Integrated Multiscale Modeling of the Nervous System: Predicting Changes in Hippocampal Network Activity by a Positive AMPA Receptor Modulator

One of the fundamental characteristics of the brain is its hierarchical organization. Scales in both space and time that must be considered when integrating across hierarchies of the nervous system are sufficiently great as to have impeded the development of routine multilevel modeling methodologies. Complex molecular interactions at the level of receptors and channels regulate activity at the level of neurons; interactions between multiple populations of neurons ultimately give rise to complex neural systems function and behavior. This spatial complexity takes place in the context of a composite temporal integration of multiple, different events unfolding at the millisecond, second, minute, hour, and longer time scales. In this study, we present a multiscale modeling methodology that integrates synaptic models into single neuron, and multineuron, network models. We have applied this approach to the specific problem of how changes at the level of kinetic parameters of a receptor-channel model are translated into changes in the temporal firing pattern of a single neuron, and ultimately, changes in the spatiotemporal activity of a network of neurons. These results demonstrate how this powerful methodology can be applied to understand the effects of a given local process within multiple hierarchical levels of the nervous system

Simulation of Postsynaptic Glutamate Receptors Reveals Critical Features of Glutamatergic Transmission

Activation of several subtypes of glutamate receptors contributes to changes in postsynaptic calcium concentration at hippocampal synapses, resulting in various types of changes in synaptic strength. Thus, while activation of NMDA receptors has been shown to be critical for long-term potentiation (LTP) and long term depression (LTD) of synaptic transmission, activation of metabotropic glutamate receptors (mGluRs) has been linked to either LTP or LTD. While it is generally admitted that dynamic changes in postsynaptic calcium concentration represent the critical elements to determine the direction and amplitude of the changes in synaptic strength, it has been difficult to quantitatively estimate the relative contribution of the different types of glutamate receptors to these changes under different experimental conditions. Here we present a detailed model of a postsynaptic glutamatergic synapse that incorporates ionotropic and mGluR type I receptors, and we use this model to determine the role of the different receptors to the dynamics of postsynaptic calcium with different patterns of presynaptic activation. Our modeling framework includes glutamate vesicular release and diffusion in the cleft and a glutamate transporter that modulates extracellular glutamate concentration. Our results indicate that the contribution of mGluRs to changes in postsynaptic calcium concentration is minimal under basal stimulation conditions and becomes apparent only at high frequency of stimulation. Furthermore, the location of mGluRs in the postsynaptic membrane is also a critical factor, as activation of distant receptors contributes significantly less to calcium dynamics than more centrally located ones. These results confirm the important role of glutamate transporters and of the localization of mGluRs in postsynaptic sites in their signaling properties, and further strengthen the notion that mGluR activation significantly contributes to postsynaptic calcium dynamics only following high-frequency stimulation. They also provide a new tool to analyze the interactions between metabotropic and ionotropic glutamate receptors

Embolisation portale droite préopératoire par voie percutanée avant hépatectomie pour métastases de cancer colorectal (à propos de 47 cas)

STRASBOURG-Medecine (674822101) / SudocSTRASBOURG-Sc. et Techniques (674822102) / SudocSudocFranceF

Embolisation d'hémostase et hémorragie du postpartum (étude rétrospective à propos de 43 cas)

STRASBOURG-Medecine (674822101) / SudocSudocFranceF

Venous thromboembolism and occult malignancy: simultaneous detection during pulmonary CT angiography with CT venography

OBJECTIVE: We explored the potential for patients with proven venous thromboembolism or pulmonary embolism (PE) to have occult malignancies detected during the same CT examination. To verify this, we compared the presence of occult malignancies identified on pulmonary artery CT angiography (CTA) and CT venography (CTV) when venous thromboembolism (VTE) was present. SUBJECTS AND METHODS: Pulmonary artery CTA combined with CTV was performed on a 16-MDCT scanner on 186 adult patients suspected of having pulmonary embolism without any known malignancies. CTV was performed from the diaphragm to the knee 180 seconds after CTA. Two radiologists evaluated the presence of VTE, that is PE or deep venous thrombosis (DVT), and tumor lesions on both examinations in consensus. The malignant nature of the possibly identified tumors was confirmed by pathologic examination. RESULTS: VTE was found in 49 patients (26%). Malignant tumors were detected in 24 patients (13%). Eleven patients with malignant tumors had VTE (46% of patients with malignant tumors; 22% with VTE and 6% of all patients). There was correlation with presence of malignancies between both and DVT and DVT associated with PE but not between presence of malignancies and PE only. Patients with DVT and those with DVT associated with PE had a risk ratio of 3.2 and 3.3, respectively, for having a malignant tumor discovered simultaneously. CONCLUSION: A high number of malignant tumors can be incidentally discovered on pulmonary artery CTA, even more so with additional CTV. Radiologists should scrutinize scans to pick up unknown malignancies, especially in patients with identified VTE

Endoscopic ultrasound-guided hepaticogastrostomy percutaneous transhepatic drainage for malignant biliary obstruction after failed endoscopic retrograde cholangiopancreatography: a retrospective expertise-based study from two centers

Background: Percutaneous transhepatic biliary drainage (PTBD) is widely performed as a salvage procedure in patients with unresectable malignant obstruction of the common bile duct (CBD) after failed endoscopic retrograde cholangiopancreatography (ERCP) or in case of surgically altered anatomy. Endoscopic ultrasound-guided hepaticogastrostomy (EU-HGS) is a more recently introduced alternative to relieve malignant obstructive jaundice. The aim of this prospective observational study was to compare the outcome, efficacy and adverse events of EU-HGS and PTBD. Methods: From April 2012 to August 2015, consecutive patients with malignant CBD obstruction who underwent EU-HGS or PTBD in two tertiary-care referral centers were included. The primary endpoint was the clinical success rate. Secondary endpoints were technical success, overall survival, procedure-related adverse events, incidence of adverse events, and reintervention rate. Results: A total of 51 patients (EU-HGS, n = 31; PTBD, n = 20) were included. Median survival was 71 days (range 25–75th percentile; 30–95) for the EU-HGS group and 78 days (range 25–75th percentile; 42–108) for the PTBD group ( p = 0.99). Technical success was achieved in all patients in both groups. Clinical success was achieved in 25 (86%) of 31 patients in the EU-HGS group and in 15 (83%) of 20 patients in the PTBD group ( p = 0.88). There was no difference in adverse events rates between the two groups (EU-HGS: 16%; PTBD: 10%) ( p = 0.69). Four deaths within 1 month (two hemorrhagic and two septic) were considered procedure related (two in the EU-HGS group and two in the PTBD group). Overall reintervention rate was significantly lower after EU-HGS ( n = 2) than after PTBD ( n = 21) ( p = 0.0001). Length of hospital stay was shorter after EU-HGS (8 days versus 15 days; p = 0.002). Conclusions: EU-HGS can be an effective and safe mini invasive-procedure alternative to PTBD, with similar success and adverse-event rates, but with lower rates of reintervention and length of hospitalization