The use of a detailed video-based locomotor pattern analysis system to assess the functional reinnervation of denervated hind limb muscles.

BACKGROUND: Spinal cord injuries induce a critical loss of motoneurons followed by irreversible locomotor function impairment. Surgical approaches combined with neuroprotective agents effectively rescue the damaged motoneurons and improve locomotor function. Our aim was to develop a reliable method which is able to provide quantifiable and in-depth data on the locomotor recovery during skeletal muscle reinnervation. NEW METHOD: Sprague-Dawley rats underwent lumbar 4 ventral root avulsion and reimplantation followed by riluzole treatment in order to rescue the injured motoneurons of the damaged pool. Control animals were operated, but received no riluzole treatment. The locomotor pattern of the hind limb was recorded biweekly on a special runway equipped with high resolution and high speed digital cameras producing both lateral and rear views simultaneously. All together 12 parameters of the hind limb movement pattern were evaluated by measuring specific joint angles, footprints and gait parameters in single video frames. Four months after the operation Fast Blue, a fluorescent retrograde tracer was applied to the L4 spinal nerve in order to label the reinnervating motoneurons. RESULTS: Our results confirmed the sensitivity of our arrangement and established strong relationship between the functional improvement and the morphological reinnervation. Moreover, we developed a correction method to make the system tolerant to the differences in the weight, step duration and step length. COMPARISON WITH EXISTING METHODS: There are no commercially available cheap, multi-parametric analysing equipment to characterise the gait in its complexity. CONCLUSIONS: Our system offers a modular, adaptable and expandable analysis on the reinnervation of the limb musculature in rodents.

The German health care Innovation Fund - An incentive for innovations to promote the integration of health care.

PURPOSE: Many health systems face challenges such as rising costs and lacking quality, both of which can be addressed by improving the integration of different health care sectors and professions. The purpose of this viewpoint is to present the German health care Innovation Fund (IF) initiated by the Federal Government to support the development and diffusion of integrated health care. DESIGN/METHODOLOGY/APPROACH: This article describes the design and rationale of the IF in detail and provides first insights into its limitations, acceptance and implementation by relevant stakeholders. FINDINGS: In its first period, the IF offered € 1.2 billion as start-up funding for model implementation and evaluation over a period of four years (2016-2019). This period was recently extended to a second round until 2024, offering € 200 million a year as from 2020. The IF is triggering the support of relevant insurers for the development of new integrated care models. In addition, strict evaluation requirements have led to a large number of health service research projects which assess structural and process improvements and thus enable evidence-based policy decisions. ORIGINALITY/VALUE: This article is the first of its kind to present the German IF to the international readership. The IF is a political initiative through which to foster innovations and promote integrated health care.

Delayed Spinal Cord-Brachial Plexus Reconnection after C7 Ventral Root Avulsion: The Effect of Reinnervating Motoneurons Rescued by Riluzole Treatment.

Ventral root avulsion induces dramatic loss of the affected spinal cord motoneurons. The neuroprotective effect of riluzole has been previously proven on the injured motoneurons: the vast majority of them can be rescued even when they have no possibility to regenerate their axons. In this study the number of injured motoneurons rescued by riluzole treatment and their capacity to reinnervate the denervated forelimb muscles was investigated. Surgical reconnection with a peripheral nerve graft between the affected spinal cord segment and the C7 spinal nerve was established immediately or with 1- and 3-week delay after avulsion. Avulsion and immediate reconnection of the motoneuron pool to the spinal nerve resulted in moderate reinnervation of the spinal nerve (281 ± 23 standard error of mean [SEM] retrogradely labeled motoneurons), whereas treatment of the injured motoneurons with riluzole yielded considerably higher numbers of reinnervating motoneurons (548 ± 18 SEM). Reconnection of the motor pool with the C7 spinal nerve with 1-week delay allowed fewer motor axons to reinnervate their targets in control and riluzole-treated animals (159 ± 21 vs. 395 ± 16 SEM). A clinically relevant 3-week delay in reconnection further reduced the number of reinnervating motoneurons (76 ± 22 SEM), but riluzole pre-treatment still enabled a significant number of rescued motoneurons (396 ± 17 SEM) to regenerate their axons into the C7 spinal nerve. These results show that those injured adult motoneurons that are rescued by riluzole treatment started immediately after the avulsion injury are able to reinnervate their targets even if they are provided with a conduit several weeks after the primary injury. This finding suggests that partial rescue of injured motoneurons with riluzole in patients who suffered a brachial plexus avulsion injury may provide an available pool of surviving motoneurons for late reconnection/reimplantation surgeries.

Purification and properties of tyrosine-sensitive 3-deoxy-D-arabino-heptolosonate-7-phosphate synthetase of Escherichia coli K12.

1. The tyrosine-sensitive allosteric first enzyme of the aromatic amino acid biosynthetic pathway, 3-deoxy-D-arabinoheptulosonate 7-phosphate synthetase (7-Phospho-2-keto-3-deoxy-D-arabino-heptonate D-erythrose 4-phosphate-lyase (pyruvate phosphorylating), EC 4.1.2.15) has been purified from a mutant strain of Escherichia coli. 2. The enzyme activity was inhibited to 50% at 2-10(-5) M tyrosine and to 90% at 2-10(-4) M tyrosine concentration. At tyrosine concentrations lower than 2-10(-5) M a cooperative interaction between tyrosine binding sites was observed. 3. Co2+ increased the enzyme activity about 2-2.5-fold. The presence of Co2+ ions stabilized the enzyme. EDTA inhibited the enzyme activity, and this inhibition was reversed by Co2+. Tyrosine-sensitive DAHP synthetase seems to be a metal containing enzyme. 4. Kinetic experiments were carried out to study the catalytic action. Contrary to earlier suggestions it is concluded, that the reaction mechanism appears to be more complex--with either the ping-pong or sequential type predominating, depending on conditions.

The specificity of the chemical modification of N6-delta 2-(isopentenyl)adenosine in purified yeast tRNA Ser.

The specific modification of N6-delta 2-(isopentenyl)adenosine in purified tRNA Ser yeast by mild treatment with KMnO4 and I2 was studied. N6-delta 2-(isopentenyl)adenosine in tRNA SER is specifically modified by iodination, providing us with a suitable method for the quantitative determination of N6-delta 2-(isopentenyl)adenosine in tRNA was found to contain 114 +/- 8 pmol/A260nm unit of N6-delta 2-(isopentenyl)adenosine and gave three labelled fractions on an RPC-5 column. The product obtained after KMnO4 treatment of tRNA Ser was not homogeneous. The enzymatic "reisopentenylation" of KMnO4-treated tRNA Ser resulted in the regeneration of only traces of the original molecule(s). Most of them had been damaged either by the KMnO4 treatment or in the incubation mixture used for "reisopentenylation".

Purification and some properties of rat liver tyrosyl-tRNA synthetase.

Rat liver cytoplasmic tyrosine:tRNA ligase (tyrosine:tRNA ligase, EC 6.1.1.1) was purified by ultracentrifugation, DEAE-cellulose chromatography and repeated phosphocellulose chromatography by more than 1500-fold. The molecular weight of the enzyme was approx. 150 000 as determined by Sephadex G-200 gel filtration. On the basis of sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the enzyme consisted of two subunits, each of 68 000 daltons. We found the following Km values for the enzyme: 13 micrometer for tyrosine and 1.7 mM for ATP in the ATP:PPi exchange reaction and 13 micrometer for tyrosine, 210 micrometer for ATP and 0.14 micrometer for tRNATyr in the aminoacylation reaction. The rate of tyrosyl-tRNA synthesis was 50-fold lower than that of ATP:PPi exchange. Addition of a saturating amount of tRNA did not affect the rate of ATP:PPi exchange.

Dichotic listening in crossed aphasia: "paradoxical" ipsilateral suppression.

In a 35-year-old right-handed man who had no personal or family history of left-handedness, left hemiparesis and predominantly motor aphasia suddenly developed following cerebrovascular accident. Clinical and laboratory data, including computerized tomographic scan, showed a clearly defined right hemisphere lesion. On dichotic listening test, a clear-cut right ear extinction was present.

Impaired grating discrimination following right hemisphere damage.

We investigated the effect of unilateral brain lesions on visual discrimination of low-, middle- and high-frequency gratings. The performance of patients with right hemisphere lesions was significantly impaired compared with that of both controls and patients with left hemisphere lesions. This impairment was largely limited to patients with right posterior hemispheric lesions and was present with all spatial frequencies. These findings run counter to the hypothesis that high and low spatial frequencies are preferentially processed by different hemispheres.

The role of the right hemisphere in processing negative sentences in context.

Given a pattern consisting of x1, x2,..., xn similar elements and y1, which is perceived as different from the former, it is more plausible to assert that y is not x rather than to assert that x is not y (Wason, J. verb. Learn verb. Behav. 4, 7-11, 1965). In order to appreciate such a difference, the entire set has to be considered. Right-hemisphere brain-damaged patients were submitted to a series of visually presented patterns, each pattern consisting of seven similar items and one dissimilar item. Their task was to complete a statement referring to a single element of each pattern. Statements were either simple affirmative or negative sentences. Errors and reaction times were recorded. Patients with a right-hemisphere injury were found to be insensitive to the plausible-implausible dimension in completing negative sentences. It is hypothesized that right-hemisphere brain-damaged patients are less adequate in this task because they are less capable in putting each element into the visual context.

Anomia for people's names.

The case of an anomia for people's names is reported. The study of this dissociation helps to clarify the difference in processing between proper and common names. Associated deficits in this and previously described cases provide support for the idea that an inability to retrieve arbitrary relations is the basis of the naming difficulty. This would confirm the role of proper names as purely referring expressions.

A category-specific deficit of spatial representation: the case of autotopagnosia.

Following a vascular lesion in the parietal cortex of the language dominant hemisphere (right in one case), two patients showed a striking dissociation between spared naming, recognition and use of their body parts and an inability in localising on verbal command the same body parts on themselves and on a mannequin (Autotopagnosia, AT). The patients were submitted to a modified version of Reed and Farah Test (1995), a test that taps the ability to encode changes of body position as opposed to changes of position of objects. Their performance differed from normal controls, showing a specific deficit in encoding body position. It is suggested that AT could be the consequence of a lesion in a specific neural circuit, located in the language dominant hemisphere, whose function is to encode the body position for both oneself and others.

Semantic and episodic memory in aphasia.

Within the framework of the distinction between episodic and semantic memory, it has been argued that these two memory Systems are organised in a hierarchical way. The hierarchical hypothesis assumes that episodic memory is a specific subsystem of semantic memory and therefore implies that episodic memory cannot exist without semantic memory. If this hypothesis is correct, it should be expected that (episodic) yes/no recognition performance would improve in patients with preserved semantic memory, following semantic encoding. In the present study we investigated the influence of semantic encoding on recognition memory performance in a population of 28 aphasic patients (AA) and 14 normal controls (NC). Experiment 1 considered recognition memory for semantically unrelated items, whereas Experiments 2 and 3 assessed recognition memory for semantically related items. In Experiment 3, but not in Experiment 2, subjects were explicitly instructed to make a semantic association between the items. AA were impaired, compared to NC, only on the recognition memory performance of Experiment 1. The ability to make a semantic association between two items was significantly and positively correlated to the ability to recognise, in a subsequent test, those same items. A further analysis showed that patients who were impaired on the semantic association task did significantly worse on the recognition task of Experiment 3 than NC and than patients who were unimpaired on the semantic association task. These findings are discussed in the context of memory deficits in aphasia and interpreted as giving support to the view that episodic memory for an item is affected by the level of semantic awareness of that same item.

Multiple-domain dissociation between impaired visual perception and preserved mental imagery in a patient with bilateral extrastriate lesions.

A brain-damaged patient is described whose pattern of performance provides insight into both the functional mechanisms and the neural structures involved in visual mental imagery. The patient became severely agnosic, alexic, achromatopsic and prosopagnosic following bilateral brain lesions in the temporo-occipital cortex. However, her mental imagery for the same visual entities that she could not perceive was perfectly preserved. This clear-cut dissociation held across all the major domains of high-level vision: object recognition, reading, colour and face processing. Our findings, together with other reports on domain-specific dissociations and functional brain imaging studies, provide evidence to support the view that visual perception and visual mental imagery are subserved by independent functional mechanisms, which do not share the same cortical implementation. In particular, our results suggest that mental imagery abilities need not be mediated by early visual cortices.

Optimal conditions for the separation of rat T lymphocytes on anti-immunoglobulin--immunoglobulin affinity columns.

The separation of rat T lymphocytes was investigated on anti-Ig--Ig columns. A simple and efficient method for the purification of rat Ig by precipitation of rat serum with sodium sulfate is presented. Protein binding characteristics of glass and plastic beads, as solid support of affinity columns, are described, as well as optimal parameters for coating beads with rat Ig (with BSA, ribonuclease and lysozyme, as comparison). Binding of Ig was primarily dependent on the concentration of the Ig solution. Maximal strong binding of Ig (6.2 X 10(3) molecules per micron2 of bead surface) was reached a 400 microng per ml concentration of purified Ig solution during 20 min of incubation. Higher concentrations increased only the amount of loosely bound Ig on the surface of beads whereas the amount of firmly bound Ig remained unchanged. Fractionation of lymphoid cell suspensions on anti-Ig--Ig affinity columns prepared at optimal conditions resulted in highly purified T-cell suspensions containing less than 1% of lymphocytes bearing surface Ig receptors.

5-Substituted-2,2'-anhydrouridines, potent inhibitors of uridine phosphorylase.

5-Substituted-2,2'-anhydrouridines are a new class of competitive inhibitors of uridine phosphorylase. The most potent member of the series is 2,2'-anhydro-5-ethyluridine with an apparent Ki value of 25 nM. These compounds are selective inhibitors of uridine phosphorylase and have no effect on thymidine phosphorylase. 5-Substituted-2,2'-anhydrouridines are no substrates of either uridine phosphorylase or thymidine phosphorylase.

Italian Multicentre Study on Dementia (SMID): a neuropsychological test battery for assessing Alzheimer's disease.

For the Italian Multicentre Study on Dementia, a longitudinal survey on Alzheimer's disease (AD) initiated in 1982, we developed a neuropsychological test battery for screening, staging and monitoring cognitive impairment in AD patients and for delineating their pattern of cognitive decline. The tests measured higher cortical functions primarily involved in AD, such as short- and long-term memory, orientation, language, and praxis, and spanned a large enough range of difficulty to minimize ceiling and floor effects. We administered this battery to 143 clinically diagnosed AD patients and 146 hospital controls whose scores were corrected for age and educational level. Interrater and test-retest reliability were substantial, as were content and concurrent validity. Five of the battery's subtests proved capable of accurately screening early demented from non-demented elderly subjects and of staging mild, moderate, severe and very severe mental impairment. The mean performance of subjects classified into these categories differed significantly on all cognitive functions tested. Follow-up studies are in progress.

When a patient can write but not copy: report of a single case.

A dissociation between spared spontaneous and impaired writing on copy is described in a patient with severe limb and constructional apraxia. Visual-perceptual abilities were normal as well as oral language and reading. The findings are discussed in the light of an information processing model of writing.

Auditory modality-specific anomia: evidence from a case of pure word deafness.

In a patient with a classical syndrome of pure word deafness following a cerebrovascular accident detailed neuropsychological examination showed an almost absolute inability to name meaningful non verbal sounds, in spite of normal recognition as demonstrated by ability to match the sound with the corresponding natural source. This selective anomia, confined to auditory modality, is discussed in view of the previous researches regarding the general field in naming disturbances, which showed that for the vaste majority of aphasics, anomia was not modality dependent. Besides that the contrasting performance of the patient who showed complete lack of phonemic analysis matched with normal recognition of some acoustic parameters of speech as prosody and stress is discussed.

Door but not four and 4 a category specific transcoding deficit in a pure acalculic patient.

We report a left parietal damaged, acalculic, non aphasic patient who showed a specific deficit in reading Arabic and spelled-out numerals. Word reading was flawless, while he showed a severe impairment in reading meaningless strings of phonemes (phonological alexia). He also showed a dissociation between the preserved ability to retrieve knowledge about general facts and the impairment in retrieving cardinal, personal and non-personal numerical facts. These findings point to a separate organization in the brain of the numerical domain.

Influence of association value in recognition of random shapes under dichhaptic presentation.

A tactile version of the Vanderplas and Garvin random shapes was given to 80 right-handed subjects, ranging in age from 6 to 13 years. Complexity was constant across the patterns: half of them were chosen from the High Association Group while the remaining patterns were selected from the Low-Association Group. Stimuli were dichhaptically presented, each pair being composed of a High Association and Low Association stimulus. The subject's response was given on each trial by pointing to the corresponding shapes froma visual display presented following the removal of the test stimuli. Analysis of the data showed that age of subjects, hemisphere (R.H. better than L.H.) and Association Value (High Association better than Low Association) were significant factors in recognition. Sex was not significant as well as none of the the interactions. Results were discussed in terms of hemispheric specialisation.