Sex differences in exercise-induced diaphragmatic fatigue in endurance-trained athletes

There is evidence that female athletes may be more susceptible to exercise-induced arterial hypoxemia and expiratory flow limitation and have greater increases in operational lung volumes during exercise relative to men. These pulmonary limitations may ultimately lead to greater levels of diaphragmatic fatigue in women. Accordingly, the purpose of this study was to determine whether there are sex differences in the prevalence and severity of exercise-induced diaphragmatic fatigue in 38 healthy endurance-trained men (n = 19; maximal aerobic capacity = 64.0 ± 1.9 ml·kg–1·min–1) and women (n = 19; maximal aerobic capacity = 57.1 ± 1.5 ml·kg–1·min–1). Transdiaphragmatic pressure (Pdi) was calculated as the difference between gastric and esophageal pressures. Inspiratory pressure-time products of the diaphragm and esophagus were calculated as the product of breathing frequency and the Pdi and esophageal pressure time integrals, respectively. Cervical magnetic stimulation was used to measure potentiated Pdi twitches (Pdi,tw) before and 10, 30, and 60 min after a constant-load cycling test performed at 90% of peak work rate until exhaustion. Diaphragm fatigue was considered present if there was a 15% reduction in Pdi,tw after exercise. Diaphragm fatigue occurred in 11 of 19 men (58%) and 8 of 19 women (42%). The percent drop in Pdi,tw at 10, 30, and 60 min after exercise in men (n = 11) was 30.6 ± 2.3, 20.7 ± 3.2, and 13.3 ± 4.5%, respectively, whereas results in women (n = 8) were 21.0 ± 2.1, 11.6 ± 2.9, and 9.7 ± 4.2%, respectively, with sex differences occurring at 10 and 30 min (P < 0.05). Men continued to have a reduced contribution of the diaphragm to total inspiratory force output (pressure-time product of the diaphragm/pressure-time product of the esophagus) during exercise, whereas diaphragmatic contribution in women changed very little over time. The findings from this study point to a female diaphragm that is more resistant to fatigue relative to their male counterparts

A phase I clinical study of inhaled nitric oxide in healthy adults

AbstractBackgroundNitric oxide (NO) is an approved pulmonary vasodilator for neonates and full term infants up to a dose of 80ppm. At 100ppm to 200ppm, NO has potent antimicrobial activities in vitro and in animal studies which suggest its therapeutic use for infectious diseases in humans. However, whether inhaled NO is safe at 160ppm in healthy human adults is unknown. The aim of the phase I study was to assess the safety of delivery and the physiologic effects of intermittent 160ppm NO in healthy human adults.MethodsTen healthy adult volunteers (5 males, 5 females; 20–62years) were recruited and inhaled 163.3ppm (SD: 4.0) NO for 30min, 5 times daily, for 5 consecutive days. Lung function and blood levels of methemoglobin, nitrites/nitrates, prothrombin, pro-inflammatory cytokines and chemokines were determined before and during treatment.ResultsAll individuals tolerated the NO treatment courses well. No significant adverse events occurred and three minor adverse events, not attributable to NO, were reported. Forced expiratory volume in 1sec % predicted and other lung function parameters, serum nitrites/nitrates, prothrombin, pro-inflammatory cytokine and chemokine levels did not differ between baseline and day 5, while methemoglobin increased significantly during the study period to a level of 0.9% (SD: 0.08) (p<0.001).ConclusionThese data suggest that inhalation of 160ppm NO for 30min, 5 times daily, for 5 consecutive days, is safe and well tolerated in healthy individuals

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Combination of ICSs and LABAs Should Be Used in the Management of Patients with COPD -- The Con Argument

The management of patients with symptomatic chronic obstructive pulmonary disease (COPD) has become more clear in the past several years. New medications have been developed and their efficacy has been evaluated using important outcomes in addition to forced expiratory volume in 1 s (FEV1), such as health-related quality of life (HRQL), frequency of exacerbations and dyspnea scores. I will review five welldesigned, randomized, controlled trials that have advanced our knowledge about the use of inhaled corticosteroids (ICSs), long-acting beta2-agonists (LABAs) and their combination