Test-retest reliability of knee kinesthesia in healthy adults

<p>Abstract</p> <p>Background</p> <p>Sensory information from mechanoreceptors in the skin, muscles, tendons, and joint structures plays an important role in joint stability. A joint injury can lead to disruption of the sensory system, which can be measured by proprioceptive acuity. When evaluating proprioception, assessment tools need to be reliable. The aim of this study was to assess the test-retest reliability of a device designed to measure knee proprioception.</p> <p>Methods</p> <p>Twenty-four uninjured individuals (14 women and 10 men) were examined with regard to test-retest reliability of knee kinesthesia, measured by the threshold to detection of passive motion (TDPM). Measurements were performed towards extension and flexion from the two starting positions, 20 degrees and 40 degrees knee joint flexion, giving four variables. The mean difference between test and retest together with the 95% confidence interval (test 2 minus test 1), the intraclass correlation coefficient (ICC_2,1), and Bland and Altman graphs with limits of agreement, were used as statistical methods for assessing test-retest reliability.</p> <p>Results</p> <p>The intraclass correlation coefficients ranged from 0.59 to 0.70 in all variables except one. No difference was found between test and retest in three of the four TDPM variables. TDPM would need to decrease between 10% and 38%, and increase between 17% and 24% in groups of uninjured subjects to be 95% confident of detecting a real change. The limits of agreement were rather wide in all variables. The variables associated with the 20-degree starting position tended to have higher intraclass correlation coefficients and narrower limits of agreement than those associated with 40 degrees.</p> <p>Conclusion</p> <p>Three TDPM variables were considered reliable for observing change in groups of subjects without pathology. However, the limits of agreement revealed that small changes in an individual's performance cannot be detected. The higher intraclass correlation coefficients and the narrower limits of agreement in the variables associated with the starting position of 20 degrees knee joint flexion, indicate that these variables are more reliable than those associated with 40 degrees. We, therefore, recommend that the TDPM be measured with a 20-degree starting position.</p

Balance in single-limb stance in healthy subjects – reliability of testing procedure and the effect of short-duration sub-maximal cycling

BACKGROUND: To assess balance in single-limb stance, center of pressure movements can be registered by stabilometry with force platforms. This can be used for evaluation of injuries to the lower extremities. It is important to ensure that the assessment tools we use in the clinical setting and in research have minimal measurement error. Previous studies have shown that the ability to maintain standing balance is decreased by fatiguing exercise. There is, however, a need for further studies regarding possible effects of general exercise on balance in single-limb stance. The aims of this study were: 1) to assess the test-retest reliability of balance variables measured in single-limb stance on a force platform, and 2) to study the effect of exercise on balance in single-limb stance, in healthy subjects. METHODS: Forty-two individuals were examined for test-retest reliability, and 24 individuals were tested before (pre-exercise) and after (post-exercise) short-duration, sub-maximal cycling. Amplitude and average speed of center of pressure movements were registered in the frontal and sagittal planes. Mean difference between test and retest with 95% confidence interval, the intraclass correlation coefficient, and the Bland and Altman graphs with limits of agreement, were used as statistical methods for assessing test-retest reliability. The paired t-test was used for comparisons between pre- and post-exercise measurements. RESULTS: No difference was found between test and retest. The intraclass correlation coefficients ranged from 0.79 to 0.95 in all stabilometric variables except one. The limits of agreement revealed that small changes in an individual's performance cannot be detected. Higher values were found after cycling in three of the eight stabilometric variables. CONCLUSIONS: The absence of systematic variation and the high ICC values, indicate that the test is reliable for distinguishing among groups of subjects. However, relatively large differences in an individual's balance performance would be required to confidently state that a change is real. The higher values found after cycling, indicate compensatory mechanisms intended to maintain balance, or a decreased ability to maintain balance. It is recommended that average speed and DEV 10; the variables showing the best reliability and effects of exercise, be used in future studies

On The Rate and Extent of Drug Delivery to the Brain

To define and differentiate relevant aspects of blood–brain barrier transport and distribution in order to aid research methodology in brain drug delivery. Pharmacokinetic parameters relative to the rate and extent of brain drug delivery are described and illustrated with relevant data, with special emphasis on the unbound, pharmacologically active drug molecule. Drug delivery to the brain can be comprehensively described using three parameters: Kp,uu (concentration ratio of unbound drug in brain to blood), CLin (permeability clearance into the brain), and Vu,brain (intra-brain distribution). The permeability of the blood–brain barrier is less relevant to drug action within the CNS than the extent of drug delivery, as most drugs are administered on a continuous (repeated) basis. Kp,uu can differ between CNS-active drugs by a factor of up to 150-fold. This range is much smaller than that for log BB ratios (Kp), which can differ by up to at least 2,000-fold, or for BBB permeabilities, which span an even larger range (up to at least 20,000-fold difference). Methods that measure the three parameters Kp,uu, CLin, and Vu,brain can give clinically valuable estimates of brain drug delivery in early drug discovery programmes

Changes in muscle-tendon unit length-force characteristics following experimentally induced photothrombotic stroke cannot be explained by changes in muscle belly structure.

Purpose The aim of this study was to assess the effects of experimentally induced photothrombotic stroke on structural and mechanical properties of rat m. flexor carpi ulnaris. Methods Two groups of Young-adult male Sprague–Dawley rats were measured: stroke (n = 9) and control (n = 7). Photothrombotic stroke was induced in the forelimb region of the primary sensorimotor cortex. Four weeks later, muscle–tendon unit and muscle belly length–force characteristics of the m. flexor carpi ulnaris, mechanical interaction with the neighbouring m. palmaris longus, the number of sarcomeres in series within muscle fibres, and the physiological cross-sectional area were measured. Results Stroke resulted in higher force and stiffness of the m. flexor carpi ulnaris at optimum muscle–tendon unit length, but only for the passive conditions. Stroke did not alter the length–force characteristics of m. flexor carpi ulnaris muscle belly, morphological characteristics, and the extent of mechanical interaction with m. palmaris longus muscle. Conclusion The higher passive force and passive stiffness at the muscle–tendon unit level in the absence of changes in structural and mechanical characteristics of the muscle belly indicates that the experimentally induced stroke resulted in an increased stiffness of the tendon

Deschloroclozapine, a potent and selective chemogenetic actuator enables rapid neuronal and behavioral modulations in mice and monkeys

The chemogenetic technology designer receptors exclusively activated by designer drugs (DREADDs) afford remotely reversible control of cellular signaling, neuronal activity and behavior. Although the combination of muscarinic-based DREADDs with clozapine-N-oxide (CNO) has been widely used, sluggish kinetics, metabolic liabilities and potential off-target effects of CNO represent areas for improvement. Here, we provide a new high-affinity and selective agonist deschloroclozapine (DCZ) for muscarinic-based DREADDs. Positron emission tomography revealed that DCZ selectively bound to and occupied DREADDs in both mice and monkeys. Systemic delivery of low doses of DCZ (1 or 3 μg per kg) enhanced neuronal activity via hM3Dq within minutes in mice and monkeys. Intramuscular injections of DCZ (100 μg per kg) reversibly induced spatial working memory deficits in monkeys expressing hM4Di in the prefrontal cortex. DCZ represents a potent, selective, metabolically stable and fast-acting DREADD agonist with utility in both mice and nonhuman primates for a variety of applications