Agitation after traumatic brain injury and predictors of outcome.

OBJECTIVES: To measure the incidence of agitation after traumatic brain injury (TBI) in an inpatient population and to identify any features associated with an adverse outcome. DESIGN: Prospective study of TBI admissions over 30 months in consecutive admissions with TBI to a regional neurorehabilitation unit. Outcome of agitation was compared to patient, injury and treatment features and any associations were sought. The presence of agitation was measured by the Agitation Behaviour Score. A good outcome for agitation was defined as a return to independent living with minimal care requirement at 6 months using an Extended Glasgow Outcome Scale (GOSE) score >4. RESULTS: Over 30 months, there were 146 TBI admissions, of whom 53 cases had agitation (36.3%). Achieving 100% follow-up, 27 (51%) had a good outcome. On a multivariable logistic regression analysis, a good outcome was associated with the type of lesions seen on CT scan, the severity of agitation and the duration of the behaviour. Alcohol excess and type of treatment used for the behaviour were initially significant on univariate testing but dropped out of the logistic regression model. CONCLUSIONS: Over a third of TBI admissions, developed agitation and poor functional outcome was associated with CT scan findings, severity and duration of agitation.

Sub-10 nm Mixing and Alloying of Cu-Ag and Cu-Ni via Accelerated Solid Diffusion.

Development of nanoscale multicomponent solid inorganic materials is often hindered by slow solid diffusion kinetics and poor precursor mixing in conventional solid-state synthesis. These shortcomings can be alleviated by combining nanosized precursor mixtures and low temperature reaction, which could reduce crystal growth and accelerate the solid diffusion at the same time. However, high throughput production of nanoparticle mixtures with tunable composition via conventional synthesis is very challenging. In this work, we demonstrate that ∼10 nm homogeneous mixing of sub-10 nm nanoparticles can be achieved via spark nanomixing at room temperature and pressure. Kinetically driven Spark Plasma Discharge nanoparticle generation and ambient processing conditions limit particle coarsening and agglomeration, resulting in sub-10 nm primary particles of as-deposited films. The intimate mixing of these nanosized precursor particles enables intraparticle diffusion and formation of Cu/Ni nanoalloy during subsequent low temperature annealing at 100 °C. We also discovered that cross-particle diffusion is promoted during the low-temperature sulfurization of Cu/Ag which tends to phase-segregate, eventually leading to the growth of sulfide nanocrystals and improved homogeneity. High elemental homogeneity, small diffusion path lengths, and high diffusibility synergically contribute to faster diffusion kinetics of sub-10 nm nanoparticle mixtures. The combination of ∼10 nm homogeneous precursors via spark nanomixing, low-temperature annealing, and a wide range of potentially compatible materials makes our approach a good candidate as a general platform toward accelerated solid state synthesis of nanomaterials.

Rehabilitation medicine in palliative care of chronic neurological conditions.

BACKGROUND: People living with long-term neurological conditions (LTNC) often require palliative care. Rehabilitation medicine specialists often coordinate the long-term care of these patients. OBJECTIVE: The aim of the present review was to undertake systematic literature searches to identify the evidence on palliative care for people with LTNC to guide rehabilitation medicine specialists caring for these patients in the UK. METHODS: We searched for evidence for (1) discussion of end of life, (2) planning for end-of-life care, (3) brief specialist palliative care interventions, (4) support for family and carers, (5) training of rehabilitation medicine specialists in palliative care, and (6) commissioning of services. The databases searched were MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, NHS Economic Evaluation Database and Health Technology Assessment Database. Evidence was assimilated using a simplified version of the Grading of Recommendations Assessment, Development and Evaluation method. RESULTS: We identified 2961 records through database searching for neurological conditions and 1261 additional records through database searches for specific symptoms. We removed duplicate records and conference presentations. We screened 3234 titles and identified 330 potentially relevant abstracts. After reading the abstracts we selected 34 studies for inclusion in the evidence synthesis. CONCLUSIONS: From the evidence reviewed we would like to recommend that we move forward by establishing a closer working relationship with specialists in palliative care and rehabilitation medicine and explore the implications for cross-specialty training.

Exploring the ability of stroke survivors in using the contralesional hemisphere to control a brain-computer interface.

Brain-computer interfaces (BCIs) have recently been shown to be clinically effective as a novel method of stroke rehabilitation. In many BCI-based studies, the activation of the ipsilesional hemisphere was considered a key factor required for motor recovery after stroke. However, emerging evidence suggests that the contralesional hemisphere also plays a role in motor function rehabilitation. The objective of this study is to investigate the effectiveness of the BCI in detecting motor imagery of the affected hand from contralesional hemisphere. We analyzed a large EEG dataset from 136 stroke patients who performed motor imagery of their stroke-impaired hand. BCI features were extracted from channels covering either the ipsilesional, contralesional or bilateral hemisphere, and the offline BCI accuracy was computed using 10 [Formula: see text] 10-fold cross-validations. Our results showed that most stroke patients can operate the BCI using either their contralesional or ipsilesional hemisphere. Those with the ipsilesional BCI accuracy of less than 60% had significantly higher motor impairments than those with the ipsilesional BCI accuracy above 80%. Interestingly, those with the ipsilesional BCI accuracy of less than 60% achieved a significantly higher contralesional BCI accuracy, whereas those with the ipsilesional BCI accuracy more than 80% had significantly poorer contralesional BCI accuracy. This study suggests that contralesional BCI may be a useful approach for those with a high motor impairment who cannot accurately generate signals from ipsilesional hemisphere to effectively operate BCI.

Efficacy of Brain-Computer Interface and the Impact of Its Design Characteristics on Poststroke Upper-limb Rehabilitation: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Background. A number of recent randomized controlled trials reported the efficacy of brain-computer interface (BCI) for upper-limb stroke rehabilitation compared with other therapies. Despite the encouraging results reported, there is a significant variance in the reported outcomes. This paper aims to investigate the effectiveness of different BCI designs on poststroke upper-limb rehabilitation. Methods. The effect sizes of pooled and individual studies were assessed by computing Hedge's g values with a 95% confidence interval. Subgroup analyses were also performed to examine the impact of different BCI designs on the treatment effect. Results. The study included 12 clinical trials involving 298 patients. The analysis showed that the BCI yielded significant superior short-term and long-term efficacy in improving the upper-limb motor function compared to the control therapies (Hedge's g = 0.73 and 0.33, respectively). Based on our subgroup analyses, the BCI studies that used the intention of movement had a higher effect size compared to those used motor imagery (Hedge's g = 1.21 and 0.55, respectively). The BCI studies using band power features had a significantly higher effect size than those using filter bank common spatial patterns features (Hedge's g = 1.25 and - 0.23, respectively). Finally, the studies that used functional electrical stimulation as the BCI feedback had the highest effect size compared to other devices (Hedge's g = 1.2). Conclusion. This meta-analysis confirmed the effectiveness of BCI for upper-limb rehabilitation. Our findings support the use of band power features, the intention of movement, and the functional electrical stimulation in future BCI designs for poststroke upper-limb rehabilitation.

Choline kinase in Cuscuta reflexa.

1. Choline kinase is a mitochondrial enzyme in Cuscuta reflexa. It can be solubilized from the particles by treatment with 350mm-sodium chloride, or by freezing and thawing. 2. Choline kinase of C. reflexa was purified by starting from the crude mitochondrial fraction. A 33-52% recovery of the enzyme, on the basis of the activity in the original homogenate, in 1200-2250-fold enrichment, was effected. 3. The purified preparation of choline kinase had a sigmoid saturation curve with respect to choline, with a Hill number of 2.3, and was inhibited by ADP (competitive in nature and allosteric in binding, with a Hill number of 2.7) and by phosphorylcholine (non-competitive and non-allosteric). The kinetic characteristics of the enzyme were consistent with the K type allosteric model of Monod et al. (1965). 4. The enzyme was desensitized, with respect to choline regulation, by prolonged storage in the cold, was activated significantly on warming before assay and was inactivated by high concentrations of sodium chloride. 5. The significance of allostery in choline kinase in relation to the intracellular regulation of phospholipid synthesis is discussed.

Guanine deaminase in rat liver and mouse liver and brain.

1. The guanine deaminase in rat liver supernatant preparations was resolved into two fractions, A and B, on DEAE-cellulose columns. The two differed in electrophoretic mobility and in various properties. The most noteworthy distinction between A and B components was that the enzyme A activity showed a sigmoid dependence on substrate concentration whereas the enzyme B showed classical Michaelis-Menten kinetics. The K(m) value of enzyme A for guanine was 5.3mum and that of enzyme B 20mum. 2. The entire guanine deaminase activity of mouse liver was contained in the 15000g supernatant of iso-osmotic homogenates. 3. A reinvestigation of the behaviour of rat brain 15000g supernatant guanine deaminase isoenzymes revealed that one enzyme had sigmoidal kinetics and the other enzyme showed a hyperbolic response. 4. Of the guanine deaminase in mouse brain iso-osmotic sucrose homogenate 80% was recovered in the 15000g supernatant and the rest from the particles. The supernatant guanine deaminase was resolvable into two fractions on DEAE-cellulose columns. One enzyme showed sigmoidal kinetics whereas the other showed a hyperbolic response to increasing substrate concentration; the K(m) values for the reaction with guanine were respectively 5 and 66mum. 5. The particulate fractions of mouse liver and brain were devoid of any overt inhibitory activity.

Modulation of guanine deaminase.

1. Guanine deaminases purified from the 15000g supernatant fraction of iso-osmotic sucrose homogenates of rat and mouse liver and brain were tested for the influence of GTP and allantoin. 2. The suffixes A and B were assigned to the isoenzyme fractions eluted from DEAE-cellulose with the lower and the higher molarity of eluent respectively. Isoenzyme A from rat liver, the activity of which showed a sigmoid dependence on substrate saturation, was activated by GTP and inhibited by allantoin. Isoenzyme B, which had a hyperbolic substrate-saturation curve, was not influenced by GTP or allantoin. 3. Isoenzyme A from rat brain, the activity of which had a sigmoid dependence on substrate concentration, was stimulated by GTP. Isoenzyme B, which showed classical Michaelis-Menten kinetics, was inhibited by allantoin. 4. Mouse liver guanine deaminase was not influenced by either GTP or allantoin. 5. Isoenzyme A from mouse brain, which had a hyperbolic substrate-saturation curve, was not influenced by GTP or allantoin but isoenzyme B, with sigmoidal kinetics, was inhibited by allantoin. 6. Mg(2+) activated, or inhibited or did not have an effect on guanine deaminase, depending on the source of the enzyme. 7. The bearing of the above findings on the possible regulation of guanine deaminase activity in vivo is discussed.

Studies on guanine deaminase and its inhibitors in rat tissue.

1. In kidney, but not in rat whole brain and liver, guanine-deaminase activity was localized almost exclusively in the 15000g supernatant fraction of iso-osmotic sucrose homogenates. However, as in brain and liver, the enzymic activity recovered in the supernatant was higher than that in the whole homogenate. The particulate fractions of kidney, especially the heavy mitochondria, brought about powerful inhibition of the supernatant guanine-deaminase activity. 2. In spleen, as in kidney, guanine-deaminase activity was localized in the 15000g supernatant fraction of iso-osmotic sucrose homogenates. However, the particulate fractions did not inhibit the activity of the supernatant. 3. Guanine-deaminase activity in rat brain was absent from the cerebellum and present only in the cerebral hemispheres. The inhibitor of guanine deaminase was located exclusively in the cerebellum, where it was associated with the particles sedimenting at 5000g from sucrose homogenates. 4. Homogenates of cerebral hemispheres, the separated cortex or the remaining portion of the hemispheres had significantly higher guanine-deaminase activity than homogenates of whole brain. The enzymic activity of the subcellular particulate fractions was nearly the same. 5. Guanine deaminase was purified from the 15000g supernatant of sucrose homogenates of whole brain. The enzyme separated as two distinct fractions, A and B, on DEAE-cellulose columns. 6. The guanine-deaminase activity of the light-mitochondrial fraction of whole brain was fully exposed and solubilized by treatment with Triton X-100, and partially purified. 7. Tested in the form of crude preparations, the inhibitor from kidney did not act on the brain and liver supernatant enzymes and the inhibitor from cerebellum did not act on kidney enzyme, but the inhibitor from liver acted on both brain and kidney enzyme. 8. The inhibitor of guanine deaminase was purified from the heavy mitochondria of whole brain and liver and the 5000g residue of cerebellum, isolated from iso-osmotic homogenates. The inhibitor appeared to be protein in nature and was heat-labile. The inhibition of the enzyme was non-competitive. 9. Kinetic, immunochemical and electrophoretic studies with the preparations purified from brain revealed that the enzyme from light mitochondria was distinct from enzyme B from the supernatant. A distinction between the two forms of supernatant enzyme was less certain. 10. Guanine deaminase isolated from light mitochondria of brain did not react with 8-azaguanine or with the inhibitor isolated from heavy mitochondria.

Guanine deaminase inhibitor from rat liver. Isolation and characterization.

1. An inhibitor of cytoplasmic guanine deaminase of rat liver was isolated from liver ;heavy mitochondrial' fraction after freezing and thawing and treatment with Triton X-100. 2. Submitochondrial fractionation revealed that the inhibitor was localized in the outer-membrane fraction. 3. The method of purification of inhibitor, involving precipitation with (NH(4))(2)SO(4) and chromatography on DEAE-cellulose, its precipitability by trichloroacetic acid and the pattern of absorption in the u.v. indicated that the inhibitor was a protein. In confirmation, tryptic digestion of the isolated material resulted in destruction of the inhibitor activity. The inhibitor was stable to acid, but labile to heat. 4. The isolated inhibitor required phosphatidylcholine (lecithin) for activity. Phosphatidylcholine also partially protected the inhibitor against heat inactivation. 5. When detergent treatment was omitted, the inhibitor activity of frozen mitochondria was precipitated by (NH(4))(2)SO(4) in a fully active form without supplementation with phosphatidylcholine, indicating that Triton X-100 ruptured the linkage between inhibitor and lipid. 6. A reconstituted sample of inhibitor-phosphatidylcholine complex was precipitated in a fully active form by dialysis against 2-mercaptoethanol, but treatment of the precipitate with NaCl yielded an extract which was inactive unless supplemented with fresh phosphatidylcholine. 7. We interpret the results as evidence that the inhibitor was present in vivo as a lipoprotein and that once the complex was dissociated by the action of detergent and the protein precipitated, there was an absolute need for exogenous phosphatidylcholine for its activity. The manner in which inhibitor associated with the outer membrane of rat liver mitochondria might regulate the activity of the enzyme in the supernatant has been suggested.

Induction of guanine deaminase and its inhibitor in rodent liver and brain.

1. Guanine deaminase activities in homogenates and supernatant fractions of liver and brain of rat and mouse were elevated by administration of guanine to the animals. The maximum induction in mouse tissues occurred within 24h and in rat tissues within 48h. 2. Mitochondria of rat (but not mouse) liver and brain contain an inhibitor of supernatant guanine deaminase, and this was also increased by guanine treatment. 3. Administration of ethionine, cycloheximide or actinomycin D prevented the guanine-dependent increase in deaminase activity and also the increase in mitochondrial inhibitory activity; chloramphenicol suppressed only the latter.