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Biomedical subjects

Steven T Moore

Publications and source records attributed to Steven T Moore.

11 recordsLinked to original sources

Effect of adenoviral mediated overexpression of fibromodulin on human dermal fibroblasts and scar formation in full-thickness incisional wounds.

Fibromodulin, a member of the small leucine-rich proteoglycan family, has been recently suggested as a biologically significant mediator of fetal scarless repair. To assess the role of fibromodulin in the tissue remodeling, we constructed an adenoviral vector expressing human fibromodulin cDNA. We evaluated the effect of adenovirus-mediated overexpression of fibromodulin in vitro on transforming growth factors and metalloproteinases in fibroblasts and in vivo on full-thickness incisional wounds in a rabbit model. In vitro, we found that Ad-Fibromodulin induced a decrease of expression of TGF-beta(1) and TGF-beta(2) precursor proteins, but an increase in expression of TGF-beta(3) precursor protein and TGF-beta type II receptor. In addition, fibromodulin overexpression resulted in decreased MMP-1 and MMP-3 protein secretion but increased MMP-2, TIMP-1, and TIMP-2 secretion, whereas MMP-9 and MMP-13 were not influenced by fibromodulin overexpression. In vivo evaluation by histopathology and tensile strength demonstrated that Ad-Fibromodulin administration could ameliorate wound healing in incisional wounds. In conclusion, although the mechanism of scar formation in adult wounds remains incompletely understood, we found that fibromodulin overexpression improves wound healing in vivo, suggesting that fibromodulin may be a key mediator in reduced scarring.

Adenoviridae↗

Long-term monitoring of gait in Parkinson's disease.

A new system for long-term monitoring of gait in Parkinson's disease (PD) has been developed and validated. The characteristics of every stride taken over 10-h epochs were acquired using a lightweight ankle-mounted sensor array that transmitted data wirelessly to a small pocket PC at a rate of 100 Hz. Stride was calculated from the vertical linear acceleration and pitch angular velocity of the leg with an accuracy of 5 cm. Results from PD patients (5) demonstrate the effectiveness of long-term monitoring of gait in a natural environment. The small, variable stride length characteristic of Parkinsonian gait, and fluctuations of efficacy associated with levodopa therapy, such as delayed onset, wearing off, and the 'off/on' effect, could reliably be detected from long-term changes in stride length.

Adult↗

Modeling locomotor dysfunction following spaceflight with Galvanic vestibular stimulation.

In this study locomotor and gaze dysfunction commonly observed in astronauts following spaceflight were modeled using two Galvanic vestibular stimulation (GVS) paradigms: (1) pseudorandom, and (2) head-coupled (proportional to the summed vertical linear acceleration and yaw angular velocity obtained from a head-mounted Inertial Measurement Unit). Locomotor and gaze function during GVS were assessed by tests previously used to evaluate post-flight astronaut performance; dynamic visual acuity (DVA) during treadmill locomotion at 80 m/min, and navigation of an obstacle course. During treadmill locomotion with pseudorandom GVS there was a 12% decrease in coherence between head pitch and vertical translation at the step frequency relative to the no GVS condition, which was not significantly different to the 15% decrease in coherence observed in astronauts following shuttle missions. This disruption in head stabilization likely resulted in a decrease in DVA equivalent to the reduction in acuity observed in astronauts 6 days after return from extended missions aboard the International Space Station (ISS). There were significant increases in time-to-completion of the obstacle course during both pseudorandom (21%) and head-coupled (14%) GVS, equivalent to an ISS astronaut 5 days post-landing. An attempt to suppress head movement was evident during both pseudorandom and head-coupled GVS while negotiating the obstacle course, with a 20 and 16%, decrease in head pitch and yaw velocity, respectively. The results of this study demonstrate that pseudorandom GVS generates many of the salient features of post-flight locomotor dysfunction observed in astronauts following short and long duration missions. An ambulatory GVS system may prove a useful adjunct to the current pre-flight astronaut training regimen.

Adult↗

Modeling postural instability with Galvanic vestibular stimulation.

In this study the effect of a pseudorandom binaural bipolar Galvanic stimulus generated by a sum of nonharmonically related sine waves on postural control was functionally assessed using computerized dynamic posturography (CDP), and the results compared to vestibulopathic patient populations and astronauts exposed to microgravity. The standardized CDP test battery comprised six sensory organization tests (SOTs) that combined three visual conditions (eyes open, eyes closed, and sway-referenced vision) with two proprioceptive conditions (fixed and sway-referenced support surfaces). Subjects (12) performed 18 randomized trials (three trials of each of the six SOTs) as a baseline, repeated the 18 trials with Galvanic vestibular stimulation (GVS), and then performed a post-GVS baseline. A 10 min rest period was inserted between each test battery. Anterioposterior postural sway increased significantly and was in the abnormal range (fifth percentile) during GVS for SOTs where visual input was compromised (sway-referenced surround) or absent. Postural stability returned to baseline when GVS was removed. An analysis of sensory input scores (somatosensory, visual, and vestibular) demonstrated the specificity of GVS in distorting vestibular input to postural control. The SOT scores observed in astronauts on landing day did not differ significantly to that generated by GVS in our normal subjects. GVS also induced a similar pattern of instability on CDP as profound bilateral vestibular loss, although not as severe. The results suggest that unpredictably varying GVS quantitatively and qualitatively models postural instability of vestibular origin.

Adult↗

Marching to the beat of the same drummer: the spontaneous tempo of human locomotion.

Laboratory studies have suggested that the preferred cadence of walking is approximately 120 steps/min, and the vertical acceleration of the head exhibits a dominant peak at this step frequency (2 Hz). These studies have been limited to short periods of walking along a predetermined path or on a treadmill, and whether such a highly tuned frequency of movement can be generalized to all forms of locomotion in a natural setting is unknown. The aim of this study was to determine whether humans exhibit a preferred cadence during extended periods of uninhibited locomotor activity and whether this step frequency is consistent with that observed in laboratory studies. Head linear acceleration was measured over a 10-h period in 20 subjects during the course of a day, which encompassed a broad range of locomotor (walking, running, cycling) and nonlocomotor (working at a desk, driving a car, riding a bus or subway) activities. Here we show a highly tuned resonant frequency of human locomotion at 2 Hz (SD 0.13) with no evidence of correlation with gender, age, height, weight, or body mass index. This frequency did not differ significantly from the preferred step frequency observed in the seminal laboratory study of Murray et al. (Murray MP, Drought AB, and Kory RC. J Bone Joint Surg 46A: 335-360, 1964). [1.95 Hz (SD 0.19)]. On the basis of the frequency characteristics of otolith-spinal reflexes, which drive lower body movement via the lateral vestibulospinal tract, and otolith-mediated collic and ocular reflexes that maintain gaze when walking, we speculate that this spontaneous tempo of locomotion represents some form of central "resonant frequency" of human movement.

Activities of Daily Living↗

Spatial orientation of optokinetic nystagmus and ocular pursuit during orbital space flight.

On Earth, eye velocity of horizontal optokinetic nystagmus (OKN) orients to gravito-inertial acceleration (GIA), the sum of linear accelerations acting on the head and body. We determined whether adaptation to micro-gravity altered this orientation and whether ocular pursuit exhibited similar properties. Eye movements of four astronauts were recorded with three-dimensional video-oculography. Optokinetic stimuli were stripes moving horizontally, vertically, and obliquely at 30 degrees/s. Ocular pursuit was produced by a spot moving horizontally or vertically at 20 degrees/s. Subjects were either stationary or were centrifuged during OKN with 1 or 0.5 g of interaural or dorsoventral centripetal linear acceleration. Average eye position during OKN (the beating field) moved into the quick-phase direction by 10 degrees during lateral and upward field movement in all conditions. The beating field did not shift up during downward OKN on Earth, but there was a strong upward movement of the beating field (9 degrees) during downward OKN in the absence of gravity; this likely represents an adaptation to the lack of a vertical 1-g bias in-flight. The horizontal OKN velocity axis tilted 9 degrees in the roll plane toward the GIA during interaural centrifugation, both on Earth and in space. During oblique OKN, the velocity vector tilted towards the GIA in the roll plane when there was a disparity between the direction of stripe motion and the GIA, but not when the two were aligned. In contrast, dorsoventral acceleration tilted the horizontal OKN velocity vector 6 degrees in pitch away from the GIA. Roll tilts of the horizontal OKN velocity vector toward the GIA during interaural centrifugation are consistent with the orientation properties of velocity storage, but pitch tilts away from the GIA when centrifuged while supine are not. We speculate that visual suppression during OKN may have caused the velocity vector to tilt away from the GIA during dorsoventral centrifugation. Vertical OKN and ocular pursuit did not exhibit orientation toward the GIA in any condition. Static full-body roll tilts and centrifugation generating an equivalent interaural acceleration produced the same tilts in the horizontal OKN velocity before and after flight. Thus, the magnitude of tilt in OKN velocity was dependent on the magnitude of interaural linear acceleration, rather than the tilt of the GIA with regard to the head. These results favor a 'filter' model of spatial orientation in which orienting eye movements are proportional to the magnitude of low frequency interaural linear acceleration, rather than models that postulate an internal representation of gravity as the basis for spatial orientation.

Acceleration↗

Functional assessment of head-eye coordination during vehicle operation.

PURPOSE: Visual impairment, resulting from ocular abnormalities or brain lesions, can significantly affect driving performance. The impact of vestibulopathy on head-eye coordination is also a concern in vehicle operation safety, yet to date there has been little functional research in this area. An understanding of decrements in driving ability resulting from visual and vestibular pathology, plus the differences in visual strategies used by novice and experienced drivers, would benefit from an objective analysis of head-eye coordination during vehicle operation. METHODS: We have developed a laptop-based system for measuring eye, head, and vehicle movement in real time. Digital video cameras mounted on lightweight swimming goggles are used to provide images of the eye and scene, allowing assessment of gaze. In addition, the use of inertial measurement units to simultaneously transduce head and vehicle movement allows us to evaluate the vestibular contribution to stable vision. RESULTS: Data was obtained from a flight simulator and while driving a car. During banking turns in the flight simulator, there was a sustained roll tilt of the head and eyes toward the scene-derived visual vertical with a combined gain of approximately 25%. One of the most complex visual tasks when driving was exiting a multistory car park, which involved the scanning of hundreds of parked vehicles with an average fixation time of approximately 100 ms. The vertical vestibulo-ocular reflex was also found to make a significant contribution to the maintenance of dynamic visual acuity even while driving on paved surfaces. CONCLUSION: These results demonstrate the viability of functional assessment of head-eye coordination during vehicle operation, and potential applications of this technology to driver assessment are discussed. Analysis of both active and reflex contributions to gaze may provide a clearer understanding of the impact of visual and vestibular impairment on driving ability.

Adult↗

Instantaneous rotation axes during active head movements.

Rotation axes were calculated during active head movements using a motion analysis system. The mean rotation axis for 1 Hz head pitch when seated was posterior (6 mm) and inferior (21 mm) to the interaural axis, shifting 16 mm downwards when standing. During seated 2 Hz head pitch the rotation axis was close to the interaural axis, shifting downwards 15 mm when standing. This downward shift suggests that cervical vertebrae were recruited during head pitch with the trunk unsupported. The proximity of the pitch axis to the otoliths implies minimal otolith activation during small-amplitude, high-frequency pitch rotations, such as those encountered during locomotion. The mean rotation axis for 1 Hz yaw rotation was located slightly posterior (10 mm) to the interaural axis at the midpoint between the vestibular labyrinths when both seated and standing. In addition, the orientation of the plane of yaw rotation relative to the stereotaxic horizontal plane (pitched 5 degrees nose-down) was essentially fixed in head coordinates, regardless of the pitch orientation of the head, suggesting that yaw movements occur about an axis restricted by the mechanical structure of the atlanto-axial joint. The results demonstrate that the instantaneous rotation axes technique overcomes the inherent instability of the helical-axis representation for small head movements.

Adult↗

Robust and real-time torsional eye position calculation using a template-matching technique.

Computation of eye rotation about the line of sight (torsion) using image processing techniques has traditionally used cross-correlation of iral signatures sampled from circular arcs centered on the pupil. We have developed a new algorithm that utilizes a template-matching technique to calculate torsional eye position. Iral signatures are obtained from two annuli centered on the pupil center. By assuming that torsional rotation of the eye is constrained between successive video frames (<2 degrees), only a small window of the previous reference signature is necessary to determine relative torsional eye displacement. This dramatically reduces the number of pixels needed for computing torsion. This algorithm is considerably faster, attains a higher accuracy, and exhibits considerably less noise than the cross-correlation technique. Running on a 800 MHz Intel-based Dual Processor Pentium III, with a Matrox frame grabber, the system is capable of processing three-dimensional eye position at a rate of 120 frames/s.

Algorithms↗

Ocular and perceptual responses to linear acceleration in microgravity: alterations in otolith function on the COSMOS and Neurolab flights.

In this paper we review space flight experiments performed by our laboratory. Rhesus monkeys were tested before and after 12 days in orbit on COSMOS flights 2044 (1989) and 2229 (1992-1993). There was a long-lasting decrease in post-flight ocular counter-rolling (70%) and vergence (50%) during off-vertical axis rotation. In one animal, the orientation of optokinetic after-nystagmus shifted by 28 degrees from the spatial vertical towards the body vertical early post-flight. Otolith-ocular and perceptual responses were also studied in four astronauts on the 17-day Neurolab shuttle mission (STS-90) in 1998. Ocular counter-rolling was unchanged in response to 1-g and 0.5-g Gy centrifugation during and after flight and to post-flight static roll tilts relative to pre-flight values. Orientation of the optokinetic nystagmus eye velocity axis to gravito-inertial acceleration (GIA) during centrifugation was also unaltered by exposure to microgravity. Perceptual orientation to the GIA was maintained in-flight, and subjects did not report sensation of translation during constant velocity centrifugation. These studies suggest that percepts and ocular responses to tilt are determined by sensing the body vertical relative to the GIA. The findings also raise the possibility that 'artificial gravity' during the Neurolab flight counteracted adaptation of these otolith-ocular responses.

Acceleration↗

Artificial gravity: a possible countermeasure for post-flight orthostatic intolerance.

Four payload crewmembers were exposed to sustained linear acceleration in a centrifuge during the Neurolab (STS-90) flight. In contrast to previous studies, otolith-ocular reflexes were preserved during and after flight. This raised the possibility that artificial gravity may have acted as a countermeasure to the deconditioning of otolith-ocular reflexes. None of the astronauts who were centrifuged had orthostatic intolerance when tested with head-up passive tilt after flight. Thus, centrifugation may also have helped maintain post-flight hemodynamic responses to orthostasis by preserving the gain of the otolith-sympathetic reflex. A comparison with two fellow Neurolab orbiter crewmembers not exposed to artificial gravity provided some support for this hypothesis. One of the two had hemodynamic changes in response to post-flight tilt similar to orthostatically intolerant subjects from previous missions. More data is necessary to evaluate this hypothesis, but if it were proven correct, in-flight short-radius centrifugation may help counteract orthostatic intolerance after space flight.

Acceleration↗