Energy efficiency in gait, activity, participation, and health status in children with cerebral palsy

The aim of the study was to establish if a relationship exists between the energy efficiency of gait, and measures of activity limitation, participation restriction, and health status in a representative sample of children with cerebral palsy (CP). Secondary aims were to investigate potential differences between clinical subtypes and gross motor classification, and to explore other relationships between the measures under investigation. A longitudinal study of a representative sample of 184 children with ambulant CP was conducted (112 males, 72 females; 94 had unilateral spastic C P, 84 had bilateral spastic C P, and six had non-spastic forms; age range 4-17y; Gross Motor Function Classification System Level I, n=57; Level II, n=91; Level III, n=22; and Level IV, n=14); energy efficiency (oxygen cost) during gait, activity limitation, participation restriction, and health status were recorded. Energy efficiency during gait was shown to correlate significantly with activity limitations; no relationship between energy efficiency during gait was found with either participation restriction or health status. With the exception of psychosocial health, all other measures showed significant differences by clinical subtype and gross motor classification. The energy efficiency of walking is not reflective of participation restriction or health status. Thus, therapies leading to improved energy efficiency may not necessarily lead to improved participation or general health.

The structural organization of aurein precursor cDNAs from the skin secretion of the Australian green and golden bell frog, Litoria aurea.

Aureins are a family of peptides (13-25 residues), some of which possess potent antimicrobial and anti-cancer properties, which have been classified into 5 subgroups based upon primary structural similarities. They were originally isolated from the defensive skin secretions of the closely related Australian bell frogs, Litoria aurea and Litoria raniformis, and of the 23 aurein peptides identified, 10 are common to both species. Using a recently developed technique, we have constructed a cDNA library from the defensive secretion of the green and golden bell frog, L. aurea, and successfully cloned a range of aurein precursor transcripts containing entire open-reading frames. All open-reading frames consisted of a putative signal peptide and an acidic pro-region followed by a single copy of aurein. The deduced precursor structures for the most active aureins (2.2 and 3.1) confirmed the presence of a C-terminal amidation motif whereas that of aurein 5.3 did not. Processed peptides corresponding in molecular mass to aureins 2.2, 2.3, 2.5, 3.1 and 5.3 were identified in the same secretion sample using LC/MS. The application of this technique thus permits parallel peptidomic and transcriptomic analyses on the same lyophilized skin secretion sample circumventing sacrifice of specimens of endangered herpetofauna.

Mice lacking alpha-tocopherol transfer protein gene have severe alpha-tocopherol deficiency in multiple regions of the central nervous system

Ataxia with vitamin E deficiency is caused by mutations in a-tocopherol transfer protein (a-TTP) gene and it can be experimentally generated in mice by a-TTP gene inactivation (a-TTP-KO). This study compared a-tocopherol (a-T) concentrations of five brain regions and of four peripheral organs from 5 months old, male and female, wild-type (WT) and a-TTP-KO mice. All brain regions of female WT mice contained significantly higher a-T than those from WT males. a-T concentration in the cerebellum was significantly lower than that in other brain regions of WT mice. These sex and regional differences in brain a-T concentrations do not appear to be determined by a-TTP expression which was undetectable in all brain regions. All the brain regions of a-TTP-KO mice were severely depleted in a-T. The concentration of another endogenous antioxidant, total glutathione, was unaffected by gender but was decreased slightly but significantly in most brain regions of a-TTP-KO mice. The results show that both gender and the hepatic a-TTP, but not brain a-TTP gene expression are important in determining a-T concentrations within the brain. Interestingly, functional abnormality (ataxia) develops only very late in a-TTP-KO mice in spite of the severe a-tocopherol deficiency in the brain starting at an early age.

MISEP method for postnonlinear blind source separation

In this letter, a standard postnonlinear blind source separation algorithm is proposed, based on the MISEP method, which is widely used in linear and nonlinear independent component analysis. To best suit a wide class of postnonlinear mixtures, we adapt the MISEP method to incorporate a priori information of the mixtures. In particular, a group of three-layered perceptrons and a linear network are used as the unmixing system to separate sources in the postnonlinear mixtures, and another group of three-layered perceptron is used as the auxiliary network. The learning algorithm for the unmixing system is then obtained by maximizing the output entropy of the auxiliary network. The proposed method is applied to postnonlinear blind source separation of both simulation signals and real speech signals, and the experimental results demonstrate its effectiveness and efficiency in comparison with existing methods.

Effect of angiotensin-related antihypertensives on brain neurotransmitter levels in rats.

The extensive clinical experience of angiotensin converting enzyme inhibitors and angiotensin AT(1) receptor antagonists as antihypertensive agents provide numerous examples of anecdotal evidence of improvements in cognition and mood. This study aimed to determine the effect of chronic treatment with the angiotensin converting enzyme inhibitor, perindopril, and the angiotensin AT(1) receptor antagonist, candesartan, on central neurotransmitter levels in the rat. Perindopril (1.0mg/kg/day) or candesartan (10mg/kg/day) was administered via the drinking water at for 1 week, while controls received water alone. At the end of treatment rats were sacrificed, brains removed and discrete regions dissected and analysed for noradrenaline, dopamine and its major metabolites, and serotonin content. As shown previously we found an increase in striatal dopamine levels after perindopril treatment, though this did not extend to the mesolimbic system with neurotransmitter levels unchanged in the hippocampus, nucleus accumbens and frontal cortex. Conversely, candesartan administration produced no change in dopamine, but significant decreases in both DOPAC and HVA in the striatum. In addition chronic candesartan infusion produced a significant increase in the levels of hippocampal noradrenaline and serotonin; and frontal cortex serotonin content. These results demonstrate that while angiotensin converting enzyme inhibitors and angiotensin AT(1) receptor antagonists act as antihypertensives by affecting the renin-angiotensin system, they have divergent actions on brain neurochemistry.

Impairments of hippocampal synaptic plasticity induced by aggregated beta-amyloid (25-35) are dependent on stimulation-protocol and genetic background

The aggregation of beta-amyloid to plaques in the brain is one of the hallmarks of Alzheimer disease (AD). Numerous studies have tried to elucidate to what degree amyloid peptides play a role in the neurodegenerative developments seen in AD. While most studies report an effect of amyloid on neural activity and cognitive abilities of rodents, there have been many inconsistencies in the results. This study investigated to what degree the different genetic backgrounds affect the outcome of beta-amyloid fragment (25-35) on synaptic plasticity in vivo in the rat hippocampus. Two strains, Wistar and Lister hooded rats, were tested. In addition, the effects of a strong (600 stimuli) and a weak stimulation protocol (100 stimuli) on impairments of LTP were analysed. Furthermore, since the state of amyloid aggregation appears to play a role in the induction of toxic processes, it was tested by dual polarisation interferometry to what degree and at what speed beta-amyloid (25-35) can aggregate in vitro. It was found that 100 nmol beta-amyloid (25-35) injected icv did impair LTP in Wistar rats when using the weak but not the strong stimulation protocol (P <0.001). One-hundred nano mole of the reverse sequence amyloid (35-25) had no effect. LTP in Lister Hooded rats was not impaired by amyloid at any stimulation protocol. The aggregation studies showed that amyloid (25-35) aggregated within hours, while amyloid (35-25) did not. These results show that the genetic background and the stimulation protocol are important variables that greatly influence the experimental outcome. The fact that amyloid (25-35) aggregated quickly and showed neurophysiological effects, while amyloid (35-25) did not aggregate and did not show any effects indicates that the state of aggregation plays an important role in the physiological effects.

The efficacy of colour cues in facilitating adaptation to opposing visuomotor rotations

We investigated visuomotor adaptation using an isometric, target-acquisition task. Following trials with no rotation, two participant groups were exposed to a random sequence of 30 degrees clockwise (CW) and 60 degrees counter-clockwise (CCW) rotations, with (DUAL-CUE), or without (DUAL-NO CUE), colour cues that enabled each environment (non-rotated, 30 degrees CW and 60 degrees CCW) to be identified. A further three groups experienced only 30 degrees CW trials or only 60 degrees CCW trials (SINGLE rotation groups) in which each visuomotor mapping was again associated with a colour cue. During training, all SINGLE groups reduced angular deviations of the cursor path during the initial portion of the movements, indicating feedforward adaptation. Consistent with the view that the adaptation occurred automatically via recalibration of the visuomotor mapping (Krakauer et al. 1999), post-training aftereffects were observed, despite colour cues that indicated that no rotation was present. For the DUAL-CUE group, angular deviations decreased with training in the 60 degrees trials, but were unchanged in the 30 degrees trials, while for the DUAL-NO CUE group angular deviations decreased for the 60 degrees CW trials but increased for the 30 degrees CW trials. These results suggest that in a dual adaptation paradigm a colour cue can permit delineation of the two environments, with a subsequent change in behaviour resulting in improved performance in at least one of these environments. Increased reaction times within the training block, together with the absence of aftereffects in the post-training period for the DUAL-CUE group suggest an explicit cue-dependent strategy was used in an attempt to compensate for the rotations.

The effect of simultaneous contractions of ipsilateral muscles on changes in corticospinal excitability induced by paired associative stimulation (PAS)

Consideration was given to means of increasing the reliability and muscle specificity of paired associative stimulation (PAS) by utilising the phenomenon of crossed-facilitation. Eight participants completed three separate sessions: isometric flexor contractions of the left wrist at 20% of maximum voluntary contraction (MVC) simultaneously with PAS (20s intervals; 14 min duration) delivered at the right median nerve and left primary motor cortex (MI); isometric contractions at 20% of MVC: and PAS only ( 14 min). Eight further participants completed two sessions of longer duration PAS (28 min): either alone or in conjunction with flexion contractions of the left wrist. Thirty motor potentials (MEPs) were evoked in the right flexor (rFCR) and extensor (rECR) carpi radialis muscles by magnetic stimulation of left M1 Prior to the interventions, immediately post-intervention, and 10 min post-intervention. Both 14 and 28 min of combined PAS and (left wrist flexion) contractions resulted in reliable increases in rFCR MEP amplitude, which were not present in rECR. In the PAS only conditions, 14 min of stimulation gave rise to unreliable increases in MEP amplitudes in rFCR and rECR, whereas 28 min of PAS induced small (unreliable) changes only for rFCR. These results support the conclusion that changes in the excitability of the corticospinal pathway induced by PAS interact with those associated with contraction of the muscles ipsilateral to the site of cortical stimulation. Furthermore, focal contractions applied by the opposite limb increase the extent and muscle specificity of the induced changes in excitability associated with PAS. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Generalisation between opposing visuomotor rotations when each is associated with visual targets and movements of different amplitude

Previous studies have attempted to identify sources of contextual information which can facilitate dual adaptation to two variants of a novel environment, which are normally prone to interference. The type of contextual information previously used can be grouped into two broad categories: that which is arbitrary to the motor system, such as a colour cue, and that which is based on an internal property of the motor system, such as a change in movement effector. The experiments reported here examined whether associating visuomotor rotations to visual targets and movements of different amplitude would serve as an appropriate source of contextual information to enable dual adaptation. The results indicated that visual target and movement amplitude is not a suitable source of contextual information to enable dual adaptation in our task. Interference was observed in groups who were exposed to opposing visuomotor rotations, or a visuomotor rotation and no rotation, both when the onset of the visuomotor rotations was sudden, or occurred gradually over the course of training. Furthermore, the pattern of interference indicated that the inability to dual adapt was a result of the generalisation of learning between the two visuomotor mappings associated with each of the visual target and movement amplitudes. (C) 2008 Elsevier B.V. All rights reserved.