The Canadian Neurological Scale (CNS) was designed to monitor mentation and motor functions in stroke patients. We assessed its validity and reliability on a group of 157 patients with a diagnosis of acute cerebrovascular accident. We determined validity by (1) correlating scale items and total score with the standard neurologic examination; (2) exploring the scale's predictive power with different end points at 6 months--the initial CNS was a significant predictor of outcome; (3) showing that the CNS had higher correlation coefficients with the initial neurologic examination than the Glasgow Coma Scale; and (4) assessing the responsiveness of the scale to change in the neurologic status of stroke patients. Interobserver reliability, measured by kappa statistics on each scale item, was good. Accordingly, we established the validity and reliability of the CNS for its use in clinical studies and in the care of stroke patients.
The results of this study underline the usefulness of CMR in patients with suspected AMC. In contrast, the diagnostic performance of CMR in patients with suspected CMC might not be sufficient to guide clinical management.
Different endurance exercise protocols lead to damage of the endothelial cell layer as evident by an increase in miRNA-126. On the other hand, resistance exercise has no impact on the endothelial cells, but leads to a destruction of muscular cells.
A series of mono- and per-6-substituted cyclodextrin derivatives were synthesized as synthetic receptors (or host molecules) of rocuronium bromide, the most widely used neuromuscular blocker in anaesthesia. By forming host-guest complexes with rocuronium, these cyclodextrin derivatives reverse the muscle relaxation induced by rocuronium in vitro and in vivo and therefore can be used as reversal agents of the neuromuscular blocker to assist rapid recovery of patients after surgery. Because this supramolecular mechanism of action does not involve direct interaction with the cholinergic system, the reversal by these compounds, e.g., compound 14 (Org 25969), is not accompanied by cardiovascular side effects usually attendant with acetylcholinesterase inhibitors such as neostigmine. The structure-activity relationships are consistent with this supramolecular mechanism of action and are discussed herein. These include the effects of binding cavity size and hydrophobic and electrostatic interaction on the reversal activities of these compounds.
BackgroundThe purpose of this study was the comparison of the calculated (MLSSC) and experimental power (MLSSE) in maximal lactate steady-state (MLSS) during cycling.Methods13 male subjects (24.2 ± 4.76 years, 72.9 ± 6.9 kg, 178.5 ± 5.9 cm, trueV˙normalO2max: 60.4 ± 8.6 ml min−1 kg−1, trueV˙normalLamax: 0.9 ± 0.19 mmol l-1 s-1) performed a ramp-test for determining the trueV˙normalO2max and a 15 s sprint-test for measuring the maximal glycolytic rate (trueV˙normalLamax). All tests were performed on a Lode-Cycle-Ergometer. trueV˙normalO2max and trueV˙normalLamax were used to calculate MLSSC. For the determination of MLSSE several 30 min constant load tests were performed. MLSSE was defined as the highest workload that can be maintained without an increase of blood-lactate-concentration (BLC) of more than 0.05 mmol l−1 min−1 during the last 20 min. Power in following constant-load test was set higher or lower depending on BLC.ResultsMLSSE and MLSSC were measured respectively at 217 ± 51 W and 229 ± 47 W, while mean difference was −12 ± 20 W. Orthogonal regression was calculated with r = 0.92 (p < 0.001).ConclusionsThe difference of 12 W can be explained by the biological variability of trueV˙normalO2max and trueV˙normalLamax. The knowledge of both parameters, as well as their individual influence on MLSS, could be important for establishing training recommendations, which could lead to either an improvement in trueV˙normalO2max or trueV˙normalLamax by performing high intensity or low intensity exercise training, respectively. Furthermore the validity of trueV˙normalLamax -test should be focused in further studies.
Cyclic AMP (cAMP) phosphodiesterase-4 (PDE4) enzymes degrade cAMP and underpin the compartmentalization of cAMP signaling through their targeting to particular protein complexes and intracellular locales. We describe the discovery and characterization of a small-molecule compound that allosterically activates PDE4 long isoforms. This PDE4-specific activator displays reversible, noncompetitive kinetics of activation (increased Vmax with unchanged Km), phenocopies the ability of protein kinase A (PKA) to activate PDE4 long isoforms endogenously, and requires a dimeric enzyme assembly, as adopted by long, but not by short (monomeric), PDE4 isoforms. Abnormally elevated levels of cAMP provide a critical driver of the underpinning molecular pathology of autosomal dominant polycystic kidney disease (ADPKD) by promoting cyst formation that, ultimately, culminates in renal failure. Using both animal and human cell models of ADPKD, including ADPKD patient-derived primary cell cultures, we demonstrate that treatment with the prototypical PDE4 activator compound lowers intracellular cAMP levels, restrains cAMP-mediated signaling events, and profoundly inhibits cyst formation. PDE4 activator compounds thus have potential as therapeutics for treating disease driven by elevated cAMP signaling as well as providing a tool for evaluating the action of long PDE4 isoforms in regulating cAMP-mediated cellular processes.
Complex performance diagnostics in sports medicine should contain maximal aerobic and maximal anaerobic performance. The requirements on appropriate stress protocols are high. To validate a test protocol quality criteria like objectivity and reliability are necessary. Therefore, the present study was performed in intention to analyze the reliability of maximal lactate production rate (V.Lamax) by using a sprint test, maximum oxygen consumption (V.O2max) by using a ramp test and, based on these data, resulting power in calculated maximum lactate-steady-state (PMLSS) especially for amateur cyclists. All subjects (n = 23, age 26 ± 4 years) were leisure cyclists. At three different days they completed first a sprint test to approximate V.Lamax. After 60 min of recreation time a ramp test to assess V.O2max was performed. The results of V.Lamax-test and V.O2max-test and the body weight were used to calculate PMLSS for all subjects. The intra class correlation (ICC) for V.Lamax and V.O2max was 0.904 and 0.987, respectively, coefficient of variation (CV) was 6.3% and 2.1%, respectively. Between the measurements the reliable change index of 0.11 mmol·l
-1s
-1 for V.Lamax and 3.3 mlkg
-1min
-1 for V.O2max achieved significance. The mean of the calculated PMLSS was 237 ± 72 W with an RCI of 9 W and reached with ICC = 0.985 a very high reliability. Both metabolic performance tests and the calculated PMLSS are reliable for leisure cyclists.
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