Live high, train low - influence on resting and post-exercise hepcidin levels.

The post-exercise hepcidin response during prolonged (>2 weeks) hypoxic exposure is not well understood. We compared plasma hepcidin levels 3 h after exercise [6 × 1000 m at 90% of maximal aerobic running velocity (vVO2max )] performed in normoxia and normobaric hypoxia (3000 m simulate altitude) 1 week before, and during 14 days of normobaric hypoxia [196.2 ± 25.6 h (median: 200.8 h; range: 154.3-234.8 h) at 3000 m simulated altitude] in 10 well-trained distance runners (six males, four females). Venous blood was also analyzed for hepcidin after 2 days of normobaric hypoxia. Hemoglobin mass (Hbmass ) was measured via CO rebreathing 1 week before and after 14 days of hypoxia. Hepcidin was suppressed after 2 (Cohen's d = -2.3, 95% confidence interval: [-2.9, -1.6]) and 14 days of normobaric hypoxia (d = -1.6 [-2.6, -0.6]). Hepcidin increased from baseline, 3 h post-exercise in normoxia (d = 0.8 [0.2, 1.3]) and hypoxia (d = 0.6 [0.3, 1.0]), both before and after exposure (normoxia: d = 0.7 [0.3, 1.2]; hypoxia: d = 1.3 [0.4, 2.3]). In conclusion, 2 weeks of normobaric hypoxia suppressed resting hepcidin levels, but did not alter the post-exercise response in either normoxia or hypoxia, compared with the pre-exposure response.

Pacing, the missing piece of the puzzle to high-intensity interval training.

This study examined physiological and perceptual responses to matched work high-intensity interval training using all-out and 2 even-paced methodologies. 15 trained male cyclists performed 3 interval sessions of three 3-min efforts with 3 min of active recovery between efforts. The initial interval session was completed using all-out pacing, with the following 2 sessions being completed with computer- and athlete-controlled pacing in a randomised and semi-counterbalanced manner. Computer- and athlete-controlled intervals were completed at the mean power from the corresponding interval during the all-out trial. Oxygen consumption and ratings of perceived exertion were recorded during each effort. 20 min following each session, participants completed a 4-km time trial and provided sessional rating of perceived exertion. Oxygen consumption was greater during all-out (54.1±6.6 ml.kg(-1).min(-1); p<0.01) and athlete-controlled (53.0±5.8 ml.kg(-1).min(-1); p<0.01) compared with computer-controlled (51.5±5.7 ml.kg(-1).min(-1)). Total time ≥85% maximal oxygen consumption was greater during all-out compared to both even-paced efforts. Sessional ratings of perceived exertion were greater after all-out compared to both even-paced sessions. Mean 4-km power output was lower after all-out compared with both even paced intervals. Distribution of pace throughout high-intensity interval training can influence perceptual and metabolic stress along with subsequent performance and should be considered during the prescription of such training.

Physical Demands of Sprinting in Professional Road Cycling.

The aim of this study was to quantify the demands of road competitions ending with sprints in male professional cycling. 17 races finished with top-5 results from 6 male road professional cyclists (age, 27.0±3.8 years; height, 1.76±0.03 m; weight, 71.7±1.1 kg) were analysed. SRM power meters were used to monitor power output, cadence and speed. Data were averaged over the entire race, different durations prior to the sprint (60, 10, 5 and 1 min) and during the actual sprint. Variations in power during the final 10 min of the race were quantified using exposure variation analysis. This observational study was conducted in the field to maximize the ecological validity of the results. Power, cadence and speed were statistically different between various phases of the race (p<0.001), increasing from 316±43 W, 95±4 rpm and 50.5±3.3 km·h(-1) in the last 10 min, to 487±58 W, 102±6 rpm and 55.4±4.7 km·h(-1) in the last min prior to the sprint. Peak power during the sprint was 17.4±1.7 W·kg(-1). Exposure variation analysis revealed a significantly greater number of short-duration high-intensity efforts in the final 5 min of the race, compared with the penultimate 5 min (p=0.010). These findings quantify the power output requirements associated with high-level sprinting in men's professional road cycling and highlight the need for both aerobic and anaerobic fitness.

Multiple effects of physical activity on molecular and cognitive signs of brain aging: can exercise slow neurodegeneration and delay Alzheimer's disease?

Western countries are experiencing aging populations and increased longevity; thus, the incidence of dementia and Alzheimer's disease (AD) in these countries is projected to soar. In the absence of a therapeutic drug, non-pharmacological preventative approaches are being investigated. One of these approaches is regular participation in physical activity or exercise. This paper reviews studies that have explored the relationship between physical activity and cognitive function, cognitive decline, AD/dementia risk and AD-associated biomarkers and processes. There is now strong evidence that links regular physical activity or exercise to higher cognitive function, decreased cognitive decline and reduced risk of AD or dementia. Nevertheless, these associations require further investigation, more specifically with interventional studies that include long follow-up periods. In particular, relatively little is known about the underlying mechanism(s) of the associations between physical activity and AD neuropathology; clearly this is an area in need of further research, particularly in human populations. Although benefits of physical activity or exercise are clearly recognised, there is a need to clarify how much physical activity provides the greatest benefit and also whether people of different genotypes require tailored exercise regimes.

Physical activity and amyloid-ß plasma and brain levels: results from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing.

Previous studies suggest physical activity improves cognition and lowers Alzheimer's disease (AD) risk. However, key AD pathogenic factors that are thought to be influenced by physical activity, particularly plasma amyloid-ß (Aß) and Aß brain load, have yet to be thoroughly investigated. The objective of this study was to determine if plasma Aß and amyloid brain deposition are associated with physical activity levels, and whether these associations differed between carriers and non-carriers of the apolipoprotein E (APOE) ε4 allele. Five-hundred and forty six cognitively intact participants (aged 60-95 years) from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing (AIBL) were included in these analyses. Habitual physical activity levels were measured using the International Physical Activity Questionnaire (IPAQ). Serum insulin, glucose, cholesterol and plasma Aß levels were measured in fasting blood samples. A subgroup (n=116) underwent (11)C-Pittsburgh compound B (PiB) positron emission tomography (PET) scanning to quantify brain amyloid load. Higher levels of physical activity were associated with higher high density lipoprotein (HDL) (P=0.037), and lower insulin (P<0.001), triglycerides (P=0.019) and Aß1-42/1-40 ratio (P=0.001). After stratification of the cohort based on APOE ε4 allele carriage, it was evident that only non-carriers received the benefit of reduced plasma Aß from physical activity. Conversely, lower levels of PiB SUVR (standardised uptake value ratio) were observed in higher exercising APOE ε4 carriers. Lower plasma Aß1-42/1-40 and brain amyloid was observed in those reporting higher levels of physical activity, consistent with the hypothesis that physical activity may be involved in the modulation of pathogenic changes associated with AD.

Hyperpolarized 129Xe MRI, 99mTc scintigraphy, and SPECT in lung ventilation imaging: a quantitative comparison.

RATIONALE AND OBJECTIVES: The current clinical standard for functional imaging of patients with lung ailments is nuclear medicine scintigraphy and Single Photon Emission Computed Tomography (SPECT) which detect the gamma decay of inhaled radioactive tracers. Hyperpolarized (HP) Xenon-129 MRI (XeMRI) of the lungs has recently been FDA approved and provides similar functional images of the lungs with higher spatial resolution than scintigraphy and SPECT. Here we compare Technetium-99m (99mTc) diethylene-triamine-pentaacetate scintigraphy and SPECT with HP XeMRI in healthy controls, asthma, and chronic obstructive pulmonary disorder (COPD) patients. MATERIALS AND METHODS: 59 subjects, healthy, with asthma, and with COPD, underwent 99mTc scintigraphy/SPECT, standard spirometry, and HP XeMRI. XeMRI and SPECT images were registered for direct voxel-wise signal comparisons. Images were also compared using ventilation defect percentage (VDP), and a standard 6-compartment method. VDP calculated from XeMRI and SPECT images was compared to spirometry. RESULTS: Median Pearson correlation coefficient for voxel-wise signal comparison was 0.698 (0.613-0.782) between scintigraphy and XeMRI and 0.398 (0.286-0.502) between SPECT and XeMRI. Correlation between VDP measures was r = 0.853, p < 0.05. VDP separated asthma and COPD from the control group and was significantly correlated with FEV1, FEV1/FVC, and FEF 25-75. CONCLUSION: HP XeMRI provides equivalent information to 99mTc SPECT and standard spirometry measures. Additionally, XeMRI is non-invasive, hence it could be used for longitudinal studies for evaluating emerging treatment for lung ailments.

Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration.

Objective: Transcutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation. Approach: In this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS. Results: Analysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle-specific motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode's position. Significance: Improvements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.

Enhanced selectivity of transcutaneous spinal cord stimulation by multielectrode configuration.

Objective.Transcutaneous spinal cord stimulation (tSCS) has been gaining momentum as a non-invasive rehabilitation approach to restore movement to paralyzed muscles after spinal cord injury (SCI). However, its low selectivity limits the types of movements that can be enabled and, thus, its potential applications in rehabilitation.Approach.In this cross-over study design, we investigated whether muscle recruitment selectivity of individual muscles could be enhanced by multielectrode configurations of tSCS in 16 neurologically intact individuals. We hypothesized that due to the segmental innervation of lower limb muscles, we could identify muscle-specific optimal stimulation locations that would enable improved recruitment selectivity over conventional tSCS. We elicited leg muscle responses by delivering biphasic pulses of electrical stimulation to the lumbosacral enlargement using conventional and multielectrode tSCS.Results.Analysis of recruitment curve responses confirmed that multielectrode configurations could improve the rostrocaudal and lateral selectivity of tSCS. To investigate whether motor responses elicited by spatially selective tSCS were mediated by posterior root-muscle reflexes, each stimulation event was a paired pulse with a conditioning-test interval of 33.3 ms. Muscle responses to the second stimulation pulse were significantly suppressed, a characteristic of post-activation depression suggesting that spatially selective tSCS recruits proprioceptive fibers that reflexively activate muscle-specific motor neurons in the spinal cord. Moreover, the combination of leg muscle recruitment probability and segmental innervation maps revealed a stereotypical spinal activation map in congruence with each electrode's position.Significance. Improvements in muscle recruitment selectivity could be essential for the effective translation into stimulation protocols that selectively enhance single-joint movements in neurorehabilitation.

Optimizing Trajectories and Inverse Kinematics for Biomechanical Analysis of Markerless Motion Capture Data.

Markerless motion capture using computer vision and human pose estimation (HPE) has the potential to expand access to precise movement analysis. This could greatly benefit rehabilitation by enabling more accurate tracking of outcomes and providing more sensitive tools for research. There are numerous steps between obtaining videos to extracting accurate biomechanical results and limited research to guide many critical design decisions in these pipelines. In this work, we analyze several of these steps including the algorithm used to detect keypoints and the keypoint set, the approach to reconstructing trajectories for biomechanical inverse kinematics and optimizing the IK process. Several features we find important are: 1) using a recent algorithm trained on many datasets that produces a dense set of biomechanically-motivated keypoints, 2) using an implicit representation to reconstruct smooth, anatomically constrained marker trajectories for IK, 3) iteratively optimizing the biomechanical model to match the dense markers, 4) appropriate regularization of the IK process. Our pipeline makes it easy to obtain accurate biomechanical estimates of movement in a rehabilitation hospital.

Reliability/Validity of the fortius trainer.

This study examined the reliability/validity of power output measured using the Fortius Virtual Reality cycle trainer. 10 cyclists (age: 28±6 years; V˙O (2)max: 60.9±7.2 ml · kg (-1) · min (-1); peak power: 393±82 W) completed three 20 km time trials on a Fortius cycle trainer. During each time trial, power output was measured at 1 Hz using the Fortius internal software and a PowerTap power monitor. Validity calculated for the Fortius trainer; Pearson correlation coefficient (r=0.99; 95% CI: 0.98-0.99; p<0.01) and typical error of estimate (3.5%; 95% CI: 3.2-3.9%), was similar to other established laboratory ergometers. No differences (F (2,16)=0.32; p=0.73) in mean 20 km power were observed between trial 1 (253±46 W), 2 (258±49 W), or 3 (255±50 W). Test-retest reliability (intraclass correlation coefficient (ICC) and coefficient of variation (CV)) was better between trial 2 and 3 (ICC=1.00 (CI: 0.98-1.00); CV: 1.6% (CI: 1.1-3.3%)) compared with trial 1 and 2 (ICC=0.98 (CI: 0.91-1.00); CV: 3.3% (CI: 2.2-6.4%)). The Fortius cycle trainer is a valid and reliable device for the measurement of power output in cyclists, thus providing an alternative to larger more expensive laboratory ergometers.

Effect of a 5-min cold-water immersion recovery on exercise performance in the heat.

BACKGROUND: This study examined the effect of a 5-min cold-water immersion (14 degrees C) recovery intervention on repeated cycling performance in the heat. METHODS: 10 male cyclists performed two bouts of a 25-min constant-paced (254 (22) W) cycling session followed by a 4-km time trial in hot conditions (35 degrees C, 40% relative humidity). The two bouts were separated by either 15 min of seated recovery in the heat (control) or the same condition with 5-min cold-water immersion (5th-10th minute), using a counterbalanced cross-over design (CP(1)TT(1) --> CWI or CON --> CP(2)TT(2)). Rectal temperature was measured immediately before and after both the constant-paced sessions and 4-km timed trials. Cycling economy and Vo(2) were measured during the constant-paced sessions, and the average power output and completion times were recorded for each time trial. RESULTS: Compared with control, rectal temperature was significantly lower (0.5 (0.4) degrees C) in cold-water immersion before CP(2) until the end of the second 4-km timed trial. However, the increase in rectal temperature (0.5 (0.2) degrees C) during CP(2) was not significantly different between conditions. During the second 4-km timed trial, power output was significantly greater in cold-water immersion (327.9 (55.7) W) compared with control (288.0 (58.8) W), leading to a faster completion time in cold-water immersion (6.1 (0.3) min) compared with control (6.4 (0.5) min). Economy and Vo(2) were not influenced by the cold-water immersion recovery intervention. CONCLUSION: 5-min cold-water immersion recovery significantly lowered rectal temperature and maintained endurance performance during subsequent high-intensity exercise. These data indicate that repeated exercise performance in heat may be improved when a short period of cold-water immersion is applied during the recovery period.

Influence of starting strategy on cycling time trial performance in the heat.

The purpose of this study was to determine the influence of starting strategy on time trial performance in the heat. Eleven endurance trained male cyclists (30+/-5 years, 79.5+/-4.6 kg, VO(2max) 58.5+/-5.0 ml x kg x (-1) min(-1)) performed four 20-km time trials in the heat (32.7+/-0.7 degrees C and 55% relative humidity). The first time trial was completed at a self-selected pace (SPTT). During the following time trials, subjects performed the initial 2.5-km at power outputs 10% above (10% ATT), 10% below (10% BTT) or equal (ETT) to that of the average power during the initial 2.5-km of the self-selected trial; the remaining 17.5-km was self-paced. Throughout each time trial, power output, rectal temperature, skin temperature, heat storage, pain intensity and thermal sensation were taken. Despite significantly (P<0.05) greater power outputs for 10% BTT (273+/-45W) compared with the ETT (267+/-48W) and 10% ATT (265+/-41W) during the final 17.5-km, overall 20-km performance time was not significantly different amongst trials. There were no differences in any of the other measured variables between trials. These data show that varying starting power by +/-10% did not affect 20 km time trial performance in the heat.

Acute physiological responses to low-intensity blood flow restriction cycling.

OBJECTIVES: Blood flow restriction (BFR) during interval cycling may stimulate aerobic and anaerobic adaptations. However, acute physiological responses to BFR interval cycling have not been extensively investigated. DESIGN: Eighteen males completed low-intensity (LI), low-intensity with BFR (LIBFR) and high-intensity (HI) interval cycling sessions in randomised and counterbalanced order. These included a standardised warm-up and three two-min intervals interspersed with two-min recovery. Interval intensity during HI, LI and LIBFR were 85%, 40% and 40% of peak power output obtained during graded exercise tests. METHODS: During LIBFR, 80% arterial occlusion was applied to both legs during the interval efforts and removed during recovery. Continuous measures of heart rate (HR), cardiac output (CO) and oxygen consumption (V˙O2) were recorded. Blood pressure (BP) and rating of perceived exertion (RPE) were measured following intervals. Blood lactate concentration was measured pre- and post-exercise. RESULTS: BP, HR, CO, V˙O2, lactate and RPE were greatest during HI. During the active intervals, BP, HR and CO were greater during LIBFR than LI. V˙O2 during recovery periods were greater in LIBFR than LI. Post-session lactate was greater during LIBFR than LI. Importantly, mean arterial pressure during interval three was significantly greater in LIBFR (124±2mmHg) than HI (114±3mmHg). CONCLUSIONS: LIBFR increases cardiovascular and metabolic stress compared with LI and could provide an alternative aerobic training method for individuals unable to perform high-intensity exercise. However, increases in mean arterial pressure during LIBFR indicates high myocardial workload, and practitioners should therefore use caution if prescribing LIBFR for vascular compromised individuals.

Ludwig Merzbacher (1875-1942): the man behind the disease.

Ludwig Merzbacher (1875-1942) is widely known for his seminal work on the pathology of the dysmyelinating CNS disease named for the clinician Friedrich Pelizaeus and himself. Yet his training, his scientific achievements and his list of publications suggest a scientist with broad interests in neuropathology, neuroscience, neurology and psychiatry. Among several studies in experimental and clinical neuropathology, Merzbacher's work on scavenger cells is the most outstanding. While working in Alois Alzheimer's laboratory in Munich in 1906/1907, Ludwig Merzbacher analyzed in great detail the reaction patterns of these cells, which are nowadays known as reactive microglia, and already attempted to elucidate their function in brain pathology.

Hans-Joachim Scherer (1906-1945), pioneer in glioma research.

Hans-Joachim Scherer was among the most creative and productive neuropathologists of his time. Working as a political refugee in Antwerp (Belgium) during 1934-41, he published landmark papers on the morphology and biology of malignant gliomas, and was the first to clearly distinguish primary and secondary glioblastomas, and growth patterns reflecting the invasion of preexisting brain tissue (secondary structures). Scherer was a controversial personality, who at the end of World War II became entangled in the Nazi euthanasia programme.

Encephalomyelitis and demyelinating diseases in patients with extracerebral malignant tumors.

We examined central nervous system (CNS) lesions in 456 patients with primary extracerebral malignant tumors. Inflammatory reactions caused by viral (progressive multifocal leukoencephalopathy (PML), herpes zoster varicella), fungal, or bacterial infections could be demonstrated in 20 patients. In a further 19 patients, the brain tissue showed lymphocyte infiltrates of unknown etiology and, in four of these, autopsy revealed probable paraneoplastic, non-bacterial, endocarditis as a possible explanation for the local inflammatory reaction. The frequency of thrombophlebitis, non-arteriosclerotic thrombosis and arteritis was significantly higher than in a control group of 2052 tumor-free patients. Focal spongiform-axonopathic lesions (24 cases) as well as diffuse leukoencephalopathy (11 cases) were interpreted as probably being at least in part paraneoplastic because the same alterations could also be observed in patients who had never undergone cytostatic or radiation therapy. The possible pathogenetic conditions are discussed and a classification of these tumor-accompanying, but not always tumor-dependent, lesions suggested.

[Hypoplasia ponto-neocerebellaris (author's transl)]. / Hypoplasia ponto-neocerebellaris.

In an otherwise healthy family three male infants fell ill with microcephaly, hypotonus of the muscles, non-specific hyperkineses, seizures, and rapid mental deterioration. In addition to microdysplasia in the cerebral cortex the main neuropathological findings were the separation of the dentate nucleus into many islets, an atypical band of the inferior olives, and deficiency of the pontocerebellar fibers in the basal part of the pons. The hypoplasia of the areas involved can be distinguished from the degenerative process in the dégénérescence systematisé optico-cochleo-dentelé (Nyssen-van Bogaert).

Adult-onset rod disease with abundant intranuclear rods.

The third case of adult-onset rod disease (nemaline myopathy) with abundant myofibrillar as well as intranuclear rods is described. The 61-year-old woman suffered from progressive weakness of proximal extremities and of the neck, mimicking polymyositis. Muscle biopsy revealed a striking myopathic pattern, with intranuclear rods occurring in 31% of the fibres. On light and electron microscopy and by immunohistochemical study, the rods differed from myofibrillar rods. The absence of alpha-actinin in intranuclear rods suggests an enhanced readiness of actin filaments to bind to diverse proteins, instead of overproduction of alpha-actinin as the pathogenetic basis of the rod formation.

Additional biochemical criteria in the differential diagnosis of myositis.

Thirty-six biopsy specimens of human biceps and vastus lateralis muscles were examined by histometric analysis and determination of enzyme activities (phosphorylase, triosephosphate dehydrogenase, 3-hydroxacyl-CoA-dehydrogenase, lactate dehydrogenase, hexose isomerase, citrate synthetase, 6-phosphogluconate dehydrogenase). The series included 13 specimens from patients suffering from a benign form of muscular dystrophy (limb girdle and Becker type of muscular dystrophy) and 12 specimens from patients with an acute (n = 5) or chronic (n = 7) form of myositis. Muscle fibres were atrophic in myositis and hypertrophic (with an increased variation of fibre diameters) in muscular dystrophies, as has been shown previously. When myositis samples were compared with either normal or dystrophic muscles, a highly significant lowering of glycolytic enzyme activity was found in chronic myositis, while the activity of 6-phosphogluconate dehydrogenase was elevated to highly significant levels. Measurements of the latter enzyme's activity might be of additional value in differentiating chronic forms of myositis from benign muscular dystrophies.

Ragged-red fibres detected in paraffin sections by a monoclonal antibody to inner mitochondrial membrane.

An immunohistochemical method is reported using the M-II68 monoclonal antibody, which detects mitochondrial accumulations ("ragged-red fibres") in routinely processed (formalin-fixed, paraffin-embedded) muscle tissue. Ten cases with electron-microscopically and histochemically proven mitochondrial myopathy featured 4% to 24% ragged-red fibres. In a series of 50 muscle biopsies without mitochondrial myopathy, scattered ragged-red fibres (less than 0.1%) were present in a few normal and pathological muscles. The immunohistochemical method is specific for mitochondria, does not require frozen tissue and permits rapid examination of large areas.