Imminent brain death: point of departure for potential heart-beating organ donor recognition

Contains fulltext : 88186.pdf (publisher's version ) (Closed access)PURPOSE: There is, in European countries that conduct medical chart review of intensive care unit (ICU) deaths, no consensus on uniform criteria for defining a potential organ donor. Although the term is increasingly being used in recent literature, it is seldom defined in detail. We searched for criteria for determination of imminent brain death, which can be seen as a precursor for organ donation. METHODS: We organized meetings with representatives from the field of clinical neurology, neurotraumatology, intensive care medicine, transplantation medicine, clinical intensive care ethics, and organ procurement management. During these meetings, all possible criteria were discussed to identify a patient with a reasonable probability to become brain dead (imminent brain death). We focused on the practical usefulness of two validated coma scales (Glasgow Coma Scale and the FOUR Score), brain stem reflexes and respiration to define imminent brain death. Further we discussed criteria to determine irreversibility and futility in acute neurological conditions. RESULTS: A patient who fulfills the definition of imminent brain death is a mechanically ventilated deeply comatose patient, admitted to an ICU, with irreversible catastrophic brain damage of known origin. A condition of imminent brain death requires either a Glasgow Coma Score of 3 and the progressive absence of at least three out of six brain stem reflexes or a FOUR score of E(0)M(0)B(0)R(0). CONCLUSION: The definition of imminent brain death can be used as a point of departure for potential heart-beating organ donor recognition on the intensive care unit or retrospective medical chart analysis.1 september 201

Cyclic and Sleep-Like Spontaneous Alternations of Brain State Under Urethane Anaesthesia

Background: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM) and quiet (slow-wave or non-REM: nREM) stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state. Methodology/Principal Findings: Long-duration, multi-site forebrain field recordings were performed in urethaneanaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG) patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame (,11 minute period). Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane. Conclusions/Significance: Our results suggest that urethane promotes a condition of behavioural unconsciousness tha

Alternating Hemiplegia of Childhood-Related Neural and Behavioural Phenotypes in Na+,K+-ATPase α3 Missense Mutant Mice

Missense mutations in ATP1A3 encoding Na(+),K(+)-ATPase α3 have been identified as the primary cause of alternating hemiplegia of childhood (AHC), a motor disorder with onset typically before the age of 6 months. Affected children tend to be of short stature and can also have epilepsy, ataxia and learning disability. The Na(+),K(+)-ATPase has a well-known role in maintaining electrochemical gradients across cell membranes, but our understanding of how the mutations cause AHC is limited. Myshkin mutant mice carry an amino acid change (I810N) that affects the same position in Na(+),K(+)-ATPase α3 as I810S found in AHC. Using molecular modelling, we show that the Myshkin and AHC mutations display similarly severe structural impacts on Na(+),K(+)-ATPase α3, including upon the K(+) pore and predicted K(+) binding sites. Behavioural analysis of Myshkin mice revealed phenotypic abnormalities similar to symptoms of AHC, including motor dysfunction and cognitive impairment. 2-DG imaging of Myshkin mice identified compromised thalamocortical functioning that includes a deficit in frontal cortex functioning (hypofrontality), directly mirroring that reported in AHC, along with reduced thalamocortical functional connectivity. Our results thus provide validation for missense mutations in Na(+),K(+)-ATPase α3 as a cause of AHC, and highlight Myshkin mice as a starting point for the exploration of disease mechanisms and novel treatments in AHC

Circadian oscillator proteins across the kingdoms of life : Structural aspects 06 Biological Sciences 0601 Biochemistry and Cell Biology

Circadian oscillators are networks of biochemical feedback loops that generate 24-hour rhythms and control numerous biological processes in a range of organisms. These periodic rhythms are the result of a complex interplay of interactions among clock components. These components are specific to the organism but share molecular mechanisms that are similar across kingdoms. The elucidation of clock mechanisms in different kingdoms has recently started to attain the level of structural interpretation. A full understanding of these molecular processes requires detailed knowledge, not only of the biochemical and biophysical properties of clock proteins and their interactions, but also the three-dimensional structure of clockwork components. Posttranslational modifications (such as phosphorylation) and protein-protein interactions, have become a central focus of recent research, in particular the complex interactions mediated by the phosphorylation of clock proteins and the formation of multimeric protein complexes that regulate clock genes at transcriptional and translational levels. The three-dimensional structures for the cyanobacterial clock components are well understood, and progress is underway to comprehend the mechanistic details. However, structural recognition of the eukaryotic clock has just begun. This review serves as a primer as the clock communities move towards the exciting realm of structural biology

Sequential Decision Making Under Uncertainty: Ordinal Uninorms vs. the Hurwicz Criterion

International audienceThis paper focuses on sequential decision problems under uncertainty, i.e. sequential problems where no probability distribution on the states that may follow an action is available. New qualitative criteria are proposed that are based on ordinal uninorms, namely R∗ and R∗. Like the Hurwicz criterion, the R∗ and R∗ uninorms arbitrate between pure pessimism and pure optimism, and generalize the Maximin and Maximax criteria. But contrarily to the Hurwicz criterion they are associative, purely ordinal and compatible with Dynamic Consistency and Consequentialism. This latter important property allow the construction of an optimal strategy in polytime, following an algorithm of Dynamic Programming