170 research outputs found
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Effects of Age and Sex on Inspiratory Muscle Activation Patterns During Exercise
Purpose: Characterize the effects of age, sex, and their interaction on inspiratory muscle
activation patterns during exercise. Methods: Twenty younger (20-30y, n=10 women) and
twenty older (60-80y, n=10 women) subjects performed an incremental cycle exercise test.
Electromyography of the scalene (EMGsca) and sternocleidomastoid (EMGscm) muscles were
measured using skin surface electrodes, while diaphragm electromyography (EMGdi) and
esophageal and transdiaphragmatic pressures were measured using an esophageal catheter.
Electromyography data were transformed into root-mean-square with a 100ms time constant.
Esophageal (PTPes) and diaphragmatic (PTPdi) pressure-time products were used as indices of
total inspiratory muscle pressure production and diaphragmatic pressure production,
respectively. Results: At absolute minute ventilations (V
E), women and older subjects had
greater EMGdi than men and younger subjects, respectively (all p<0.05), but no differences were
noted when V
E was expressed in relative terms (all p>0.05). Women had greater EMGsca activity
than men at absolute and relative levels of V
E (all p<0.05). Older subjects had greater EMGsca
than younger subjects when V
E was expressed relative (all p<0.05) but not absolute terms (all
p>0.05). At absolute and relative levels of V
E, women and older subjects had greater EMGscm
than men and younger subjects, respectively (all p<0.05). Women and older subjects had a
greater PTPdi/PTPes at a V
E of 70 l·min-1 than men and younger subjects, respectively (both
p<0.05), but no differences were noted when V
E was expressed in relative terms (all p>0.05). No
significant interactions between age and sex were noted (all p>0.05). Conclusion: Age and sex
significantly affect inspiratory muscle activation patterns during exercise; however, the extent of
the effects depends on whether comparisons are made at a solute or relative V
E.This study was supported by the British Columbia Lung Association
(BCLA). YMS, PBD, and AHR were supported by graduate scholarships from the Natural
Sciences and Engineering Research Council of Canada (NSERC). PBD and MRS were
supported by fellowships from the University of British Columbia and BCLA. JAG was
supported by a Scholar Award from the Michael Smith Foundation for Health Research, a New
Investigator Award from the Providence Health Care Research Institute and St. Paul’s Hospital
Foundation, and a Canadian Institutes of Health Research Clinical Rehabilitation New Investigator Award
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Manipulation of mechanical ventilatory constraint during moderate intensity exercise does not influence dyspnoea in healthy older men and women
© 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society. KEY POINT SUMMARY:The perceived intensity of exertional breathlessness (i.e. dyspnoea) is higher in older women than in older men, possibly due to sex-difference respiratory system morphology. During exercise at a given absolute intensity or minute ventilation, older women have a greater degree of mechanical ventilatory constraint (i.e. work of breathing and expiratory flow limitation) than their male counterparts, which may lead to a greater perceived intensity of dyspnoea. Using a single-blind randomized study design, we experimentally manipulated the magnitude of mechanical ventilatory constraint during moderate-intensity exercise at ventilatory threshold in healthy older men and women. We found that changes in the magnitude of mechanical ventilatory constraint within the physiological range had no effect on dyspnoea in healthy older adults. When older men and women perform submaximal exercise at a moderate intensity, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. We sought to determine the effect of manipulating mechanical ventilatory constraint during submaximal exercise on dyspnoea in older men and women. METHODS:Eighteen healthy subjects (60-80 y; 9 men, 9 women) completed two days of testing. On Day 1, subjects performed pulmonary function testing and a maximal incremental cycle exercise test. On Day 2, subjects performed three 6-min bouts of cycling at ventilatory threshold, in a single-blind randomized manner, while breathing: i) normoxic helium-oxygen (HEL) to reduce the work of breathing (Wb ) and alleviate expiratory flow limitation (EFL); ii) through an inspiratory resistance (RES) of ∼5 cmH2 O·l-1 ·s-1 to increase Wb ; and iii) ambient air as a control (CON). Oesophageal pressure, diaphragm electromyography, and sensory responses (using the category-ratio 10 Borg scale) were monitored throughout exercise. RESULTS:During the HEL condition, there was a significant decrease in Wb (men: -21 ± 6%, women: -17 ± 10%) relative to CON (both p < 0.01). Moreover, if EFL was present during CON (4 men, 5 women), it was alleviated during HEL. Conversely, during the RES condition, Wb (men: 42 ± 19%, women: 50 ± 16%) significantly increased relative to CON (both p < 0.01). There was no main effect of sex on Wb (p = 0.59). Across conditions, women reported significantly higher dyspnoea intensity than men (2.9 ± 0.9 vs. 1.9 ± 0.8 Borg scale units, p < 0.05). Despite significant differences in the degree of mechanical ventilatory constraint between conditions, dyspnoea intensity was unaffected, independent of sex (p = 0.46). CONCLUSION:When older men and women perform submaximal exercise at a moderate intensity, mechanical ventilatory constraint does not contribute significantly to the sensation of dyspnoea. This article is protected by copyright. All rights reserved.Natural Science and Engineering Research Council of Canada (NSERC)
British Columbia Lung Association (BCLA
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Demonstration of the event identification capabilities of the NEXT-White detector
In experiments searching for neutrinoless double-beta decay, the possibility of identifying the two emitted electrons is a powerful tool in rejecting background events and therefore improving the overall sensitivity of the experiment. In this paper we present the first measurement of the efficiency of a cut based on the different event signatures of double and single electron tracks, using the data of the NEXT-White detector, the first detector of the NEXT experiment operating underground. Using a 228Th calibration source to produce signal-like and background-like events with energies near 1.6 MeV, a signal efficiency of 71.6 ± 1.5 stat± 0.3 sys% for a background acceptance of 20.6 ± 0.4 stat± 0.3 sys% is found, in good agreement with Monte Carlo simulations. An extrapolation to the energy region of the neutrinoless double beta decay by means of Monte Carlo simulations is also carried out, and the results obtained show an improvement in background rejection over those obtained at lower energies. [Figure not available: see fulltext.
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Radiogenic backgrounds in the NEXT double beta decay experiment
Natural radioactivity represents one of the main backgrounds in the search for neutrinoless double beta decay. Within the NEXT physics program, the radioactivity- induced backgrounds are measured with the NEXT-White detector. Data from 37.9 days of low-background operations at the Laboratorio Subterráneo de Canfranc with xenon depleted in 136Xe are analyzed to derive a total background rate of (0.84±0.02) mHz above 1000 keV. The comparison of data samples with and without the use of the radon abatement system demonstrates that the contribution of airborne-Rn is negligible. A radiogenic background model is built upon the extensive radiopurity screening campaign conducted by the NEXT collaboration. A spectral fit to this model yields the specific contributions of 60Co, 40K, 214Bi and 208Tl to the total background rate, as well as their location in the detector volumes. The results are used to evaluate the impact of the radiogenic backgrounds in the double beta decay analyses, after the application of topological cuts that reduce the total rate to (0.25±0.01) mHz. Based on the best-fit background model, the NEXT-White median sensitivity to the two-neutrino double beta decay is found to be 3.5σ after 1 year of data taking. The background measurement in a Qββ±100 keV energy window validates the best-fit background model also for the neutrinoless double beta decay search with NEXT-100. Only one event is found, while the model expectation is (0.75±0.12) events. [Figure not available: see fulltext.]
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Energy calibration of the NEXT-White detector with 1% resolution near Q ββ of 136Xe
Excellent energy resolution is one of the primary advantages of electroluminescent high-pressure xenon TPCs. These detectors are promising tools in searching for rare physics events, such as neutrinoless double-beta decay (ββ0ν), which require precise energy measurements. Using the NEXT-White detector, developed by the NEXT (Neutrino Experiment with a Xenon TPC) collaboration, we show for the first time that an energy resolution of 1% FWHM can be achieved at 2.6 MeV, establishing the present technology as the one with the best energy resolution of all xenon detectors for ββ0ν searches. [Figure not available: see fulltext.
Effects of clusterin over-expression on metastatic progression and therapy in breast cancer
<p>Abstract</p> <p>Background</p> <p>Clusterin is a secreted glycoprotein that is upregulated in a variety of cell lines in response to stress, and enhances cell survival. A second nuclear isoform of clusterin that is associated with cell death has also been identified. The aim of this study was to determine the role(s) of the secretory isoform in breast tumor progression and metastasis.</p> <p>Methods</p> <p>To investigate the role of secretory clusterin in the biology of breast cancer tumor growth and resistance to therapy we have engineered an MCF-7 cell line (MCF-7CLU) that over-expresses clusterin. We have measured the <it>in vitro </it>effects of clusterin over-expression on cell cycle, cell death, and sensitivity to TNFalpha and tamoxifen. Using an orthotopic model of breast cancer, we have also determined the effects of over-expression of clusterin on tumor growth and metastatic progression.</p> <p>Results</p> <p>In vitro, over-expression of secretory clusterin alters the cell cycle kinetics and decreases the rate of cell death, resulting in the enhancement of cell growth. Over-expression of secretory clusterin also blocks the TNFalpha-mediated induction of p21 and abrogates the cleavage of Bax to t-Bax, rendering the MCF-7CLU cells significantly more resistant to the cytokine than the parental cells. Orthotopic primary tumors derived from MCF-7CLU cells grow significantly more rapidly than tumors derived from parental MCF-7 cells and, unlike the parental cells, metastasize frequently to the lungs.</p> <p>Conclusions</p> <p>These data suggest that secretory clusterin, which is frequently up-regulated in breast cancers by common therapies, including anti-estrogens, may play a significant role in tumor growth, metastatic progression and subsequent drug resistance in surviving cells.</p
Clues to Neuro-Degeneration in Niemann-Pick Type C Disease from Global Gene Expression Profiling
BACKGROUND: Niemann-Pick Type C (NPC) disease is a neurodegenerative disease that is characterized by the accumulation of cholesterol and glycosphingolipids in the late endocytic pathway. The majority of NPC cases are due to mutations in the NPC1 gene. The precise function of this gene is not yet known. METHODOLOGY/PRINCIPAL FINDINGS: Using cDNA microarrays, we analyzed the genome-wide expression patterns of human fibroblasts homozygous for the I1061T NPC1 mutation that is characterized by a severe defect in the intracellular processing of low density lipoprotein-derived cholesterol. A distinct gene expression profile was identified in NPC fibroblasts from different individuals when compared with fibroblasts isolated from normal subjects. As expected, NPC1 mutant cells displayed an inappropriate homeostatic response to accumulated intracellular cholesterol. In addition, a number of striking parallels were observed between NPC disease and Alzheimer's disease. CONCLUSIONS/SIGNIFICANCE: Many genes involved in the trafficking and processing of amyloid precursor protein and the microtubule binding protein, tau, were more highly expressed. Numerous genes important for membrane traffic and the cellular regulation of calcium, metals and other ions were upregulated. Finally, NPC fibroblasts exhibited a gene expression profile indicative of oxidative stress. These changes are likely contributors to the pathophysiology of Niemann-Pick Type C disease
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