Lactate: brain fuel in human traumatic brain injury: a comparison with normal healthy control subjects.

We evaluated the hypothesis that lactate shuttling helps support the nutritive needs of injured brains. To that end, we utilized dual isotope tracer [6,6-(2)H2]glucose, that is, D2-glucose, and [3-(13)C]lactate techniques involving arm vein tracer infusion along with simultaneous cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Traumatic brain injury (TBI) patients with nonpenetrating brain injuries (n=12) were entered into the study following consent of patients' legal representatives. Written and informed consent was obtained from control volunteers (n=6). Patients were studied 5.7±2.2 (mean±SD) days post-injury; during periods when arterial glucose concentration tended to be higher in TBI patients. As in previous investigations, the cerebral metabolic rate for glucose (CMRgluc, i.e., net glucose uptake) was significantly suppressed following TBI (p<0.001). However, lactate fractional extraction, an index of cerebral lactate uptake related to systemic lactate supply, approximated 11% in both healthy control subjects and TBI patients. Further, neither the CMR for lactate (CMRlac, i.e., net lactate release), nor the tracer-measured cerebral lactate uptake differed between healthy controls and TBI patients. The percentages of lactate tracer taken up and released as (13)CO2 into the JB accounted for 92% and 91% for control and TBI conditions, respectively, suggesting that most cerebral lactate uptake was oxidized following TBI. Comparisons of isotopic enrichments of lactate oxidation from infused [3-(13)C]lactate tracer and (13)C-glucose produced during hepatic and renal gluconeogenesis (GNG) showed that 75-80% of (13)CO2 released into the JB was from lactate and that the remainder was from the oxidation of glucose secondarily labeled from lactate. Hence, either directly as lactate uptake, or indirectly via GNG, peripheral lactate production accounted for ∼70% of carbohydrate (direct lactate uptake+uptake of glucose from lactate) consumed by the injured brain. Undiminished cerebral lactate fractional extraction and uptake suggest that arterial lactate supplementation may be used to compensate for decreased CMRgluc following TBI

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain

Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Multiplex Networks to Characterize Seizure Development in Traumatic Brain Injury Patients

Traumatic brain injury (TBI) may cause secondary debilitating problems, such as post-traumatic epilepsy (PTE), which occurs with unprovoked recurrent seizures, months or even years after TBI. Currently, the Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) has been enrolling moderate-severe TBI patients with the goal to identify biomarkers of epileptogenesis that may help to prevent seizure occurrence and better understand the mechanism underlying PTE. In this work, we used a novel complex network approach based on segmenting T1-weighted Magnetic Resonance Imaging (MRI) scans in patches of the same dimension (network nodes) and measured pairwise patch similarities using Pearson's correlation (network connections). This network model allowed us to obtain a series of single and multiplex network metrics to comprehensively analyze the different interactions between brain components and capture structural MRI alterations related to seizure development. We used these complex network features to train a Random Forest (RF) classifier and predict, with an accuracy of 70 and a 95% confidence interval of [67, 73%], which subjects from EpiBioS4Rx have had at least one seizure after a TBI. This complex network approach also allowed the identification of the most informative scales and brain areas for the discrimination between the two clinical groups: seizure-free and seizure-affected subjects, demonstrating to be a promising pilot study which, in the future, may serve to identify and validate biomarkers of PTE

Offer of methodology for the bio-environmental qualification of green spaces by ecophysiological coefficients

Uno de los mayores problemas que enfrentan las urbes modernas es su crecimiento horizontal en base a cemento y asfalto, cubriendo grandes extensiones. Su resultado es un importante incremento de la temperatura llamado efecto "isla de calor", aspecto de particular importancia en años venideros por el creciente calentamiento global, a lo cual se añade la contaminación por gases y partículas. Las áreas destinadas a mitigar parcialmente estos efectos son los denominados espacios verdes, los cuales representan una mancha en el mapa. Sin embargo, su impacto termodinámico a nivel ambiental desde el punto de vista del confort y calidad de vida humanos puede ser muy variable según como esté diseñado. Este trabajo pretende establecer una metodología de aplicación en cualquier región, para calificar cuantitativamente el valor de los diferentes tipos de espacios verdes como modificadores ambientales, ya sean ejecutados o a nivel de proyecto. A través de esta metodología se determinan índices o coeficientes regionales objetivos y de sencilla aplicación. Para desarrollar estos índices, a los espacios verdes se aplican, adaptados, principios de la termodinámica de superficies húmedas y de la ecofisiología. A través de procedimientos matemáticos y conceptos fisiológicos se concluye en fórmulas para calcular índices regionales de aplicación directa en la evaluación de proyectos. A modo de comprobación de la metodología se determina el valor ambiental comparativo de diferentes tipos de espacios verdes correspondientes al sistema integrado de espacios verdes de la ciudad de MendozaOne of the greatest problems of the modern large cities is their horizontal growth on the basis of cement, covering great extensions. Its results in an important increase of temperature. It is called effect "heat island". It is too adds to the contamination by gases and particles. The areas destined to partially mitigate these effects are the denominated green spaces, which represent a spot in the map. Respect to the comfort and quality of life, its impact can be variable according to as it is designed. This work tries to establish a quantitatively methodology to describe the environmental value of these green spaces, made or at level of projects, through objective indices, of simple application and employable in any region of the world where the problematic one arises. In order to develop these indices, principles of the thermodynamics of humid surfaces and the ecofisiology were adapt at the green spaces. By mathematical procedures and physiological concepts it calculate regional indices of direct application in the evaluation of green spaces projects. As a verification methodology, the comparative environmental indices were determined: four areas of the integrated system of green spaces of the city of Mendoza, Argentina: two seats, two sections of a street and a projected park.Fil: Carrieri, Sergio A.. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Codina, Ramón A.. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Manzano, Enrique R.. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Videla, Eugenia. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Vespa, María Juliana. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Kocsis, Cecilia Adriana. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Ferro Malecki, Marianela. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción AgropecuariaFil: Fioretti, Sonia B.. Universidad Nacional de Cuyo. Facultad de Ciencias Agrarias. Departamento de Producción Agropecuari

Infrared neurostimulation in ex-vivo rat sciatic nerve using 1470 nm wavelength.

OBJECTIVE: To design and implement a setup for ex-vivo optical stimulation for exploring the effect of several key parameters (optical power and pulse duration), activation features (threshold, spatial selectivity) and recovery characteristics (repeated stimuli) in peripheral nerves. APPROACH: A nerve chamber allowing ex-vivo electrical and optical stimulation was designed and built. A 1470 nm light source was chosen to stimulate the nerve. A photodiode module was implemented for synchronization of the electrical and optical channels. MAIN RESULTS: Compound Neural Action Potentials (CNAPs) were successfully generated with infrared light pulses of 200-2000 µs duration and power in the range of 3-10 W. These parameters determine a radiant exposure for stimulation in the range 1.59-4.78 J/cm2. Recruitment curves were obtained by increasing durations at a constant power level. Neural activation threshold is reached at a mean radiant exposure of 3.16 ± 0.68 J/cm2 and mean pulse energy of 3.79 ± 0.72 mJ. Repetition rates of 2-10 Hz have been explored. In 8 out of 10 sciatic nerves, repeated light stimuli induced a sensitisation effect in that the CNAP amplitude progressively grows, representing an increasing number of recruited fibres. In 2 out of 10 sciatic nerves, CNAPs were composed of a succession of peaks corresponding to different conduction velocities. SIGNIFICANCE: The reported sensitisation effect could shed light on the mechanism underlying Infrared NeuroStimulation (INS). Our results suggest that, in sharp contrast with electrical stimuli, optical pulses could recruit slow fibres early on. This more physiological order of recruitment opens the perspective for specific neuromodulation of fibre population who remained poorly accessible until now. Short high-power light pulses at wavelengths below 1.5 µm offer interesting perspectives for neurostimulation

Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant Factor VIIa for Warfarin Reversal

INTRODUCTION: Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation. METHODS: Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDrFVIIa (1000 or 1200 mcg) for emergent warfarin reversal from August 2007 to October 2011. The primary end-points were achievement of an INR 1.5 or less for efficacy and thromboembolic events for safety. RESULTS: Seventy-four PCC3 and 32 LDrFVIIa patients were analyzed. Baseline demographics, reason for warfarin reversal, and initial INR were equivalent. There was no difference in the use of vitamin K or fresh frozen plasma. More LDrFVIIa patients achieved an INR of 1.5 or less (71.9% vs. 33.8%, p =0.001). The follow-up INR was lower after LDrFVIIa (1.25 vs. 1.75, p < 0.05) and the percent change in INR was larger after LDrFVIIa (54.1% vs. 38.8%, p = 0.002). There was no difference in the number of thromboembolic events (2 LDrFVIIa vs. 5 PCC3, p = 1.00), mortality, length of hospital stay, or cost. CONCLUSIONS: Based on achieving a goal INR of 1.5 or less, LDrFVIIa was more likely than PCC3 to reverse warfarin anticoagulation. Thromboembolic events were equivalent in patients receiving PCC3 and LDrFVIIa