Biomechanical analysis of body movements of myoelectric prosthesis users during standardized clinical tests

Objective: The objective clinical evaluation of user's capabilities to handle their prosthesis is done using various tests which primarily focus on the task completion speed and do not explicitly account for the potential presence of compensatory motions. Given that the excessive body compensation is a common indicator of inadequate prosthesis control, tests which include subjective observations on the quality of performed motions have been introduced. However, these metrics are then influenced by the examiner's opinions, skills, and training making them harder to standardize across patient pools and compare across different prosthetic technologies. Here we aim to objectively quantify the severity of body compensations present in myoelectric prosthetic hand users and evaluate the extent to which traditional objective clinical scores are still able to capture them. Methods: We have instructed 9 below-elbow prosthesis users and 9 able-bodied participants to complete three established objective clinical tests: Box-and-Blocks-Test, Clothespin-Relocation-Test, and Southampton-Hand-Assessment-Procedure. During all tests, upper-body kinematics has been recorded. Results: While the analysis showed that there are some correlations between the achieved clinical scores and the individual body segment travel distances and average speeds, there were only weak correlations between the clinical scores and the observed ranges of motion. At the same time, the compensations were observed in all prosthesis users and, for the most part, they were substantial across the tests. Conclusion: The sole reliance on the currently available objective clinical assessment methods seems inadequate as the compensatory movements are prominent in prosthesis users and yet not sufficiently accounted for

The long-term effects of an implantable drop foot stimulator on gait in hemiparetic patients

Drop foot is a frequent abnormality in gait after central nervous system lesions. Different treatment strategies are available to functionally restore dorsal extension during swing phase in gait. Orthoses as well as surface and implantable devices for electrical stimulation of the peroneal nerve may be used in patients who do not regain good dorsal extension. While several studies investigated the effects of implanted systems on walking speed and gait endurance, only a few studies have focussed on the system’s impact on kinematics and long-term outcomes. Therefore, our aim was to further investigate the effects of the implanted system ActiGait on gait kinematics and spatiotemporal parameters for the first time with a 1-year follow-up period. 10 patients were implanted with an ActiGait stimulator, with 8 patients completing baseline and follow-up assessments. Assessments included a 10-m walking test, video-based gait analysis and a Visual Analogue Scale (VAS) for health status. At baseline, gait analysis was performed without any assistive device as well as with surface electrical stimulation. At follow-up patients walked with the ActiGait system switched off and on. The maximum dorsal extension of the ankle at initial contact increased significantly between baseline without stimulation and follow-up with ActiGait (p = 0.018). While the spatio-temporal parameters did not seem to change much with the use of ActiGait in convenient walking speed, patients did walk faster when using surface stimulation or ActiGait compared to no stimulation at the 10-m walking test at their fastest possible walking speed. Patients rated their health better at the 1-year follow-up. In summary, a global improvement in gait kinematics compared to no stimulation was observed and the long-term safety of the device could be confirmed

The genetic versus pharmacological invalidation of the cannabinoid CB1 receptor results in differential effects on non-associative memory and forebrain monoamine concentrations in mice

Original article can be found at: http://www.sciencedirect.com/science/journal/10747427 Copyright Elsevier Inc. DOI : 10.1016/j.nlm.2007.07.013Peer reviewe

The CB1 cannabinoid receptor antagonist AM251 blocks amphetamine-induced behavioural sensitization together with monoamine changes in the mouse nucleus accumbens and hippocampus

Original article can be found at: http://www.sciencedirect.com/ Copyright Elsevier [Full text of this article is not available in the UHRA]Endogenous cannabinoids modulate the activity of dopamine reward pathways and may play a role in the development of behavioural sensitization to psychostimulants. Here, we investigated the effects of the CB1 cannabinoid receptor antagonist AM251 on amphetamine-induced locomotor sensitization in mice. Furthermore, we measured post-mortem monoamine concentrations in nucleus accumbens and hippocampus after termination of the behavioural tests. The results can be summarized as follows: Mice pre-treated with AM251 (3 mg/kg; i.p.) showed less sensitivity to the psychomotor stimulant as well as locomotor sensitizing effects of amphetamine (2 mg/kg; i.p.) resembling previous results obtained with CB1 receptor-deficient animals. Furthermore, the behavioural effects of AM251 were paralleled by increased dopamine concentration in nucleus accumbens and increased serotonin concentration/turnover rate in hippocampus, respectively. The present data indicate that under normal conditions activation of the CB1 receptor facilitates those adaptive responses elicited by repeated psychostimulant administration and resulting in sensitization, possibly by reducing dopamine biosynthesis and serotonin turnover in the nucleus accumbens and hippocampus.Peer reviewe

Functional outcome scores with standard myoelectric prostheses in below-elbow amputees

OBJECTIVE: To report normative outcome data of prosthetic hand function in below elbow amputees using four different objective measurements closely related to activities of daily living (ADL). DESIGN: Seventeen patients who underwent prosthetic fitting after unilateral below-elbow amputation were enrolled in this study. Global upper extremity function was evaluated using the Action Research Arm Test (ARAT), Southampton Hand Assessment Procedure (SHAP), the Clothespin-Relocation Test (CPRT) and the Box and Block Test (BBT), which monitor hand and extremity function. RESULTS: The patients achieved a mean ARAT score of 35.06 ± 4.42 of 57. The average SHAP score was 65.12 ± 13.95 points. The mean time for the CPRT was 22.57 ± 7.50 seconds and the mean score in the BBT was 20.90 ± 5.74. CONCLUSIONS: In the current economic situation of health care systems, demonstrating the effectiveness and necessity of rehabilitation interventions is of major importance. This study reports outcome data of below-elbow amputees and provides a useful guide for expected prosthetic user performance

Comparison of intra-accumbens injection of histamine with histamine H1-receptor antagonist chlorpheniramine in effects on reinforcement and memory parameters

Original article can be found at: http://www.sciencedirect.com Copyright Elsevier [Full text of this article is not available in the UHRA]Histaminergic neurons are located exclusively in the tuberomammillary nuclei (TM) of the hypothalamus from where they project to many regions of the brain including the basal ganglia. Earlier experiments led to the hypothesis that neuronal histamine (HA), particularly in relation to the H1 receptor, has an inhibitory role in learning and reward-related processes. Based on this premise, the objective of the present study was to compare HA with the H1-receptor antagonist d-chlorpheniramine (CPR) in effects on reinforcement and memory parameters after injection into different subregions of the rat nucleus accumbens (NAcc). In the first experiment, mnemoactive effects of CPR (0.1–10 μg) were assessed after injection into the caudal or rostral part of the NAcc with the one-trial uphill avoidance task as a measure of learning. The data show that intra-NAcc injection of CPR (10 μg) facilitated retention of the task, when the compound was administered immediately after training. This effect was evident only when CPR was administered into the caudal-shell but not into the rostral pole of the NAcc providing evidence for anatomical specificity of the intra-NAcc induced promotion of memory. In the second experiment, possible mnemonic and reinforcing effects of HA (0.001–1 μg) were gauged after injection of the amine into the caudal NAcc, using post-trial application in the uphill avoidance task to assess effects on learning and place preference as an index of reinforcing properties. The data show that caudal-NAcc injection of HA (0.1 μg) improved retention of the avoidance task and produced place preference indicative of a reinforcing action. The finding that intra-NAcc injection of HA can facilitate learning and has reinforcing effects is at variance with the proposed inhibitory nature of neuronal HA in reward-related processes. Thus, the disinhibition of reinforcement and facilitation of learning found earlier after partial destruction of TM-intrinsic neurons might not necessarily be related to a lesion-induced reduction of the HAergic tone. The observation that CPR has behavioral effects quite similar to HA suggests that the mnemoactive and reinforcing action of this compound might involve pharmacodynamic aspects beyond its antagonistic activity at H1-receptive sites.Peer reviewe

The role of the CB1 cannabinoid receptor and its endogenous ligands, anandamide and 2-arachidonoylglycerol, in amphetamine-induced behavioural sensitization

Original article can be found at: http://www.sciencedirect.com/science/journal/01664328 Copyright Elsevier B. V. DOI: 10.1016/j.bbr.2007.09.022 [Full text of this article is not available in the UHRA]Cannabinoid receptors and their endogenous ligands (endocannabinoids) have been implicated in cocaine and amphetamine reward. Their role in psychostimulant-induced behavioural sensitization still has to be determined. The purpose of the present study was, for one, to compare the effects of a pharmacological and genetic manipulation of CB1 cannabinoid receptors on amphetamine-induced locomotor sensitization in mice, and, secondly, to quantify the concentration of anandamide and 2-arachidonoylglycerol in different forebrain areas of behaviourally sensitized animals. The results can be summarized as follows: CB1 knockout mice failed to sensitize to the locomotor stimulant effects of amphetamine. On the contrary, administration of the CB1 receptor antagonist SR141716A (rimonabant; 3 mg/kg; i.p.) increased amphetamine sensitization in wild-type animals, indicating that the difference between CB1 knockouts and SR141716A treated animals could be due to the ‘chronic’ versus ‘acute’ loss of CB1 receptor function, or, alternatively, that SR141716A could exert pharmacological effects beyond its proposed CB1 antagonistic action. Furthermore, sensitized wild-type mice and animals, which had received a single amphetamine injection on the challenge day, both had increased anandamide concentrations in the dorsal striatum and decreased anandamide levels in the ventral striatum, comprising nucleus accumbens. 2-Arachidonoylglycerol levels were decreased in the ventral striatum of sensitized animals only. Together, these findings suggest that prolonged activation of dopamine receptors could alter endocannabinoid levels and support the proposed involvement of the CB1 receptor in amphetamine sensitization.Peer reviewe

Dual inhibition of the terminal oxidases eradicates antibiotic‐tolerant Mycobacterium tuberculosis

Abstract The approval of bedaquiline has placed energy metabolism in the limelight as an attractive target space for tuberculosis antibiotic development. While bedaquiline inhibits the mycobacterial F1F0 ATP synthase, small molecules targeting other components of the oxidative phosphorylation pathway have been identified. Of particular interest is Telacebec (Q203), a phase 2 drug candidate inhibitor of the cytochrome bcc:aa3 terminal oxidase. A functional redundancy between the cytochrome bcc:aa3 and the cytochrome bd oxidase protects M. tuberculosis from Q203‐induced death, highlighting the attractiveness of the bd‐type terminal oxidase for drug development. Here, we employed a facile whole‐cell screen approach to identify the cytochrome bd inhibitor ND‐011992. Although ND‐011992 is ineffective on its own, it inhibits respiration and ATP homeostasis in combination with Q203. The drug combination was bactericidal against replicating and antibiotic‐tolerant, non‐replicating mycobacteria, and increased efficacy relative to that of a single drug in a mouse model. These findings suggest that a cytochrome bd oxidase inhibitor will add value to a drug combination targeting oxidative phosphorylation for tuberculosis treatment