Time lag between oscillatory pressure and flow affecting accuracy of forced oscillation technique

<p>Abstract</p> <p>Background</p> <p>The forced oscillation technique (FOT) is a simple method for assessing the oscillatory mechanics of the respiratory system. The oscillatory properties, respiratory system resistance (Rrs) and reactance (Xrs), are calculated from the oscillatory pressure/flow relationship. Although the FOT has been a well-established technique, some detailed experimental conditions would be different among institutions.</p> <p>Methods</p> <p>We evaluated whether time lags produced by the experimental conditions such as different positions of the sensors can affect the accuracy of the FOT. If the position of the pressure sensor is different from the flow sensor, a time lag may occur in the measurements. The effect of the time lag was studied by numerical analysis.</p> <p>Results</p> <p>Rrs was estimated to be increased and Xrs decreased with an increase in the time lag, especially at a high oscillatory frequency of the medium-frequency range (5-35 Hz). At the high-frequency range (10-500 Hz), Rrs and Xrs were strikingly different in the values of the time lag.</p> <p>Conclusion</p> <p>A time lag between the oscillatory pressure and flow may be involved in the accuracy of the FOT, suggesting that it needs to be minimized or compensated for with signal processing. Researchers should pay attention to such detailed experimental conditions of the FOT apparatus.</p

Positive Autoregulation Delays the Expression Phase of Mammalian Clock Gene Per2

In mammals, cellular circadian rhythms are generated by a transcriptional-translational autoregulatory network that consists of clock genes that encode transcriptional regulators. Of these clock genes, Period1 (Per1) and Period2 (Per2) are essential for sustainable circadian rhythmicity and photic entrainment. Intriguingly, Per1 and Per2 mRNAs exhibit circadian oscillations with a 4-hour phase difference, but they are similarly transactivated by CLOCK-BMAL1. In this study, we investigated the mechanism underlying the phase difference between Per1 and Per2 through a combination of mathematical simulations and molecular experiments. Mathematical analyses of a model for the mammalian circadian oscillator demonstrated that the slow synthesis and fast degradation of mRNA tend to advance the oscillation phase of mRNA expression. However, the phase difference between Per1 and Per2 was not reproduced by the model, which implemented a 1.1-fold difference in degradation rates and a 3-fold difference in CLOCK-BMAL1 mediated inductions of Per1 and Per2 as estimated in cultured mammalian cells. Thus, we hypothesized the existence of a novel transcriptional activation of Per2 by PER1/2 such that the Per2 oscillation phase was delayed. Indeed, only the Per2 promoter, but not Per1, was strongly induced by both PER1 and PER2 in the presence of CLOCK-BMAL1 in a luciferase reporter assay. Moreover, a 3-hour advance was observed in the transcriptional oscillation of the delta-Per2 reporter gene lacking cis-elements required for the induction by PER1/2. These results indicate that the Per2 positive feedback regulation is a significant factor responsible for generating the phase difference between Per1 and Per2 gene expression

Rifaximin Exerts Beneficial Effects Independent of its Ability to Alter Microbiota Composition

Rifaximin has clinical benefits in minimal hepatic encephalopathy (MHE) but the mechanism of action is unclear. The antibiotic-dependent and -independent effects of rifaximin need to be elucidated in the setting of MHE-associated microbiota. To assess the action of rifaximin on intestinal barrier, inflammatory milieu and ammonia generation independent of microbiota using rifaximin

Novel Respiratory Impedance-Based Phenotypes Reflect Different Pathophysiologies in Chronic Obstructive Pulmonary Disease Patients.

Purpose: The forced oscillation technique (FOT) is a non-invasive method to measure respiratory impedance, the respiratory resistance (Rrs) and reactance (Xrs). The disease probability measure (DPM) is a useful computed tomography (CT) imaging variable for the assessment of gas trapping and emphysema in patients with chronic obstructive pulmonary disease (COPD) using pairs of inspiratory and expiratory CT images. We aimed to develop FOT-based phenotypes and determine whether the phenotypes and their imaging characteristics could facilitate the understanding of COPD pathophysiology.Patients and methods: FOT and spirometry were examined in 164 COPD patients and 22 non-COPD smokers. COPD patients were divided into four FOT-based phenotypes (NL, normal group; RD, resistance-dominant group; XD, reactance-dominant group; and MIX, mixed group) based on the 3rd quartile values of R5 (Rrs at 5Hz) and X5 (Xrs at 5Hz) in the non-COPD group. The emphysematous lesions and the airway lesions were quantitatively assessed in CT images by low attenuation volume and the square root of the wall area of a hypothetical airway with an internal perimeter of 10 mm (√Aaw at Pi10), respectively. DPM imaging analysis was also performed in 131 COPD patients. We investigated the differences in COPD parameters between the FOT-based phenotypes.Results: √Aaw at Pi10 were significantly higher in the RD, XD, and MIX groups than in the NL group. The XD group showed lower pulmonary function and higher dyspnea scores than the RD group. No significant changes in DPM values were observed between the RD and the NL groups. The gas-trapping area was significantly higher in the XD group than in the NL group. The MIX group showed the highest dyspnea score, most emphysematous lesions, and the lowest forced expiratory volume in 1 s % predicted value.Conclusion: The FOT-based phenotyping may be useful to assess pathophysiological changes of COPD with CT assessments