Comparing continuous and intermittent exercise. An "isoeffort" and "isotime" approach

The present study proposes an alternative way of comparing performance and acute physiological responses to continuous exercise with those of intermittent exercise, ensuring similar between-protocol overall effort (isoeffort) and the same total duration of exercise (isotime). This approach was expected to overcome some drawbacks of traditional methods of comparison. Fourteen competitive cyclists (20±3 yrs) performed a preliminary incremental test and four experimental 30-min self-paced protocols, i.e. one continuous and three passive-recovery intermittent exercise protocols with different workto- rest ratios (2 = 40:20s, 1 = 30:30s and 0.5 = 20:40s). A "maximal session effort" prescription was adopted for this experimental design. As expected, a robust perceived exertion template was observed irrespective of exercise protocol. Similar between-protocol pacing strategies further support the use of the proposed approach in competitive cyclists. Total work, oxygen uptake and heart rate mean values were significantly higher (P<0.05) in the continuous compared to intermittent protocols, while lactate values were lower. Manipulating the work-to-rest ratio in intermittent exercise, total work, oxygen uptake and heart rate mean values decreased with the decrease in the work-to-rest ratio, while lactate values increased. Despite this complex physiological picture, all protocols showed similar ventilatory responses and a nearly perfect relationship between respiratory frequency and perceived exertion. In conclusion, our data indicate that overall effort and total duration of exercise are two critical parameters that should both be controlled when comparing continuous with intermittent exercise. On an isoeffort and isotime basis, the work-to-rest ratio manipulation affects physiological responses in a different way from what has been reported in literature with traditional methods of comparison. Finally, our data suggest that during intermittent exercise respiratory frequency reflects physiological strain better than oxygen uptake, heart rate and blood lactate

Novel bicistronic lentiviral vectors correct beta-Hexosaminidase deficiency in neural and hematopoietic stem cells and progeny: implications for in vivo and ex vivo gene therapy of GM2 gangliosidosis

The favorable outcome of in vivo and ex vivo gene therapy approaches in several Lysosomal Storage Diseases suggests that these treatment strategies might equally benefit GM2 gangliosidosis. Tay-Sachs and Sandhoff disease (the main forms of GM2 gangliosidosis) result from mutations in either the HEXA or HERB genes encoding, respectively, the alpha- or beta-subunits of the lysosomal beta-Hexosaminidase enzyme. In physiological conditions, alpha- and beta-subunits combine to generate beta-Hexosaminidase A (HexA, alpha beta) and beta-Hexosaminidase B (HexB, 1313). A major impairment to establishing in vivo or ex vivo gene therapy for GM2 gangliosidosis is the need to synthesize the alpha- and beta-subunits at high levels and with the correct stoichiometric ratio, and to safely deliver the therapeutic products to all affected tissues/organs. Here, we report the generation and in vitro validation of novel bicistronic lentiviral vectors (LVs) encoding for both the murine and human codon optimized Hexa and Hex!) genes. We show that these LVs drive the safe and coordinate expression of the alpha- and beta-subunits, leading to supranormal levels of beta-Hexosaminidase activity with prevalent formation of a functional HexA in SD murine neurons and glia, murine bone marrow-derived hematopoietic stem/progenitor cells (HSPCs), and human SD fibroblasts. The restoration/overexpression of beta-Hexosaminidase leads to the reduction of intracellular GM2 ganglioside storage in transduced and in cross-corrected SD murine neural progeny, indicating that the transgenic enzyme is secreted and functional. Importantly, bicistronic LVs safely and efficiently transduce human neurons/glia and CD34 + HSPCs, which are target and effector cells, respectively, in prospective in vivo and ex vivo GT approaches. We anticipate that these bicistronic LVs may overcome the current requirement of two vectors co-delivering the alpha- or beta-subunits genes. Careful assessment of the safety and therapeutic potential of these bicistronic LVs in the SD murine model will pave the way to the clinical development of LV-based gene therapy for GM2 gangliosidosis

117: Naive and memory T regulatory cells respond to mesenchymal cells regulation

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Differential control of respiratory frequency and tidal volume during high-intensity interval training

New Findings: What is the central question of this study? By manipulating recovery intensity and exercise duration during high-intensity interval training (HIIT), we tested the hypothesis that fast inputs contribute more than metabolic stimuli to respiratory frequency (fR) regulation. What is the main finding and its importance? Respiratory frequency, but not tidal volume, responded rapidly and in proportion to changes in workload during HIIT, and was dissociated from some markers of metabolic stimuli in response to both experimental manipulations, suggesting that fast inputs contribute more than metabolic stimuli to fR regulation. Differentiating between fR and tidal volume may help to unravel the mechanisms underlying exercise hyperpnoea. Given that respiratory frequency (fR) has been proposed as a good marker of physical effort, furthering the understanding of how fR is regulated during exercise is of great importance. We manipulated recovery intensity and exercise duration during high-intensity interval training (HIIT) to test the hypothesis that fast inputs (including central command) contribute more than metabolic stimuli to fR regulation. Seven male cyclists performed an incremental test, a 10 and a 20 min continuous time trial (TT) as preliminary tests. Subsequently, recovery intensity and exercise duration were manipulated during HIIT (30 s work and 30 s active recovery) by performing four 10 min and one 20 min trial (recovery intensities of 85, 70, 55 and 30% of the 10 min TT mean workload; and 85% of the 20 min TT mean workload). The work intensity of the HIIT sessions was self-paced by participants to achieve the best performance possible. When manipulating recovery intensity, fR, but not tidal volume (VT), showed a fast response to the alternation of the work and recovery phases, proportional to the extent of workload variations. No association between fR and gas exchange responses was observed. When manipulating exercise duration, fR and rating of perceived exertion were dissociated from VT, carbon dioxide output and oxygen uptake responses. Overall, the rating of perceived exertion was strongly correlated with fR (r = 0.87; P < 0.001) but not with VT. These findings may reveal a differential control of fR and VT during HIIT, with fast inputs appearing to contribute more than metabolic stimuli to fR regulation. Differentiating between fR and VT may help to unravel the mechanisms underlying exercise hyperpnoea

Whole-body vibrations exposure while walking in place

The human body is exposed to vibration while walking on manufacturing platforms or in transports. In order to minimize the risk of pathologies, anti-vibration equipment can be designed to limit the vibration transmitted to specific body segments. Prevention strategies have been developed starting from the vibration transmissibility and from the apparent mass of standing subjects. Little have been done for the optimization of anti-vibration devices for walking workers. Our work aims at investigating the response of the human body while walking in place. For this purpose, a dedicated experimental procedure involving seven participants walking in place over a vibrating platform has been developed. Participants were exposed to harmonic excitation with six different frequencies (5, 10, 15, 20, 25, and 30 Hz), with an amplitude of 2 m.s−2. The inertial force exerted by the walking subjects exposed to the stimulus was measured by four load cells supporting the platform. Simultaneously, tridimensional acceleration signals were collected at the participant right shank, low-back, and mouth. Vibration transmissibility as well as apparent mass were computed as a function of the excitation frequency. Results indicated a higher transmissibility of the vibration at 5 Hz and 10 Hz. Further, the apparent mass of the participants walking in place was estimated between the values reported in the literature when standing in neutral position and when standing in neutral position with knee bent. Future works will include an electromyographical analysis of lower-limb muscles with respect to the excitation frequenc