Telemetered Heart Rates of Free-Living Uinta Ground Squirrels in Response to Social Interactions

Free-living Uinta ground squirrels (Spermophilus armatus) were instrumented with miniaturized ECG radio-transmitters to measure their short-term and long-term heart rate responses to social interactions. A continuous trapping and direct observation program prior to and during the study provided complete behavioral and life history information for virtually all ground squirrels on the 22-acre study area. Three broad categories of heart rate information were obtained: responses by squirrels (1) in their burrows, (2) above ground during social interactions, and (3) above ground when animals were not fighting and when conspecifics were both absent and present. Marked changes in the heart rate of ground squirrels occurred even as animals behaved in their burrows and conspecifics were absent. Some changes were caused by motor behaviors and appeared commensurate with different degrees of physical exertion. Others were evident among inactive animals and took the form of diurnal cardiac rhythms which were independent of immediate motor behavior hut nonetheless attuned to aboveground activity cycles. The heart rate of all ground squirrels increased well above burrow baselines when animals behaved aboveground. The greatest elevations occurred during social interactions which ranged from mere threat to physical combat. Combat encounters elicited responses which frequently exceeded 400 beats/minute as compared to burrow and aboveground baselines for inactive animals of 269 and 284 beats/minute , respectively. Threat interactions produced less dramatic increases, but because threat usually lasted longer, it was perhaps as stressful as combat. There were no significant differences between peak responses of dominants and subordinates, initiates and recipients of aggression, or sex and age classes. However, the duration of cardiac response was less for dominants and hence, they apparently experienced less stress than subordinates. Increases in heart rate, independent of motor behavior and immediate social interactions, were also observed as female ground squirrels roamed within and/or made occasional excurs ions outside their home ranges. These cardiac changes occurred regardless of the presence or absence of conspecifics in the vicinity. It was concluded that such cardiac acceleration represented chronic response to social interactions and was elicited by spatial factors, specifically spatial familiarity, which acted as conditioned stimuli (previously paired with combat). Such chronic responses were greatest during the initial establishment of territories by females, decreased during territoriality, and increased again following the breakdown of territoriality. So territoriality acted to reduce the magnitude of heart rate response and hence, stress among females. The mere presence of conspecifics within the immediate vicinity of an instrumented ground squirrel tended to elevate its heart rate. Therefore, even in the absence of overt social interactions, conditions of crowding also contributed towards chronic stress in the population. The effects upon heart rate with respect to an individual\u27s sex, age, reproductive condilion, and its spatial and social relationship with neighboring ground squirrels are also discussed. Finally, the roles which social and nonsocial factors play in regulating animal numbers on the study are described

Abnormal Leg Muscle Latencies and Relationship to Dyscoordination and Walking Disability after Stroke

The purpose was to determine timing characteristics of leg muscle latencies for patients following stroke (>12 months) who had persistent coordination and gait deficits, and to determine the relationships among abnormal latencies, dyscoordination, and gait deficits. We compared nine healthy controls and 27 stroke survivors. Surface electromyography measured activation and deactivation latencies of knee flexor and extensor muscles during a ballistic knee flexion task, consistency of latencies across repetitions, and close coupling between agonist and antagonist muscle latencies. We measured Fugl-Meyer (FM) coordination and the functional gait measure, six minute walk test (6MWT). For stroke subjects, there were significant delays of muscle activation and deactivation, abnormal inconsistency, and abnormal decoupled agonist and antagonist activations. There was good correlation between activation latencies and FM and 6MWT. Results suggest abnormal timing characteristics underlie coordination impairment and dysfunctional gait. These abnormal muscle activation and deactivation timing characteristics are important targets for rehabilitation

Construction of Efficacious Gait and Upper Limb Functional Interventions Based on Brain Plasticity Evidence and Model-Based Measures For Stroke Patients

For neurorehabilitation to advance from art to science, it must become evidence-based. Historically, there has been a dearth of evidence from which to construct rehabilitation interventions that are properly framed, accurately targeted, and credibly measured. In many instances, evidence of treatment response has not been sufficiently robust to demonstrate a change in function that is clinically, statistically, and economically important. Research evidence of activity-dependent central nervous system (CNS) plasticity and the requisite motor learning principles can be used to construct an efficacious motor recovery intervention. Brain plasticity after stroke refers to the regeneration of brain neuronal structures and/or reorganization of the function of neurons. Not only can CNS structure and function change in response to injury, but also, the changes may be modified by "activity". For gait training or upper limb functional training for stroke survivors, the "activity" is motor behavior, including coordination and strengthening exercise and functional training that comprise motor learning. Critical principles of motor learning required for CNS activity-dependent plasticity include: close-to-normal movements, muscle activation driving practice of movement; focused attention, repetition of desired movements, and training specificity. The ultimate goal of rehabilitation is to restore function so that a satisfying quality of life can be experienced. Accurate measurement of dysfunction and its underlying impairments are critical to the development of accurately targeted interventions that are sufficiently robust to produce gains, not only in function, but also in quality of life. The Classification of Functioning, Disability, and Health Model (ICF) model of disablement, put forth by the World Health Organization, can provide not only some guidance in measurement level selection, but also can serve as a guide to incorporate function and quality of life enhancement as the ultimate goals of rehabilitation interventions. Based on the evidence and principles of activity-dependent plasticity and motor learning, we developed gait training and upper limb functional training protocols. Guided by the ICF model, we selected and developed measures with characteristics rendering them most likely to capture change in the targeted aspects of intervention, as well as measures having membership not only in the impairment, but also in the Daly and Ruff: Evidence-based stroke motor interventions TheScientificWorldJOURNAL (2007) 7, 2031-2045 2032 functional or life role participation levels contained in the ICF model. We measured response to innovative gait training using a knee flexion coordination measure, coefficient of coordination consistency (ACC) of relative hip/knee (H/K) movement across multiple steps (H/K ACC), and milestones of participation in life role activities. We measured response to upper limb functional training according to measures designed to quantify functional gains in response to treatment targeted at wrist/hand or shoulder elbow training (Arm Motor Ability Test for wrist/hand (AMAT W/H) or shoulder/elbow (AMAT S/E)). We found that there was a statistically significant advantage for adding FES-IM gait training to an otherwise comparable and comprehensive gait training, according to the following measures: H/K ACC, the measure of consistently executed hip/knee coordination during walking; a specific measure of isolated joint knee flexion coordination; and a measure of multiple coordinated gait components. Further, enhanced gains in gait component coordination were robust enough to result in achievement of milestones in participation in life role activities. In the upper limb functional training study, we found that robotics + motor learning (ROB ML; shoulder/elbow robotics practice plus motor learning) produced a statistically significant gain in AMAT S/E; whereas functional electrical stimulation + motor learning (FES ML) did not. We found that FES ML (wrist/hand FES plus motor learning) produced a statistically significant gain in AMAT W/H; whereas ROB ML did not. These results together, support the phenomenon of training specificity in that the most practiced joint movements improved in comparison to joint movements that were practiced at a lesser intensity and frequency. Both ROB ML and FES ML protocols addressed an array of impairments thought to underlie dysfunction. If we are willing to adhere to the ICF model, we accept the challenge that the goal of rehabilitation is life role participation, with functional improvement as in important intermediary step. The ICF model suggests that we intervene at multiple lower levels (e.g., pathology and impairment) in order to improve the higher levels of function and life role participation. The ICF model also suggests that we measure at each level. Not only can we then understand response to treatment at each level, but also, we can begin to understand relationships between levels (e.g., impairment and function). With the ICF model proffering the challenge of restoring life role participation, it then becomes important to design and test interventions that result in impairment gains sufficiently robust to be reflected in functional activities and further, in life role participation. Fortunately, CNS plasticity and associated motor learning principles can serve well as the basis for generating such interventions. These principles were useful in generating both efficacious gait training and efficacious upper limb functional training interventions. These principles led to the use of therapeutic agents (FES and robotics) so that close-to-normal movements could be practiced. These principles supported the use of specific therapeutic agents (BWSTT, FES, and robotics) so that sufficient movement repetition could be provided. These principles also supported incorporation of functional task practice and the demand of attention to task practice within the intervention. The ICF model provided the challenge to restore function and life role participation. The means to that end was provided by principles of CNS plasticity and motor learning

Development of a novel 3D culture system for screening features of a complex implantable device for CNS repair

Tubular scaffolds which incorporate a variety of micro- and nanotopographies have a wide application potential in tissue engineering especially for the repair of spinal cord injury (SCI). We aim to produce metabolically active differentiated tissues within such tubes, as it is crucially important to evaluate the biological performance of the three-dimensional (3D) scaffold and optimize the bioprocesses for tissue culture. Because of the complex 3D configuration and the presence of various topographies, it is rarely possible to observe and analyze cells within such scaffolds in situ. Thus, we aim to develop scaled down mini-chambers as simplified in vitro simulation systems, to bridge the gap between two-dimensional (2D) cell cultures on structured substrates and three-dimensional (3D) tissue culture. The mini-chambers were manipulated to systematically simulate and evaluate the influences of gravity, topography, fluid flow, and scaffold dimension on three exemplary cell models that play a role in CNS repair (i.e., cortical astrocytes, fibroblasts, and myelinating cultures) within a tubular scaffold created by rolling up a microstructured membrane. Since we use CNS myelinating cultures, we can confirm that the scaffold does not affect neural cell differentiation. It was found that heterogeneous cell distribution within the tubular constructs was caused by a combination of gravity, fluid flow, topography, and scaffold configuration, while cell survival was influenced by scaffold length, porosity, and thickness. This research demonstrates that the mini-chambers represent a viable, novel, scale down approach for the evaluation of complex 3D scaffolds as well as providing a microbioprocessing strategy for tissue engineering and the potential repair of SCI

Variability of Individual Platelet Reactivity Over Time in Patients Treated With Clopidogrel Insights From the ELEVATE–TIMI 56 Trial

AbstractBackgroundThe degree of antiplatelet response to clopidogrel has been associated with clinical outcomes. Studies have investigated whether adjustment of antiplatelet therapies based on a single platelet function test is beneficial.ObjectivesThe aim of the study was to test the stability of platelet reactivity measurements over time among patients treated with standard and double doses of clopidogrel.MethodsThe ELEVATE–TIMI 56 (Escalating Clopidogrel by Involving a Genetic Strategy–Thrombolysis In Myocardial Infarction 56) investigators genotyped 333 patients with coronary artery disease and randomized them to various clopidogrel regimens. Patients with at least 2 platelet function results on the same maintenance dose of clopidogrel (75 mg or 150 mg) were analyzed. Platelet aggregation was measured using P2Y12 reaction units (PRU).ResultsIn total, the mean platelet reactivity and the total number of nonresponders (PRU ≥230) with clopidogrel did not change between 2 periods for the 75-mg (22.4% vs. 21.9%; p = 0.86) and 150-mg doses of clopidogrel (11.5% vs. 11.5%; p = 1.00). In contrast, when evaluating each patient individually, 15.7% of patients taking clopidogrel 75 mg and 11.4% of patients taking 150 mg had a change in their responder status when tested at 2 different time points (p < 0.001). Despite being treated with the same dose of clopidogrel, >40% of patients had a change in PRU >40 on serial sampling, which approximates the average PRU difference caused by increasing the clopidogrel dose from 75 mg to 150 mg.ConclusionsMeasurements of platelet reactivity vary over time in a significant proportion of patients. Thus, treatment adjustment according to platelet function testing at a single time point might not be sufficient for guiding antiplatelet therapy in clinical or research settings. (Escalating Clopidogrel by Involving a Genetic Strategy–Thrombolysis In Myocardial Infarction 56 [ELEVATE–TIMI 56]; NCT01235351

Genetic Risk Score to Identify Risk of Venous Thromboembolism in Patients With Cardiometabolic Disease

BACKGROUND –: Venous thromboembolism (VTE) is a major cause of cardiovascular morbidity and mortality with a known genetic contribution. We tested the performance of a genetic risk score (GRS) for its ability to predict VTE in three cohorts of patients with cardiometabolic disease. METHODS –: We included patients from the FOURIER, PEGASUS-TIMI 54, and SAVOR-TIMI 53 trials (history of atherosclerosis, myocardial infarction, and diabetes, respectively) who consented for genetic testing and were not on baseline anticoagulation. We calculated a VTE GRS based on 297 SNPs with established genome-wide significance. Patients were divided into tertiles of genetic risk. Cox proportional hazards models were used to calculate hazard ratios for VTE across genetic risk groups. The polygenic risk score was compared to available clinical risk factors (age, obesity, smoking, history of heart failure, diabetes) and common monogenic mutations. RESULTS –: A total of 29,663 patients were included in the analysis with a median follow-up of 2.4 years, of whom 174 had a VTE event. There was a significantly increased gradient of risk across VTE genetic risk tertiles (p-trend <0.0001). After adjustment for clinical risk factors, patients in the intermediate and high genetic risk groups had a 1.88-fold (95% CI 1.23–2.89, p=0.004) and 2.70-fold (95% CI 1.81–4.06, p<0.0001) higher risk of VTE compared to patients with low genetic risk. In a continuous model adjusted for clinical risk factors, each standard deviation increase in the GRS was associated with a 47% (95% CI 29–68) increased risk of VTE (p<0.0001). CONCLUSIONS –: In a broad spectrum of patients with cardiometabolic disease, a polygenic risk score is a strong, independent predictor of VTE after accounting for available clinical risk factors, identifying 1/3 of patients who have a risk of VTE comparable to that seen with established monogenic thrombophilia

Atomic Resonance and Scattering

Contains reports on six research projects.National Science Foundation (PHY83-06273)Joint Services Electronics Program (DAAL03-86-K-0002)National Science Foundation (PHY84-11483)U.S. Navy-Office of Naval Research (Grant N00014-79-C-0183)Joint Services Electronics Program (Contract DAAG29-83-K-0003)National Science Foundation (Grant PHY83-07172-A01)U.S. Navy - Office of Naval Research (Grant N00014-83-K-0695)National Science Foundation (Grant CHE84-21392