High Altitude Exposure Research Articles

S-23-1: OCCUPATIONAL AND ENVIRONMENTAL INFLUENCES ON HYPERTENSION

In this brief review I shall try to discuss several topics related to hypertension which maybe associated with occupational and environmental effects. Effects of dietary sodium will not be discussed as these are extensively discussed elsewhere. Occupational stress is difficult to define but there seems to be a relationship between high demands and relatively low control, and blood pressure in both men and women despite different professional distribution. Noise, a relatively less recognized stressor that may be associated with hypertension Both industrial noise and urban noise. Recently due to the Covid19 lockdown and reduction of aircraft noise in relevant areas a reduction of blood-pressure was noted. Seasonal variation with rise of blood pressure during cold and perhaps shorter daytime light seasons, and subsequent reduction in the summer with its higher temperatures and longer light hours is one environmental factor. Air pollution, especially that associated with high level small particulate matter equal to, or smaller than 0.25 μm, was associated with hypertension in several studies, with quite and ethnic and geographic variability. High altitude exposure (higher than 2500 m), involves hypoxemia (in addition to radiation, cold temperatures, and dehydration because of dryness of inhaled air), resulting in renin angiotensin system activation and sympathetically induced vascular contraction, and elevation of pulse rate and blood-pressure at rest and an exaggerated increase during exercise. Immigration seems to be associated with hypertension through different mechanisms in different populations. Mechanisms of these effects are not well understood though some must be mediated through sympathetic activation, others through the renin angiotensin system though, hypoxemia, altered redox state and inflammation all might participate along with other mechanisms

A Pharmacodynamic Evaluation of the Protective Effects of Roxadustat Against Hypoxic Injury at High Altitude.

To investigate roxadustat's preventive effects on hypoxia damage in the quick ascent to high altitude. The roxadustat (7.8 mg/kg, 15.6 mg/kg, and 31.2 mg/kg) and control groups of BALB/C mice were distributed at random. To evaluate roxadustat's anti-hypoxic effectiveness at the recommended dose, an atmospheric pressure closed hypoxic experiment was used. Wistar rats were randomly assigned to groups that received normal oxygen, hypoxic, acetazolamide, or roxadustat in order to evaluate the protective effects against hypoxic damage. Animal blood was obtained for arterial blood-gas analysis, inflammatory factors, and the identification of oxidative stress indicators. Animal tissues were removed for pathological investigation. In each group, the mice's survival time was noticeably extended compared to the normal oxygen group. The medium dose had the best time extension rate at 19.05%. Blood SatO2 and PaO2 were significantly higher in the roxadustat group compared to the hypoxic group. Erythrocyte content, hemoglobin content, and hematocrit were also significantly higher. Plasma levels of IL-6, TNF-α, and IFN-γ were also significantly lower in the roxadustat group. Roxadustat can also improve the level of oxidative stress in the tissues of hypoxic rats. According to the results of HE staining, roxadustat could greatly lessen the harm done to rat heart, brain, lung, liver, and kidney tissue as a result of hypoxia. Roxadustat can greatly reduce inflammation, oxidative stress, and tissue damage brought on by hypoxia, showing that it can significantly enhance the body's ability to adapt to high altitude exposure.

Cognition and Neuropsychological Changes at Altitude-A Systematic Review of Literature.

High-altitude (HA) exposure affects cognitive functions, but studies have found inconsistent results. The aim of this systematic review was to evaluate the effects of HA exposure on cognitive functions in healthy subjects. A structural overview of the applied neuropsychological tests was provided with a classification of superordinate cognitive domains. A literature search was performed using PubMed up to October 2021 according to PRISMA guidelines. Eligibility criteria included a healthy human cohort exposed to altitude in the field (at minimum 2440 m [8000 ft]) or in a hypoxic environment in a laboratory, and an assessment of cognitive domains. The literature search identified 52 studies (29 of these were field studies; altitude range: 2440 m-8848 m [8000-29,029 ft]). Researchers applied 112 different neuropsychological tests. Attentional capacity, concentration, and executive functions were the most frequently studied. In the laboratory, the ratio of altitude-induced impairments (64.7%) was twice as high compared to results showing no change or improved results (35.3%), but altitudes studied were similar in the chamber compared to field studies. In the field, the opposite results were found (66.4 % no change or improvements, 33.6% impairments). Since better acclimatization can be assumed in the field studies, the findings support the hypothesis that sufficient acclimatization has beneficial effects on cognitive functions at HA. However, it also becomes apparent that research in this area would benefit most if a consensus could be reached on a standardized framework of freely available neurocognitive tests.

Machine Learning Based on Event-Related EEG of Sustained Attention Differentiates Adults with Chronic High-Altitude Exposure from Healthy Controls.

(1) Objective: The aim of this study was to examine the effect of high altitude on inhibitory control processes that underlie sustained attention in the neural correlates of EEG data, and explore whether the EEG data reflecting inhibitory control contain valuable information to classify high-altitude chronic hypoxia and plain controls. (2) Methods: 35 chronic high-altitude hypoxic adults and 32 matched controls were recruited. They were required to perform the go/no-go sustained attention task (GSAT) using event-related potentials. Three machine learning algorithms, namely a support vector machine (SVM), logistic regression (LR), and a decision tree (DT), were trained based on the related ERP components and neural oscillations to build a dichotomous classification model. (3) Results: Behaviorally, we found that the high altitude (HA) group had lower omission error rates during all observation periods than the low altitude (LA) group. Meanwhile, the ERP results showed that the HA participants had significantly shorter latency than the LAs for sustained potential (SP), indicating vigilance to response-related conflict. Meanwhile, event-related spectral perturbation (ERSP) analysis suggested that lowlander immigrants exposed to high altitudes may have compensatory activated prefrontal cortexes (PFC), as reflected by slow alpha, beta, and theta frequency-band neural oscillations. Finally, the machine learning results showed that the SVM achieved the optimal classification F1 score in the later stage of sustained attention, with an F1 score of 0.93, accuracy of 92.54%, sensitivity of 91.43%, specificity of 93.75%, and area under ROC curve (AUC) of 0.97. The results proved that SVM classification algorithms could be applied to identify chronic high-altitude hypoxia. (4) Conclusions: Compared with other methods, the SVM leads to a good overall performance that increases with the time spent on task, illustrating that the ERPs and neural oscillations may provide neuroelectrophysiological markers for identifying chronic plateau hypoxia.

Proliferative Retinopathy Associated with Repeated High-Altitude Exposure in a Patient with Sickle Cell Trait.

Broadhead Geoffrey K., Henry E. Wiley, David Peprah, Kenneth Olumba, and Alisa T. Thavikulwat. Proliferative retinopathy associated with repeated high-altitude exposure in a patient with sickle cell trait. High Alt Med Biol. 23:369-371, 2022.-Sickle cell trait (SCT), a carrier state characterized by one normal copy of the beta-globin gene (producing hemoglobin A) and one abnormal variant (producing hemoglobin S), is typically asymptomatic and very low risk for manifestations of hemoglobinopathy, including development of retinopathy. Reported cases of proliferative retinopathy in patients with SCT have occurred in the context of concurrent ocular or systemic disease. We report a case of an otherwise healthy patient with SCT who developed proliferative retinopathy requiring surgical intervention in the setting of significant exposure to high altitude through increased work hours as a flight attendant in the month leading to her presentation. Significant high-altitude exposure may contribute to development of retinopathy in patients with sickle trait. Practitioners should consider the possibility of sickle cell retinopathy in patients with sickle trait in these circumstances.

Proteomic analysis reveals proteins and pathways associated with declined testosterone production in male obese mice after chronic high-altitude exposure.

Obesity is common in highland areas owing to lifestyle alterations. There are pieces of evidence to suggest that both obesity and hypoxia may promote oxidative stress, leading to hypogonadism in males. These findings indicate an increased risk of hypogonadism in obese males following hypoxia exposure. However, the mechanisms underlying the disease process remain unclear. The current study aims to explore the mechanism of testosterone production dysfunction in obese male mice exposed to a chronic high-altitude hypoxia environment. An obese male mouse model was generated by inducing obesity in mice via a high-fat diet for 14 weeks, and the obese mice were then exposed to a high-altitude hypoxia environment for 24 days. Sera and testicular tissues were collected to detect serum lipids, sex hormone level, and testicular oxidative stress indicators. Morphological examination was performed to assess pathological alterations in testicular tissues and suborganelles in leydig cells. Proteomic alterations in testicular tissues were investigated using quantitative proteomics in Obese/Control and Obese-Hypoxia/Obese groups. The results showed that chronic high-altitude hypoxia exposure aggravated low testosterone production in obese male mice accompanied by increased testicular oxidative stress and histological damages. In total, 363 and 242 differentially expressed proteins (DEPs) were identified in the two comparison groups, Obese/Control and Obese-Hypoxia/Obese, respectively. Functional enrichment analysis demonstrated that several significant functional terms and pathways related to testosterone production were altered in the two comparison groups. These included cholesterol metabolism, steroid hormone biosynthesis, peroxisome proliferator-activated receptor (PPAR) signaling pathway, oxidative stress responses, as well as retinol metabolism. Finally, 10 representative DEPs were selected for parallel reaction monitoring verification. Among them, StAR, DHCR7, NSDHL, CYP51A1, FDPS, FDX1, CYP11A1, ALDH1A1, and GPX3 were confirmed to be downregulated in the two groups. Chronic hypoxia exposure could exacerbate low testosterone production in obese male mice by influencing the expression of key proteins involved in steroid hormone biosynthesis, cholesterol biosynthesis, oxidative stress responses and retinol metabolism.

High-Altitude Hypoxia Exposure Induces Iron Overload and Ferroptosis in Adipose Tissue.

High altitude (HA) has become one of the most challenging environments featuring hypobaric hypoxia, which seriously threatens public health, hence its gradual attraction of public attention over the past decade. The purpose of this study is to investigate the effect of HA hypoxia on iron levels, redox state, inflammation, and ferroptosis in adipose tissue. Here, 40 mice were randomly divided into two groups: the sea-level group and HA hypoxia group (altitude of 5000 m, treatment for 4 weeks). Total iron contents, ferrous iron contents, ROS generation, lipid peroxidation, the oxidative enzyme system, proinflammatory factor secretion, and ferroptosis-related biomarkers were examined, respectively. According to the results, HA exposure increases total iron and ferrous iron levels in both WAT and BAT. Meanwhile, ROS release, MDA, 4-HNE elevation, GSH depletion, as well as the decrease in SOD, CAT, and GSH-Px activities further evidenced a phenotype of redox imbalance in adipose tissue during HA exposure. Additionally, the secretion of inflammatory factors was also significantly enhanced in HA mice. Moreover, the remarkably changed expression of ferroptosis-related markers suggested that HA exposure increased ferroptosis sensitivity in adipose tissue. Overall, this study reveals that HA exposure is capable of inducing adipose tissue redox imbalance, inflammatory response, and ferroptosis, driven in part by changes in iron overload, which is expected to provide novel preventive targets for HA-related illness.

Clinical and biochemical indices of people with high-altitude experience linked to acute mountain sickness

BackgroundAcute mountain sickness (AMS) is a major health issue for people travelling to high altitudes. This study was designed to comprehensively evaluate the changes in clinical characteristics and biochemical indices of high-altitude travelers and determine whether these changes were associated with AMS. MethodsA total of 14 clinical indices and 52 biochemical indices were determined in 22 subjects before and during acute high-altitude exposure. Six hours after passive ascent to 3648 m (Lhasa, China), the Lake Louise Scoring (LLS) system 2018 was used to assess AMS, which was defined as headache with a total LLS ≥3. ResultsBefore travelling to high altitudes, uric acid (UA), platelet distribution width (PDW), mitral peak E velocity (MVE), and ejection fraction (EF) were significantly higher in AMS-resistant individuals than in AMS-susceptible ones (all p < 0.05). A good predictive value of UA (0.817, 95% CI: 0.607–1.000) and PDW (0.844, 95% CI: 0.646–1.000) for AMS-susceptible subjects was found. With high-altitude experience, 14 subjects were diagnosed as having AMS. Compared with non-AMS, the changes in UA and number of neutrophils in AMS presented a significant difference (all p < 0.05). The high-altitude-induced changes in UA, area under the curve, specificity, and sensitivity for identifying AMS were 0.883 (95% CI: 0.738–1.000), 83.30%, and 90.00%, respectively. ConclusionHuman presents a compensatory physiological and biochemical response to high-altitude travel at early phase. The UA concentration before travel and its trend with high-altitude experience exhibited good performance for identifying AMS.

Proteomic Analysis Reveals That Mitochondria Dominate the Hippocampal Hypoxic Response in Mice.

Hypoxic stress occurs in various physiological and pathological states, such as aging, disease, or high-altitude exposure, all of which pose a challenge to many organs in the body, necessitating adaptation. However, the exact mechanisms by which hypoxia affects advanced brain function (learning and memory skills in particular) remain unclear. In this study, we investigated the effects of hypoxic stress on hippocampal function. Specifically, we studied the effects of the dysfunction of mitochondrial oxidative phosphorylation using global proteomics. First, we found that hypoxic stress impaired cognitive and motor abilities, whereas it caused no substantial changes in the brain morphology or structure of mice. Second, bioinformatics analysis indicated that hypoxia affected the expression of 516 proteins, of which 71.1% were upregulated and 28.5% were downregulated. We demonstrated that mitochondrial function was altered and manifested as a decrease in NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4 expression, accompanied by increased reactive oxygen species generation, resulting in further neuronal injury. These results may provide some new insights into how hypoxic stress alters hippocampal function via the dysfunction of mitochondrial oxidative phosphorylation.

Disrupted gut microbiota aggravates working memory dysfunction induced by high-altitude exposure in mice.

The widely accepted microbiome-gut-brain axis (MGBA) hypothesis may be essential for explaining the impact of high-altitude exposure on the human body, especially brain function. However, studies on this topic are limited, and the underlying mechanism remains unclear. Therefore, this study aimed to determine whether high-altitude-induced working memory dysfunction could be exacerbated with gut microbiota disruption. C57BL/6 mice were randomly divided into three groups: control, high-altitude exposed (HAE), and high-altitude exposed with antibiotic treatment (HAE-A). The HAE and HAE-A groups were exposed to a low-pressure oxygen chamber (60-65 kPa) simulating the altitude of 3,500-4,000 m for 14 days, The air pressure level for the control group was maintained at 94.5 kPa. Antibiotic water (mixed with 0.2 g/L of ciprofloxacin and 1 g/L of metronidazole) was provided to the HAE-A group. Based on the results of the novel object test and P300 in the oddball behavioral paradigm training test, working memory dysfunction was aggravated by antibiotic treatment. We determined the antioxidant capacity in the prefrontal cortex and found a significant negative influence (p < 0.05) of disturbed gut microbiota on the total antioxidant capacity (T-AOC) and malondialdehyde (MDA) content, as well as the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The same trend was also observed in the apoptosis-related functional protein content and mRNA expression levels in the prefrontal cortex, especially the levels of bcl-2, Bax, and caspase-3. The high-altitude environment and antibiotic treatment substantially affected the richness and diversity of the colonic microbiota and reorganized the composition and structure of the microbial community. S24-7, Lachnospiraceae, and Lactobacillaceae were the three microbial taxa with the most pronounced differences under the stimulation by external factors in this study. In addition, correlation analysis between colonic microbiota and cognitive function in mice demonstrated that Helicobacteraceae may be closely related to behavioral results. Disrupted gut microbiota could aggravate working memory dysfunction induced by high-altitude exposure in mice, indicating the existence of a link between high-altitude exposure and MGBA.

Effects of acute high-altitude exposure on working memory: A functional near-infrared spectroscopy study.

Inadequate oxygen availability may lead to impairment of neurocognitive functions. The aim of the present study was to investigate the effect of acute high-altitude exposure on the cerebral hemodynamic response and working memory. The same subjects performed working memory exercises with forward and backward digit span tasks both under normal oxygen conditions and in large simulated hypobaric hypoxia chambers, and a series of physiological parameters were evaluated. Functional near-infrared spectroscopy was used to measure cerebral blood flow changes in the dorsolateral prefrontal cortex (DLPFC) during the tasks. Compared with normoxic conditions, under hypoxic conditions, the heart rate and blood pressure increased, blood oxygen saturation decreased significantly, and the forward task had similar accuracy and response time, while the backward task had lower accuracy and longer response time. Neuroimaging analysis showed increased activation in the DLPFC during the forward task and deactivation during the backward task under hypobaric hypoxia conditions. Acute high-altitude exposure leads to physiological adaptations. The abnormal hemodynamic responses of the DLPFC to hypoxia at low pressure reveal the disruption of neurocognitive function by acute high-altitude exposure, which compromises complex cognitive functions, and provides a promising application for functional near infrared spectroscopy in the exploration of neural mechanisms in the brain during high-altitude exposure.

Inflammation in Pulmonary Hypertension and Edema Induced by Hypobaric Hypoxia Exposure.

Exposure to high altitudes generates a decrease in the partial pressure of oxygen, triggering a hypobaric hypoxic condition. This condition produces pathophysiologic alterations in an organism. In the lung, one of the principal responses to hypoxia is the development of hypoxic pulmonary vasoconstriction (HPV), which improves gas exchange. However, when HPV is exacerbated, it induces high-altitude pulmonary hypertension (HAPH). Another important illness in hypobaric hypoxia is high-altitude pulmonary edema (HAPE), which occurs under acute exposure. Several studies have shown that inflammatory processes are activated in high-altitude illnesses, highlighting the importance of the crosstalk between hypoxia and inflammation. The aim of this review is to determine the inflammatory pathways involved in hypobaric hypoxia, to investigate the key role of inflammation in lung pathologies, such as HAPH and HAPE, and to summarize different anti-inflammatory treatment approaches for these high-altitude illnesses. In conclusion, both HAPE and HAPH show an increase in inflammatory cell infiltration (macrophages and neutrophils), cytokine levels (IL-6, TNF-α and IL-1β), chemokine levels (MCP-1), and cell adhesion molecule levels (ICAM-1 and VCAM-1), and anti-inflammatory treatments (decreasing all inflammatory components mentioned above) seem to be promising mitigation strategies for treating lung pathologies associated with high-altitude exposure.

Assessment of hypoxia tolerance to high-altitude exposure following sleep deprivation

Objectives: The adverse effects of hypoxia and sleep deprivation (SD) have been studied separately but there is little literature on their effects when acting in conjunction. Hence, the effects of SD on hypoxia tolerance and cognitive performance when exposed to altitude were investigated. Material and Methods: In a cross-sectional repetitive measure design, 15 healthy volunteers assessed on cognitive performance were made to perform cognitive tests (Dual Task Test, Stroop Test [ST], and Digit Symbol Substitution Test [DSST] of Psychometric Evaluation Designed for Aviators test battery) on the ground and at a simulated altitude of 17,000 ft in a hypobaric chamber on 4 days. On the 2nd and 3rd day, the tests were done following 2 h of SD the previous night, and on the 4th day, the same was repeated following normal recovery sleep. Heart rate (HR) and respiratory rate (RR) were measured on the ground and 17,000 ft. The Lake Louise Acute Mountain Sickness (LLAMS) scores were used to assess the severity of symptoms of hypoxia and time to arterial oxygen desaturation of 75% was used to measure hypoxia tolerance. Results: Although not statistically significant, the LLAMS scores showed an increasing trend on SD days with an improvement in recovery of sleep. No statistically significant differences in the HR (F = 0.569, P = 0.637) and RR (F = 0.569, P = 0.637) were observed across the days of SD or recovery. The time to oxygen desaturation to 75% also showed no significant effect (F = 0.587, P = 0.625). A statistically significant increase in response times of two cognitive tests (ST and DSST) was observed on exposure to altitude on all 4 days. The three cognitive tests did not show any statistically significant effect following 2 h of SD or recovery. Conclusion: The study could not elicit a statistically significant effect of 2 h of SD across 2 consecutive nights on the cognitive performance measures on exposure to hypoxia.

Effects of high altitude on renal physiology and kidney diseases.

The hypobaric and hypoxic conditions of high-altitude areas exert adverse effects on the respiratory, circulatory and nervous systems. The kidneys have an abundant blood supply (20%-25% of cardiac output) and high blood flow; thus, they are susceptible to the effects of hypoxia. However, the effects of acute and chronic exposure to high altitudes on renal physiology and pathology are not fully understood. Moreover, few studies have investigated the impact of high-altitude exposure on patients with chronic kidney disease or acute kidney injury. In this review, we summarized changes in renal physiology and renal pathology due to high-altitude exposure as well as the impact of high-altitude exposure on existing kidney diseases, with the aim of informing the prevention and treatment of kidney diseases at high altitudes.

Gypenosides (GPs) alleviates hypoxia-induced injury in PC12 cells and enhances tolerance to anoxia in C57BL/6 mice.

Oxygen is a necessary substance for life activities, but reduced oxygen utilization due to high altitude exposure and respiratory dysfunction diseases could lead to pathological changes in the organisms. Herein gypenosides, the active ingredients in the food and medicine resource plant Gynostemma pentaphyllum (Thunb.) Makino were found to alleviate hypoxia-induced injury in PC12 cells. Moreover, hypoxia induced an increase in Ca2+ and reactive oxygen species content, and such patterns were both significantly reduced by gypenosides treatment. At the same time, gypenosides significantly blocked the decrease of both NO content and mitochondrial membrane potential caused by hypoxia. Furthermore, gypenosides gavage treatment significantly prolonged the survival time of C57BL/6 mice in confinement up to 24.3% and enhanced the locomotor ability of mice. Therefore, gypenosides have good neuroprotective effects and hypoxia tolerance activity and have the prospect of being developed as a preventive and therapeutic drug for hypoxia-related diseases. PRACTICAL APPLICATIONS: Gypenosides can enhance tolerance of cells and mice to hypoxia and have the potential to be developed into hypoxia-resistant health food and drugs.

Lactobacillus johnsonii YH1136 plays a protective role against endogenous pathogenic bacteria induced intestinal dysfunction by reconstructing gut microbiota in mice exposed at high altitude.

BackgroundIntestinal microbiota plays an important role in maintaining the microecological balance of the gastrointestinal tract in various animals. Disturbances in the intestinal microbiota may lead to the proliferation of potentially pathogenic bacteria that become the dominant species, leading to intestinal immune disorders, intestinal inflammation, and other intestinal diseases. Numerous studies have been confirmed that high-altitude exposure affects the normal function of the intestine and the composition of the intestinal microbiota. However, it is still necessary to reveal the changes in intestinal microbiota in high-altitude exposure environments, and clarify the relationship between the proliferation of potentially pathogenic bacteria and intestinal injury in this environment. In addition, explored probiotics that may have preventive effects against intestinal diseases.Methods and resultsC57BL/6 mice were randomly divided into three groups, a high-altitude group (HA), control group (C), and high-altitude probiotic group (HAP). The HA and HAP groups were subjected to hypoxia modeling for 14 days in a low-pressure oxygen chamber with daily gavage of 0.2 mL of normal saline (HA) and Lactobacillus johnsonii YH1136 bacterial fluid (HAP), while the control group was fed normally. L. johnsonii YH1136 was isolated from feces of a healthy Tibetan girl in Baingoin county, the Nagqu region of the Tibet Autonomous Region, at an altitude of 5000 meters. Our observations revealed that gavage of YH1136 was effective in improving the damage to the intestinal barrier caused by high-altitude exposure to hypoxic environments and helped to reduce the likelihood of pathogenic bacteria infection through the intestinal barrier. It also positively regulates the intestinal microbiota to the extent of Lactobacillus being the dominant microbiome and reducing the number of pathogenic bacteria. By analyzing the expression profile of ileal microRNAs and correlation analysis with intestinal microbiota, we found that Staphylococcus and Corynebacterium1 cooperated with miR-196a-1-3p and miR-3060-3p, respectively, to play a regulatory role in the process of high-altitude hypoxia-induced intestinal injury.ConclusionThese findings revealed the beneficial effect of L. johnsonii YH1136 in preventing potential endogenous pathogenic bacteria-induced intestinal dysfunction in high-altitude environments. The mechanism may be related to the regulation of intestinal injury from the perspective of the gut microbiota as well as miRNAs.

Identification of Suitable Reference Genes for Lowlanders Exposed to High Altitude and Ladakhi Highlanders.

Sharma, Vandana, Rajeev Varshney, and Niroj Kumar Sethy. Identification of suitable reference genes for lowlanders exposed to high altitude and Ladakhi highlanders. High Alt Med Biol. 23:319-329, 2022. Background: Identifying a stable and reliable reference gene (RG) is a prerequisite for the unbiased and unambiguous analysis of gene expression data. It has become evident that conventionally used housekeeping genes such as beta-actin (ACTB), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and peptidylprolyl Isomerase A (PPIA) exhibit varied expression patterns under hypoxia. Hence, the identification of stable RGs for humans exposed to hypobaric hypoxia can enhance the accuracy of gene expression studies by limiting the negligent use of random housekeeping genes. Methods: Using TaqMan™ array-based quantitative real-time quantitative polymerase chain reaction, we evaluated the expression of 32 commonly used human RGs among lowlanders at Delhi (altitude 216 m, SL), lowlanders at Leh (altitude 3,524 m) after 1 day (HA-D1) and 7 days (HA-D7), as well as indigenous Ladakhi highlanders at the same altitude. The expression stability of the RGs was evaluated using geNorm, NormFinder, BestKeeper, Delta CT method, and RefFinder algorithms. Results: Our studies identify TATA-box binding protein (TBP), proteasome 26S subunit, ATPase 4 (PSMC4), and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) as the most stable human RGs for normalizing human gene expression under hypobaric hypoxia. In addition, we report the combination of TBP and cyclin-dependent kinase inhibitor 1B (CDKN1B) as the most stable RG for studying lowlander gene expression during high-altitude exposure. In contrast, RPL30 and 18S exhibited maximum variation across study groups and were identified as the least stable RGs.

Strengthening Altitude Knowledge: A Delphi Study to Define Minimum Knowledge of Altitude Illness for Laypersons Traveling to High Altitude.

Berendsen, Remco R., Peter Bärtsch, Buddha Basnyat, Marc Moritz Berger, Peter Hackett, Andrew M. Luks, Jean-Paul Richalet, Ken Zafren, Bengt Kayser, and the STAK Plenary Group. Strengthening altitude knowledge: a Delphi study to define minimum knowledge of altitude illness for laypersons traveling to high altitude. High Alt Med Biol. 23:330-337, 2022. Introduction: A lack of knowledge among laypersons about the hazards of high-altitude exposure contributes to morbidity and mortality from acute mountain sickness (AMS), high-altitude cerebral edema (HACE), and high-altitude pulmonary edema (HAPE) among high-altitude travelers. There are guidelines regarding the recognition, prevention, and treatment of acute-altitude illness for experts, but essential knowledge for laypersons traveling to high altitudes has not been defined. We sought expert consensus on the essential knowledge required for people planning to travel to high altitudes. Methods: The Delphi method was used. The panel consisted of two moderators, a core expert group and a plenary expert group. The moderators made a preliminary list of statements defining the desired minimum knowledge for laypersons traveling to high altitudes, based on the relevant literature. These preliminary statements were then reviewed, supplemented, and modified by a core expert group. A list of 33 statements was then presented to a plenary group of experts in successive rounds. Results: It took three rounds to reach a consensus. Of the 10 core experts invited, 7 completed all the rounds. Of the 76 plenary experts, 41 (54%) participated in Round 1, and of these 41 a total of 32 (78%) experts completed all three rounds. The final list contained 28 statements in 5 categories (altitude physiology, sleeping at altitude, AMS, HACE, and HAPE). This list represents an expert consensus on the desired minimum knowledge for laypersons planning high-altitude travel. Conclusion: Using the Delphi method, the STrengthening Altitude Knowledge initiative yielded a set of 28 statements representing essential learning objectives for laypersons who plan to travel to high altitudes. This list could be used to develop educational interventions.

Insight into the Effects of High-Altitude Hypoxic Exposure on Learning and Memory.

The earth land area is heterogeneous in terms of elevation; about 45% of its land area belongs to higher elevation with altitude above 500 meters compared to sea level. In most cases, oxygen concentration decreases as altitude increases. Thus, high-altitude hypoxic stress is commonly faced by residents in areas with an average elevation exceeding 2500 meters and those who have just entered the plateau. High-altitude hypoxia significantly affects advanced neurobehaviors including learning and memory (L&M). Hippocampus, the integration center of L&M, could be the most crucial target affected by high-altitude hypoxia exposure. Based on these points, this review thoroughly discussed the relationship between high-altitude hypoxia and L&M impairment, in terms of hippocampal neuron apoptosis and dysfunction, neuronal oxidative stress disorder, neurotransmitters and related receptors, and nerve cell energy metabolism disorder, which is of great significance to find potential targets for medical intervention. Studies illustrate that the mechanism of L&M damaged by high-altitude hypoxia should be further investigated based on the entire review of issues related to this topic.

Urban-rural disparities in the association between long-term exposure to high altitude and malnutrition among children under 5 years old: evidence from a cross-sectional study in Tibet.

To assess urban-rural disparities in the association between long-term exposure to high altitude and malnutrition among children under 5 years old. A three-stage, stratified, cluster sampling was used to randomly select eligible individuals from July to October 2020. The data of participants, including demographic characteristics, altitude of residence, and nutritional status, were collected via questionnaire and physical examination. Tibet, China. Children under 5 years old in Tibet. Totally, 1975 children under 5 years old were included in this study. We found that an additional 1000 m increase in altitude was associated with decreased Z-scores of height-for-age (β = -0·23, 95 % CI: -0·38, -0·08), Z-scores of weight-for-age (β = -0·24, 95 % CI: -0·39, -0·10). The OR for stunting and underweight were 2·03 (95 % CI: 1·51 to 2·73) and 2·04 (95 % CI: 1·38 to 3·02) per 1000 m increase in altitude, respectively; and OR increased rapidly at an altitude above 3500 m. The effects of long-term exposure to high altitudes on the prevalence of underweight in rural children were higher than that in urban children (P < 0·05). High-altitude exposure is tightly associated with malnutrition among children under 5 years old. Improving children's nutrition is urgently needed in areas above 3500 m, especially in rural ones.