Age-dependent ventilator-induced lung injury: Mathematical modeling, experimental data, and statistical analysis.

A variety of pulmonary insults can prompt the need for life-saving mechanical ventilation; however, misuse, prolonged use, or an excessive inflammatory response, can result in ventilator-induced lung injury. Past research has observed an increased instance of respiratory distress in older patients and differences in the inflammatory response. To address this, we performed high pressure ventilation on young (2-3 months) and old (20-25 months) mice for 2 hours and collected data for macrophage phenotypes and lung tissue integrity. Large differences in macrophage activation at baseline and airspace enlargement after ventilation were observed in the old mice. The experimental data was used to determine plausible trajectories for a mathematical model of the inflammatory response to lung injury which includes variables for the innate inflammatory cells and mediators, epithelial cells in varying states, and repair mediators. Classification methods were used to identify influential parameters separating the parameter sets associated with the young or old data and separating the response to ventilation, which was measured by changes in the epithelial state variables. Classification methods ranked parameters involved in repair and damage to the epithelial cells and those associated with classically activated macrophages to be influential. Sensitivity results were used to determine candidate in-silico interventions and these interventions were most impact for transients associated with the old data, specifically those with poorer lung health prior to ventilation. Model results identified dynamics involved in M1 macrophages as a focus for further research, potentially driving the age-dependent differences in all macrophage phenotypes. The model also supported the pro-inflammatory response as a potential indicator of age-dependent differences in response to ventilation. This mathematical model can serve as a baseline model for incorporating other pulmonary injuries.

Metabolic Reprogramming of Ovarian Cancer Spheroids during Adhesion.

Ovarian cancer remains a deadly disease and its recurrence disease is due in part to the presence of disseminating ovarian cancer aggregates not removed by debulking surgery. During dissemination in a dynamic ascitic environment, the spheroid cells' metabolism is characterized by low respiration and fragmented mitochondria, a metabolic phenotype that may not support secondary outgrowth after adhesion. Here, we investigated how adhesion affects cellular respiration and substrate utilization of spheroids mimicking early stages of secondary metastasis. Using different glucose and oxygen levels, we investigated cellular metabolism at early time points of adherence (24 h and less) comparing slow and fast-developing disease models. We found that adhesion over time showed changes in cellular energy metabolism and substrate utilization, with a switch in the utilization of mostly glutamine to glucose but no changes in fatty acid oxidation. Interestingly, low glucose levels had less of an impact on cellular metabolism than hypoxia. A resilience to culture conditions and the capacity to utilize a broader spectrum of substrates more efficiently distinguished the highly aggressive cells from the cells representing slow-developing disease, suggesting a flexible metabolism contributes to the stem-like properties. These results indicate that adhesion to secondary sites initiates a metabolic switch in the oxidation of substrates that could support outgrowth and successful metastasis.

Multiple immunity-related genes control susceptibility of Arabidopsis thaliana to the parasitic weed Phelipanche aegyptiaca.

Parasitic weeds represent a major threat to agricultural production across the world. Little is known about which host genetic pathways determine compatibility for any host-parasitic plant interaction. We developed a quantitative assay to characterize the growth of the parasitic weed Phelipanche aegyptiaca on 46 mutant lines of the host plant Arabidopsis thaliana to identify host genes that are essential for susceptibility to the parasite. A. thaliana host plants with mutations in genes involved in jasmonic acid biosynthesis/signaling or the negative regulation of plant immunity were less susceptible to P. aegyptiaca parasitization. In contrast, A. thaliana plants with a mutant allele of the putative immunity hub gene Pfd6 were more susceptible to parasitization. Additionally, quantitative PCR revealed that P. aegyptiaca parasitization leads to transcriptional reprograming of several hormone signaling pathways. While most tested A. thaliana lines were fully susceptible to P. aegyptiaca parasitization, this work revealed several host genes essential for full susceptibility or resistance to parasitism. Altering these pathways may be a viable approach for limiting host plant susceptibility to parasitism.

Mechanistic insights into the effect of humidity on airborne influenza virus survival, transmission and incidence.

Influenza incidence and seasonality, along with virus survival and transmission, appear to depend at least partly on humidity, and recent studies have suggested that absolute humidity (AH) is more important than relative humidity (RH) in modulating observed patterns. In this perspective article, we re-evaluate studies of influenza virus survival in aerosols, transmission in animal models and influenza incidence to show that the combination of temperature and RH is equally valid as AH as a predictor. Collinearity must be considered, as higher levels of AH are only possible at higher temperatures, where it is well established that virus decay is more rapid. In studies of incidence that employ meteorological data, outdoor AH may be serving as a proxy for indoor RH in temperate regions during the wintertime heating season. Finally, we present a mechanistic explanation based on droplet evaporation and its impact on droplet physics and chemistry for why RH is more likely than AH to modulate virus survival and transmission.

Comparison of Treadmill Trip-Like Training Versus Tai Chi to Improve Reactive Balance Among Independent Older Adult Residents of Senior Housing: A Pilot Controlled Trial.

BACKGROUND: There is growing interest in using perturbation-based balance training to improve the reactive response to common perturbations (eg, tripping and slipping). The goal of this study was to compare the efficacy of treadmill-based reactive balance training versus Tai Chi performed at, and among independent residents of, older adult senior housing. METHODS: Thirty-five residents from five senior housing facilities were allocated to either treadmill-based reactive balance training or Tai Chi training. Both interventions were performed three times per week for 4 weeks, with each session lasting approximately 30 minutes. A battery of balance tests was performed at baseline, and again 1 week, 1 month, 3 months, and 6 months post-training. The battery included six standard clinical tests of balance and mobility, and a test of reactive balance performance. RESULTS: At baseline, no significant between-group differences were found for any balance tests. After training, reactive balance training participants had better reactive balance than Tai Chi participants. Maximum trunk angle was 13.5° smaller among reactive balance training participants 1 week after training (p = .01), and a reactive balance rating was 24%-31% higher among reactive balance training participants 1 week to 6 months after training (p < .03). Clinical tests showed minimal differences between groups at any time point after training. CONCLUSION: Trip-like reactive balance training performed at senior housing facilities resulted in better rapid balance responses compared with Tai Chi training.