Haemodynamic changes in trauma Kirkman, E.; Watts, S.
British journal of anaesthesia : BJA,
08/2014, Letnik:
113, Številka:
2
Journal Article
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Trauma is the leading cause of death during the first four decades of life in the developed countries. Its haemodynamic response underpins the patient’s initial ability to survive, and the response ...to treatment and subsequent morbidity and resolution. Trauma causes a number of insults including haemorrhage, tissue injury (nociception) and, predominantly, in military casualties, blast from explosions. This article discusses aspects of the haemodynamic responses to these insults and subsequent treatment. ‘Simple’ haemorrhage (blood loss without significant volume of tissue damage) causes a biphasic response: mean arterial blood pressure (MBP) is initially maintained by the baroreflex (tachycardia and increased vascular resistance, Phase 1), followed by a sudden decrease in MAP initiated by a second reflex (decrease in vascular resistance and bradycardia, Phase 2). Phase 2 may be protective. The response to tissue injury attenuates Phase 2 and may cause a deleterious haemodynamic redistribution that compromises blood flow to some vital organs. In contrast, thoracic blast exposure augments Phase 2 of the response to haemorrhage. However, hypoxaemia from lung injury limits the effectiveness of hypotensive resuscitation by augmenting the attendant shock state. An alternative strategy (‘hybrid resuscitation’) whereby tissue perfusion is increased after the first hour of hypotensive resuscitation by adopting a revised normotensive target may ameliorate these problems. Finally, morphine also attenuates Phase 2 of the response to haemorrhage in some, but not all, species and this is associated with poor outcome. The impact on human patients is currently unknown and is the subject of a current physiological investigation.
As the kynurenine pathway's links to inflammation, the immune system, and neurological disorders became more apparent, it attracted more and more attention. It is the main pathway through which the ...liver breaks down Tryptophan and the initial step in the creation of nicotinamide adenine dinucleotide (NAD+) in mammals. Immune system activation and the buildup of potentially neurotoxic substances can result from the dysregulation or overactivation of this pathway. Therefore, it is not shocking that kynurenines have been linked to neurological conditions (Depression, Parkinson's, Alzheimer's, Huntington's Disease, Schizophrenia, and cognitive deficits) in relation to inflammation. Nevertheless, preclinical research has demonstrated that kynurenines are essential components of the behavioral analogs of depression and schizophrenia-like cognitive deficits in addition to mediators associated with neurological pathologies due to their neuromodulatory qualities. Neurodegenerative diseases have been extensively associated with neuroactive metabolites of the kynurenine pathway (KP) of tryptophan breakdown. In addition to being a necessary amino acid for protein synthesis, Tryptophan is also transformed into the important neurotransmitters tryptamine and serotonin in higher eukaryotes. In this article, a summary of the KP, its function in neurodegeneration, and the approaches being used currently to target the route therapeutically are discussed.
Physical activity shows promise for reduced risk of Alzheimer's disease (AD) and protection against cognitive decline among individuals with and without AD. Older adults face many barriers to ...adoption of physically active lifestyles and people with AD face even further challenges. Physical activity is a promising non-pharmacological approach to improve depressive symptoms, but little is known about the impact of depressive symptoms as a potential barrier to engagement in physical activity. The present study aimed to investigate depressive symptoms as a potential barrier for participation in physical activity across a range of dementia severity.
We used longitudinal structural equation modelling to investigate the bi-directional relationship between depressive symptoms and physical activity in 594 older adults with and without AD over a 2 year longitudinal follow up. Participants ranged from no cognitive impairment to moderately severe AD.
We found that depressive symptoms predicted reduced engagement in subsequent physical activity, but physical activity did not predict subsequent reductions in depressive symptoms.
We conclude that depressive symptoms may be an important barrier to engagement in physical activity that may be addressed in clinical practice and intervention research.
Five bioactive glasses based on 49.5SiO
2–1.1P
2O
5–(23.0(1
−
x))CaO–
xMgO–26.4Na
2O
mol.% were synthesised where CaO was replaced progressively on a molar basis by MgO (where 0
⩽
x
⩽
1). The glasses ...were characterised by
31P and
29Si magic angle spinning nuclear magnetic resonance (MAS NMR) spectroscopy, dilatometry, differential thermal analysis (DTA) and density measurements with the aim of gaining a comprehensive understanding of the structure–property relationships.
The
31P NMR spectra of the glasses exhibited well-defined resonances at
ca. 9–14
ppm, corresponding to a Q
0 orthophosphate environment. Full substitution of MgO caused a downfield shift of
ca. 5
ppm, implying the preferential association of sodium with the orthophosphate species. The
29Si NMR spectra exhibited a peak at
ca. −79
ppm, indicating a Q
2 silicon species, along with a shoulder at
ca. −90
ppm, corresponding to a Q
3 species. On addition of MgO, the Q
3 shoulder was seen to progressively increase in magnitude. These results suggest that MgO, rather than depolymerising the silicate network by acting as a network modifier, is behaving in part, as an intermediate oxide. Deconvolution of the
29Si NMR peaks suggest that, although 86% of the magnesium oxide is acting traditionally as a network modifying cation, up to 14% of the magnesium oxide is entering the silicate network as tetrahedral, MgO
4, removing network modifying ions for charge compensation and resulting in the observed polymerisation of the silicate network. Correspondingly, both the glass transition temperature and dilatometric softening point values were seen to decrease whilst the thermal expansion coefficient values rose, with increasing MgO content. This was due to the significantly lower bond strength, of Mg–O compared to Si–O, weakening the glass network.
Modifications in chromatin structure have been widely implicated in memory and cognition, most notably using hippocampal-dependent memory paradigms including object recognition, spatial memory, and ...contextual fear memory. Relatively little is known, however, about the role of chromatin-modifying enzymes in amygdala-dependent memory formation. Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically examine the role of p300/CBP histone acetyltransferase (HAT) activity in the consolidation and reconsolidation of auditory Pavlovian fear memories. We show that local infusions of c646, a selective pharmacological inhibitor of p300/CBP activity, shortly following either fear conditioning or fear memory retrieval impair training and retrieval-related regulation of histone acetylation in the lateral nucleus of the amygdala (LA). Furthermore, we show that intra-LA infusion of c646 significantly impairs fear memory consolidation, reconsolidation, and associated neural plasticity in the LA. Our findings collectively suggest that p300/CBP HAT activity is critical for the consolidation and reconsolidation of amygdala-dependent Pavlovian fear memories.
The study of the cellular and molecular mechanisms underlying the consolidation and reconsolidation of traumatic fear memories has progressed rapidly in recent years, yet few compounds have emerged ...that are readily useful in a clinical setting for the treatment of anxiety disorders such as post-traumatic stress disorder (PTSD). Here, we use a combination of biochemical, behavioral, and neurophysiological methods to systematically investigate the ability of garcinol, a naturally-occurring histone acetyltransferase (HAT) inhibitor derived from the rind of the fruit of the Kokum tree (Garcina indica), to disrupt the consolidation and reconsolidation of Pavlovian fear conditioning, a widely studied rodent model of PTSD. We show that local infusion of garcinol into the rat lateral amygdala (LA) impairs the training and retrieval-related acetylation of histone H3 in the LA. Further, we show that either intra-LA or systemic administration of garcinol within a narrow window after either fear conditioning or fear memory retrieval significantly impairs the consolidation and reconsolidation of a Pavlovian fear memory and associated neural plasticity in the LA. Our findings suggest that a naturally-occurring compound derived from the diet that regulates chromatin function may be useful in the treatment of newly acquired or recently reactivated traumatic memories.
Spin-transfer torque random access memory (STT-RAM) is a potentially revolutionary universal memory technology that combines the capacity and cost benefits of DRAM, the fast read and write ...performance of SRAM, the non-volatility of Flash, and essentially unlimited endurance. In order to realize a small cell size, high speed and achieve a fully functional STT-RAM chip, the MgO-barrier magnetic tunnel junctions (MTJ) used as the core storage and readout element must meet a set of performance requirements on switching current density, voltage, magneto-resistance ratio (MR), resistance-area product (RA), thermal stability factor (¿) , switching current distribution, read resistance distribution and reliability. In this paper, we report the progress of our work on device design, material improvement, wafer processing, integration with CMOS, and testing for a demonstration STT-RAM test chip, and projections based on modeling of the future characteristics of STT-RAM.
Numerical homogenization enables efficient computational analysis and design of multiscale structures made of micro-architected materials including lattice unit cells. However, predicting yield is ...nontrivial because it requires accurate and efficient predictions of the maximum stress inside the homogenized unit cells. To address this challenge, we develop a macroscale anisotropic yield function for micro-architected materials. The yield function depends on the three-dimensional macroscale stress state and the parameters describing a family of micro-architectures, such as the radii of the struts in a lattice unit cell. To ensure accuracy, we determine the maximum stress using three-dimensional continuum finite-element analysis. To ensure efficiency, we construct surrogate models from the aforementioned high-fidelity results for yield prediction. To reduce simulation costs and surrogate modeling complexity, we leverage orthotropic symmetry commonly found in lattice unit cells. In this paper, we provide a thorough presentation of group representations and the systematic procedure to exploit orthotropic domain symmetry in homogenization and surrogate modeling. We illustrate the use of linear homogenization results to predict yield in specific unit cells without further simulations. We furthermore show that surrogate modeling presents a viable option for anisotropic yield prediction in a continuously parametrized family of micro-architectures. More specifically, despite the dimensionality and degree of nonlinearity in the maximum micro von Mises stress within the unit cell, the surrogate models can predict it with less than 5% error at least 90% of the time. Moreover, the largest under-prediction error, which is more critical than the over-prediction error, is typically less than 10%.
•Maximum microscale stress can be predicted by tracking a few locations in the unit cell.•Numerical homogenization in 3D is expedited using symmetry group representations.•Anisotropic yield via homogenization analysis has the expected invariance properties.•The above findings enable efficient surrogate models for predicting lattice yield.
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