25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Transcriptional Phase Variation of a Type III Restriction-Modification System in Helicobacter pylori

Phase variation is important in bacterial pathogenesis, since it generates antigenic variation for the evasion of immune responses and provides a strategy for quick adaptation to environmental changes. In this study, a Helicobacter pylori clone, designated MOD525, was identified that displayed phase-variable lacZ expression. The clone contained a transcriptional lacZ fusion in a putative type III DNA methyltransferase gene (mod, a homolog of the gene JHP1296 of strain J99), organized in an operon-like structure with a putative type III restriction endonuclease gene (res, a homolog of the gene JHP1297), located directly upstream of it. This putative type III restriction-modification system was common in H. pylori, as it was present in 15 out of 16 clinical isolates. Phase variation of the mod gene occurred at the transcriptional level both in clone MOD525 and in the parental H. pylori strain 1061. Further analysis showed that the res gene also displayed transcriptional phase variation and that it was cotranscribed with the mod gene. A homopolymeric cytosine tract (C tract) was present in the 5′ coding region of the res gene. Length variation of this C tract caused the res open reading frame (ORF) to shift in and out of frame, switching the res gene on and off at the translational level. Surprisingly, the presence of an intact res ORF was positively correlated with active transcription of the downstream mod gene. Moreover, the C tract was required for the occurrence of transcriptional phase variation. Our finding that translation and transcription are linked during phase variation through slipped-strand mispairing is new for H. pylori

Predictors of elevated cardiac troponin T on admission in ST-segment elevation myocardial infarction

Background In patients with ST-segment elevation acute myocardial infarction (STEMI), elevated cardiac troponin T (cTnT) on admission is associated with poorer outcomes despite early reperfusion. Presentation delay is thought to be the most important factor for the elevation of cTnT on admission. We evaluated presentation delay and other potential predictors of elevated cTnT on admission in patients treated with primary percutaneous coronary interventions (PCI) for STEMI. Methods CTnT was measured upon arrival in the PCI centre in 444 patients with acute STEMI. An elevated cTnT was defined as >0.05 mu g/L. Results The mean age was 61.7 years and patients were admitted at a median of 155 min after symptom onset. Almost 50% had an elevated cTnT on admission. Patients with a positive cTnT on admission were less likely to have successful primary PCI (87 versus 93%, P = 0.048) and had significantly higher rates of one-year mortality (4.9 versus 1.3%, P = 0.031). There was a significant association between presentation delay and the prevalence of elevated admission cTnT, but even patients with early presentation ( Conclusion In patients with STEMI, the prevalence of elevated cTnT on admission is high, even in patients with early presentation. Independent predictors of elevated cTnT on admission are presentation delay, increasing age and anterior MI location

Predictors of elevated cardiac troponin T on admission in ST-segment elevation myocardial infarction

Background In patients with ST-segment elevation acute myocardial infarction (STEMI), elevated cardiac troponin T (cTnT) on admission is associated with poorer outcomes despite early reperfusion. Presentation delay is thought to be the most important factor for the elevation of cTnT on admission. We evaluated presentation delay and other potential predictors of elevated cTnT on admission in patients treated with primary percutaneous coronary interventions (PCI) for STEMI.Methods CTnT was measured upon arrival in the PCI centre in 444 patients with acute STEMI. An elevated cTnT was defined as &gt;0.05 mu g/L.Results The mean age was 61.7 years and patients were admitted at a median of 155 min after symptom onset. Almost 50% had an elevated cTnT on admission. Patients with a positive cTnT on admission were less likely to have successful primary PCI (87 versus 93%, P = 0.048) and had significantly higher rates of one-year mortality (4.9 versus 1.3%, P = 0.031). There was a significant association between presentation delay and the prevalence of elevated admission cTnT, but even patients with early presentation (Conclusion In patients with STEMI, the prevalence of elevated cTnT on admission is high, even in patients with early presentation. Independent predictors of elevated cTnT on admission are presentation delay, increasing age and anterior MI location.</p

Effect of using the HEART score in patients with chest pain in the emergency department: A Stepped-wedge, cluster randomized trial

Background: The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score is an easy-to-apply instrument to stratify patients with chest pain according to their short-term risk for major adverse cardiac events (MACEs), but its effect on daily practice is unknown. Objective: To measure the effect of use of the HEART score on patient outcomes and use of health care resources. Design: Stepped-wedge, cluster randomized trial. (Clinical Trials.gov: NCT01756846) Setting: Emergency departments in 9 Dutch hospitals. Patients: Unselected patients with chest pain presenting at emergency departments in 2013 and 2014. Intervention: All hospitals started with usual care. Every 6 weeks, 1 hospital was randomly assigned to switch to "HEART care," during which physicians calculated the HEART score to guide patient management. Measurements: For safety, a noninferiority margin of a 3.0% absolute increase in MACEs within 6 weeks was set. Other outcomes included use of health care resources, quality of life, and cost-effectiveness. Results: A total of 3648 patients were included (1827 receiving usual care and 1821 receiving HEART care). Six-week incidence of MACEs during HEART care was 1.3% lower than during usual care (upper limit of the 1-sided 95% CI, 2.1% [within the noninferiority margin of 3.0%]). In low-risk patients, incidence of MACEs was 2.0% (95% CI, 1.2% to 3.3%). No statistically significant differences in early discharge, readmissions, recurrent emergency department visits, outpatient visits, or visits to general practitioners were observed. Limitation: Physicians were hesitant to refrain from admission and diagnostic tests in patients classified as low risk by the HEART score. Conclusion: Using the HEART score during initial assessment of patients with chest pain is safe, but the effect on health care resources is limited, possibly due to nonadherence to management recommendations