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Assessing the efficacy of botulinum neurotoxin (BoNT) in vivo is essential given the growing number of BoNT products used in the clinic. Here, we evaluated the dynamic weight bearing (DWB) test for sensitivity to paralytic effects of BoNT-A following intramuscular administration. The toxin was administered into the gastrocnemius lateralis as a single bolus or into the gastrocnemius lateralis and medialis as two boluses. The effects of BoNT-A in DWB were compared to those in the compound muscle action potential (CMAP) and the Digit Abduction Score (DAS) tests. Female Sprague-Dawley rats received an acute, intramuscular (i.m.) injection of BoNT-A1 (0.1, 1, 10 pg/rat) into the right gastrocnemius muscle, while the left received vehicle. The DWB and CMAP tests were performed one-two days after the injection in order to detect the onset of sub-maximal BoNT-A activity. Both tests were preceded by the DAS test. BoNT-A produced dose-related reductions in both the weight-bearing and surface-bearing outcomes of up to 60% while showing moderate activity in the DAS. BoNT-A effects in the DWB test were well-aligned with those in the CMAP test, which showed dose-dependent reductions in CMAP amplitude and the area under the curve (AUC; up to 100%) as well as increases in latency (up to 130%). The efficacy of BoNT-A in DWB and CMAP was more pronounced with two boluses. Thus, the DWB test can be used to assess the properties of BoNTs following i.m. administration. It can be used to assess the candidate therapies and is more ethical than the mouse lethality assay., Highlights • The dynamic weight bearing test measures activity of botulinum neurotoxin in vivo. • The weight bearing test can be combined with other in vivo tests. • Botulinum neurotoxin is more active when injected as two boluses than as one.

This study aimed at developing a quantitative testing battery for dogs' stifle functionality, as, unlike in human medicine, currently none is available in the veterinary field. Forty-three dogs with surgically treated unilateral cranial cruciate ligament rupture and 21 dogs with no known musculoskeletal problems were included. Eight previously studied tests: compensation in sitting and lying positions, symmetry of thrust in hindlimbs when rising from lying and sitting, static weight bearing, stifle flexion and extension and muscle mass symmetry, were summed into the Finnish Canine Stifle Index (FCSI). Sensitivities and specificities of the dichotomised FCSI score were calculated against orthopaedic examination, radiological and force platform analysis and a conclusive assessment (combination of previous). One-way analysis of variance (ANOVA)was used to evaluate FCSI score differences between the groups. Cronbach's alpha for internal consistency was calculated. The range of the index score was 0-263, with a proposed cut-off value of 60 between 'adequate' and 'compromised' functional performance. In comparison to the conclusive assessment, the sensitivity and specificity of the FCSI were 90 per cent and 90.5 per cent, respectively. Cronbach's alpha for internal reliability of the FCSI score was 0.727. An estimate of the surgically treated and control dogs' FCSI scores were 105 (95 per cent CI 93 to 116) and 20 (95 per cent CI 4 to 37), respectively. The difference between the groups was significant (P

Background: Focal task specific dystonia occurs preferentially during performance of a specific task. There may be an inefficiently high grip force when doing manipulative tasks other than the trigger task, possibly reflecting a generalised impairment of sensory-motor integration. Objective: To examine how well subjects with writer’s cramp (n = 4) or musician’s cramp (n = 5) adapted their grip force when lifting a new object or catching a weight. Methods: Nine patients with focal hand dystonia and 10 controls were studied. Experiments addressed different motor behaviours: (A) lifting and holding an object; (B) adjusting grip force in anticipation of or in reaction to a change in load force by catching a small weight dropped expectedly or unexpectedly into a hand held receptacle. Results: In (A), patients produced a grip force overshoot during the initial lifts; force overflow was most pronounced in those with writer’s cramp. Patients and controls adjusted their grip force to object weight within one or two lifts, though patients settled to a steady force level above normal. In (B), patients with focal hand dystonia and normal controls showed similar predictive grip force adjustments to expected changes in object load, suggesting that this aspect of sensory-motor integration was normal. Patients had a shorter latency of grip force response than controls after an unexpected load increase, reflecting either a greater level of preparatory motor activity or a disinhibited spinal reflex response. Conclusions: The overall increased grip force in patients with focal hand dystonia is likely to be a prelearned phenomenon rather than a primary disorder of sensory-motor integration.

We consider the constitutive law of paper and its relation to a spatially inhomogeneous, random paper structure, the so-called formation. Under biaxial tensile loading, paper may be taken as an elastic-plastic hardening material, modelled here by a hyperbolic tangent law. The fact that paper is a quasi-two-dimensional solid offers a chance to inspect its formation via a basis-weight distribution (mass per unit area), and then carry out cross-correlations of two planar fields: the formation versus the strain (or stress) field resulting from a fine-mesh finite-element simulation of a sheet of paper subjected to a specified in-plane loading. The simulation requires an assumption of constitutive coefficients as a function of formation, and the higher the resultant cross-correlation, the better the assumed constitutive law. With this methodology we conclude that the higher the basis-weight, the higher the local stiffness and strength of the paper (on millimetre scales) in two very different cases: a Crayola sketch-paper and a paperboard. We next set up a Boolean model of paper formation, where each grain plays the role of a floc of cellulose fibres. First, we employ a computational-mechanics fibre-network model to demonstrate the effects of formation on non-uniform strain fields in the elastic regime. Moving on to the inelastic regime, we treat flocs as continuum ellipses, and, employing the resulting relation between formation and constitutive coefficients, we study scale-dependent homogenization of paper and establish that the representative volume element in the sense of Hill (1963 J. Mech. Phys. Solids 11, 357-372) is approximately reached on scales about 10 times larger than the floc size.

Background: Antipsychotic treatment in schizophrenia is frequently associated with extrapyramidal side effects. Objective behavioural measures to evaluate the severity of extrapyramidal side effects in the clinical setting do not exist. Objectives: This study was designed to investigate grasping movements in five drug naive and 13 medicated subjects with schizophrenia and to compare their performance with that of 18 healthy control subjects. Deficits of grip force performance were correlated with clinical scores of both parkinson-like motor disability and psychiatric symptom severity Methods: Participants performed vertical arm movements with a handheld instrumented object and caught a weight that was dropped into a handheld cup either expectedly from the opposite hand or unexpectedly from the experimenter’s hand. The scaling of grip force and the temporospatial coupling between grip and load force profiles was analysed. The psychiatric symptom severity was assessed by the positive and negative symptom score of schizophrenia and the brief psychiatric rating scale. Extrapyramidal symptoms were assessed by the unified Parkinson’s disease rating scale. Results: Drug naive subjects with schizophrenia performed similar to healthy controls. In contrast, medicated subjects with schizophrenia exhibited excessive grip force scaling and impaired coupling between grip and load force profiles. These performance deficits were strongly correlated with the severity of both extrapyramidal side effects related to antipsychotic therapy and negative symptoms related to the underlying pathology. Conclusions: These data provide preliminary evidence that deficits of sensorimotor performance in schizophrenia are, at least in part, related to the side effects of antipsychotic treatment. The investigation of grasping movements may provide a sensitive measure to objectively evaluate extrapyramidal side effects related to antipsychotic therapy.