Preclinical models are essential for understanding respiratory physiology and disease, but their translational impact is limited by the absence of standardized reference frameworks. Unlike clinical practice, where lung function is interpreted using prediction equations and z-scores, preclinical studies report absolute values, hampering comparability. We established reference equations for airway resistance, tissue damping, tissue elastance, and end-expiratory lung volume in 182 healthy Sprague Dawley and Wistar rats. Using generalized additive models for location, scale, and shape (GAMLSS), we modeled mean and variability as functions of body mass, sex, strain, and positive end-expiratory pressure. The models showed excellent fit and cross-validation, enabling accurate z-score derivation at the individual level. Sex and strain significantly influenced outcomes. Open-source calculators support direct integration into workflows. This framework introduces clinical-style reference equations into preclinical respiratory research, enhancing reproducibility and aligning animal measurements with clinical standards, with implications for computational models, study design, and translational research.
This study examines how diabetes mellitus and physiological aging influence the nanomechanical behavior of rat rib cortical bone using combined static and dynamic nanoindentation. Ribs from young control, old, and streptozotocin-induced diabetic rats were analyzed to quantify both intrinsic and frequency-dependent mechanical properties. Static nanoindentation revealed markedly higher hardness and elastic modulus in the diabetic group (0.47 ± 0.22 GPa and 9.53 ± 3.03 GPa, respectively) compared to controls (0.11 ± 0.03 GPa and 3.21 ± 0.51 GPa; p < 0.001). The modulus-to-hardness ratio, an indicator of fracture toughness, was reduced from 30.34 in controls to 20.45 in diabetics, suggesting increased stiffness but greater brittleness. Dynamic nanoindentation (0–4.5 Hz) demonstrated significant aging-related changes in the storage and loss moduli (p < 0.001), while the loss factor (tan δ < 1) and viscosity remained similar across groups, indicating predominantly solid-like behavior. These results show that diabetes stiffens bone tissue through matrix-level alterations, whereas aging primarily affects its viscoelastic damping capacity. The combined static–dynamic nanoindentation protocol provides a robust framework for distinguishing disease- and age-related bone degradation at the tissue scale. Translationally, the findings help explain why bones in diabetic or elderly individuals may fracture despite normal mineral density, underscoring the need to assess bone quality beyond conventional densitometry.
Introduction: In the most severe cases of COVID-19, patients develop acute pneumonia leading to severe gas exchange defects, necessitating veno-venous extracorporeal membrane oxygenation (V-V ECMO) support. While persistent post-COVID pulmonary symptoms are expected in these patients, the long-term ventilation-perfusion mismatch has not been characterized. Therefore, we aimed at assessing these disturbances in post-COVID patients who have received V-V ECMO support. Methods: Mainstream volumetric capnography was conducted on post-COVID patients who had undergone V-V ECMO support (COVID group, n=9) one year after their hospital discharge. These results were then compared with data from a matched healthy control group (CTRL group, n=9). The study focused on determining the slopes of the second (S2V) and third (S3V) phases of the capnogram, as well as measuring both the Bohr physiological and Fowler anatomical dead spaces. Results: In the COVID group, we obtained a significant decrease in the S2V compared to the CTRL group (193±45 vs. 264±52 mmHg/s, p<0.05) and a significant increase in the S3V (12.1±6.6 vs. 6.7±3.7 mmHg/s, p<0.05). No differences in anatomical or physiological dead space parameters were observed between the study groups. Conclusion: An elevation in S3V suggests persistent ventilation-perfusion mismatch one year after hospital discharge following severe COVID-19 pneumonia. Conversely, a diminished S2V may be indicative of compromised small airway function. These findings underscore the importance of long-term pulmonary rehabilitation for patients who have undergone V-V ECMO support due to severe acute viral pneumonia. Funding: OTKA-NKFIH 138032