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The atria can go into dilation when stenosis or insufficiency of valvular apparatus occurs. The atrial kick contributes to a stroke volume of around 20%, and its contribution increases when there is diastolic dysfunction owing to the elevation of atrial pressure. An increased atrial volume is an independent predictor of adverse cardiovascular events, including stroke and congestive heart failure. Accordingly, accurate measurement of the atrial size has become increasingly relevant to clinical practice. Most clinical studies have used echocardiographic measurements, because echocardiography is the most accepted and best validated modality for atrial volume quantification.

There are several devices for haemodynamic monitoring in the ICU. In low-risk postsurgical patients, haemodynamic monitoring of noninvasive blood pressure, heart rate and EtCO2 will be able to provide sufficient data to diagnose an unexpected haemodynamic instability. In high-risk or in intermediate-risk postsurgical patients, it may be sufficient to perform a SVV monitoring to guide the haemodynamic optimization and the patient’s preload management. In major and more complex surgical procedures, where “mixed shock” can occur (e.g. in abdominal emergency surgery or in a patient with pre-existing cardiomyopathy or valve disease or pulmonary hypertension), a complete and more invasive haemodynamic assessment must be performed with a calibrated device for the cardiac output measurement or a combined PAC with a SVV measuring tool.

Recent advances in fast volumetric imaging have enabled rapid generation of large amounts of multi-dimensional functional data. While many computer frameworks exist for data storage and analysis of the multi-gigabyte Ca 2+ imaging experiments in neurons, they are less useful for analyzing Ca 2+ dynamics in astrocytes, where transients do not follow a predictable spatio-temporal distribution pattern. In this manuscript, we provide a detailed protocol and commentary for recording and analyzing three-dimensional (3D) Ca 2+ transients through time in GCaMP6f-expressing astrocytes of adult brain slices in response to axonal stimulation, using our recently developed tools to perform interactive exploration, filtering, and time-correlation analysis of the transients. In addition to the protocol, we release our in-house software tools and discuss parameters pertinent to conducting axonal stimulation/response experiments across various brain regions and conditions. Our software tools are available from the Volterra Lab webpage at https://wwwfbm.unil.ch/dnf/group/glia-an-active-synaptic-partner/member/volterra-andrea-volterra in the form of software plugins for Image J (NIH)-a de facto standard in scientific image analysis. Three programs are available: MultiROI_TZ_profiler for interactive graphing of several movable ROIs simultaneously, Gaussian_Filter5D for Gaussian filtering in several dimensions, and Correlation_Calculator for computing various cross-correlation parameters on voxel collections through time.

Duration >120 minutes of extracorporeal circulation (ECC) during cardiopulmonary bypass procedure was associated to an increased risk of candidemia in the intensive care unit (ICU). To evaluate oral nystatin prophylaxis in cardiac surgery considering its exclusive effect on Candida, in the absence of systemic effects and selection of resistant strains to polyene. We conducted an observational study in the postcardiac surgery ICU of Policlinico "Umberto I" of Rome. From January 2014, all patients with a prolonged ECC >120 minutes were systematically treated with oral nystatin (Prophylaxis group). This group was compared with all patients hospitalised in the same ICU, who have not received oral nystatin after ECC >120 minutes (No prophylaxis group). Overall, 672 consecutive patients were analyzed: 318 (47.3%) patients belonged to the no prophylaxis group, and 354 (52.7%) patients to the prophylaxis group. Diagnosis of candidemia was confirmed in 7 (2.2%) patients, all belonged to the no prophylaxis group. At multivariate analysis, oral nystatin prophylaxis showed a protective effect for development of candidemia after cardiac surgery. Oral nystatin prophylaxis, in patients who underwent a ECC >120 minutes, seems to reduce development of candidemia; however, the real efficacy of such prophylaxis approach requires further investigation.

Positron emission tomography / computed tomography (PET/CT) and PET / magnetic resonance (PET/MR) with several tracers has been used to investigate the cellular physiopathology of brain tumors. For prediction of tumor grading, [18F]-fluorodeoxyglucose ([18F]-FDG) is more accurate than most amino acid tracers, while amino acid tracers, typically 11C-methionine, L-3,4-dihydroxyphenylalanine ([18F]-fluorodopa) and to a lesser extent O-(2-[18F]-fluoroethyl)-L-tyrosine, are more accurate than [18F]-FDG for the distinction between tumor recurrence and radiation necrosis. Changes after therapy as well as baseline tracer uptake in untreated patients have prognostic value. Post-surgical scans can be used for identification of residual tumor. PET, in combination with MR, is increasingly used for the definition of the tumor volume that has to be targeted by radiation therapy. Identification of the metabolically active volume can also be used to direct stereotaxic biopsy. Other tracers have been developed to explore different biochemical processes, for example hypoxia ([18F]-fluoromisonidazole), DNA synthesis (3-deoxy-3-[18F]-fluorothymidine, and membrane proliferation (radiolabeled choline). However, these radiopharmaceuticals presently have a more uncertain role in the clinical routine, even though some interesting results are emerging from the first clinical studies. The recent development of PET/MR hybrid scanners has represented a technological breakthrough with immediate consequences on improved diagnostic and research capabilities, as well as on logistical issues favorable for the patient, who can perform two examinations at a single time (“one-stop-shop”). This is particularly true for simultaneous systems in which the PET is within the magnetic field and the traditional PET detection system, classically based on photomultipliers, is replaced by magnetic field-insensitive avalanche photodiodes or silicon-based elements. The combination of the PET/ and MR has already proved to provide a complex synergistic effect. However, the use of PET/MR scanners is currently limited to restricted research centers owing to high costs, demanding maintenance, and necessary interdisciplinary personnel.

Summary Purpose Dravet syndrome (DS) is caused by dominant mutations of the SCN1A gene, encoding the NaV1.1 sodium channel α subunit. Gene targeted mouse models of DS mutations replicate patients' phenotype and show reduced γ-aminobutyric acid (GABA)ergic inhibition. However, little is known on the properties of network hyperexcitability and on properties of seizure generation in these models. In fact, seizures have been studied thus far with surface electroencephalography (EEG), which did not show if specific brain regions are particularly involved. We have investigated hyperexcitability and epileptiform activities generated in neuronal networks of a mouse model of DS. Methods We have studied heterozygous NaV1.1 knock-out mice performing field potential recordings in combined hippocampal/cortical slices in vitro and video/depth electrode intracerebral recordings in vivo during hyperthermia-induced seizures. Key Findings In slices, we have disclosed specific signs of hyperexcitability of hippocampal circuits in both the pre-epileptic and epileptic periods, and a specific epileptiform activity was generated in the hippocampus upon application of the convulsant 4-aminopyridine in the epileptic period. During in vivo hyperthermia-induced seizures, we have observed selective hippocampal activity in early preictal phases and pronounced hippocampal activity in the ictal phase. Significance We have identified specific epileptiform activities and signs of network hyperexcitability, and disclosed the important role of the hippocampus in seizure generation in this model. These activities may be potentially used as targets for screenings of antiepileptic approaches.

The current debate on the classification of seizures and epilepsies introduced the concept of epileptic networks that define focal epileptiform activities (Berg et al., 2010). The term epileptic network extends the notion of epileptic focus and introduces the idea that enhanced excitability within ensemble of strongly interconnected neurons/networks may promote the generation of region-specific synchronous pathologic discharges. This hypothesis has led to the proposition that some forms of idiopathic (and even acquired) epilepsy may represent a specific network dysfunction, due to enduring propensity of the network/system itself as a whole to generate seizures (Avanzini et al., 2012). The existence of predetermined functional network substrates supporting the generation of synchronous activity patterns may represent one of the prerequisites for the definition of system or network epilepsy. Studies in a number of animal models of generalized epilepsy demonstrated that specific patterns of epileptiform discharges entrain the thalamocortical system (Gloor & Fariello, 1988; Danober et al., 1998; van Luijtelaar & Sitnikova, 2006; Leresche et al., 2012). The hippocampal-parahippocampal region represents another cortical system that is activated as a whole in models of temporal lobe epilepsy and limbic seizures (Avoli et al., 2002; Uva et al., 2005; McIntyre & Gilby, 2008). To gain more information about the cellular and network determinants of seizure generation in these areas, detailed in vitro studies were performed on brain tissue slices. In vitro slices, however, do not allow for an extensive and thorough analysis of network activities, because of the obvious limitations of the preparation itself. Isolated en block brain preparations (de Curtis et al., 1994; Luhmann et al., 2000; Khalilov et al., 2003; Uva et al., 2005) could be better suited for studying the propensity of extended, interconnected cortical regions to generate seizure-like events. We have previously reported that coexisting, but regionally independent, seizure patterns can be induced in brains of guinea pigs maintained in vitro by arterial perfusion by acute pharmacologic manipulations with proepileptic drugs (de Curtis et al., 1994; Uva et al., 2005). Moreover, in Carriero et al. (2010) we have recently demonstrated that in the presence of the potassium channel blocker 4-aminopyridine (4AP; Llinas et al., 1976; Avoli & Perreault, 1987; Perreault & Avoli, 1991), the olfactory cortices and the hippocampal-parahippocampal regions generate independent seizure-like discharges that do not reciprocally interact (Carriero et al., 2010), despite the anatomic and functional connections, and that show a completely different seizure pattern. We extend here the study of ictal discharges recorded in the olfactory system, which is known to be a seizure-prone region (Piredda & Gale, 1985), in this model of ictogenesis, to verify whether this region can be considered as a network system for seizure generation and to unveil the network and cellular mechanisms that sustain this peculiar activity.

In vitro studies performed on brain slices demonstrate that the potassium channel blocker 4-aminopyridine (4AP, 50 μM) discloses electrographic seizure activity and interictal discharges. These epileptiform patterns have been further analyzed here in a isolated whole guinea pig brain in vitro by using field potential recordings in olfactory and limbic structures. In 8 of 13 experiments runs of fast oscillatory activity ( fast runs, FRs) in the piriform cortex (PC) propagated to the lateral entorhinal cortex (EC), hippocampus and occasionally to the medial EC. Early and late FRs were asynchronous in the hemispheres showed different duration [1.78 ± 0.51 and 27.95 ± 4.55 (SD) s, respectively], frequency of occurrence (1.82 ± 0.49 and 34.16 ± 6.03 s) and frequency content (20–40 vs. 40–60 Hz). Preictal spikes independent from the FRs appeared in the hippocampus/EC and developed into ictal-like discharges that did not propagate to the PC. Ictal-like activity consisted of fast activity with onset either in the hippocampus ( n = 6) or in the mEC ( n = 2), followed by irregular spiking and sequences of diffusely synchronous bursts. Perfusion of the N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid (100 μM) did not prevent FRs, increased the duration of limbic ictal-like discharges and favored their propagation to olfactory structures. The AMPA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (50 μM) blocked ictal-like events and reduced FRs. In conclusion, 4AP-induced epileptiform activities are asynchronous and independent in olfactory and hippocampal-entorhinal regions. Epileptiform discharges in the isolated guinea pig brain show different pharmacological properties compared with rodent in vitro slices.