Oxygen

Age-related macular degeneration (AMD) is an age-associated disease characterized by damage to the central retina and represents a leading cause of acquired blindness, with increasing prevalence in aging populations. However, effective therapeutic options remain limited. The accumulation of dysfunctional mitochondria in retinal pigment epithelial (RPE) cells leads to excessive production of reactive oxygen species (ROS), triggering cellular senescence and cell death that contribute to the pathogenesis of AMD. Therefore, removal of accumulated dysfunctional mitochondria in senescent RPE cells is expected to treat AMD. Herein, we investigated transferrin (Trf)-modified mitophagy-inducing dual-drug nanocarriers (Trf-M-NCs) for the treatment of a senescent RPE cell. To evaluate efficacy, we used sodium iodate-treated ARPE-19 cells. The Trf-M-NCs exhibited significantly higher uptake by ARPE-19 cells than the unmodified M-NCs. Importantly, Trf-M-NC treatment alleviated cellular senescence by restoring the mitochondrial functions. Furthermore, Trf-M-NC treatment not only restored the production of α-ketoglutarate, an essential energy source for photoreceptor cells, but also reduced the secretion of IL-6, a key inflammatory cytokine. These findings suggest that improving mitochondrial quality in RPE cells is a novel and promising therapeutic approach for AMD.

Background: During an apnea, oxygen depletion occurs at all tissue levels, so apnea duration is influenced by the mammalian dive reflex, which includes a bradycardia resulting in reduced cardiac oxygen consumption. This study aimed to examine the relationships between heart rate (HR), peripheral estimation of O₂ (SpO₂), deltoid and respiratory muscle oxygenation (SmO₂), and apnea duration. Methods: The study included 10 breath-hold divers (BHD), 39 ± 10 years of age, with body height of 184.3 ± 3.5 cm, body mass of 84.0 ± 9.2 kg, and 16.2 ± 9.7 years of apnea experience. The BHD performed three preparatory apneas followed by three maximal apneas with 5 min of supine rest between each apnea. During all apneas (duration, 115–323 s; involuntary breathing movements (IBMs), 7–35), SmO₂ (measured via NIRS on intercostals (respiratory) and deltoid (locomotor) muscles), heart rate, and SpO₂ (measured via forehead sensor) were obtained. Results: The smallest disagreement in oxygen levels was between intercostal SmO₂ and SpO₂ during the easy-going phase (no IBMs), whereas deltoid desaturation values were more variable. During the struggle phase, Intercostal SmO₂, moderately, and Deltoid SmO₂, strongly, differed from SpO₂. Correlations between apnea duration and O₂ saturation showed that only Intercostal SmO₂ (r = −0.71; p = 0.03) was significantly related to apnea duration. There was also a significant correlation between HR and SpO₂ in the struggle phase (r = −0.58; p = 0.05). Conclusions: These findings suggest that during the struggle phase, SpO₂ and SmO₂ are not highly connected and that local and systemic oxygen levels in the blood are depleted at different rates. Furthermore, the HR response during the struggle phase affected only SpO₂, which indicates that lowering the heart rate may help prevent more rapid deoxygenation. Lastly, the intercostal trend of deoxygenation could be interpreted as respiratory muscle work, suggesting that the increased work of respiratory muscles may prolong apnea duration.

The purpose of this analysis is to report on the clinical efficacy of Continuous Diffusion of Oxygen (CDO) therapy in real-world clinical practice and compare those results to data published in controlled clinical studies. For the real-world clinical results, a Prospective Patients Database (PPD) of 764 patients treated using CDO therapy in a broad range of clinical practices across a wide range of wound types and wound locations was analyzed. The objectives included analyzing the clinical efficacy of CDO therapy across multiple wound types and anatomical locations, testing the data for robustness, and comparing the efficacy to results from controlled clinical studies for CDO and NPWT. The PPD data is also analyzed for efficacy among the sexes and by age for older patients in the Medicare population. The robustness of the PPD data is tested using various non- and semi-parametric statistical tools, including the Kaplan–Meier and Cox proportional hazard (PH) models, among others. The results show that CDO therapy is highly efficacious with an average healing success rate of 76.3% in real-world application, ranging from 71.2% to 84.1% for different wound types. The Medicare age population had an average age of 78 years old and similar healing rates to the overall population, with slightly better results for pressure ulcers in the older patient population. The PPD data proved to be extremely robust in every test method, demonstrating substantially equivalent efficacy in various wound types and locations, as well as between men and women. The PPD results for CDO compared favorably to clinical trial results for CDO and NPWT. Both clinical trial and PPD data for CDO exhibited better healing rates when compared to NPWT. Kaplan–Meier analysis shows that CDO use in clinical practice has 79.2% full closure in 112 days, as compared to NPWT, which has 43.2% full closure in the same timeframe for similar wound sizes and severity. These results demonstrate not only that CDO is highly efficacious in clinical practice, but that the efficacy is also similar across all wound types and locations in the body. CDO also compares very favorably to NPWT.