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51.

Background

Pump speed optimization in patients implanted with a ventricular assist device represents a major challenge during the follow-up period. We present our findings on whether combined invasive hemodynamic ramp tests and cardiopulmonary exercise testing (CPX) can help optimize patient management.

Methods

Eighteen patients implanted with a HeartMate 3 (HM3) device underwent ramp tests with right heart catheterization (including central venous pressure [CVP], pulmonary artery pressure, pulmonary capillary wedge pressure [PCWP], and blood pressure) and echocardiography. Data were recorded at up to 4 speed settings. Speed changes were in steps of 200 revolutions/min (rpm). Evaluation of functional capacity by CPX was conducted according to the modified Bruce protocol.

Results

Only 30% of patients had normal PCWPs at their original rpm settings. In going from lowest to highest speeds, cardiac output improved by 0.25 ± 0.35 L/min/step (total change, 1.28 ± 0.3 L/min), and PCWP decreased by 1.9 ± 0.73 mm Hg/step (total change, 6 ± 1.6 mm Hg). CVP and systolic blood pressure did not change significantly with rpm. The rpm assessment was adjusted based on test results to achieve CVPs and PCWPs as close to normal limits as possible, which was feasible in all patients. On CPX, all patients demonstrated good performance (peak VO2, 16.8 ± 3.5 mL/kg/min).

Conclusion

Hemodynamic ramp testing provides an objective means of optimizing rpm, and has the potential to provide good exercise tolerance.  相似文献   
52.
Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology.  相似文献   
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In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.  相似文献   
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