Objective Incomplete spinal cord injury (iSCI) disrupts motor control and limits the ability to coordinate muscles for overground walking. Inappropriate muscle activity has been proposed as a source of clinically observed walking deficits after iSCI. We hypothesized that persons with iSCI exhibit lower locomotor complexity compared to able-body (AB) controls as reflected by fewer motor modules, as well as, altered module composition and activation. Methods Eight persons with iSCI and eight age-matched AB controls walked overground at prescribed cadences. Electromyograms of fourteen single leg muscles were recorded. Nonnegative matrix factorization was used to identify the composition and activation of motor modules, which represent groups of consistently co-activated muscles that accounted for 90% of variability in muscle activity. Results Motor module number, composition, and activation were significantly altered in persons with iSCI as compared to AB controls during overground walking at self-selected cadences. However, there was no significant difference in module number between persons with iSCI and AB controls when cadence and assistive device were matched. Conclusions Muscle coordination during overground walking is impaired after chronic iSCI. Significance Our results are indicative of neuromuscular constraints on muscle coordination after iSCI. Altered muscle coordination contributes to person-specific gait deficits during overground walking.
Autoimmune hepatitis (AIH) in humans arises spontaneously in genetically susceptible individuals and is associated with the presence of Th1 cells in the liver. The understanding of AIH has advanced more slowly than that of other organ-specific autoimmune diseases, however, largely because of the lack of an appropriate animal model. We now describe a new mouse model characterized by spontaneous development of necroinflammatory hepatitis that is restricted by genetic background. Mice deficient in the immunomodulatory cytokine TGF-β1 were extensively back-bred to the BALB/c background. The BALB/c background dramatically modified the phenotype of TGF-β1−/− mice: specifically, BALB/c-TGF-β1−/− mice developed a lethal necroinflammatory hepatitis that was not observed in TGF-β1−/− mice on a different genetic background. BALB/c background TGF-β1−/− livers contained large numbers of activated CD4+ T cells that produced large quantities of IFN-γ, but little IL-4, identifying them as Th1 cells. BALB/c background TGF-β1−/−/IFN-γ−/− double knockout mice, generated by cross-breeding, did not develop necroinflammatory hepatitis, demonstrating that IFN-γ is mechanistically required for its pathogenesis. This represents the first murine model of hepatitis that develops spontaneously, is restricted by genetic background, and is dependent upon the Th1 cytokine IFN-γ, and that thus recapitulates these important aspects of AIH.
Acute high-intensity exercise coupled with motor practice improves the retention of motor learning in neurologically intact adults. However, whether exercise could improve the retention of locomotor learning after stroke is still unknown. Here, we investigated the effect of exercise intensity and timing on the retention of a novel locomotor learning task (i.e. split-belt treadmill walking) after stroke. Thirty-seven people post stroke participated in two sessions, 24 h apart, and were allocated to active control (CON), treadmill walking (TMW), or total body exercise on a cycle ergometer (TBE). In session 1, all groups exercised for a short bout (∼5 min) at low (CON) or high (TMW and TBE) intensity and before (CON and TMW) or after (TBE) the locomotor learning task. In both sessions, the locomotor learning task was to walk on a split-belt treadmill in a 2:1 speed ratio (100% and 50% fast-comfortable walking speed) for 15 min. To test the effect of exercise on 24 h retention, we applied behavioural and computational analyses. Behavioural data showed that neither high-intensity group showed greater 24 h retention compared to CON, and computational data showed that 24 h retention was attributable to a slow learning process for sensorimotor adaptation. Our findings demonstrated that acute exercise coupled with a locomotor adaptation task, regardless of its intensity and timing, does not improve retention of the novel locomotor task after stroke. We postulate that exercise effects on motor learning may be context specific (e.g. type of motor learning and/or task) and interact with the presence of genetic variant (BDNF Val66Met).
Aims/hypothesis It is recommended that patients with diabetes reduce their intake of saturated fat and increase their intake of monounsaturated fat or carbohydrate. However, high-carbohydrate diets may result in higher saturated fatty acids in VLDL-triacylglycerol. This is attributed to de novo lipogenesis, although synthesis of specific fatty acids is rarely measured. The objective of this study was to examine the contribution of de novo fatty acid synthesis to VLDL-triacylglycerol composition. It was hypothesised that levels of total and de novo synthesised fatty acids would increase with increased carbohydrate intake in diabetic participants. Methods Seven individuals with type 2 diabetes mellitus and seven matched non-diabetic controls consumed two diets differing in fat energy (lower fat <25%, higher fat >35%) for 3 days in a randomised crossover design. Blood samples were drawn before and 24 h after the ingestion of 2 H-labelled water. ResultsIn the control participants, the higher-fat diet resulted in a 40% reduction in VLDL-triacylglycerol fatty acids because of decreases in myristic, palmitic, palmitoleic and linoleic acids, but the opposite trend occurred in participants with diabetes. The lower-fat diet increased the fractional synthesis rate by 35% and 25% in the control and diabetes participants, respectively (range: 0-33%). Palmitate accounted for 71% of fatty acids synthesised (range: 44-84% total de novo synthesised fatty acids). Conclusions/interpretation 2 H incorporation was used for the first time in humans showing variability in the synthesis rate of specific fatty acids, even palmitic acid. A lower-fat diet stimulated saturated fatty acid synthesis at high rates, but no net stimulation of synthesis of any fatty acid occurred in the diabetes group. The implications of this finding for our understanding of lipid metabolism in diabetes require further investigation.
The effect of dietary intake of high palmitic acid levels in combination with other fatty acids in normal subjects was assessed. Palmitic acid (10% of energy) was fed in conjunction with decreasing levels of linoleic acid to determine if a threshold level of linoleic acid prevented palmitic acid from being hypercholesterolaemic. Healthy subjects received each of the diet treatments for 21 days, followed by washout periods of 7 days. In a second experiment, the effect of exchanging palmitic acid for trans fatty acids on plasma lipoprotein cholesterol levels and on rates for endogenous synthesis of cholesterol in normal subjects was investigated. Diet treatment lasted for 30 days. On day 30 of each diet treatment, a priming dose of deuterium was consumed, followed by a subsequent blood sample at 24 h. Blood cholesterol fractions were isolated and analysed by isotope ratio mass spectrometry to measure cholesterol fractional synthetic rates. In the first experiment, total plasma cholesterol levels increased as the percentage of linoleic acid decreased. The data indicated that high levels of palmitic acid were not hypercholesterolaemic if intake of linoleic acid was greater than 4.5% of energy. When the diet contained trans fatty acids plasma total and low-density lipoprotein-cholesterol increased and cholesterol synthesis increased with a decrease in high-density lipoprotein-cholesterol.
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