A novel mechanical lung model of pulmonary diseases to assist with teaching and training

BACKGROUND: A design concept of low-cost, simple, fully mechanical model of a mechanically ventilated, passively breathing lung is developed. An example model is built to simulate a patient under mechanical ventilation with accurate volumes and compliances, while connected directly to a ventilator. METHODS: The lung is modelled with multiple units, represented by rubber bellows, with adjustable weights placed on bellows to simulate compartments of different superimposed pressure and compliance, as well as different levels of lung disease, such as Acute Respiratory Distress Syndrome (ARDS). The model was directly connected to a ventilator and the resulting pressure volume curves recorded. RESULTS: The model effectively captures the fundamental lung dynamics for a variety of conditions, and showed the effects of different ventilator settings. It was particularly effective at showing the impact of Positive End Expiratory Pressure (PEEP) therapy on lung recruitment to improve oxygenation, a particulary difficult dynamic to capture. CONCLUSION: Application of PEEP therapy is difficult to teach and demonstrate clearly. Therefore, the model provide opportunity to train, teach, and aid further understanding of lung mechanics and the treatment of lung diseases in critical care, such as ARDS and asthma. Finally, the model's pure mechanical nature and accurate lung volumes mean that all results are both clearly visible and thus intuitively simple to grasp

Minimal Model of Lung Mechanics for Optimising Ventilator Therapy in Critical Care

Positive pressure mechanical ventilation (MV) has been utilised in the care of critically ill patients for over 50 years. MV essentially provides for oxygen delivery and carbon dioxide removal by the lungs in patient with respiratory failure or insufficiency from any cause. However, MV can be injurious to the lungs, particularly when high tidal pressures or volumes are used in the management of Acute Respiratory Distress Syndrome (ARDS) or similar acute lung injuries. The hallmark of ARDS is extensive alveolar collapse resulting in hypoxemia and carbon dioxide retention. Application of Positive End Expiratory Pressure (PEEP) is used to prevent derecruitment of alveolar units. Hence, there is a delicate trade-off between applied pressure and volume and benefit of lung recruitment. Current clinical practice lacks a practical method to easily determine the patient specific condition at the bedside without excessive extra tests and intervention. Hence, individual patient treatment is primarily a mixture of "one size- fits-all" protocols and/or the clinician's intuition and experience. A quasi-static, minimal model of lung mechanics is developed based on fundamental lung physiology and mechanics. The model consists of different components that represent a particular mechanism of the lung physiology, and the total lung mechanics are derived by combining them in a physiologically relevant and logical manner. Three system models are developed with varying levels of physiological detail and clinical practicality. The final system model is designed to be directly relevant in current ICU practice using readily available non-invasive data. The model is validated against a physiologically accurate mechanical simulator and clinical data, with both approaches producing clinically significant results. Initial validation using mechanical simulator data showed the model's versatility and ability to capture all physiologically relevant mechanics. Validation using clinical data showed its practicality as a clinical tool, its robustness to noise and/or unmodelled mechanics, and its ability to capture patient specific responses to change in therapy. The model's capability as a predictive clinical tool was assessed with an average prediction error of less than 9% and well within clinical significance. Furthermore, the system model identified parameters that directly indicate and track patient condition, as well as their responsiveness to the treatment, which is a unique and potentially valuable clinical result. Full clinical validation is required, however the model shows significant potential to be fully adopted as a part of standard ventilator treatment in critical care

Immaturin-Nuclease as a Model System for a Gene-Programmed Sexual Development and Rejuvenescence in <i>Paramecium</i> Life History

Fertilization-initiated development and adult-onset aging are standard features in the life history of eukaryotes. In Paramecium, the number of cell divisions after the birth of a new generation is an essential parameter of sexual phase transition and aging. However, the gene driving this process and its evolutionary origin have not yet been elucidated. Here we report several critical outcomes obtained by molecular genetics, immunofluorescence microscopy, transformation by microinjection, and enzymological analysis. The cloned immaturin gene induces sexual rejuvenation in both mature and senescent cells by microinjection. The immaturin gene originated from proteobacteria’s glutathione-S-transferase (GST) gene. However, immaturin has been shown to lose GST activity and instead acquire nuclease activity. In vitro substrates for immaturin-nuclease are single- and double-stranded DNA, linear and circular DNA, and single-stranded viral genome RNA such as coronavirus. Anti-immaturin antibodies have shown that the subcellular localizations of immaturin are the macronucleus, cytoplasm, cell surface area, and cilia. The phase transition of sexuality is related to a decrease in the intracellular abundance of immaturin. We propose that sexual maturation and rejuvenation is a process programmed by the immaturin gene, and the sexual function of each age is defined by both the abundance and the intracellular localization mode of the immaturin-nuclease