Using crutches during walking possibly reduces gait imagery accuracy among healthy young and older adults.

[Purpose] Although crutches are widely used in the field of rehabilitation to improve gait performance, patients usually have difficulties using them, and this may increase their risks for falls. This study aimed to define the accuracy of gait imagery during walking with and without crutches, in healthy young and older adults, using the mental chronometry method. [Participants and Methods] Overall, 99 healthy young (mean age, 20.2 ± 1.0 years) and 39 healthy older adults (mean age, 71.3 ± 2.9 years) performed the imagery and execution tasks, which involved walking through a distance of 10 meters both with and without crutches. Using the mental chronometry method, the accuracy of the motor imagery was defined as the difference between the imagery time and the actual execution time. Two-way analysis of variance and one-sample t-tests were performed to evaluate the accuracy of the gait imagery. [Results] Both the young and older adults significantly overestimated their gait speeds when using crutches; the overestimation was larger among the older adults. [Conclusion] The overestimations indicate that participants estimated their gait speeds with crutches to be faster than their actual speeds. Therefore, using crutches decreased the accuracy of gait imagery and might therefore increase an individual's risk of falling during walking.

Intraclass correlation coefficient of trunk muscle thicknesses in different positions measured using ultrasonography.

[Purpose] This study aimed to clarify the required number of measurements to calculate trunk muscle thickness at each position. [Participants and Methods] The participants were 30 elderly males aged >65 years. The right lumbar multifidus (L2), lumbar multifidus (L5), erector spinae, transversus abdominis, internal oblique, and external oblique muscle thicknesses were measured on longitudinal images obtained using ultrasonography in the lying, sitting, and standing positions. Two measurement values for each muscle thickness was used to calculate the intraclass correlation coefficient (1.1-1.5). [Results] The intraclass correlation coefficients of the abdominal muscle thickness measurements with "great reliabilities" were as follows: 1.3-1.5 for the external oblique muscle and 1.2-1.5 for the internal oblique and transversus abdominis muscles in the lying position; 1.3-1.5 for the external oblique and transversus abdominis muscles and 1.2-1.5 for the internal oblique muscle in the sitting position; the intraclass correlation coefficient in the standing position was 1.5 for the external oblique muscle 1.1-1.5 for the internal oblique muscle and 1.3-1.5 for the transversus abdominis muscle. In all the positions, the intraclass correlation coefficient of the measurements of the back-muscle thicknesses ranged from 1.1 to 1.5 for the right lumbar multifidus (L2), lumbar multifidus (L5), and erector spinae. [Conclusion] Depending on the posture, the abdominal muscles require multiple measurements, whereas the back muscles only require a single measurement.

Forms of direction change during walking and effect on movement and reaction time.

[Purpose] To elucidate factors that affect walking before and after direction changes and their effects on reaction time by investigating different angles of direction changes. [Participants and Methods] A total of 29 healthy young males and females participated in this study. The task was to walk along a 20-m path and perform three direction changes while walking: straight walking, 45° direction change, and 90° direction change. Step length and probe reaction time (P-RT) were measured before and after the point of direction change. A two-factor repeated measures analysis of variance was applied to measure P-RT and step length before and after direction changes. [Results] A significant effect was observed for step length and P-RT immediately before and after direction changes. An interaction was also observed between the angle of direction change and the step length before and after the direction change. When compared with the straight walk, a significant effect was observed at 45° and 90° direction changes. [Conclusion] While walking, 90° direction changes are suggested to be more difficult than 45° direction changes, and 45° direction changes are more difficult than walking in a straight line.

Effects of active and passive light-touch support on postural stability during tandem standing.

[Purpose] Light-touch support (consisting of a load <100 g) is useful for reducing postural sway while standing and walking. However, it is unclear which types of touch and somatosensory inputs are more effective for improving postural control. This study aimed to clarify the effects of active and passive light-touch support, with and without visual information, on postural stability during tandem standing. [Participants and Methods] Eleven young healthy adults maintained tandem standing for 30 s under six conditions. The independent variables were light-touch condition (no, active or passive) and visual condition (eyes open or closed). Postural sway, as measured using a force plate, was considered to indicate postural stability. [Results] There was significantly less postural sway with active light touch compared with passive and no touch. Passive light touch resulted in significantly less sway than no touch. In addition, there was less postural sway with active light compared to passive light touch, especially with the eyes closed. The light-touch support force did not differ between conditions. [Conclusion] Both active and passive light-touch improved postural stability in comparison to no-touch. Active light-touch support significantly improved postural stability. These results could be used to inform therapeutic interventions within clinical settings.

Clinical Impact of the Introduction of an Early Rehabilitation Protocol on Infectious Complications in Patients after Gastrointestinal Cancer Surgery.

BACKGROUND: The clinical importance of postoperative rehabilitation for cancer patients has recently attracted much attention. However, it remains uncertain whether early rehabilitation can prevent infectious complications in patients undergoing gastrointestinal cancer surgery. METHODS: The study group consisted of 259 patients who underwent laparoscopic or open surgery for gastrointestinal cancer at our institution between December 2012 and November 2016. Our department proposed a new early rehabilitation protocol for such patients to encourage physical activity after surgery. The protocol was clinically introduced on July 21, 2015. We divided the study subjects into two groups: those who were admitted before the introduction of the new protocol and those admitted after. The frequency of infectious complications, including respiratory infections, and the length of hospital stay after surgery were compared between the two groups. RESULTS: No adverse cardiovascular event associated with the early rehabilitation protocol was experienced. After the protocol was introduced, more than 80% of patients started exercising on the first day after surgery. For patients undergoing open surgery, the frequency of infectious complications was significantly reduced with the introduction of the protocol (p<0.05). Moreover, when open surgery was performed, the protocol significantly shortened the length of hospital stay (p<0.05). CONCLUSION: Our proposed early rehabilitation protocol for patients who have undergone gastrointestinal cancer surgery was considered to be safe and feasible. The protocol may prevent infectious complications and shorten the hospital stay after such surgery.

A local glutamate-glutamine cycle sustains synaptic excitatory transmitter release.

Biochemical studies suggest that excitatory neurons are metabolically coupled with astrocytes to generate glutamate for release. However, the extent to which glutamatergic neurotransmission depends on this process remains controversial because direct electrophysiological evidence is lacking. The distance between cell bodies and axon terminals predicts that glutamine-glutamate cycle is synaptically localized. Hence, we investigated isolated nerve terminals in brain slices by transecting hippocampal Schaffer collaterals and cortical layer I axons. Stimulating with alternating periods of high frequency (20 Hz) and rest (0.2 Hz), we identified an activity-dependent reduction in synaptic efficacy that correlated with reduced glutamate release. This was enhanced by inhibition of astrocytic glutamine synthetase and reversed or prevented by exogenous glutamine. Importantly, this activity dependence was also revealed with an in-vivo-derived natural stimulus both at network and cellular levels. These data provide direct electrophysiological evidence that an astrocyte-dependent glutamate-glutamine cycle is required to maintain active neurotransmission at excitatory terminals.

A novel in vivo method for isolating antibodies from a phage display library by neuronal retrograde transport selectively yields antibodies against p75(NTR.).

The neurotrophin receptor p75(NTR) is utilized by a variety of pathogens to gain entry into the central nervous system (CNS). We tested if this entry portal might be exploited using a phage display library to isolate internalizing antibodies that target the CNS in vivo. By applying a phage library that expressed human single chain variable fragment (scFv) antibodies on their surface to a transected sciatic nerve, we showed that (1) phage conjugated to anti-p75(NTR) antibody or phage scFv library pre-panned against p75(NTR) are internalized by neurons expressing p75(NTR); (2) subsequent retrograde axonal transport separates internalized phage from the applied phage; and, (3) internalized phage can be recovered from a proximal ligature made on a nerve. This approach resulted in 13-fold increase in the number of phage isolated from the injured nerve compared with the starting population, and isolation of 18 unique internalizing p75(NTR) antibodies that were transported from the peripheral nerve into the spinal cord, through the blood-brain barrier. In addition, antibodies recognizing other potentially internalized antigens were identified through in vivo selection using a fully diverse library. Because p75(NTR) expression is upregulated in motor neurons in response to injury and in disease, the p75(NTR) antibodies may have substantial potential for cell-targeted drug/gene delivery. In addition, this novel selection method provides the potential to generate panels of antibodies that could be used to identify further internalization targets, which could aid drug delivery across the blood-brain barrier.

Extrasynaptic glutamate and inhibitory neurotransmission modulate ganglion cell participation during glutamatergic retinal waves.

During the first 2 wk of mouse postnatal development, transient retinal circuits give rise to the spontaneous initiation and lateral propagation of depolarizations across the ganglion cell layer (GCL). Glutamatergic retinal waves occur during the second postnatal week, when GCL depolarizations are mediated by ionotropic glutamate receptors. Bipolar cells are the primary source of glutamate in the inner retina, indicating that the propagation of waves depends on their activation. Using the fluorescence resonance energy transfer-based optical sensor of glutamate FLII81E-1µ, we found that retinal waves are accompanied by a large transient increase in extrasynaptic glutamate throughout the inner plexiform layer. Using two-photon Ca(2+) imaging to record spontaneous Ca(2+) transients in large populations of cells, we found that despite this spatially diffuse source of depolarization, only a subset of neurons in the GCL and inner nuclear layer (INL) are robustly depolarized during retinal waves. Application of the glutamate transporter blocker dl-threo-ß-benzyloxyaspartate (25 µM) led to a significant increase in cell participation in both layers, indicating that the concentration of extrasynaptic glutamate affects cell participation in both the INL and GCL. In contrast, blocking inhibitory transmission with the GABAA receptor antagonist gabazine and the glycine receptor antagonist strychnine increased cell participation in the GCL without significantly affecting the INL. These data indicate that during development, glutamate spillover provides a spatially diffuse source of depolarization, but that inhibitory circuits dictate which neurons within the GCL participate in retinal waves.

Glutamine is required for persistent epileptiform activity in the disinhibited neocortical brain slice.

The neurotransmitter glutamate is recycled through an astrocytic-neuronal glutamate-glutamine cycle in which synaptic glutamate is taken up by astrocytes, metabolized to glutamine, and transferred to neurons for conversion back to glutamate and subsequent release. The extent to which neuronal glutamate release is dependent upon this pathway remains unclear. Here we provide electrophysiological and biochemical evidence that in acutely disinhibited rat neocortical slices, robust release of glutamate during sustained epileptiform activity requires that neurons be provided a continuous source of glutamine. We demonstrate that the uptake of glutamine into neurons for synthesis of glutamate destined for synaptic release is not strongly dependent on the system A transporters, but requires another unidentified glutamine transporter or transporters. Finally, we find that the attenuation of network activity through inhibition of neuronal glutamine transport is associated with reduced frequency and amplitude of spontaneous events detected at the single-cell level. These results indicate that availability of glutamine influences neuronal release of glutamate during periods of intense network activity.

Imaging of glutamate in brain slices using FRET sensors.

The neurotransmitter glutamate is the mediator of excitatory neurotransmission in the brain. Release of this signaling molecule is carefully controlled by multiple mechanisms, yet the methods available to measure released glutamate have been limited in spatial and/or temporal domains. We have developed a novel technique to visualize glutamate release in brain slices using three purified fluorescence (Forster) energy resonance transfer (FRET)-based glutamate sensor proteins. Using a simple loading protocol, the FRET sensor proteins diffuse deeply into the extracellular space and remain functional for many tens of minutes. This allows imaging of glutamate release in brain slices with simultaneous electrophysiological recordings and provides temporal and spatial resolution not previously possible. Using this glutamate FRET sensor loading and imaging protocol, we show that changes in network excitability and glutamate re-uptake alter evoked glutamate transients and produce correlated changes in evoked-cortical field potentials. Given the sophisticated advantages of brain slices for electrophysiological and imaging protocols, the ability to perform real-time imaging of glutamate in slices should lead to key insights in brain function relevant to plasticity, development and pathology. This technique also provides a unique assay of network activity that compliments alternative techniques such as voltage-sensitive dyes and multi-electrode arrays.

Modulation of epileptiform activity by glutamine and system A transport in a model of post-traumatic epilepsy.

Epileptic activity arises from an imbalance in excitatory and inhibitory synaptic transmission. To determine if alterations in the metabolism of glutamate, the primary excitatory neurotransmitter, might contribute to epilepsy we directly and indirectly modified levels of glutamine, an immediate precursor of synaptically released glutamate, in the rat neocortical undercut model of hyperexcitability and epilepsy. We show that slices from injured cortex take up glutamine more readily than control slices, and an increased expression of the system A transporters SNAT1 and SNAT2 likely underlies this difference. We also examined the effect of exogenous glutamine on evoked and spontaneous activity and found that addition of physiological concentrations of glutamine to perfusate of slices isolated from injured cortex increased the incidence and decreased the refractory period of epileptiform potentials. By contrast, exogenous glutamine increased the amplitude of evoked potentials in normal cortex, but did not induce epileptiform potentials. Addition of physiological concentrations of glutamine to perfusate of slices isolated from injured cortex greatly increased abnormal spontaneous activity in the form of events resembling spreading depression, again while having no effect on slices from normal cortex. Interestingly, similar spreading depression like events were noted in control slices at supraphysiological levels of glutamine. In the undercut cortex addition of methylaminoisobutyric acid (MeAIB), an inhibitor of the system A glutamine transporters attenuated all physiological effects of added glutamine suggesting that uptake through these transporters is required for the effect of glutamine. Our findings support a role for glutamine transport through SNAT1 and/or SNAT2 in the maintenance of abnormal activity in this in vitro model of epileptogenesis and suggest that system A transport and glutamine metabolism are potential targets for pharmacological intervention in seizures and epilepsy.