Hemolysis contributes to anemia during long-duration space flight

Anemia in astronauts has been noted since the first space missions, but the mechanisms contributing to anemia in space flight have remained unclear. Here, we show that space flight is associated with persistently increased levels of products of hemoglobin degradation, carbon monoxide in alveolar air and iron in serum, in 14 astronauts throughout their 6-month missions onboard the International Space Station. One year after landing, erythrocytic effects persisted, including increased levels of hemolysis, reticulocytosis and hemoglobin. These findings suggest that the destruction of red blood cells, termed hemolysis, is a primary effect of microgravity in space flight and support the hypothesis that the anemia associated with space flight is a hemolytic condition that should be considered in the screening and monitoring of both astronauts and space tourists.

Redundancy of Humidification at Upper Respiratory Tract, a Plausible Cause of Corona Pandemic - A Hypothesis Based on Thermodynamic Analysis-

The respiratory tract humidification transforms inspired air from whatever temperature and humidity it is, to alveolar air at 37°C at 100 % RH (relative humidity). This is a key thermodynamic and heat and mass transfer process and is as critical as the actual respiration. The normal body temperature of humans is also around 37°C. A simple mathematical analysis is done by replacing figures of moisture content for 100% saturation level at 37°C in the alveolar partial pressure table, by those at 39°C and 30°C and then recalculating partial pressure figures of oxygen and carbon dioxide. The result is startling and deciphers the significance of 37°C. As of today, there is probably no place on the earth where one can have ambient air at 37°C concurrently with 100% RH. Such is the uniqueness of alveolar air parameters. Apparently this uniqueness is threatened by climate change. We are ourselves infringing on this ‘Natural Selection’. At certain places we have pushed ourselves, closer to 37°C at 100% RH, as an outcome of massive urbanization and industrialization. As a result the key critical process of humidification and conditioning of inspired air, essentially at the upper respiratory tract URT, has gone redundant. A process becomes redundant, when its primary purpose is achieved beforehand. The redundancy has weakened respiratory immune defense systems as well and allowed all viruses like Sars-Cov-2, an unchallenged access to reach alveoli and enter through ACE2 receptors. Free access meteorological data of places like Wuhan indicates that the average humidity at these places were higher than 75% and concurrently temperatures were above 30°C during later part of 2019.Wuhan acted as starting point to the pandemic, where some people had a weak or disabled immune defense due to the redundancy in upper respiratory tract (URT). Once the infections crossed a threshold, it escalated into a pandemic.At ‘Climate Change’ meets, increase in ambient temperature concurrently with rising humidity due to massive urbanization and industrialization, and increased use of water for various industrial processes, needs to be on top of the agenda. Enthalpy, a thermodynamic property of atmospheric air, becomes a good indicator of the concurrent effect of high temperature and high humidity. Enthalpy of air crossing 70 KJ/Kg level may be set as warning sign for impending viral attack.Key Words: Relative Humidity, Alveolar Air, Natural Selection, Redundancy, Wuhan, Climate Change, Enthalpy

Alveolar air leak and paraseptal emphysema in severe COVID-19 disease

Background Corona virus 2019 (COVID-19) pandemic spread in the world as a great medical crisis. Its pathophysiology, manifestations, complications, and management are not completely defined, yet. In this study frequency of alveolar air leak in critically ill COVID-19 subjects is explored. Methods A total of 820 critically ill COVID-19 subjects who admitted with respiratory insufficiency to ICUs of Sina University Hospital from March 2020 to June 2021 were included. All their chest x ray (CXR) and Computed tomography (CT) of chest were reviewed. All alveolar air leak episodes (pneumothorax, pneumomediastinum, pneumopericardium, subcutaneous emphysema) suspected films reviewed by attending intensivist and radiologist. Results Of the 820 ill COVID-19 subjects in ICUs, 492(60%) were male, and 328 (40%) were female. The Mean age of 820 subjects was 60.84 + 16.82. 584 (71.22%) of subjects were non-intubated, and 236 (28.78%) were intubated. Alveolar air leak occurred in 98 (11.95%) of subjects. Alveolar air leak episodes include pneumothorax in 26 (3.17%), subcutaneous emphysema in 72 (8.78%), pneumomediastinum in 9 (1.10%), and pneumopericardium in 1 (0.12%) of subjects. The mean age in non-intubated subjects was 59.65 + 16.84, and for intubated subjects was 63 + 16.42. There was a significant difference in age between the groups who get intubated, versus not intubated P 0.001. Of the 584 non-intubated subjects, 31 (5.31%) had subcutaneous emphysema, of the 236 intubated subjects, 41 (17.37%) had subcutaneous emphysema. Difference between groups was statistically significant, P <0.001. When we compared intubated and non-intubated patients in case of total numbers of alveolar air leak episodes, the difference was statistically significant P <0.001. Conclusion According to this study, intubation was implemented more in older patients. Also, invasive ventilation was significantly associated with subcutaneous emphysema and total number of alveolar air leak episodes. In every patient with exaggeration of hypoxia, dyspnea or chest pain, pneumothorax should be kept in mind as a differential diagnosis. Keywords: COVID-19; Respiratory failure; Alveolar air leak; Paraseptal emphysema

Competitive and/or cooperative interactions of graphene-family materials and benzo[a]pyrene with pulmonary surfactant: a computational and experimental study

Background Airborne nanoparticles can be inhaled and deposit in human alveoli, where pulmonary surfactant (PS) molecules lining at the alveolar air–water interface act as the first barrier against inhaled nanoparticles entering the body. Although considerable efforts have been devoted to elucidate the mechanisms underlying nanoparticle-PS interactions, our understanding on this important issue is limited due to the high complexity of the atmosphere, in which nanoparticles are believed to experience transformations that remarkably change the nanoparticles’ surface properties and states. By contrast with bare nanoparticles that have been extensively studied, relatively little is known about the interactions between PS and inhaled nanoparticles which already adsorb contaminants. In this combined experimental and computational effort, we investigate the joint interactions between PS and graphene-family materials (GFMs) with coexisting benzo[a]pyrene (BaP). Results Depending on the BaP concentration, molecular agglomeration, and graphene oxidation, different nanocomposite structures are formed via BaPs adsorption on GFMs. Upon deposition of GFMs carrying BaPs at the pulmonary surfactant (PS) layer, competition and cooperation of interactions between different components determines the interfacial processes including BaP solubilization, GFM translocation and PS perturbation. Importantly, BaPs adsorbed on GFMs are solubilized to increase BaP’s bioavailability. By contrast with graphene adhering on the PS layer to release part of adsorbed BaPs, more BaPs are released from graphene oxide, which induces a hydrophilic pore in the PS layer and shows adverse effect on the PS biophysical function. Translocation of graphene across the PS layer is facilitated by BaP adsorption through segregating it from contact with PS, while translocation of graphene oxide is suppressed by BaP adsorption due to the increase of surface hydrophobicity. Graphene extracts PS molecules from the layer, and the resultant PS depletion declines with graphene oxidation and BaP adsorption. Conclusion GFMs showed high adsorption capacity towards BaPs to form nanocomposites. Upon deposition of GFMs carrying BaPs at the alveolar air–water interface covered by a thin PS layer, the interactions of GFM-PS, GFM-BaP and BaP-PS determined the interfacial processes of BaP solubilization, GFM translocation and PS perturbation.

Discriminant Profiles of Volatile Compounds in the Alveolar Air of Patients with Squamous Cell Lung Cancer, Lung Adenocarcinoma or Colon Cancer

The objective of the present work was to analyze volatile compounds in alveolar air in patients with squamous cell lung cancer, lung adenocarcinoma or colon cancer, to prepare algorithms able to discriminate such specific pathological conditions. The concentration of 95 volatile compounds was measured in the alveolar air of 45 control subjects, 36 patients with lung adenocarcinoma, 25 patients with squamous cell lung cancer and 52 patients with colon cancer. Volatile compounds were measured with ion molecule reaction mass spectrometry (IMR-MS). An iterated least absolute shrinkage and selection operator multivariate logistic regression model was used to generate specific algorithms and discriminate control subjects from patients with different kinds of cancer. The final predictive models reached the following performance: by using 11 compounds, patients with lung adenocarcinoma were identified with a sensitivity of 86% and specificity of 84%; nine compounds allowed us to identify patients with lung squamous cell carcinoma with a sensitivity of 88% and specificity of 84%; patients with colon adenocarcinoma could be identified with a sensitivity of 96% and a specificity of 73% using a model comprising 13 volatile compounds. The different alveolar profiles of volatile compounds, obtained from patients with three different kinds of cancer, suggest dissimilar biological–biochemistry conditions; each kind of cancer has probably got a specific alveolar profile.

Lung developmental arrest caused by PDGF-A deletion: consequences for the adult mouse lung

PDGF-A is a key contributor to lung development in mice. Its expression is needed for secondary septation of the alveoli and deletion of the gene leads to abnormally enlarged alveolar air spaces in mice. In humans, the same phenotype is the hallmark of bronchopulmonary dysplasia (BPD), a disease that affects premature babies and may have long lasting consequences in adulthood. So far, the knowledge regarding adult effects of developmental arrest in the lung is limited. This is attributable to few follow-up studies of BPD survivors and lack of good experimental models that could help predict the outcomes of this early age disease for the adult individual. In this study, we used the constitutive lung-specific Pdgfa deletion mouse model to analyze the consequences of developmental lung defects in adult mice. We assessed lung morphology, physiology, cellular content, ECM composition and proteomics data in mature mice, that perinatally exhibited lungs with a BPD-like morphology. Histological and physiological analyses both revealed that enlarged alveolar air spaces remained until adulthood, resulting in higher lung compliance and higher respiratory volume in knockout mice. Still, no or only small differences were seen in cellular, ECM and protein content when comparing knockout and control mice. Taken together, our results indicate that Pdgfa deletion-induced lung developmental arrest has consequences for the adult lung at the morphological and functional level. In addition, these mice can reach adulthood with a BPD-like phenotype, which makes them a robust model to further investigate the pathophysiological progression of the disease and test putative regenerative therapies.

GAS COMPOSITION OF ALVEOLAR AIR AND TOLERABILITY OF PERSONAL RESPIRATORY PROTECTION EQUIPMENT

Introduction. When using personal protective equipment for respiratory organs of an insulating type in case of depletion of a regenerative cartridge, hypoxic-hypercapnic changes in the gas composition of the body occur, which have a negative effect on the tolerance of personal protective equipment for respiratory organs. The combination of additional respiratory resistance with hypoxia and hypercapnia further worsens the tolerance of respiratory protective equipment. The purpose of this study was to study the tolerance of personal respiratory protection when changing the gas composition of the alveolar air. Material and methods. The study was conducted on healthy subjects of both sexes (78 people), aged 20 to 36 years. To simulate the conditions for the use of personal respiratory protective equipment, inspiratory resistive respiratory loads of 20% of the maximum intraoral pressure were used during the Mueller test. The tolerance of respiratory protective equipment was evaluated using the Borg visual analog scale of dyspnea, which reflected the level of subjective discomfort occurring due to additional respiratory resistance is turned on. The methodology for changing the gas composition of the alveolar air in the subjects consisted of using a system that allowed adding oxygen from the line to the closed spirograph circuit and turning the carbon dioxide adsorber on and off. Results. The tolerance of personal respiratory protection is associated with the nature of the gas composition of the alveolar air. A minimum of subjective discomfort was observed in the presence of hyperoxic-hypocapnic composition of the pulmonary air; on the contrary, an increase in subjective discomfort on the Borg scale was observed with a reduced oxygen content and an increased concentration of carbon dioxide. The use of personal respiratory protective equipment against the background of hypoxia-hypercapnia negatively changes the functional state of the body: there was observed an increase in physiological expenditures by leading effectors. Normalization of the gas composition of the body under the use of personal respiratory protection did not lead to complete optimization of the functional state of the subjects. Conclusion. Hypoxia and hypercapnia arising from the depletion of regenerative cartridges of the respiratory protective equipment of an insulating type leads to a significant deterioration in the tolerance to additional respiratory resistance. The alleged mechanism of this phenomenon should be considered as an increase in fatigue of the respiratory muscles.