulus-response correspondence.

Distributional analyses and event-related brain potential were used to show that effects of irrelevant spatial stimulus-response correspondence consist of 2 qualitatively different automatic components that can be distinguished on the basis of their dependencies on relative response speed and on computational requirements of the primary task. One component reflects priming of the spatially corresponding response by an abrupt stimulus onset that does not depend on the nature of the primary task. This unconditional component exhibits a biphasic pattern, with initial facilitation later turning into inhibition, analogous to that found for spatial cuing in visual detection tasks. The 2nd component reflects automatic generalization of task-defined transformations of relevant stimulus information to spatial codes; this conditional component does not depend on relative response speed. Possible connectionist implementations of the conditional mechanism are discussed.

Urinary volume, creatinine and thiocyanate of Africans of a tropical savanna region.

For 130 healthy African subjects of savanna region, the 24 h urine output was found to be of the order of 1000 ml. This appears somewhat less than levels found among temperate region peoples. These results permit one to grossly evaluate 24 h excretion of substances on rapid field studies. The creatinine urine excretions found, confirm the known characteristics--the variability with age, sex and amount of muscular tissue. Further the 24 h excretion cannot be accurately measured when one calculates it on the basis of urine creatinine excretion of a single micturition; therefore for an accurate measure one needs controlled 24-h urine collections. The urine thiocyanate excretion of this non-goitrous population on a low cassava diet is significantly lower than that found in an endemic goitrous population.