The role of inspiratory muscle training in the management of asthma and exercise-induced bronchoconstriction.

Asthma is a pathological condition comprising of a variety of symptoms which affect the ability to function in daily life. Due to the high prevalence of asthma and associated healthcare costs, it is important to identify low-cost alternatives to traditional pharmacotherapy. One of these low cost alternatives is the use of inspiratory muscle training (IMT), which is a technique aimed at increasing the strength and endurance of the diaphragm and accessory muscles of respiration. IMT typically consists of taking voluntary inspirations against a resistive load across the entire range of vital capacity while at rest. In healthy individuals, the most notable benefits of IMT are an increase in diaphragm thickness and strength, a decrease in exertional dyspnea, and a decrease in the oxygen cost of breathing. Due to the presence of expiratory flow limitation in asthma and exercise-induced bronchoconstriction, dynamic lung hyperinflation is common. As a result of varying operational lung volumes, due in part to hyperinflation, the respiratory muscles may operate far from the optimal portion of the length-tension curve, and thus may be forced to operate against a low pulmonary compliance. Therefore, the ability of these muscles to generate tension is reduced, and for any given level of ventilation, the work of breathing is increased as compared to non-asthmatics. Evidence that IMT is an effective treatment for asthma is inconclusive, due to limited data and a wide variation in study methodologies. However, IMT has been shown to decrease dyspnea, increase inspiratory muscle strength, and improve exercise capacity in asthmatic individuals. In order to develop more concrete recommendations regarding IMT as an effective low-cost adjunct in addition to traditional asthma treatments, we recommend that a standard treatment protocol be developed and tested in a placebo-controlled clinical trial with a large representative sample.

Methazolamide Plus Aminophylline Abrogates Hypoxia-Mediated Endurance Exercise Impairment.

In hypoxia, endurance exercise performance is diminished; pharmacotherapy may abrogate this performance deficit. Based on positive outcomes in preclinical trials, we hypothesized that oral administration of methazolamide, a carbonic anhydrase inhibitor, aminophylline, a nonselective adenosine receptor antagonist and phosphodiesterase inhibitor, and/or methazolamide combined with aminophylline would attenuate hypoxia-mediated decrements in endurance exercise performance in humans. Fifteen healthy males (26 ± 5 years, body-mass index: 24.9 ± 1.6 kg/m(2); mean ± SD) were randomly assigned to one of four treatments: placebo (n = 9), methazolamide (250 mg; n = 10), aminophylline (400 mg; n = 9), or methazolamide (250 mg) with aminophylline (400 mg; n = 8). On two separate occasions, the first in normoxia (FIO2 = 0.21) and the second in hypoxia (FIO2 = 0.15), participants sat for 4.5 hours before completing a standardized exercise bout (30 minutes, stationary cycling, 100 W), followed by a 12.5-km time trial. The magnitude of time trial performance decrement in hypoxia versus normoxia did not differ between placebo (+3.0 ± 2.7 minutes), methazolamide (+1.4 ± 1.7 minutes), and aminophylline (+1.8 ± 1.2 minutes), all with p > 0.09; however, the performance decrement in hypoxia versus normoxia with methazolamide combined with aminophylline was less than placebo (+0.6 ± 1.5 minutes; p = 0.01). This improvement may have been partially mediated by increased SpO2 in hypoxia with methazolamide combined with aminophylline compared with placebo (73% ± 3% vs. 79% ± 6%; p < 0.02). In conclusion, coadministration of methazolamide and aminophylline may promote endurance exercise performance during a sojourn at high altitude.

Regulators of human white adipose browning: evidence for sympathetic control and sexual dimorphic responses to sprint interval training.

The conversion of white adipose to the highly thermogenic beige adipose tissue has been proposed as a potential strategy to counter the unfavorable consequences of obesity. Three regulators of this conversion have recently emerged but information regarding their control is limited, and contradictory. We present two studies examining the control of these regulators. Study 1: In 10 young men, the plasma concentrations of irisin and fibroblast growth factor 21 (FGF21) were determined prior to and during activation of the sympathetic nervous system via hypoxic gas breathing (FIO2 = 0.11). The measurements were performed twice, once with and once without prior/concurrent sympathetic inhibition via transdermal clonidine administration. FGF21 was unaffected by basal sympathetic inhibition (338±113 vs. 295±80 pg/mL; P = 0.43; mean±SE), but was increased during hypoxia mediated sympathetic activation (368±135); this response was abrogated (P = 0.035) with clonidine (269±93). Irisin was unaffected by sympathetic inhibition and/or hypoxia (P>0.21). Study 2: The plasma concentration of irisin and FGF21, and the skeletal muscle protein content of fibronectin type III domain containing 5 (FNDC5) was determined in 19 young adults prior to and following three weeks of sprint interval training (SIT). SIT decreased FGF21 (338±78 vs. 251±36; P = 0.046) but did not affect FNDC5 (P = 0.79). Irisin was decreased in males (127±18 vs. 90±23 ng/mL; P = 0.045) and increased in females (139±14 vs. 170±18). Collectively, these data suggest a potential regulatory role of acute sympathetic activation pertaining to the browning of white adipose; further, there appears to be a sexual dimorphic response of irisin to SIT.

Greater muscle protein synthesis and mitochondrial biogenesis in males compared with females during sprint interval training.

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.

Using geoelectrons to search for velocity-dependent spin-spin interactions.

We use the recently developed model of the electron spins within Earth to investigate all of the six possible long-range velocity-dependent spin-spin interactions associated with the exchange of an ultralight (mz'<10(-10) eV) or massless intermediate vector boson. Several laboratory experiments have established upper limits on the energy associated with various fermion-spin orientations relative to Earth. We combine the results from three of these experiments with the geoelectron-spin model to obtain bounds on the velocity-dependent interactions that couple electron spin to the spins of electrons, neutrons, and protons. Five of the six possible potentials investigated were previously unbounded. In the long-range limit we have improved the bound on the sixth potential by 30 orders of magnitude.

Limit on the electron electric dipole moment in gadolinium-iron garnet.

A new method for the detection of the electron electric dipole moment (EDM) using a solid is described. The method involves the measurement of a voltage induced across the solid by the alignment of the sample's magnetic dipoles in an applied magnetic field, H. A first application of the method to GdIG has resulted in a limit on the electron EDM of 5 x 10(-24)e cm, which is a factor of 40 below the limit obtained from the only previous solid-state EDM experiment. The result is limited by the imperfect discrimination of an unexpectedly large voltage that is even upon the reversal of the sample magnetization.

Tests of time-reversal invariance in atoms, molecules, and the neutron.

Sensitive experiments have been developed that search for electric dipole moments of atoms, molecules, and the neutron. These experiments play an important role in deciding which of the myriad theoretical models correctly describes violations of the principle of time-reversal invariance.

Response of coexisting underacting superior oblique and overacting inferior oblique muscles to inferior oblique weakening.

One hundred twenty-six eyes with inferior oblique overaction and coexisting superior oblique underaction were retrospectively studied pre- and postoperatively. The data show that weakening the inferior oblique corrected the underaction of the superior oblique, and that overcorrection of the underacting superior oblique was unusual. Eyes were selected for study if superior oblique underaction coexisted with inferior oblique overaction preoperatively. The operation chosen for the inferior oblique in every case was determined by the quantity of inferior oblique overaction and whether prior surgery on the inferior oblique had been performed. A denervation and extirpation was the final inferior oblique weakening procedure in all except three of these eyes. Congenital or acquired superior oblique palsy cases were not included in this study. To eliminate eyes with superior oblique palsy, we excluded any patient with a history of serious head trauma; a vertical deviation in the primary position greater than 5 prism diopters except if caused by dissociated vertical deviation; the complaint of torsional diplopia controlled by an anomalous head posture; or a positive Bielschowsky head tilt test. The mean preoperative superior oblique action was -2.4 on a scale of 0 to 4, and this corrected to a mean postoperative action of -0.2, (P less than .001). This was accompanied by a change in the mean inferior oblique action of +3.8 to -0.2, (P less than .001). These same results were found regardless of the preoperative action of either the inferior or superior oblique. With regard to the postoperative superior oblique action, 22 cases were undercorrected, 2 were overcorrected, and 102 were normal.