BackgroundThis study assessed lung models for the influence of respiratory mechanics and inspiratory effort on breathing pattern and simulator-ventilator cycling synchronization in non-invasive ventilation.Material/MethodsA Respironics V60 ventilator was connected to an active lung simulator modeling mildly restrictive, severely restrictive, obstructive and mixed obstructive/restrictive profiles. Pressure-support ventilation (PSV) and proportional-assist ventilation (PAV) were set to obtain similar tidal volume (VT). PAV was applied at flow assist (FA) 40–90% of resistance (Rrs) and volume assist (VA) 40–90% of elastance (Ers). Measurements were performed with system air leak of 25–28 L/minute. Ventilator performance and simulator-ventilator asynchrony were evaluated.ResultsAt comparable VT, PAV had slightly lower peak inspiratory flow and higher driving pressure compared with PSV. Premature cycling occurred in the obstructive, severely restrictive and mildly restrictive models. During PAV, time for airway pressure to achieve 90% of maximum during inspiration (T90) in the severely restrictive model was shorter than those of the obstructive and mixed obstructive/restrictive models and close to that measured in the PSV mode. Increasing FA level reduced inspiratory trigger workload (PTP300) in obstructive and mixed obstructive/restrictive models. Increasing FA level decreased inspiratory time (TI) and tended to aggravate premature cycling, whereas increasing VA level attenuated this effect.ConclusionsPAV with an appropriate combination of FA and VA decreases work of breathing during the inspiratory phase and improves simulator-ventilator cycling synchrony. FA has greater impact than VA in the adaptation to inspiratory effort demand. High VA level might help improve cycling synchrony.
Objective To evaluate the accuracy of respiratory mechanics using dynamic signal analysis during noninvasive pressure support ventilation (PSV). Methods A Respironics V60 ventilator was connected to an active lung simulator to model normal, restrictive, obstructive, and mixed obstructive and restrictive profiles. The PSV was adjusted to maintain tidal volumes (VT) that achieved 5.0, 7.0, and 10.0 mL/kg body weight, and the positive end-expiration pressure (PEEP) was set to 5 cmH2O. Ventilator performance was evaluated by measuring the flow, airway pressure, and volume. The system compliance (Crs) and airway resistance (inspiratory and expiratory resistance, Rinsp and Rexp, respectively) were calculated. Results Under active breathing conditions, the Crs was overestimated in the normal and restrictive models, and it decreased with an increasing pressure support (PS) level. The Rinsp calculated error was approximately 10% at 10.0 mL/kg of VT, and similar results were obtained for the calculated Rexp at 7.0 mL/kg of VT. Conclusion Using dynamic signal analysis, appropriate tidal volume was beneficial for Rrs, especially for estimating Rexp during assisted ventilation. The Crs measurement was also relatively accurate in obstructive conditions.
Background: Hyperactivity of the mechanistic target of rapamycin complex 1 (mTORC1) is implicated in a variety of diseases such as cancer and diabetes. Treatment may benefit from effective mTORC1 inhibition, which can be achieved by preventing arginine from disrupting the cytosolic arginine sensor for mTORC1 subunit 1 (CASTOR1)-GTPase-activating proteins toward RAGS subcomplex 2 (GATOR2) complex through binding with CASTOR1. An attractive idea is to determine analogues of arginine that are as competent as arginine in binding with CASTOR1, but without disrupting the CASTOR1-GATOR2 interaction. Materials and Methods: Molecular dynamics simulations were performed for binding of arginine analogues with CASTOR1 and binding free energy, hydrogen bond formation, and root mean squared deviation and root mean square fluctuation kinetics were then calculated. Results: The binding free energy calculations revealed that N α-acetylarginine, citrulline, and norarginine have sufficient binding affinity with CASTOR1 to compete with arginine. The hydrogen bond analysis revealed that norarginine, N αacetyl-arginine and D-arginine have proficient H-bonds that can facilitate their entering the narrow binding pocket. Conclusion: Norarginine and N α-acetyl-arginine are the top drug candidates for mTORC1 inhibition, with N α-acetylarginine being the best choice. Mechanistic target of rapamycin (mTOR) in complex with regulatory-associated protein of mTOR (RAPTOR) and mTOR-associated protein, LST8 homolog (LST8) is referred as mTOR complex 1 (mTORC1). It is implicated in diseases in which growth is deregulated and homeostasis is compromised (1). Deregulated mTORC1 signalling fuels the destructive growth of cancer. Overstimulation of the mTORC1 pathway by excess food consumption may be a crucial factor underlying the diabetes epidemic (2-4). Recent findings suggest that mTORC1 signalling controls the rate at which cells and tissues age, and that inhibiting mTORC1 may represent a promising avenue for increasing longevity (5). In particular, dysregulation of signalling pathways upstream of mTORC1 can cause human diseases such as cancer, metabolic diseases, neurological disorders, and autoimmune diseases (6, 7). In order for cells to grow and proliferate by manufacturing more proteins, the cells must ensure that they have the resources (energy, nutrients, oxygen, and growth factors) available in order for mRNA translation to begin (5, 8, 9).
The human respiratory system is not entirely symmetric, and regional respiratory diseases can further enlarge this difference in most cases. Therefore, the lungs perform differently. This paper explored the possibilities of suppressing and enhancing the performance of a diseased lung with different high-frequency ventilation (HFV) frequencies by experimenting, as well as modeling, the oscillatory airflow distribution between the left and right lungs. The experimental setup mainly consisted of a physical respiratory model, a signal acquisition device, and a high-frequency oscillation ventilator. This ventilator outputs a positive sinusoidal air-pressure during inspiration. On these bases, a series of experiments were also conducted with different compliances and resistances in the left and the right lungs. The experiments demonstrated that the oscillatory flow distribution is primarily correlated with the oscillation frequency and the regional lung compliance.
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