Sprint interval training (SIT) and traditional endurance training elicit similar physiological adaptations. From the perspective of metabolic function, superior glucose regulation is a common characteristic of endurance-trained adults. Accordingly, we have investigated the hypothesis that short-term SIT will increase insulin sensitivity in sedentary/recreationally active humans. Thirty one healthy adults were randomly assigned to one of three conditions: (1) −1 min −1 : % EE 11 ± 2, 14 ± 3, 23 ± 2 vs. 11 ± 1, 16 ± 2, 25 ± 3; P = 0.79). Combined data from both studies revealed no effect of SIT on fasted circulating concentrations of glucose, insulin, adiponectin, pigment epithelial-derived factor, non-esterified fatty acids or noradrenaline (all P > 0.05). Sixteen minutes of high-intensity exercise over 14 days augments insulin sensitivity but does not affect the thermogenic response to β-AR stimulation. Abbreviations β-AR, beta-adrenergic receptor; EE, energy expenditure; FFM, fat-free mass; GLUT4, glucose transporter 4; NEFA, non-esterified fatty acids; PEDF, pigment epithelial-derived factor; RER, respiratory exchange ratio; SIT, sprint interval training;V O 2 ,peak , peak oxygen uptake.

Improved endurance exercise performance in adult humans after sprint interval training (SIT) has been attributed to mitochondrial biogenesis. However, muscle protein synthesis (MPS) and mitochondrial biogenesis during SIT have not been measured, nor have sex-specific differences. We hypothesized that males and females would have similar rates of MPS, mitochondrial biogenesis, and synthesis of individual proteins during SIT. Deuterium oxide (D2O) was orally administered to 21 adults [11 male, 10 female; mean age, 23±1 yr; body mass index (BMI), 22.8±0.6 kg/m(2); mean± SE] for 4 wk, to measure protein synthesis rates while completing 9 sessions of 4-8 bouts of 30 s duration on a cycle ergometer separated by 4 min of active recovery. Samples of the vastus lateralis were taken before and 48 h after SIT. SIT increased maximum oxygen uptake (VO(2max), males 43.4±2.1-44.0±2.3; females 39.5±0.9-42.5±1.3 ml/kg/min; P=0.002). MPS was greater in the males than in the females in the mixed (~150%; P < 0.001), cytosolic (~135%; P=0.038), and mitochondrial (~135%; P=0.056) fractions. The corresponding ontological clusters of individual proteins were significantly greater in the males than in the females (all P<0.00001). For the first time, we document greater MPS and mitochondrial biogenesis during SIT in males than in females and describe the synthetic response of individual proteins in humans during exercise training.

Primary aging in adult humans is associated with a progressive, tonic activation of the peripheral sympathetic nervous system (SNS). The purpose of this SNS activation and its physiological impact are, however, unknown. We hypothesize that the chronic stimulation of the SNS with aging is driven in part by a progressive accumulation of body fat. This "error" is sensed by the central nervous system via increases in adiposity-sensitive humoral signals (e.g., leptin, insulin) that cross the blood-brain barrier, activate subcortical areas involved in the regulation of energy balance (e.g., ventromedial hypothalamus), and stimulate SNS outflow to peripheral tissues. The SNS activation is intended to increase ␤-adrenergic thermogenesis in order to expend excess energy as heat rather than by storage of fat. Recent evidence, however, indicates that these adjustments are not effective in augmenting energy expenditure with aging. Indeed, older sedentary adults demonstrate reduced, not increased, ␤-adrenergic stimulation of metabolic rate because of reduced tissue responsiveness, presumably mediated by SNS-induced impairment of ␤-adrenergic signaling. As a result, age-associated SNS activation, initiated as a consequence of accumulating adiposity with the intent of preventing further fat storage, ironically, may in time evolve into a potential mechanism contributing to the development of obesity with aging. Diabetes 53: 276 -284, 2004 T he sympathetic nervous system (SNS) is an essential tool for the central nervous system (CNS) in achieving its regulatory goal of maintaining organismic homeostasis. CNS-mediated SNS activation is produced during short-term changes in the physiological state (acute exercise, assumption of the upright posture) as well as in response to chronic pathophysiological disorders (congestive heart failure, essential hypertension). During such conditions typically both the purpose (teleology) and the physiological impact (failure or success in producing the intended effect) of the SNS activation are readily apparent.It has been recognized for over 25 years that the SNS becomes progressively activated with increasing age in adult humans, independent of development of clinical disease (1,2). Yet, after more than a quarter of a century of investigating the specific changes that occur in SNS function with human aging, we still have no clear understanding of what this age-associated SNS activation is intended to accomplish or its physiological (or pathophysiological) consequences.Our laboratory has been studying the effects of adult aging on the human SNS for more than a decade (2-11). In the present discussion, we first advance a unified working hypothesis addressing the question of why the SNS becomes tonically and progressively activated with aging. We approach this key issue from the standpoint that the chronic increase in SNS activity with aging is somehow intended to preserve homeostasis. We then address the important question of whether the SNS activation produced by this action is effective in a...

The transactive response DNA binding protein (TDP-43) proteinopathies describe a clinico-pathological spectrum of multi-system neurodegeneration that spans motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) and frontotemporal lobar degeneration (FTLD). We have identified four male patients who presented with the clinical features of a pure MND/ALS phenotype (without dementia) but who had distinctive cortical and cerebellar pathology that was different from other TDP-43 proteinopathies. All patients initially presented with weakness of limbs and respiratory muscles and had a family history of MND/ALS. None had clinically identified cognitive decline or dementia during life and they died between 11 and 32 months after symptom onset. Neuropathological investigation revealed lower motor neuron involvement with TDP-43-positive inclusions typical of MND/ALS. In contrast, the cerebral pathology was atypical, with abundant star-shaped p62-immunoreactive neuronal cytoplasmic inclusions in the cerebral cortex, basal ganglia and hippocampus, while TDP-43-positive inclusions were sparse. This pattern was also seen in the cerebellum where p62-positive, TDP-43-negative inclusions were frequent in granular cells. Western blots of cortical lysates, in contrast to those of sporadic MND/ALS and FTLD-TDP, showed high p62 levels and low TDP-43 levels with no high molecular weight smearing. MND/ALS-associated SOD1, FUS and TARDBP gene mutations were excluded; however, further investigations revealed that all four of the cases did show a repeat expansion of C9orf72, the recently reported cause of chromosome 9-linked MND/ALS and FTLD. We conclude that these chromosome 9-linked MND/ALS cases represent a pathological sub-group with abundant p62 pathology in the cerebral cortex, hippocampus and cerebellum but with no significant associated cognitive decline.

The principals of rehabilitation medicine are to prevent muscle atrophy and improve mobility. Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with muscle atrophy and yet many patients do not undergo pulmonary rehabilitation until they have been in stable health for some time. We investigated the outcome of a supervised home exercise programme initiated immediately after hospitalisation for an exacerbation of COPD. Thirty-one patients were randomised into an exercise group (n=16, FEV(1) 0.94+/-0.34 L) and a control group (n=15, FEV(1) 1.08+/-0.33 L). The exercise group received a twice-weekly supervised exercise programme, in their homes, for 6 weeks. Spirometry, exercise capacity, isometric muscle strength, dyspnea level, quality of life at baseline and 6 weeks as well as subsequent exacerbations were quantified. At 6 weeks, the exercise group, improved the shuttle walk test (198 m+/-95-304+/-136 m) and increased 3 min step test capacity (119+/-40-163+/-26s) (both P<0.001). Knee extensor muscle strength and quality of life scores also increased. Neither exercise capacity nor muscle strength altered in the control group. Follow-up at 3 months showed that three of the control group and none of the exercise group had experienced subsequent exacerbations (P=0.06). Early rehabilitation via a home from hospital programme improved exercise tolerance, muscle strength, dyspnea scores, quality of life in COPD patients and reduced the number of subsequent exacerbations.

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Objective (1) Evaluate feasibility and acceptability of a mindfulness-based group in adolescent girls at-risk for type 2 diabetes (T2D) with depressive symptoms, and (2) compare efficacy of a mindfulness-based versus cognitive-behavioral group for decreasing depressive symptoms and improving insulin resistance. Design and setting Parallel-group, randomized controlled pilot trial conducted at a university. Participants Thirty-three girls 12-17y with overweight/obesity, family history of diabetes, and elevated depressive symptoms were randomized to a six-week mindfulness-based (n=17) or cognitive-behavioral program (n=16). Interventions Both interventions included six, one-hour weekly group sessions. The mindfulness-based program included guided mindfulness awareness practices. The cognitive-behavioral program involved cognitive restructuring and behavioral activation. Main outcome measures Adolescents were evaluated at baseline, post-intervention, and six-months. Feasibility/acceptability were measured by attendance and program ratings. Depressive symptoms were assessed by validated survey. Insulin resistance was determined from fasting insulin and glucose, and dual energy x-ray absorptiometry was used to assess body composition. Results Most adolescents attended ≥80% sessions (mindfulness:92% versus cognitive-behavioral:87%, p=1.00). Acceptability ratings were strong. At post-treatment and six-months, adolescents in the mindfulness condition had greater decreases in depressive symptoms than adolescents in the cognitive-behavioral condition (ps<.05). Compared to the cognitive-behavioral condition, adolescents in the mindfulness-based intervention also had greater decreases in insulin resistance and fasting insulin at post-treatment, adjusting for fat mass and other covariates (ps<.05). Conclusions A mindfulness-based intervention shows feasibility and acceptability in girls at-risk for T2D with depressive symptoms. Compared to a cognitive-behavioral program, after the intervention, adolescents who received mindfulness showed greater reductions in depressive symptoms and better insulin resistance.

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