Diferencia venoarterial de Pco2 como predictor de disfunción miocárdica en niños con sepsis severa y choque séptico.

Introducción: La sepsis es una de las principales causas de morbilidad y mortalidad en la población pediátrica a nivel mundial, siendo la disminución del gasto cardiaco uno de los principales factores asociados a mortalidad. Se ha planteado la diferencia venoarterial de pCO2 como predictor de la función miocárdica en pacientes con sepsis, sin embargo hasta el momento no hay estudios en la población pediátrica que lo evalúen. Objetivo: Determinar la capacidad predictora y las características operativas de la diferencia venoarterial de pCO2, como predictor de disfunción miocárdica en pacientes pediátricos con sepsis severa y choque séptico. Métodos: Para alcanzar los objetivos del estudio, se llevo a cabo un estudio prospectivo de pruebas diagnósticas. Se realizó ecocardiograma y diferencia venoarterial de pCO2 en cada paciente, posteriormente se calculó las características operativas de la diferencia venoarterial de pCO2 para determinar su utilidad. Resultados: Se incluyeron 71 pacientes. La mediana de la diferencia venoarterial de pCO2 no fue significativamente mayor en los pacientes que tuvieron disfunción cardiaca en el ecocardiograma en comparación con los que no tuvieron disfunción. Se encontró una relación estadísticamente significativa de valores de 1,5 a 2,1 mmHg, como predictor negativo de disfunción miocárdica con una sensibilidad de 100% y una especificidad de 88%. Conclusiones: La diferencia venoarterial de pCO2 requiere de estudios mas extensos para determinar la probabilidad como predictor de disfunción miocárdica en pacientes pediátricos con sepsis severa y choque séptico, incluso cuando otros biomarcadores se encuentran dentro de límites normales.

Autonomic dysfunction in patients with migrane associated dizziness (MAD)

The goal of this project is to identify what effect vestibular stimulation has on the reaction of the autonomic nervous system, as measured by blood pressure, blood-oxygen saturation levels, and heart rate monitoring, on subjects with migraine associated dizziness (MAD) as compared to healthy non-MAD subjects.

Iron Uptake and Homeostasis in Microorganisms

Preface. Iron is considered to be a minor element employed, in a variety of forms, by nearly all living organisms. In some cases, it is utilised in large quantities, for instance for the formation of magnetosomes within magnetotactic bacteria or during use of iron as a respiratory donor or acceptor by iron oxidising or reducing bacteria. However, in most cases the role of iron is restricted to its use as a cofactor or prosthetic group assisting the biological activity of many different types of protein. The key metabolic processes that are dependent on iron as a cofactor are numerous; they include respiration, light harvesting, nitrogen fixation, the Krebs cycle, redox stress resistance, amino acid synthesis and oxygen transport. Indeed, it is clear that Life in its current form would be impossible in the absence of iron. One of the main reasons for the reliance of Life upon this metal is the ability of iron to exist in multiple redox states, in particular the relatively stable ferrous (Fe2+) and ferric (Fe3+) forms. The availability of these stable oxidation states allows iron to engage in redox reactions over a wide range of midpoint potentials, depending on the coordination environment, making it an extremely adaptable mediator of electron exchange processes. Iron is also one of the most common elements within the Earth’s crust (5% abundance) and thus is considered to have been readily available when Life evolved on our early, anaerobic planet. However, as oxygen accumulated (the ‘Great oxidation event’) within the atmosphere some 2.4 billion years ago, and as the oceans became less acidic, the iron within primordial oceans was converted from its soluble reduced form to its weakly-soluble oxidised ferric form, which precipitated (~1.8 billion years ago) to form the ‘banded iron formations’ (BIFs) observed today in Precambrian sedimentary rocks around the world. These BIFs provide a geological record marking a transition point away from the ancient anaerobic world towards modern aerobic Earth. They also indicate a period over which the bio-availability of iron shifted from abundance to limitation, a condition that extends to the modern day. Thus, it is considered likely that the vast majority of extant organisms face the common problem of securing sufficient iron from their environment – a problem that Life on Earth has had to cope with for some 2 billion years. This struggle for iron is exemplified by the competition for this metal amongst co-habiting microorganisms who resort to stealing (pirating) each others iron supplies! The reliance of micro-organisms upon iron can be disadvantageous to them, and to our innate immune system it represents a chink in the microbial armour, offering an opportunity that can be exploited to ward off pathogenic invaders. In order to infect body tissues and cause disease, pathogens must secure all their iron from the host. To fight such infections, the host specifically withdraws available iron through the action of various iron depleting processes (e.g. the release of lactoferrin and lipocalin-2) – this represents an important strategy in our defence against disease. However, pathogens are frequently able to deploy iron acquisition systems that target host iron sources such as transferrin, lactoferrin and hemoproteins, and thus counteract the iron-withdrawal approaches of the host. Inactivation of such host-targeting iron-uptake systems often attenuates the pathogenicity of the invading microbe, illustrating the importance of ‘the battle for iron’ in the infection process. The role of iron sequestration systems in facilitating microbial infections has been a major driving force in research aimed at unravelling the complexities of microbial iron transport processes. But also, the intricacy of such systems offers a challenge that stimulates the curiosity. One such challenge is to understand how balanced levels of free iron within the cytosol are achieved in a way that avoids toxicity whilst providing sufficient levels for metabolic purposes – this is a requirement that all organisms have to meet. Although the systems involved in achieving this balance can be highly variable amongst different microorganisms, the overall strategy is common. On a coarse level, the homeostatic control of cellular iron is maintained through strict control of the uptake, storage and utilisation of available iron, and is co-ordinated by integrated iron-regulatory networks. However, much yet remains to be discovered concerning the fine details of these different iron regulatory processes. As already indicated, perhaps the most difficult task in maintaining iron homeostasis is simply the procurement of sufficient iron from external sources. The importance of this problem is demonstrated by the plethora of distinct iron transporters often found within a single bacterium, each targeting different forms (complex or redox state) of iron or a different environmental condition. Thus, microbes devote considerable cellular resource to securing iron from their surroundings, reflecting how successful acquisition of iron can be crucial in the competition for survival. The aim of this book is provide the reader with an overview of iron transport processes within a range of microorganisms and to provide an indication of how microbial iron levels are controlled. This aim is promoted through the inclusion of expert reviews on several well studied examples that illustrate the current state of play concerning our comprehension of how iron is translocated into the bacterial (or fungal) cell and how iron homeostasis is controlled within microbes. The first two chapters (1-2) consider the general properties of microbial iron-chelating compounds (known as ‘siderophores’), and the mechanisms used by bacteria to acquire haem and utilise it as an iron source. The following twelve chapters (3-14) focus on specific types of microorganism that are of key interest, covering both an array of pathogens for humans, animals and plants (e.g. species of Bordetella, Shigella, , Erwinia, Vibrio, Aeromonas, Francisella, Campylobacter and Staphylococci, and EHEC) as well as a number of prominent non-pathogens (e.g. the rhizobia, E. coli K-12, Bacteroides spp., cyanobacteria, Bacillus spp. and yeasts). The chapters relay the common themes in microbial iron uptake approaches (e.g. the use of siderophores, TonB-dependent transporters, and ABC transport systems), but also highlight many distinctions (such as use of different types iron regulator and the impact of the presence/absence of a cell wall) in the strategies employed. We hope that those both within and outside the field will find this book useful, stimulating and interesting. We intend that it will provide a source for reference that will assist relevant researchers and provide an entry point for those initiating their studies within this subject. Finally, it is important that we acknowledge and thank wholeheartedly the many contributors who have provided the 14 excellent chapters from which this book is composed. Without their considerable efforts, this book, and the understanding that it relays, would not have been possible. Simon C Andrews and Pierre Cornelis

Towards a model-based integration of co-registered electroencephalography/functional magnetic resonance imaging data with realistic neural population meshes

Brain activity can be measured with several non-invasive neuroimaging modalities, but each modality has inherent limitations with respect to resolution, contrast and interpretability. It is hoped that multimodal integration will address these limitations by using the complementary features of already available data. However, purely statistical integration can prove problematic owing to the disparate signal sources. As an alternative, we propose here an advanced neural population model implemented on an anatomically sound cortical mesh with freely adjustable connectivity, which features proper signal expression through a realistic head model for the electroencephalogram (EEG), as well as a haemodynamic model for functional magnetic resonance imaging based on blood oxygen level dependent contrast (fMRI BOLD). It hence allows simultaneous and realistic predictions of EEG and fMRI BOLD from the same underlying model of neural activity. As proof of principle, we investigate here the influence on simulated brain activity of strengthening visual connectivity. In the future we plan to fit multimodal data with this neural population model. This promises novel, model-based insights into the brain's activity in sleep, rest and task conditions.

Direct evidence for attention-dependent influences of the frontal eye-fields on feature-responsive visual cortex

Voluntary selective attention can prioritize different features in a visual scene. The frontal eye-fields (FEF) are one potential source of such feature-specific top-down signals, but causal evidence for influences on visual cortex (as was shown for "spatial" attention) has remained elusive. Here, we show that transcranial magnetic stimulation (TMS) applied to right FEF increased the blood oxygen level-dependent (BOLD) signals in visual areas processing "target feature" but not in "distracter feature"-processing regions. TMS-induced BOLD signals increase in motion-responsive visual cortex (MT+) when motion was attended in a display with moving dots superimposed on face stimuli, but in face-responsive fusiform area (FFA) when faces were attended to. These TMS effects on BOLD signal in both regions were negatively related to performance (on the motion task), supporting the behavioral relevance of this pathway. Our findings provide new causal evidence for the human FEF in the control of nonspatial "feature"-based attention, mediated by dynamic influences on feature-specific visual cortex that vary with the currently attended property.

Complex spatiotemporal haemodynamic response following sensory stimulation in the awake rat

Detailed understanding of the haemodynamic changes that underlie non-invasive neuroimaging techniques such as blood oxygen level dependent functional magnetic resonance imaging is essential if we are to continue to extend the use of these methods for understanding brain function and dysfunction. The use of animal and in particular rodent research models has been central to these endeavours as they allow in-vivo experimental techniques that provide measurements of the haemodynamic response function at high temporal and spatial resolution. A limitation of most of this research is the use of anaesthetic agents which may disrupt or mask important features of neurovascular coupling or the haemodynamic response function. In this study we therefore measured spatiotemporal cortical haemodynamic responses to somatosensory stimulation in awake rats using optical imaging spectroscopy. Trained, restrained animals received non-noxious stimulation of the whisker pad via chronically implanted stimulating microwires whilst optical recordings were made from the contralateral somatosensory cortex through a thin cranial window. The responses we measure from un-anaesthetised animals are substantially different from those reported in previous studies which have used anaesthetised animals. These differences include biphasic response regions (initial increases in blood volume and oxygenation followed by subsequent decreases) as well as oscillations in the response time series of awake animals. These haemodynamic response features do not reflect concomitant changes in the underlying neuronal activity and therefore reflect neurovascular or cerebrovascular processes. These hitherto unreported hyperemic response dynamics may have important implications for the use of anaesthetised animal models for research into the haemodynamic response function.

A dynamic causal model of the coupling between pulse stimulation and neural activity

We present a dynamic causal model that can explain context-dependent changes in neural responses, in the rat barrel cortex, to an electrical whisker stimulation at different frequencies. Neural responses were measured in terms of local field potentials. These were converted into current source density (CSD) data, and the time series of the CSD sink was extracted to provide a time series response train. The model structure consists of three layers (approximating the responses from the brain stem to the thalamus and then the barrel cortex), and the latter two layers contain nonlinearly coupled modules of linear second-order dynamic systems. The interaction of these modules forms a nonlinear regulatory system that determines the temporal structure of the neural response amplitude for the thalamic and cortical layers. The model is based on the measured population dynamics of neurons rather than the dynamics of a single neuron and was evaluated against CSD data from experiments with varying stimulation frequency (1–40 Hz), random pulse trains, and awake and anesthetized animals. The model parameters obtained by optimization for different physiological conditions (anesthetized or awake) were significantly different. Following Friston, Mechelli, Turner, and Price (2000), this work is part of a formal mathematical system currently being developed (Zheng et al., 2005) that links stimulation to the blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) signal through neural activity and hemodynamic variables. The importance of the model described here is that it can be used to invert the hemodynamic measurements of changes in blood flow to estimate the underlying neural activity.

The resting-state neurovascular coupling relationship: rapid changes in spontaneous neural activity in the somatosensory cortex are associated with haemodynamic fluctuations that resemble stimulus-evoked haemodynamics

Although promise exists for patterns of resting-state blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) brain connectivity to be used as biomarkers of early brain pathology, a full understanding of the nature of the relationship between neural activity and spontaneous fMRI BOLD fluctuations is required before such data can be correctly interpreted. To investigate this issue, we combined electrophysiological recordings of rapid changes in multi-laminar local field potentials from the somatosensory cortex of anaesthetized rats with concurrent two-dimensional optical imaging spectroscopy measurements of resting-state haemodynamics that underlie fluctuations in the BOLD fMRI signal. After neural ‘events’ were identified, their time points served to indicate the start of an epoch in the accompanying haemodynamic fluctuations. Multiple epochs for both neural ‘events’ and the accompanying haemodynamic fluctuations were averaged. We found that the averaged epochs of resting-state haemodynamic fluctuations taken after neural ‘events’ closely resembled the temporal profile of stimulus-evoked cortical haemodynamics. Furthermore, we were able to demonstrate that averaged epochs of resting-state haemodynamic fluctuations resembling the temporal profile of stimulus-evoked haemodynamics could also be found after peaks in neural activity filtered into specific electroencephalographic frequency bands (theta, alpha, beta, and gamma). This technique allows investigation of resting-state neurovascular coupling using methodologies that are directly comparable to that developed for investigating stimulus-evoked neurovascular responses.

Effects of pramipexole on the processing of rewarding and aversive taste stimuli

Rationale: Pramipexole, a D2/D3 dopamine receptor agonist, has been implicated in the development of impulse control disorders in patients with Parkinson's disease. Investigation of single doses of pramipexole in healthy participants in reward-based learning tasks has shown inhibition of the neural processing of reward, presumptively through stimulation of dopamine autoreceptors. Objectives: This study aims to examine the effects of pramipexole on the neural response to the passive receipt of rewarding and aversive sight and taste stimuli. Methods: We used functional magnetic resonance imaging to examine the neural responses to the sight and taste of pleasant (chocolate) and aversive (mouldy strawberry) stimuli in 16 healthy volunteers who received a single dose of pramipexole (0.25 mg) and placebo in a double-blind, within-subject, design. Results: Relative to placebo, pramipexole treatment reduced blood oxygen level-dependent activation to the chocolate stimuli in the areas known to play a key role in reward, including the ventromedial prefrontal cortex, the orbitofrontal cortex, striatum, thalamus and dorsal anterior cingulate cortex. Pramipexole also reduced activation to the aversive condition in the dorsal anterior cingulate cortex. There were no effects of pramipexole on the subjective ratings of the stimuli. Conclusions: Our results are consistent with an ability of acute, low-dose pramipexole to diminish dopamine-mediated responses to both rewarding and aversive taste stimuli, perhaps through an inhibitory action of D2/3 autoreceptors on phasic burst activity of midbrain dopamine neurones. The ability of pramipexole to inhibit aversive processing might potentiate its adverse behavioural effects and could also play a role in its proposed efficacy in treatment-resistant depression.

Satiation attenuates BOLD activity in brain regions involved in reward and increases activity in dorsolateral prefrontal cortex: an fMRI study in healthy volunteers

BACKGROUND: Neural responses to rewarding food cues are significantly different in the fed vs. fasted (>8 h food-deprived) state. However, the effect of eating to satiety after a shorter (more natural) intermeal interval on neural responses to both rewarding and aversive cues has not been examined. OBJECTIVE: With the use of a novel functional magnetic resonance imaging (fMRI) task, we investigated the effect of satiation on neural responses to both rewarding and aversive food tastes and pictures. DESIGN: Sixteen healthy participants (8 men, 8 women) were scanned on 2 separate test days, before and after eating a meal to satiation or after not eating for 4 h (satiated vs. premeal). fMRI blood oxygen level-dependent (BOLD) signals to the sight and/or taste of the stimuli were recorded. RESULTS: A whole-brain cluster-corrected analysis (P < 0.05) showed that satiation attenuated the BOLD response to both stimulus types in the ventromedial prefrontal cortex (vmPFC), orbitofrontal cortex, nucleus accumbens, hypothalamus, and insula but increased BOLD activity in the dorsolateral prefrontal cortex (dlPFC; local maxima corrected to P ≤ 0.001). A psychophysiological interaction analysis showed that the vmPFC was more highly connected to the dlPFC when individuals were exposed to food stimuli when satiated than when not satiated. CONCLUSIONS: These results suggest that natural satiation attenuates activity in reward-related brain regions and increases activity in the dlPFC, which may reflect a "top down" cognitive influence on satiation. This trial was registered at clinicaltrials.gov as NCT02298049.

Carregadores de oxigênio a base de níquel suportado em materiais mesooros para aplicação na recirculação química com reforma (RQR)

Oxygen carriers are metal oxides which have the ability to oxidize and reduce easily by various cycles. Due to this property these materials are widely usedin Chemical-Looping Reforming processes to produce H2 and syngas. In this work supports based on MCM-41 and La-SiO2 were synthesized by hydrothermal method. After the synthesis step they were calcined at 550°C for 2 hours and characterized by TG, XRD, surface area using the BET method and FTIR spectroscopy. The deposition of active phase, in this case Nickel, took place in the proportions of 5, 10 and 20% by weight of metallic nickel, for use as oxygen carriers.The XRD showed that increasing in the content of Ni supported on MCM-41 resulted in a decrease in spatial structure and lattice parameter of the material. The adsorption and desorption curves of the MCM-41 samples exhibited variations with the increase of Ni deposited. Surface area, average pore diameter and wall density of silica showed significant changes , due to the increase of the active phase on the mesoporous material. By other hand, in the samples with La-SiO2 composition was not observed peaks characteristic of hexagonal structure, in the XRD diffractogram. The adsorption/desorption isotherms of nitrogen observed are type IV, characteristic of mesoporous materials. The catalytic test indicates that the supports have no influence in the process, but the nickel concentration is very important, because the results for minor concentration of nickel are not good. The ratio H2/O2 was close to 2, for all 15 cycles involving the test storage capacity of O2, indicating that the materials are effective for oxygen transport

Dexmedetomidine Alters the Cardiovascular Response During Infra-Renal Aortic Cross-Clamping in Sevoflurane-Anesthetized Dogs

Some properties of the volatile anesthetics, such as vasodilatation and myocardial depression, combined with the sympathetic inhibition that alpha 2-agonists can produce may determine hemodynamic alterations during aortic, surgery. The interaction between dexmedetomidine (DEX), an alpha 2-agonist, and sevoflurane during aortic surgery is unknown. We studied the effects of DEX on hemodynamics and systemic oxygenation during aortic cross-clamping (Aox) and unclamping (UAox) in sevoflurane-anesthetized dogs Twenty dogs were. anesthetized with sevoflurane and were randomly assigned to two groups prior to Aox and UAox: control, n = 10, received saline infusion only, and DEX (1 mu g.kg(-1) load followed by 1 mu g.kg(-1).h(-1) infusion), n = 10. Hemodynamic and oxygenation variables were measured at baseline, after saline or DEX loading dose, 20 and 40 min after Aox, and 20 and 40 min after UAox. After DEX administration, heart rate, cardiac index l and systemic oxygen transport index (131021) were lower than in control group. Aox increased mean arterial pressure (MAP) and systemic vascular resistance index (SVRI) in both groups, but the effects were greater with DEX. Cl, heart rate, and DO(2)I were lower, while central venous pressure (CVP) and pulmonary artery occlusion pressure were higher in DEX compared to control. After UAox, MAP, CVP and SVRI were maintained higher in DEX in relation to control. We conclude that in sevoflurane-anesthetized dogs DEX alters the cardiovascular response during aortic surgery.

Maintaining Tissue Perfusion in High-Risk Surgical Patients: A Systematic Review of Randomized Clinical Trials

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

On the role of synchrony for neuron-astrocyte interactions and perceptual conscious processing

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Flooding tolerance of Tabebuia cassinoides: Metabolic, morphological and growth responses

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)