The nature of the memory trace and its neurocomputational implications.

The brain processes underlying cognitive tasks must be very robust. Disruptions such as the destruction of large numbers of neurons, or the impact of alcohol and lack of sleep do not have negative effects except when they occur in an extreme form. This robustness implies that the parameters determining the functioning of networks of individual neurons must have large ranges or there must exist stabilizing mechanisms that keep the functioning of a network within narrow bounds. The simulation of a minimal neuronal architecture necessary to study cognitive tasks is described, which consists of a loop of three cell-assemblies. A crucial factor in this architecture is the critical threshold of a cell-assembly. When activated at a level above the critical threshold, the activation in a cell-assembly is subject to autonomous growth, which leads to an oscillation in the loop. When activated below the critical threshold, excitation gradually extinguishes. In order to circumvent the large parameter space of spiking neurons, a rate-dependent model of neuronal firing was chosen. The resulting parameter space of 12 parameters was explored by means of a genetic algorithm. The ranges of the parameters for which the architecture produced the required oscillations and extinctions, turned out to be relatively narrow. These ranges remained narrow when a stabilizing mechanism, controlling the total amount of activation, was introduced. The architecture thus shows chaotic behaviour. Given the overall stability of the operation of the brain, it can be concluded that there must exist other mechanisms that make the network robust. Three candidate mechanisms are discussed: synaptic scaling, synaptic homeostasis, and the synchronization of neural spikes.

Feasibility of a molecular screening method for detection of Salmonella enterica and Campylobacter jejuni in a routine community-based clinical microbiology laboratory.

Conventional diagnostic methods for the detection of Salmonella enterica and Campylobacter jejuni are laborious and time-consuming procedures, resulting in final results, for the majority of specimens, only after 3 to 4 days. Molecular detection can improve the time to reporting of the final results from several days to the next day. However, molecular assays for the detection of gastrointestinal pathogens directly from stool specimens have not made it into the routine clinical microbiology laboratory. In this study we have assessed the feasibility of a real-time PCR-based molecular screening method (MSM), aimed at S. enterica and C. jejuni, in the daily practice of a routine clinical microbiology laboratory. We have prospectively analyzed 2,067 stool specimens submitted for routine detection of gastrointestinal bacterial pathogens over a 7-month period. The MSM showed 98 to 100% sensitivity but routine culture showed only 77.8 to 86.8% sensitivity when an extended "gold standard" that included all culture-positive and all MSM-positive specimens, as confirmed by an independent secondary PCR of a different target gene, was used. An overall improvement in the rate of detection of both pathogens of 15 to 18% was observed. Both approaches performed nearly identically with regard to the specificity, positive predictive value, and negative predictive value, with the values for MSM being 99.7%, 93.1 to 96.6%, and 99.8 to 100%, respectively, and those for routine culture being 100%, 100%, and 97.6 to 99.5%, respectively. Finally, the final results were reported between 3 and 4 days earlier for negative specimens compared to the time of reporting of the results of routine culture. Positive specimens, on the other hand, required an additional 2 days to obtain a final result compared to the time required for routine culture, although preliminary MSM PCR-positive results were reported, on average, 2.9 to 3.8 days before the final routine culture results were reported. In conclusion, MSM can be incorporated into the daily practice of a routine clinical microbiology laboratory with ease. Furthermore, it provides an improvement in the screening for S. enterica and C. jejuni and substantially improves the time to the reporting of negative results.

The importance of vacA, cagA, and iceA genotypes of Helicobacter pylori infection in peptic ulcer disease and gastroesophageal reflux disease.

OBJECTIVE: To study the relationship between the presence of H. pylori virulence factors and clinical outcome in H. pylori infected patients. METHODS: DNA was isolated from an antral biopsy sample and vacA, cagA, and iceA genotype were determined by PCR and a reverse hybridization technique in 183 patients with culture-proven H. pylori infection: 51 with peptic ulcer disease (PUD), 62 with gastroesophageal reflux disease (GERD), and 70 with a normal endoscopy (gastritis only; GO). RESULTS: Forty-four samples (24%) showed more than one allelic variant in the vacA s- or in-region and/or both iceA1 and iceA2 genotypes, indicating multiple strain infection. These were excluded from statistical analysis. vacA s1 and cagA were significantly more common in PUD than in GERD and GO. Logistic regression analysis showed that GERD patients were more often infected with strains lacking both cagA and iceA than GO patients (OR = 0.36; CI = 0.15-0.89). Trend analysis showed that GERD patients were most often infected with less virulent strains (p < 0.002). CONCLUSION: Multiple strain infection is common. H. pylori strains possessing the vacA s1 genotype and/or cagA are associated with PUD. GERD patients, infected with H. pylori, mostly carry less virulent strains possessing neither cagA nor iceA1. Our findings support the hypothesis that virulent strains protect against the development of GERD.