Altitude Acclimatization Research Articles

In Vitro and In Silico Studies for the Identification of Potent Metabolites of Some High-Altitude Medicinal Plants from Nepal Inhibiting SARS-CoV-2 Spike Protein.

Despite ongoing vaccination programs against COVID-19 around the world, cases of infection are still rising with new variants. This infers that an effective antiviral drug against COVID-19 is crucial along with vaccinations to decrease cases. A potential target of such antivirals could be the membrane components of the causative pathogen, SARS-CoV-2, for instance spike (S) protein. In our research, we have deployed in vitro screening of crude extracts of seven ethnomedicinal plants against the spike receptor-binding domain (S1-RBD) of SARS-CoV-2 using an enzyme-linked immunosorbent assay (ELISA). Following encouraging in vitro results for Tinospora cordifolia, in silico studies were conducted for the 14 reported antiviral secondary metabolites isolated from T. cordifolia-a species widely cultivated and used as an antiviral drug in the Himalayan country of Nepal-using Genetic Optimization for Ligand Docking (GOLD), Molecular Operating Environment (MOE), and BIOVIA Discovery Studio. The molecular docking and binding energy study revealed that cordifolioside-A had a higher binding affinity and was the most effective in binding to the competitive site of the spike protein. Molecular dynamics (MD) simulation studies using GROMACS 5.4.1 further assayed the interaction between the potent compound and binding sites of the spike protein. It revealed that cordifolioside-A demonstrated better binding affinity and stability, and resulted in a conformational change in S1-RBD, hence hindering the activities of the protein. In addition, ADMET analysis of the secondary metabolites from T. cordifolia revealed promising pharmacokinetic properties. Our study thus recommends that certain secondary metabolites of T. cordifolia are possible medicinal candidates against SARS-CoV-2.

Re: “Stroke at Moderate and High Altitude” by Syed et al.

High Altitude Medicine & BiologyVol. 23, No. 4 Letters to the EditorRe: “Stroke at Moderate and High Altitude” by Syed et al.Marika Falla, Giacomo Strapazzon, Corrado Angelini, and Guido GiardiniMarika FallaAddress correspondence to: Marika Falla, MD, PhD, Department of Neurology, General Hospital of Bolzano, Via Lorenzo Böhler 5, Bolzano 39100, Italy E-mail Address: marikafalla@yahoo.ithttps://orcid.org/0000-0001-7477-3020Institute of Mountain Emergency Medicine, Eurac Research, Bolzano, Italy.Department of Neurology, General Hospital of Bolzano, Bolzano, Italy.Search for more papers by this author, Giacomo Strapazzonhttps://orcid.org/0000-0002-4402-8633Institute of Mountain Emergency Medicine, Eurac Research, Bolzano, Italy.Search for more papers by this author, Corrado Angelinihttps://orcid.org/0000-0002-9554-8794Department of Neurosciences, University of Padova, Padova, Italy.Search for more papers by this author, and Guido GiardiniMountain Medicine and Neurology Centre, Valle d'Aosta Regional Hospital, Aosta, Italy.Search for more papers by this authorPublished Online:23 Dec 2022https://doi.org/10.1089/ham.2022.0087AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Re: “Stroke at Moderate and High Altitude” by Syed et al. ." High Altitude Medicine & Biology, 23(4), pp. 380–381FiguresReferencesRelatedDetails Volume 23Issue 4Dec 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Marika Falla, Giacomo Strapazzon, Corrado Angelini, and Guido Giardini.Re: “Stroke at Moderate and High Altitude” by Syed et al..High Altitude Medicine & Biology.Dec 2022.380-381.http://doi.org/10.1089/ham.2022.0087Published in Volume: 23 Issue 4: December 23, 2022Online Ahead of Print:December 9, 2022PDF download

Steady-state chemoreflex drive captures ventilatory acclimatization during incremental ascent to high altitude: Effect of acetazolamide.

Ventilatory acclimatization (VA) is important to maintain adequate oxygenation with ascent to high altitude (HA). Transient hypoxic ventilatory response tests lack feasibility and fail to capture the integrated steady-state responses to chronic hypoxic exposure in HA fieldwork. We recently characterized a novel index of steady-state respiratory chemoreflex drive (SSCD), accounting for integrated contributions from central and peripheral respiratory chemoreceptors during steady-state breathing at prevailing chemostimuli. Acetazolamide is often utilized during ascent for prevention or treatment of altitude-related illnesses, eliciting metabolic acidosis and stimulating respiratory chemoreceptors. To determine if SSCD reflects VA during ascent to HA, we characterized SSCD in 25 lowlanders during incremental ascent to 4240 m over 7 days. We subsequently compared two separate subgroups: no acetazolamide (NAz; n= 14) and those taking an oral prophylactic dose of acetazolamide (Az; 125 mg BID; n= 11). At 1130/1400 m (day zero) and 4240 m (day seven), steady-state measurements of resting ventilation (V̇I ; L/min), pressure of end-tidal (PET )CO2 (Torr), and peripheral oxygen saturation (SpO2 ; %) were measured. A stimulus index (SI; PET CO2 /SpO2 ) was calculated, and SSCD was calculated by indexing V̇I against SI. We found that (a) both V̇I and SSCD increased with ascent to 4240 m (day seven; V̇I : +39%, p< 0.0001, Hedges' g= 1.52; SSCD: +56.%, p< 0.0001, Hedges' g= 1.65), (b) and these responses were larger in the Az versus NAz subgroup (V̇I : p= 0.02, Hedges' g= 1.04; SSCD: p= 0.02, Hedges' g= 1.05). The SSCD metric may have utility in assessing VA during prolonged stays at altitude, providing a feasible alternative to transient chemoreflex tests.

Diagnostic, facteurs de risque et prévention des pathologies de la haute altitude

AbstractExposure to high altitude requires gradual acclimatization. When it is not respected, specific pathologies can arise, the minor form of which is acute mountain sickness (headaches, digestive disorders, fatigue, insomnia) and the complicated forms are high altitude pulmonary and cerebral edema which are life-threatening emergencies. Preventive treatment is essentially based on a gradual ascent (400 m rule) and acetazolamide. Curative treatment involves rest, analgesics for minor forms, reoxygenation (descent, oxygen, recompression chamber) and corticosteroids for severe forms. To treat pulmonary edema, additional calcium channel blockers or PDE5 inhibitors are given to lower pulmonary arterial pressure. A mountain medicine consultation with a hypoxia exercise test makes it possible to detect subjects at risk of developing serious forms and to offer advice adapted to each individual.

Adrenergic restraint of blood flow and high-altitude acclimatization.

Adrenergic restraint of blood flow and high-altitude acclimatization.

The Human Carotid Body and its Role in Ventilatory Acclimatization to Hypoxia

The Human Carotid Body and its Role in Ventilatory Acclimatization to Hypoxia

Variables Influencing the Pressure and Volume of the Pulmonary Circulation as Risk Factors for Developing High Altitude Pulmonary Edema (HAPE).

At altitudes above 2500 m, the risk of developing high altitude pulmonary edema (HAPE) grows with the increases in pulmonary arterial pressure. HAPE is characterized by severe pulmonary hypertension, though the incidence and relevance of individual risk factors are not yet predictable. However, the systolic pulmonary pressure (SPAP) and peak in tricuspid regurgitation velocity (TVR) are crucial factors when diagnosing pulmonary hypertension by echocardiography. The SPAP and TVR of 27 trekkers aged 20-65 years en route to the Solu Khumbu region of Nepal were assessed. Echocardiograph measurements were performed at Lukla (2860 m), Gorak Shep (5170 m), and the summit of Kala Patthar (5675 m). The altitude profile and the participants' characteristics were also compiled for correlation with the measured data. The results showed a highly significant increase in SPAP and TVR after ascending Kala Patthar. The study revealed a lower increase of SPAP and TVR in the group of older participants, although the respective initial measurements at Gorak Shep were significantly higher for this group. A similar finding occurred in those using Diamox® as prophylaxis. There was an inverse relationship between TVR and SPAP, the peripheral capillary oxygen saturation, and heart rate. The echocardiograph results indicated that older people are an at-risk group for developing HAPE. A conservative interpretation of the basic tactical rules for altitudes should be followed for older trekkers or trekkers with known problems of altitude acclimatization ("slow acclimatizer") as SPAP elevates with age. The prophylactic use of Acetazolamide (Diamox®) should be avoided where not necessary for acute medical reasons. Acetazolamide leads to an increase of SPAP, and this may potentially enhance the risk of developing HAPE. Arterial oxygen saturation measurements can provide an indicator for the self-assessment for the risk of developing HAPE and a rule of thumb for the altitude profile, but does not replace a HAPE diagnosis. Backpack weight, sex, workload (actual ascent speed), and pre-existing diseases were not statistically significant factors related to SPAP and TVR (p ≤ 0.05).

Acute high altitude exposure, acclimatization and re-exposure on nocturnal breathing.

Background: Effects of prolonged and repeated high-altitude exposure on oxygenation and control of breathing remain uncertain. We hypothesized that prolonged and repeated high-altitude exposure will improve altitude-induced deoxygenation and breathing instability. Methods: 21 healthy lowlanders, aged 18-30y, underwent two 7-day sojourns at a high-altitude station in Chile (4–8 hrs/day at 5,050 m, nights at 2,900 m), separated by a 1-week recovery period at 520 m. Respiratory sleep studies recording mean nocturnal pulse oximetry (SpO2), oxygen desaturation index (ODI, >3% dips in SpO2), breathing patterns and subjective sleep quality by visual analog scale (SQ-VAS, 0–100% with increasing quality), were evaluated at 520 m and during nights 1 and 6 at 2,900 m in the 1st and 2nd altitude sojourn. Results: At 520 m, mean ± SD nocturnal SpO2 was 94 ± 1%, ODI 2.2 ± 1.2/h, SQ-VAS 59 ± 20%. Corresponding values at 2,900 m, 1st sojourn, night 1 were: SpO2 86 ± 2%, ODI 23.4 ± 22.8/h, SQ-VAS 39 ± 23%; 1st sojourn, night 6: SpO2 90 ± 1%, ODI 7.3 ± 4.4/h, SQ-VAS 55 ± 20% (p < 0.05, all differences within corresponding variables). Mean differences (Δ, 95%CI) in acute effects (2,900 m, night 1, vs 520 m) between 2nd vs 1st altitude sojourn were: ΔSpO2 0% (-1 to 1), ΔODI -9.2/h (-18.0 to -0.5), ΔSQ-VAS 10% (-6 to 27); differences in acclimatization (changes night 6 vs 1), between 2nd vs 1st sojourn at 2,900 m were: ΔSpO2 -1% (-2 to 0), ΔODI 11.1/h (2.5 to 19.7), ΔSQ-VAS -15% (-31 to 1). Conclusion: Acute high-altitude exposure induced nocturnal hypoxemia, cyclic deoxygenations and impaired sleep quality. Acclimatization mitigated these effects. After recovery at 520 m, repeated exposure diminished high-altitude-induced deoxygenation and breathing instability, suggesting some retention of adaptation induced by the first altitude sojourn while subjective sleep quality remained similarly impaired.

Ventilatory And Cardiovascular Acclimatization Remains Unchanged Following Active Versus Passive Ascent To 3600 m

PURPOSE: Sympathetic stimulation, induced by intense endurance exercise, may alter the process of ventilatory and cardiovascular acclimatization. The purpose of this study was to examine the magnitude and time course of ventilatory and cardiovascular acclimatization following active and passive ascent to 3600 m. METHODS: Forty-one healthy unacclimatized Soldiers (n = 41, mean ± SD; age = 26 ± 5 yr; body weight = 83.5 ± 11.6 kg; VO2max = 47.9 ± 5.5 ml · kg−1 · min−1) were tested at sea level (SL) in Ft. Leonard Wood, MO, flown to Taos Ski Valley, NM (2845 m) where they arrived around 1400 m, and then either hiked (n = 21; 5.0 km, 15.5% mean grade) or were driven (n = 20; 30-min drive) to a high altitude (HA) ski patrol facility located at 3600 m. Energy expenditure during ascent was measured with an ankle accelerometer. Portable real-time capnography was used to measure end-tidal carbon dioxide partial pressure (PETCO2) after 10 min of sitting at SL, after 19 h (HA2), 43 h (HA3), and 67 h (HA4) at HA. Mean arterial blood pressure (MAP), heart rate (HR), and pulse arterial oxygen saturation (SpO2) were measured at the same time (~0900) as PETCO2 RESULTS: The active group expended a greater (P < 0.05) amount of energy (745 ± 435 kcal) than the passive group (55 ± 10 kcal) during ascent. There were no differences between groups in terms of ventilatory and cardiovascular acclimatization so data were combined. Resting PETCO2 (mmHg) decreased (P < 0.05) from SL (37.5 ± 3.35) to HA2 (33.5 ± 3.71), remained stable from HA2 to HA3 (33.8 ± 3.73) and decreased further (P < 0.05) from HA3 to HA4 (30.8 ± 4.9). Resting MAP and HR, respectively, increased (P < 0.05) from SL (89.9 ± 6.9 mmHg; 65.7 ± 9.8 bpm) to HA2 (100.0 ± 7.2 mmHg; 78.7 ± 10.1 bpm), MAP decreased (P < 0.05) but HR remained unchanged from HA2 to HA3 (96.9 ± 7.1 mmHg; 78.5 ± 15.4 bpm), and both stayed consistent from HA3 to HA4 (98.1 ± 7.1 mmHg; 80.1 ± 12.9 bpm). Resting SpO2 (%) decreased (P < 0.05) from SL (97.6 ± 1.3) to HA2 (88.7 ± 3.1), increased (P < 0.05) from HA2 to HA3 (89.7 ± 2.9), and remained unchanged from HA3 to HA4 (89.1 ± 3.2). CONCLUSION: Ventilatory and cardiovascular acclimatization occurred at HA but sympathetic stimulation and increased metabolic rate due to the active ascent did not change the magnitude or time course of either of these processes. Authors’ views not official U.S. Army or DoD policy. Funding: USAMRDC

Inflammatory gene expression during acute high‐altitude exposure

The molecular signalling pathways that regulate inflammation and the response to hypoxia share significant crosstalk and appear to play major roles in high‐altitude acclimatization and adaptation. Several studies demonstrate increases in circulating candidate inflammatory markers during acute high‐altitude exposure, but significant gaps remain in our understanding of how inflammation and immune function change at high altitude and whether these responses contribute to high‐altitude pathologies, such as acute mountain sickness. To address this, we took an unbiased transcriptomic approach, including RNA sequencing and direct digital mRNA detection with NanoString, to identify changes in the inflammatory profile of peripheral blood throughout 3 days of high‐altitude acclimatization in healthy sea‐level residents (n = 15; five women). Several inflammation‐related genes were upregulated on the first day of high‐altitude exposure, including a large increase in HMGB1 (high mobility group box 1), a damage‐associated molecular pattern (DAMP) molecule that amplifies immune responses during tissue injury. Differentially expressed genes on the first and third days of acclimatization were enriched for several inflammatory pathways, including nuclear factor‐κB and Toll‐like receptor (TLR) signalling. Indeed, both TLR4 and LY96, which encodes the lipopolysaccharide binding protein (MD‐2), were upregulated at high altitude. Finally, FASLG and SMAD7 were associated with acute mountain sickness scores and peripheral oxygen saturation levels on the first day at high altitude, suggesting a potential role of immune regulation in response to high‐altitude hypoxia. These results indicate that acute high‐altitude exposure upregulates inflammatory signalling pathways and might sensitize the TLR4 signalling pathway to subsequent inflammatory stimuli. Key points Inflammation plays a crucial role in the physiological response to hypoxia.High‐altitude hypoxia exposure causes alterations in the inflammatory profile that might play an adaptive or maladaptive role in acclimatization.In this study, we characterized changes in the inflammatory profile following acute high‐altitude exposure.We report upregulation of novel inflammation‐related genes in the first 3 days of high‐altitude exposure, which might play a role in immune system sensitization.These results provide insight into how hypoxia‐induced inflammation might contribute to high‐altitude pathologies and exacerbate inflammatory responses in critical illnesses associated with hypoxaemia.

Effects of moderate altitude on the physical performance of elite female soccer players during an official soccer tournament

The aim of this study was to investigate the effects of moderate altitude (2800 m) on neuromuscular performance, body-mass, rating of perceived exertion, total quality recovery, and global positioning system–motion variables (distance covered, sprint distance, number of accelerations, and top-speed) during soccer training and official matches. Seventeen professional female soccer players performed vertical jump tests and were weighed over seven days during the altitude acclimatization. Global positioning system–motion variables, rating of perceived exertion, and total quality recovery were assessed over two training sessions at 2800 m and compared to the metrics collected during two sessions at sea level. Global positioning system–motion variables were measured during six official matches played at 2800 m and compared to six matches at sea level. Vertical jump height and body-mass did not change during acclimatization ( p &gt; 0.05). Rating of perceived exertion was higher and total quality recovery was lower after training sessions at altitude ( p &lt; 0.05). Total distance covered ( p = 0.002), total sprint distance ( p = 0.016), and total distance covered per minute ( p = 0.02) decreased and rating of perceived exertion increased ( p = 0.012) in the matches at moderate altitude compared to sea level. No differences were observed for top-speed and acceleration ( p &gt; 0.05). These findings suggest that moderate altitude can lead to substantial decreases in the physical performance (especially in total sprint distance), increased rating of perceived exertion, decreased total quality recovery in female players. These occurrences are critical to soccer performance.

Differential effects of high-altitude exposure on markers of oxidative stress, antioxidant capacity, and iron profiles.

High-altitude (HA) exposure may stimulate significant physiological and molecular changes, resulting in HA-related illnesses. HA may impact oxidative stress, antioxidant capacity, and iron homeostasis, yet it is unclear how both repeated exposure and HA acclimatization may modulate such effects. Therefore, we assessed the effects of weeklong repeated daily HA exposure (2,900-5,050 m) in altitude-naïve individuals (n = 21 individuals, 13 females, mean ± SD, 25.3 ± 3.7 yr) to mirror the working schedule of HA workers (n = 19 individuals, all males, 41.1 ± 9.4 yr) at the Atacama Large Millimeter Array (ALMA) Observatory (San Pedro de Atacama, Chile). Markers of oxidative stress, antioxidant capacity, and iron homeostasis were measured in blood plasma. Levels of protein oxidation (P < 0.001) and catalase activity (P = 0.023) increased and serum iron (P < 0.001), serum ferritin (P < 0.001), and transferrin saturation (P < 0.001) levels decreased with HA exposure in both groups. HA workers had lower levels of oxidative stress, and higher levels of antioxidant capacity, iron supply, and hemoglobin concentration as compared with altitude-naïve individuals. On a second week of daily HA exposure, changes in levels of protein oxidation, glutathione peroxidase, and nitric oxide metabolites were lower as compared with the first week in altitude-naïve individuals. These results indicate that repeated exposure to HA may significantly alter oxidative stress and iron homeostasis, and the degree of such changes may be dependent on if HA is visited naïvely or routinely. Further studies are required to fully elucidate differences in HA-induced changes in oxidative stress and iron homeostasis profiles among visitors of HA.

A Celebration of the Extraordinary Life of Late Professor Tatiana V. Serebrovskaya (Kyiv, Ukraine) in Advancing Hypoxia Science and Medicine.

High Altitude Medicine & BiologyVol. 23, No. 3 Brief ReportA Celebration of the Extraordinary Life of Late Professor Tatiana V. Serebrovskaya (Kyiv, Ukraine) in Advancing Hypoxia Science and MedicineErik R. Swenson, Robert T. Mallet, Lei Xi, Eugenia Manukhina, Fred Downey, Johannes Burtscher, Hannelore Ehrenreich, and Martin BurtscherErik R. SwensonVA Puget Health Care System, University of Washington, Seattle, Washington, USA.Search for more papers by this author, Robert T. MalletDepartment of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA.Search for more papers by this author, Lei XiPauley Heart Center, Division of Cardiology, Department of Internal Medicine, Virginia Commonwealth University, Richmond, Virginia, USA.Search for more papers by this author, Eugenia ManukhinaDepartment of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA.Search for more papers by this author, Fred DowneyDepartment of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, Texas, USA.Search for more papers by this author, Johannes BurtscherDepartment of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.Search for more papers by this author, Hannelore EhrenreichClinical Neuroscience, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany.Search for more papers by this author, and Martin BurtscherAddress correspondence to: Martin Burtscher, MD, PhD, Department of Sport Science, University of Innsbruck, Innsbruck A-6020, Austria E-mail Address: martin.burtscher@uibk.ac.atDepartment of Sport Science, University of Innsbruck, Innsbruck, Austria.Search for more papers by this authorPublished Online:14 Sep 2022https://doi.org/10.1089/ham.2022.0046AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"A Celebration of the Extraordinary Life of Late Professor Tatiana V. Serebrovskaya (Kyiv, Ukraine) in Advancing Hypoxia Science and Medicine." High Altitude Medicine & Biology, 23(3), pp. 284–285FiguresReferencesRelatedDetails Volume 23Issue 3Sep 2022 InformationCopyright 2022, Mary Ann Liebert, Inc., publishersTo cite this article:Erik R. Swenson, Robert T. Mallet, Lei Xi, Eugenia Manukhina, Fred Downey, Johannes Burtscher, Hannelore Ehrenreich, and Martin Burtscher.A Celebration of the Extraordinary Life of Late Professor Tatiana V. Serebrovskaya (Kyiv, Ukraine) in Advancing Hypoxia Science and Medicine.High Altitude Medicine & Biology.Sep 2022.284-285.http://doi.org/10.1089/ham.2022.0046Published in Volume: 23 Issue 3: September 14, 2022Online Ahead of Print:August 2, 2022PDF download

Clinician's Corner: Counseling Patients with Pulmonary Vascular Disease Traveling to High Altitude

Ulrich, Silvia, Mona Lichtblau, Simon R. Schneider, Stéphanie Saxer, and Konrad E. Bloch, Clinician's corner: counseling patients with pulmonary vascular disease traveling to high altitude. High Alt Med Biol. 23:201-208, 2022.-Pulmonary vascular diseases (PVDs) with precapillary pulmonary hypertension (PH), such as pulmonary arterial or chronic thromboembolic PH, impair exercise performance and survival in patients. Vasodilators and other treatments improve quality of life and prognosis to an extent in patients who have PVDs as chronic disorders. Obviously, patients with PVD wish to participate in usual daily activities, including travel to popular settlements and mountainous regions located at high altitude. However, the pulmonary hemodynamic impairment due to PVD leads to blood and tissue hypoxia, particularly during exercise and sleep. It is thus of concern that alveolar hypoxia at higher altitude may exacerbate patients' symptoms and lead to decompensation. Current PH guidelines discourage high-altitude exposure for fear of altitude-related adverse health effects. However, several recent well-designed prospective and randomized trials show that despite altitude-induced hypoxemia, pulmonary hemodynamic changes and impairment of exercise performance in patients with PVD are similar to the responses in healthy people or in patients with mild chronic obstructive pulmonary disease. The vast majority of patients with PVD can tolerate short-term exposure to moderate altitudes up to 2,500 m. For the roughly 10% of patients with stable disease who develop severe hypoxemia when ascending to 2,500 m, they respond well to low-level supplemental oxygen support. The best low-altitude predictors for adverse health effects at high altitude are the known clinical risk factors for PVD such as symptoms, functional class, exercise capacity, and exertional oxygen desaturation, whereas hypoxia altitude simulation testing is of little additive value. In any case, patients should be instructed that altitude-related adverse health effects may be difficult to predict and that in case of worsening symptoms, immediate accompanied descent to lower altitude and oxygen therapy are required. Patients with severe hypoxemia near sea level may safely visit high-altitude regions up to 1,500-2,000 m while continuing oxygen therapy and avoiding strenuous exercise. All PH patients should be counseled before any high-altitude sojourn by doctors with experience in PVD and high-altitude medicine and have an action plan for the occurrence of severe hypoxemia and other altitude-related conditions such as acute mountain sickness.

High-Altitude Pulmonary Edema in the Context of COVID-19

High-altitude pulmonary edema (HAPE) and COVID-19 pneumonia are different diseases, but HAPE-susceptible individuals (whose susceptibility often has a genetic basis) can also suffer from severe COVID-19. We hypothesized that certain pathogenic mechanisms might overlap if such a coincidence occurs, since these patients could react to alveolar hypoxia with a more intense and heterogeneously distributed pulmonary vasoconstriction than non-HAPE-susceptible patients. It is also not known how future altitude acclimatization might affect lowlanders with COVID-19 pulmonary sequelae, and how the loss of adaptation to chronic hypoxia might differ by genetic lineage among highland natives who have recovered from severe COVID-19 around the world. Although the incidence of CoV-2 in high-altitude locations seems to be lower, a correct differential diagnosis of both conditions is essential, especially in high-altitude areas where health resources are scarce, considering that there is sometimes a similarity between COVID-19 pneumonia and HAPE.

Integrative analysis of the steroidal alkaloids distribution and biosynthesis of bulbs Fritillariae Cirrhosae through metabolome and transcriptome analyses

BackgroundBulbus Fritillariae Cirrhosae (BFC) is an endangered high-altitude medicine and food homology plant with anti-tumor, anti-asthmatic, and antitussive activities as it contains a variety of active ingredients, especially steroidal alkaloids. Bulbus Fritillariae Thunbergia (BFT) is another species of Fritillaria that grows at lower altitude areas. Production of plant-derived active ingredients through a synthetic biology strategy is one of the current hot topics in biological research, which requires a complete understanding of the related molecular pathways. Our knowledge of the steroidal alkaloid biosynthesis in Fritillaria species is still very limited.ResultsTo promote our understanding of these pathways, we performed non-target metabolomics and transcriptome analysis of BFC and BFT. Metabolomics analysis identified 1288 metabolites in BFC and BFT in total. Steroidal alkaloids, including the proposed active ingredients of Fritillaria species peimine, peimisine, peiminine, etc., were the most abundant alkaloids detected. Our metabolomics data also showed that the contents of the majority of the steroidal alkaloids in BFC were higher than in BFT. Further, our comparative transcriptome analyses between BFC and BFT identified differentially expressed gene sets among these species, which are potentially involved in the alkaloids biosynthesis of BFC.ConclusionThese findings promote our understanding of the mechanism of steroidal alkaloids biosynthesis in Fritillaria species.

Village Evaluation and Classification Guidance of a County in Southeast Gansu Based on the Rural Revitalization Strategy

The rural revitalization strategy is a key strategic deployment to resolve the “San Nong” (Agriculture, Rural Areas, and Farmers) issue and attain agricultural and rural modernization in the new era. The strategy has practical significance in determining the differentiation principle of rural areas, identifying their development types, and elucidating the goal orientation of rural revitalization. Starting from the current situation of villages in Gangu County, this study thoroughly analyzes and evaluates the functions of the village system using the ArcGIS spatial analysis method, with urban–rural overall planning as the core concept and various function and correcting factor evaluations as the basis. Based on the functional characteristics of different dimensions, villages in Gangu County were categorized as follows: Weihe River Valley high-efficiency economic zone, Sandu River Taiwan grain and vegetable multi-characteristic economic zone, North Front Mountain grain, vegetable, medicine, and oil zone, South Front Mountain grain, vegetable, and oil zone, North Back Mountain grain, oil, and medicine zone, and South Back Mountain grain and economic zone as corresponding planning strategies for classified development guidance.

Mountain Emergency Medicine Review, 1st edition

Mountain Emergency Medicine Review, 1st edition

Chronic Hypoxia Blunts the Hypoxic Ventilatory Response in Neonatal and Adult Rats

Chronic hypoxia (CH) may affect the control of breathing differently in neonatal versus adult mammals. It is widely accepted that CH blunts the hypoxic ventilatory response (HVR) in neonatal rats but augments hypoxic ventilation in adult rats. However, there is also evidence that longer durations of CH can progressively attenuate the HVR in adult rats too. Therefore, we predicted that short durations of CH (3 days) would blunt the HVR in neonatal rats and augment the HVR in adult rats, but that longer durations of CH (7 days) would blunt the HVR in adult rats. To test these predictions, rats were exposed to 12% O2 (CH) or room air (Control) for 3 days as neonates (from P0 to P3, or from P7 to P10) or as young adults. Baseline ventilation (21% O2) and the acute HVR (12% O2) were measured by plethysmography immediately following the exposure. The adult rats were then returned to the CH and Control chambers for 4 more days before repeating the breathing measurements. Although Sprague‐Dawley rats were used in all experiments, adults from two different commercial suppliers (Charles River Laboratories and Envigo) were used to determine whether genetic background might influence the results. Baseline ventilation was greater in all CH groups regardless of their age, consistent with ventilatory acclimatization. With the exception of CH rats at P10 in which peak hypoxic ventilation (i.e., minute ventilation during the first minute of 12% O2) was also greater than in Controls, hypoxic ventilation was generally similar between CH and Control groups or reduced in the CH group. Accordingly, the change in ventilation from baseline (i.e., HVR) was blunted by CH regardless of the age of the rats, the duration of the CH exposure (adults only), or the substrain of Sprague‐Dawley rat (adults only). The order in which test gases were presented during breathing measurements (i.e., 21% O2 – 12% O2 vs. 12% O2 – 21% O2) did not influence the calculated HVR in adult rats. We conclude that the respiratory plasticity elicited by normobaric CH is similar across ages in Sprague‐Dawley rats.

Proteomic and Morphological Profiling of Mice Ocular Tissue During High-altitude Acclimatization Process: An Animal Study at Lhasa.

PurposeHigh-altitude environment mainly with hypobaric hypoxia could induce pathological alterations in ocular tissue. Previous studies have mostly focused on sporadic case reports and simulated high-altitude hypoxia experiments. This aim of this study was to explore the proteomic and morphological changes of ocular tissue in mice at real altitude environment.MethodsIn this study, mice were flown from Chengdu (elevation: 500 m) to Lhasa (elevation: 3600 m). After exposure for 1day, 3, 6, 10, 20, 30, and 40days, the mice were euthanatized to obtain blood and ocular tissue. Serological tests, ocular pathological examinations, integral ocular proteomics analysis, and Western blot were conducted.ResultsWe focused on acute phase (1–3 days) and chronic phase (>30 days) during high-altitude acclimatization. Serum interleukin-1 was increased at 3 days, while superoxide dismutase, interleukin-6, and tumor necrosis factor-α showed no statistical changes. H&E staining demonstrated that the cornea was edematous at 3 days and exhibited slower proliferation at 30 days. The choroid showed a consistently significant thickening, while there existed no noticeable changes in retinal thickness. Overall, 4073 proteins were identified, among which 71 and 119 proteins were detected to have significant difference at 3 days and 40 days when compared with the control group. Functional enrichment analysis found the differentiated proteins at 3 days exposure functionally related with response to radiation, dephosphorylation, negative regulation of cell adhesion, and erythrocyte homeostasis. Moreover, the differential profiles of the proteins at 40 days exposure exhibited changes of regulation of complement activation, regulation of protein activation cascade, regulation of humoral immune response, second-messenger-mediated signaling, regulation of leukocyte activation, and cellular iron homeostasis. Interestingly, we found the ocular proteins with lactylation modification were increased along high-altitude adaptation.ConclusionThis is the first work reporting the ocular proteomic and morphological changes at real high-altitude environment. We expect it would deep the understanding of ocular response during altitude acclimatization.