These findings disclose an innovative, non-invasive strategy to induce therapeutic neovascularization in a mouse model of HLI, emerging as a novel approach in the treatment of critical limb ischemia patients.

Changes in lung mechanics are frequently inferred from intact-chest measures of total respiratory system mechanics without consideration of the chest wall contribution. The participation of lungs and chest wall in respiratory mechanics has not been evaluated systematically in small animals commonly used in respiratory research. Thus, we compared these contributions in intact-chest mice, rats, and rabbits and further characterized the influence of positive end-expiratory pressure (PEEP). Forced oscillation technique was applied to anesthetized mechanically ventilated healthy animals to obtain total respiratory system impedance (Zrs) at 0, 3, and 6 cmH2O PEEP levels. Esophageal pressure was measured by a catheter-tip micromanometer to separate Zrs into pulmonary (ZL) and chest wall (Zcw) components. A model containing a frequency-independent Newtonian resistance (RN), inertance, and a constant-phase tissue damping (G) and elastance (H) was fitted to Zrs, ZL, and Zcw spectra. The contribution of Zcw to RN was negligible in all species and PEEP levels studied. However, the participation of Zcw in G and H was significant in all species and increased significantly with increasing PEEP and animal size (rabbit > rat > mice). Even in mice, the chest wall contribution to G and H was still considerable, reaching 47.0 ± 4.0(SE)% and 32.9 ± 5.9% for G and H, respectively. These findings demonstrate that airway parameters can be assessed from respiratory system mechanical measurements. However, the contribution from the chest wall should be considered when intact-chest measurements are used to estimate lung parenchymal mechanics in small laboratory models (even in mice), particularly at elevated PEEP levels. NEW & NOTEWORTHY In species commonly used in respiratory research (rabbits, rats, mice), esophageal pressure-based estimates revealed negligible contribution from the chest wall to the Newtonian resistance. Conversely, chest wall participation in the viscoelastic tissue mechanical parameters increased with body size (rabbit > rat > mice) and positive end-expiratory pressure, with contribution varying between 30 and 50%, even in mice. These findings demonstrate the potential biasing effects of the chest wall when lung tissue mechanics are inferred from intact-chest measurements in small laboratory animals.

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BACKGROUND: MD-PhD programmes throughout the world provide a platform for medical trainees to commit to a physician-scientist career, qualifying with both a medical degree (MD or equivalent) and Doctor of Philosophy (PhD). However, there are limited studies assessing the characteristics of MD-PhD programmes in Europe and the outcomes of MD-PhD students and graduates. PURPOSE: This study aims at a first country-wise exploration of characteristics, opinions, and academic outcomes of MD-PhD students and graduates in Europe. METHODS: Two questionnaires were developed to assess the demographics, MD-PhD programme characteristics, opinions, future career paths and academic outcomes of European MD-PhD students and graduates. An online survey of 278 MD-PhD students and 121 MD-PhD graduates from nine and six European countries, respectively, was completed between April 2016 and December 2017. The country-wise categorical responses were then compared through chi-square analysis followed by multiple logistic regression. RESULTS: Responses from 266 MD-PhD students and 117 MD-PhD graduates were considered valid. Significant country-wise differences (p <0.05) were observed for age group, resident status, clinical time allocation, duration of studies, sources of funding, publications, average impact factor of the journals in which the research was published, satisfaction with the duration of MD-PhD studies and future career choices of MD-PhD students. Responses related to self-perception about clinical and research competence and challenges faced during MD-PhD training did not show a significant country-wise difference. CONCLUSION:The MD-PhD workforce in Europe is highly diverse in their demographics, programme characteristics and career paths but does not differ in opinions related to the challenges faced. The results of this study may be helpful for implementation and improvement of MD-PhD programmes.