Rapidly improving ARDS differs clinically and biologically from persistent ARDS.

BACKGROUND: Rapidly improving acute respiratory distress syndrome (RIARDS) is an increasingly appreciated subgroup of ARDS in which hypoxemia improves within 24 h after initiation of mechanical ventilation. Detailed clinical and biological features of RIARDS have not been clearly defined, and it is unknown whether RIARDS is associated with the hypoinflammatory or hyperinflammatory phenotype of ARDS. The purpose of this study was to define the clinical and biological features of RIARDS and its association with inflammatory subphenotypes. METHODS: We analyzed data from 215 patients who met Berlin criteria for ARDS (endotracheally intubated) and were enrolled in a prospective observational cohort conducted at two sites, one tertiary care center and one urban safety net hospital. RIARDS was defined according to previous studies as improvement of hypoxemia defined as (i) PaO2:FiO2 > 300 or (ii) SpO2: FiO2 > 315 on the day following diagnosis of ARDS (day 2) or (iii) unassisted breathing by day 2 and for the next 48 h (defined as absence of endotracheal intubation on day 2 through day 4). Plasma biomarkers were measured on samples collected on the day of study enrollment, and ARDS phenotypes were allocated as previously described. RESULTS: RIARDS accounted for 21% of all ARDS participants. Patients with RIARDS had better clinical outcomes compared to those with persistent ARDS, with lower hospital mortality (13% vs. 57%; p value < 0.001) and more ICU-free days (median 24 vs. 0; p value < 0.001). Plasma levels of interleukin-6, interleukin-8, and plasminogen activator inhibitor-1 were significantly lower among patients with RIARDS. The hypoinflammatory phenotype of ARDS was more common among patients with RIARDS (78% vs. 51% in persistent ARDS; p value = 0.001). CONCLUSIONS: This study identifies a high prevalence of RIARDS in a multicenter observational cohort and confirms the more benign clinical course of these patients. We report the novel finding that RIARDS is characterized by lower concentrations of plasma biomarkers of inflammation compared to persistent ARDS, and that hypoinflammatory ARDS is more prevalent among patients with RIARDS. Identification and exclusion of RIARDS could potentially improve prognostic and predictive enrichment in clinical trials.

Establishment of a reference interval for total carbon dioxide using indirect methods in Chinese populations living in high-altitude areas: A retrospective real-world analysis.

BACKGROUND: Hypoxia leads to different concentrations of the bicarbonate buffer system in Tibetan people. Indirect methods were used to establish the reference interval (RI) for total carbon dioxide (tCO2) based on big data from the adult population of Tibet, a high-altitude area in Western China. METHODS: Anonymous tCO2 test data (n = 442,714) were collected from the People's Hospital of the Tibet Autonomous Region from January 2018, to December 2021. Multiple linear regression and variance component analyses were performed to assess the effects of sex, age, and race on tCO2 levels. Indirect methods, including Hoffmann, Bhattacharya, expectation maximization (EM), kosmic and refineR, were used to calculate the total RI and ethnicity-partitioned RI. RESULTS: A total of 230,821 real-world tCO2 test results were eligible. Sex, age, and race were significantly associated with the tCO2 levels. The total and ethnically-partitioned RIs estimated using the five indirect methods were comparable. The total RI of tCO2 was 14-24 mmol/L (calculated using Hoffmann and refineR) and 15-24 mmol/L (Bhattacharya, EM and kosmic). For Han nationality, the RIs were 14-25 mmol/L (calculated using Hoffmann and Bhattacharya), 16-23 mmol/L (EM), 15-24 mmol/L (kosmic), and 14.2-24.5 mmol/L (refineR). For the Tibetan population, the RIs were 14-24 mmol/L (calculated using Hoffmann and refineR), 15-24 mmol/L (Bhattacharya and kosmic), and 15-23 mmol/L (EM). The established RIs were significantly lower than those living at lower altitudes area (22-29 mmol/L) that was provided by the manufacturer. CONCLUSION: The tCO2 RI of the populations living on the Tibetan Plateau was significantly lower than those at the lower altitudes. The RIs established using indirect methods are suitable for clinical applications in Tibet.

[Activity of the telomerase complex before and after CPAP therapy in patients with obstructive sleep apnea syndrome]. / Aktivnost' telomeraznogo kompleksa na fone SIPAP-terapii u patsientov s sindromom obstruktivnogo apnoe sna.

OBJECTIVE: To evaluate changes in the activity of the telomerase complex in patients with obstructive sleep apnea (OSA) before and after continuous positive airway pressure (CPAP) therapy. MATERIAL AND METHODS: In accordance with the objectives of the stages of the study of telomers-telomerase relationships, we maintained the unified design of the study described earlier. The main group 1 (MG1), n=35, consisted of men, aged 53.4 [45.5-60.1] years with characteristic complaints indicating of OSA. The main group 2 (MG2) included the same patients before and after 6 months of CPAP therapy. Blood sampling was performed after the first diagnostic polysomnography (PSG) and after 6 months of CPAP in the morning after the second PSG. The control group (CG) consisted of 26 men, comparable in age and the presence of chronic diseases. Questionnaire, PSG and blood sampling were conducted in CG as well. All participants signed an informed consent. RESULTS: As a result of the STOP-BANG questionnaire conducted before PSG, all patients in the MG1 had scores from 5 to 8. The scores on the Epworth scale were more than 5 points. In the MG2 apnea-hypopnea index decreased from 20.1 to 6.4 ev/hour, the desaturation index decreased from 15.6 to 7.1 ev/hour after 6 months of CPAP. Statistically significant differences in changes in the activity of the telomerase complex were revealed, which after treatment significantly exceed the values of these indicators before treatment. So, telomerase reverse transcriptase value was 0.04 (0.009; 0.06) in the MG1, after treatment it was 0.07 (0.06; 0.09) in the MG2 and 0.134 (0.009; 0.18) in the CG. Telomerase RNA subunit TER1 values were 0.06 (0.03; 0.09), 0.07 (0.05; 0.09) and 0.136 (0.04; 0.17), respectively. However, despite the activation of the telomerase complex during CPAP therapy in patients with OSA, in the CG its activity is significantly higher in comparison with the MG1 and MG2. CONCLUSION: In OSA accompanied by intermittent hypoxia, a decrease in the activity of the telomerase complex was shown. Elimination of nocturnal hypoxia and improvement of breathing during sleep is accompanied by an increase in the activity of the components of the telomerase complex.

The Effect of Hypoxia Inducible Factor -1 Alpha and Vascular Endothelial Growth Factor Level in Type 2 Diabetes Microvascular Complications and Development.

Background: Angiogenesis in diabetic patients is often caused by hyperglycemia induced by hypoxia. Objective: The aim of this study was to analyze the serum level of Hypoxia Inducible Factor -1α (HIF-1α) and Vascular Endothelial Growth Factor (VEGF) between March until Desember 2020. Methods: This is a cross-sectional analytic methods, 135 patients with Type 2 Diabetes 48 samples with Microvascular complication and 87 samples with non-microvascular complication were recruited from the various primary health care centers in Medan city and surrounding areas in North Sumatera. VEGF levels and HIF-1α tested were done with ELISA methods in the laboratory of Medical Faculty, Universitas Sumatera Utara. Statistical analysis was performed using the IBM SPSS Statistics version 24. The significance level was set up to 0.005. Results: The median HIF-1 levels in patients with microvascular complications were lower than those without microvascular complications, with a range of HIF-1α values in non-complicated samples (0.02-13.96) ng/ml and a range of HIF-1α values in vascular complications (0.52- 8.87) mg/dL. There was a significant difference in HIF-1α levels in patients with Type-2 DM with complications compared to those without complications (p<0.05). Median VEGF levels were higher in complicated Type-2 DM. There was no difference in VEGF levels in patients with Type-2 DM with complications compared to those without complications (p > 0.005). Conclusion: HIF-1α and VEGF levels showed the development in vascularity. With the higher level of HIF-1α, an increase in VEGF levels were found, indicating the angiogenesis is occurring. Although complications have not yet occurred, it is predicted that high VEGF values will cause vascular complications in the future.

Effect of Normobaric Hypoxia on Alterations in Redox Homeostasis, Nitrosative Stress, Inflammation, and Lysosomal Function following Acute Physical Exercise.

Hypoxia is a recognized inducer of oxidative stress during prolonged physical activity. Nevertheless, previous studies have not systematically examined the effects of normoxia and hypoxia during acute physical exercise. The study is aimed at evaluating the relationship between enzymatic and nonenzymatic antioxidant barrier, total antioxidant/oxidant status, oxidative and nitrosative damage, inflammation, and lysosomal function in different acute exercise protocols under normoxia and hypoxia. Fifteen competitive athletes were recruited for the study. They were subjected to two types of acute cycling exercise with different intensities and durations: graded exercise until exhaustion (GE) and simulated 30 km individual time trial (TT). Both exercise protocols were performed under normoxic and hypoxic (FiO2 = 16.5%) conditions. The number of subjects was determined based on our previous experiment, assuming the test power = 0.8 and α = 0.05. We demonstrated enhanced enzymatic antioxidant systems during hypoxic exercise (GE: ↑ catalase (CAT), ↑ superoxide dismutase; TT: ↑ CAT) with a concomitant decrease in plasma reduced glutathione. In athletes exercising in hypoxia, redox status was shifted in favor of oxidation reactions (GE: ↑ total oxidant status, ↓ redox ratio), leading to increased oxidation/nitration of proteins (GE: ↑ advanced oxidation protein products (AOPP), ↑ ischemia-modified albumin, ↑ 3-nitrotyrosine, ↑ S-nitrosothiols; TT: ↑ AOPP) and lipids (GE: ↑ malondialdehyde). Concentrations of nitric oxide and its metabolites (peroxynitrite) were significantly higher in the plasma of hypoxic exercisers with an associated increase in inflammatory mediators (GE: ↑ myeloperoxidase, ↑ tumor necrosis factor-alpha) and lysosomal exoglycosidase activity (GE: ↑ N-acetyl-ß-hexosaminidase, ↑ ß-glucuronidase). Our study indicates that even a single intensive exercise session disrupts the antioxidant barrier and leads to increased oxidative and nitrosative damage at the systemic level. High-intensity exercise until exhaustion (GE) alters redox homeostasis more than the less intense exercise (TT, near the anaerobic threshold) of longer duration (20.2 ± 1.9 min vs. 61.1 ± 5.4 min-normoxia; 18.0 ± 1.9 min vs. 63.7 ± 3.0 min-hypoxia), while hypoxia significantly exacerbates oxidative stress, inflammation, and lysosomal dysfunction in athletic subjects.

Increased Circulating Endothelin 1 Is Associated With Postoperative Hypoxemia in Infants With Single-Ventricle Heart Disease Undergoing Superior Cavopulmonary Anastomosis.

Background Inadequate pulmonary vascular growth results in morbidity for many children with single-ventricle heart disease (SVHD). Endothelin 1 (ET1) is a potent vasoconstrictor and stimulator of pulmonary artery smooth muscle proliferation. Circulating ET1 levels and their association with outcomes have not been studied during early SVHD palliation. We aimed to define circulating levels of ET1 in patients with SVHD undergoing stage 2 palliation and evaluate their relationship to postoperative hypoxemia. We hypothesized that patients with SVHD with higher ET1 concentration would have a greater post-stage 2 hypoxemia. Methods and Results Prospective cohort study of 55 subjects with SVHD undergoing stage 2 palliation and 50 controls. Samples for ET1 analysis were collected at preoperation (systemic and pulmonary vein) and 2, 24, and 48 hours postoperation for cases and a single time point for controls. The primary outcome was percentage of first 48 postoperative hours with clinically significant hypoxemia (saturation, <70%). ET1 concentration was lower in preoperative cases than controls (2.2 versus 2.7 pg/mL; P=0.0015) and in the pulmonary vein than systemic vein (1.7 versus 2.2 pg/mL; P<0.001). ET1 level increased by 2 hours postoperation and trended back to baseline by 48 hours. Higher preoperative pulmonary vein ET1 and 2 hours postoperative ET1 were associated with larger hypoxemia burden (10.6% versus 2.7% [P=0.0081]; and 7.6% versus 3.2% [P=0.01], respectively). Multivariable testing demonstrated ET1 concentration and cardiopulmonary bypass time were associated with hypoxemia, whereas catheterization measurements and clinical variables were not. Conclusions Infants with SVHD with higher perioperative ET1 concentration experience more post-stage 2 hypoxemia. ET1 activity may be a modifiable risk factor of pulmonary vascular inadequacy for stage 2 palliation.

Cavefish cope with environmental hypoxia by developing more erythrocytes and overexpression of hypoxia-inducible genes.

Dark caves lacking primary productivity can expose subterranean animals to hypoxia. We used the surface-dwelling (surface fish) and cave-dwelling (cavefish) morphs of Astyanax mexicanus as a model for understanding the mechanisms of hypoxia tolerance in the cave environment. Primitive hematopoiesis, which is restricted to the posterior lateral mesoderm in other teleosts, also occurs in the anterior lateral mesoderm in Astyanax, potentially pre-adapting surface fish for hypoxic cave colonization. Cavefish have enlarged both hematopoietic domains and develop more erythrocytes than surface fish, which are required for normal development in both morphs. Laboratory-induced hypoxia suppresses growth in surface fish but not in cavefish. Both morphs respond to hypoxia by overexpressing hypoxia-inducible factor 1 (hif1) pathway genes, and some hif1 genes are constitutively upregulated in normoxic cavefish to similar levels as in hypoxic surface fish. We conclude that cavefish cope with hypoxia by increasing erythrocyte development and constitutive hif1 gene overexpression.

Complex networks analysis reinforces centrality hematological role on aerobic-anaerobic performances of the Brazilian Paralympic endurance team after altitude training.

This study investigated the 30-days altitude training (2500 m, LHTH-live and training high) on hematological responses and aerobic-anaerobic performances parameters of high-level Paralympic athletes. Aerobic capacity was assessed by 3000 m run, and anaerobic variables (velocity, force and mechanical power) by a maximal 30-s semi-tethered running test (AO30). These assessments were carried out at low altitude before (PRE) and after LHTH (5-6 and 15-16 days, POST1 and POST2, respectively). During LHTH, hematological analyzes were performed on days 1, 12, 20 and 30. After LHTH, aerobic performance decreased 1.7% in POST1, but showed an amazing increase in POST2 (15.4 s reduction in the 3000 m test, 2.8%). Regarding anaerobic parameters, athletes showed a reduction in velocity, force and power in POST1, but velocity and power returned to their initial conditions in POST2. In addition, all participants had higher hemoglobin (Hb) values at the end of LHTH (30 days), but at POST2 these results were close to those of PRE. The centrality metrics obtained by complex networks (pondered degree, pagerank and betweenness) in the PRE and POST2 scenarios highlighted hemoglobin, hematocrit (Hct) and minimum force, velocity and power, suggesting these variables on the way to increasing endurance performance. The Jaccard's distance metrics showed dissimilarity between the PRE and POST2 graphs, and Hb and Hct as more prominent nodes for all centrality metrics. These results indicate that adaptive process from LHTH was highlighted by the complex networks, which can help understanding the better aerobic performance at low altitude after 16 days in Paralympic athletes.

Effects of an acute exercise bout in hypoxia on extracellular vesicle release in healthy and prediabetic subjects.

The purpose of this study is to investigate exosome-like vesicle (ELV) plasma concentrations and markers of multivesicular body (MVB) biogenesis in skeletal muscle in response to acute exercise. Seventeen healthy [body mass index (BMI): 23.5 ± 0.5 kg·m-2] and 15 prediabetic (BMI: 27.3 ± 1.2 kg·m-2) men were randomly assigned to two groups performing an acute cycling bout in normoxia or hypoxia ([Formula: see text] 14.0%). Venous blood samples were taken before (T0), during (T30), and after (T60) exercise, and biopsies from m. vastus lateralis were collected before and after exercise. Plasma ELVs were isolated by size exclusion chromatography, counted by nanoparticle tracking analysis (NTA), and characterized according to international standards, followed by expression analyses of canonical ELV markers in skeletal muscle. In the healthy normoxic group, the total number of particles in the plasma increased during exercise from T0 to T30 (+313%) followed by a decrease from T30 to T60 (-53%). In the same group, an increase in TSG101, CD81, and HSP60 protein expression was measured after exercise in plasma ELVs; however, in the prediabetic group, the total number of particles in the plasma was not affected by exercise. The mRNA content of TSG101, ALIX, and CD9 was upregulated in skeletal muscle after exercise in normoxia, whereas CD9 and CD81 were downregulated in hypoxia. ELV plasma abundance increased in response to acute aerobic exercise in healthy subjects in normoxia, but not in prediabetic subjects, nor in hypoxia. Skeletal muscle analyses suggested that this tissue did not likely play a major role of the exercise-induced increase in circulating ELVs.

Establishing prognostic significance of hypoxia predictors in patients with acute cerebral pathology.

OBJECTIVES: This research aims to study the prognostic role of serum S100 as a predictor of mortality in vascular and traumatic brain injuries. METHODS: This prospective cohort study involved 219 patients. In the blood serum, neuron-specific markers (S100, NSE) and glucose, acid-base state and gas composition of arterial blood were obtained at admission, on the 3rd, 5th and 7th days of patients' stay in the intensive care unit. RESULTS: The most significant risk factor for an unfavorable outcome is the marker S100 with a cut-off point of 0.2 mcg/l. The analysis results indicate a statistically significant direct relationship between S100 > 0.2 mcg/l and NSE ≥ 18.9 ng/ml compared to other variables, while the chance ratio (OR) is 11.9 (95%CI:3.2927-1.6693;). With blood sugar increase above 7.4 mmol/l, the OR is 3.82 (95% CI: 2.1289-0.5539;); with a Glasgow scale below 13 points, the OR is 3.69 (95% CI: 2.1316-0.4819;); with an increase in pCO2 < 43.5 mm Hg, the OR was 3.15 (95% CI: 1.8916- 0.4062;). The obtained model certainty measure according to pseudo R2 Nagelkerke criterion is 263.5, showing the excellent quality of the mathematical model's predictive ability. The developed prognostic model, including the dependent variable S100 and independent variables as predictors of a poor outcome of NSE, pCO2, GCS and Hb, reached a cut-off point of 84.51%, AUC - 0.88 with high levels of sensitivity and specificity: 91.89% and 64.14%, respectively. NOVELTY: This model can be used to predict the outcome in patients with acute cerebral pathology.

Association between Interleukin-6 and vitamin D serum levels in patients with obstructive sleep apnea syndrome and impact of long-term continuous positive airway pressure therapy on biomarker levels.

OBJECTIVE: Hypoxia induces interleukin-6 (IL-6) production in obstructive sleep apnea syndrome (OSAS). Low serum 25 hydroxyvitamin D (25(OH)D) levels have been linked to OSAS susceptibility. Serum 25(OH)D levels have been negatively correlated with serum IL-6 levels in patients with chronic inflammation. No data exist to assess whether there is a correlation between 25(OH)D and IL-6 serum levels in OSAS, while the impact of continuous positive airway pressure (CPAP) therapy on IL-6 or 25(OH)D levels needs further investigation. We aimed to compare the serum 25(OH)D and IL-6 levels between OSAS patients and controls, examine a possible correlation between 25(OH)D and IL-6 levels and the changes of their concentrations after twelve months of CPAP therapy in OSAS patients. METHODS: 15 newly-diagnosed OSAS patients and 15 non-apneic controls were recruited. Serum IL-6 and 25(OH)D levels were measured in the study population at baseline and twelve months after CPAP initiation in OSAS patients. RESULTS: IL-6 levels were elevated in OSAS patients than controls and were positively and negatively correlated with body mass index (BMI) and minimum oxyhemoglobin saturation (minSpO2), respectively. Diabetes mellitus, BMI and minSpO2 independently predicted IL-6 levels. No difference was found in 25(OH)D levels between groups. No correlation between IL-6 and 25(OH)D levels was detected. Effective CPAP therapy did not impact IL-6 or 25(OH)D levels after one year in OSAS patients. CONCLUSIONS: No correlation between IL-6 and 25(OH)D levels was found. IL-6 levels were significantly elevated in OSAS patients than the controls and positively correlated with BMI, diabetes mellitus, and nocturnal hypoxemia.

SWIFT: A deep learning approach to prediction of hypoxemic events in critically-Ill patients using SpO2 waveform prediction.

Hypoxemia is a significant driver of mortality and poor clinical outcomes in conditions such as brain injury and cardiac arrest in critically ill patients, including COVID-19 patients. Given the host of negative clinical outcomes attributed to hypoxemia, identifying patients likely to experience hypoxemia would offer valuable opportunities for early and thus more effective intervention. We present SWIFT (SpO2 Waveform ICU Forecasting Technique), a deep learning model that predicts blood oxygen saturation (SpO2) waveforms 5 and 30 minutes in the future using only prior SpO2 values as inputs. When tested on novel data, SWIFT predicts more than 80% and 60% of hypoxemic events in critically ill and COVID-19 patients, respectively. SWIFT also predicts SpO2 waveforms with average MSE below .0007. SWIFT predicts both occurrence and magnitude of potential hypoxemic events 30 minutes in the future, allowing it to be used to inform clinical interventions, patient triaging, and optimal resource allocation. SWIFT may be used in clinical decision support systems to inform the management of critically ill patients during the COVID-19 pandemic and beyond.

Exposure to Normobaric Hypoxia Combined with a Mixed Diet Contributes to Improvement in Lipid Profile in Trained Cyclists.

This study aimed to analyze the effects of live high-train low method (LH-TL) and intermittent hypoxic training (IHT) with a controlled mixed diet on lipid profile in cyclists. Thirty trained male cyclists at a national level with at least six years of training experience participated in the study. The LH-TL group was exposed to hypoxia (FiO2 = 16.5%) for 11-12 h a day and trained under normoxia for 3 weeks. In the IHT group, participants followed the IHT routine three times a week under hypoxia (FiO2 = 16.5%) at lactate threshold intensity. The control group (N) lived and trained under normoxia. The results showed that the 3-week LH-TL method significantly improved all lipid profile variables. The LH-TL group showed a significant increase in HDL-C by 9.0% and a decrease in total cholesterol (TC) by 9.2%, LDL-C by 18.2%, and triglycerides (TG) by 27.6%. There were no significant changes in lipid profiles in the IHT and N groups. ∆TG and ∆TC were significantly higher in the LH-TL group compared to the N group. In conclusion, hypoxic conditions combined with a mixed diet can induce beneficial changes in lipid profile even in highly trained athletes. The effectiveness of the hypoxic stimulus is closely related to the hypoxic training method.

Comparison of the Adaptive Capacity in Old and Young Wistar Rats to Stress Exposure and Acute Hypoxic Hypoxia.

We compared behavioral and psychoemotional manifestations of young and old male Wistar rats in elevated plus-maze, the levels of corticosterone and testosterone, as well as the resistance to acute hypoxic hypoxia before and after stress exposure (10-min swimming sessions over 10 days). The behavioral characteristics, responses of the main stress hormone corticosterone, and resistance to acute hypoxic hypoxia were identical in both age groups before and after stress. A distinguishing feature was pronounced flattening of the psychoemotional manifestations in old animals. The main adaptive differences between young and old rats were revealed in the response of circulating testosterone to stress.

Serum Serotonin as a Biomarker of the Efficacy of PAP-Therapy in Sleep Apnea Syndrome.

Serum serotonin levels were determined by HPLC in 30 patients with diagnosed obstructive sleep apnea syndrome before and after 3-month course of PAP-therapy and in 14 subjects without obstructive sleep apnea symptoms. It was found that elimination of hypoxic conditions was associated with an increase in serotonin level. The results demonstrate the effectiveness of PAP-therapy during sleep and allow assessing the role of serotonin as a potential biomarker of intermittent hypoxia during sleep.

Plasma endostatin correlates with hypoxia and mortality in COVID-19-associated acute respiratory failure.

Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease. Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection. Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan-Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival. Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p < 0.001), arterial oxygen tension (r = -0.2, p = 0.01), lactate (r = 0.2, p = 0.04), C-reactive protein (r = 0.2, p = 0.04), ferritin (r = 0.2, p = 0.09), D-dimer (r = 0.2, p = 0.08) and IL-6 (r = 0.4, p < 0.001). Nonsurvivors at 30 days had higher plasma endostatin levels than survivors (72 ± 26 vs 56 ± 16 ng/ml, p = 0.01). Receiving operating characteristic curve (area under the curve 0.7) showed that plasma endostatin >46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin <46.2 ng/ml. Conclusion: Our results suggest that plasma endostatin is an early biomarker for disease severity in COVID-19.

Sex differences in the effect of acute intermittent hypoxia on respiratory modulation of sympathetic activity.

Sex-related differences in respiratory modulation of sympathetic activity have been observed in rodent models of sleep apnea [intermittent hypoxia (IH)]. In light of sex disparities in the respiratory response to acute IH in humans as well as changes in respiratory modulation of muscle sympathetic nerve activity (MSNA) in clinical sleep apnea, we examined sex-related differences in respiratory modulation of MSNA following acute IH. We hypothesized that respiratory modulation of MSNA would be altered in both male and female participants after IH; however, the respiratory patterning of MSNA following IH would be sex specific. Heart rate, MSNA, and respiration were evaluated in healthy male (n = 21, 30 ± 5 yr) and female (n = 10, 28 ± 5 yr) participants during normoxic rest before and after 30 min of IH. Respiratory modulation of MSNA was assessed by fitting polynomials to cross-correlation histograms constructed between sympathetic spikes and respiration. MSNA was elevated after IH in male (20 ± 6 to 24 ± 8 bursts/min) and female (19 ± 8 to 22 ± 10 bursts/min) participants (P < 0.01). Both male and female participants exhibited respiratory modulation of MSNA (P < 0.01); however, the pattern differed by sex. After IH, modulation of MSNA within the breath was reduced in male participants (P = 0.03) but increased in female participants (P = 0.02). Both male and female adults exhibit changes in respiratory patterning of MSNA after acute IH; however, this pattern differs by sex. These data support sex disparities in respiratory modulation of MSNA and may have implications for conditions such as sleep apnea.

Adrenergically induced translocation of red blood cell ß-adrenergic sodium-proton exchangers has ecological relevance for hypoxic and hypercapnic white seabass.

White seabass (Atractoscion nobilis) increasingly experience periods of low oxygen (O2; hypoxia) and high carbon dioxide (CO2, hypercapnia) due to climate change and eutrophication of the coastal waters of California. Hemoglobin (Hb) is the principal O2 carrier in the blood and in many teleost fishes Hb-O2 binding is compromised at low pH; however, the red blood cells (RBC) of some species regulate intracellular pH with adrenergically stimulated sodium-proton-exchangers (ß-NHEs). We hypothesized that RBC ß-NHEs in white seabass are an important mechanism that can protect the blood O2-carrying capacity during hypoxia and hypercapnia. We determined the O2-binding characteristics of white seabass blood, the cellular and subcellular response of RBCs to adrenergic stimulation, and quantified the protective effect of ß-NHE activity on Hb-O2 saturation. White seabass had typical teleost Hb characteristics, with a moderate O2 affinity (Po2 at half-saturation; P50 2.9 kPa) that was highly pH-sensitive (Bohr coefficient -0.92; Root effect 52%). Novel findings from super-resolution microscopy revealed ß-NHE protein in vesicle-like structures and its translocation into the membrane after adrenergic stimulation. Microscopy data were corroborated by molecular and phylogenetic results and a functional characterization of ß-NHE activity. The activation of RBC ß-NHEs increased Hb-O2 saturation by ∼8% in normoxic hypercapnia and by up to ∼20% in hypoxic normocapnia. Our results provide novel insight into the cellular mechanism of adrenergic RBC stimulation within an ecologically relevant context. ß-NHE activity in white seabass has great potential to protect arterial O2 transport during hypoxia and hypercapnia but is less effective during combinations of these stressors.

Heterogeneity of human adaptations to bed rest and hypoxia: a retrospective analysis within the skeletal muscle oxidative function.

This retrospective study was designed to analyze the interindividual variability in the responses of different variables characterizing the skeletal muscle oxidative function to normoxic (N-BR) and hypoxic (H-BR) bed rests and to a hypoxic ambulatory confinement (H-AMB) of 10 and 21 days. We also assessed whether and how the addition of hypoxia to bed rest might influence the heterogeneity of the responses. In vivo measurements of O2 uptake and muscle fractional O2 extraction were carried out during an incremental one-leg knee-extension exercise. Mitochondrial respiration was assessed in permeabilized muscle fibers. A total of 17 subjects were included in this analysis. This analysis revealed a similar variability among subjects in the alterations induced by N-BR and H-BR both in peak O2 uptake (SD: 4.1% and 3.3% after 10 days; 4.5% and 8.1% after 21 days, respectively) and peak muscle fractional O2 extraction (SD: 5.9% and 7.3% after 10 days; 6.5% and 7.3% after 21 days), independently from the duration of the exposure. The individual changes measured in these variables were significantly related (r = 0.66, P = 0.004 after N-BR; r = 0.61, P = 0.009 after H-BR). Mitochondrial respiration showed a large variability of response after both N-BR (SD: 25.0% and 15.7% after 10 and 21 days) and H-BR (SD: 13.0% and 19.8% after 10 and 21 days); no correlation was found between N-BR and H-BR changes. When added to bed rest, hypoxia altered the individual adaptations within the mitochondria but not those intrinsic to the muscle oxidative function in vivo, both after the short- and medium-term exposures.