DATA in BRIEF of: Adaptative mechanisms indicated by placental protein expression changes in high-altitude Tibetan women during vaginal delivery.

Over a period of 30,000 to 40,000 years, high-altitude Tibetans have physiologically and genetically adapted to conditions such as hypoxia, low temperature, and high-intensity ultraviolet radiation. Based on the unique physiological and morphological characteristics of the Tibetan people, they have outstanding hypoxia adaptation skills and can continue to thrive in plateau hypoxia. The placenta of high-altitude Tibetans is protected from oxidative stress during delivery; however, little is known about changes in placental protein expression during vaginal delivery. In this study, we aimed to reveal these adaptive mechanisms by studying changes in placental protein expression during vaginal delivery in high-altitude Tibetans, low-altitude Tibetans, and low-altitude Han populations. Studying the changing mechanisms of maternal responses to hypoxia at high altitudes can reveal the molecular mechanisms of maternal and fetal adaptation to hypoxia at high altitudes and provide theories for preventing and treating maternal hypoxia and intrauterine growth and development restriction caused by other diseases.

Combined intermittent hypoxic exposure at rest and continuous hypoxic training can maintain elevated hemoglobin mass after a hypoxic camp.

Athletes use hypoxic living and training to increase hemoglobin mass (Hbmass), but Hbmass declines rapidly upon return to sea level. We investigated whether Intermittent Hypoxic Exposure (IHE) + Continuous Hypoxic Training (CHT) after return to sea level maintained elevated Hbmass, and if changes in Hbmass were transferred to changes in maximal oxygen uptake (V̇O2max) and exercise performance. Hbmass was measured in 58 endurance athletes before (PRE), after (POST1), and 30 days after (POST2) a 27 ± 4-day training camp in hypoxia (n=44, HYP) or at sea level (n=14, SL). After return to sea level, 22 athletes included IHE (2 h rest) + CHT (1 h training) into their training every third day for one month (HYPIHE+CHT), whereas the other 22 HYP athletes were not exposed to IHE or CHT (HYPSL). Hbmass increased from PRE to POST1 in both HYPIHE+CHT (4.4 ± 0.7%, mean ± SEM) and HYPSL (4.1 ± 0.6%) (both p<0.001). Compared to PRE, Hbmass at POST2 remained 4.2 ± 0.8% higher in HYPIHE+CHT (p<0.001) and1.9 ± 0.5% higher in HYPSL (p=0.023), indicating a significant difference between the groups (p=0.002). In SL, no significant changes were observed in Hbmass with mean alterations between -0.5% and 0.4%. V̇O2max and time to exhaustion during an incremental treadmill test (n=35) were elevated from PRE to POST2 only in HYPIHE+CHT (5.8 ± 1.2% and 5.4 ± 1.4%, respectively, both p<0.001). IHE+CHT possesses the potential to mitigate the typical decline in Hbmass commonly observed during the initial weeks after return to sea level.

Soil organic matter and water content affect the community characteristics of arbuscular mycorrhizal fungi in Helan mountain, an arid desert grassland area in China.

Introduction: Arbuscular mycorrhizal fungi (AMF) are vital in terrestrial ecosystems. However, the community structure characteristics and influencing factors of AMF in the forest ecosystems of arid desert grassland areas require further investigation. Methods: Therefore, we employed high-throughput sequencing technology to analyze the soil AMF community characteristics at different elevations in the Helan mountains. Results: The results revealed that significant differences (P < 0.05) were observed in the soil physicochemical properties among different elevations, and these properties exhibited distinct trends with increasing elevation. Through high-throughput sequencing, we identified 986 operational taxonomic units (OTUs) belonging to 1 phylum, 4 classes, 6 orders, 12 families, 14 genera, and 114 species. The dominant genus was Glomus. Furthermore, significant differences (P < 0.05) were observed in the α-diversity of the soil AMF community across different elevations. Person correlation analysis, redundancy analysis (RDA), and Monte Carlo tests demonstrated significant correlations between the diversity and abundance of AMF communities with soil organic matter (OM) (P < 0.01) and soil water content (WC) (P < 0.05). Discussion: This study provides insights into the structural characteristics of soil AMF communities at various altitudes on the eastern slope of Helan mountain and their relationships with soil physicochemical properties. The findings contribute to our understanding of the distribution pattern of soil AMF and its associations with environmental factors in the Helan mountains, as well as the stability of forest ecosystems in arid desert grassland areas.

Assessment of metabolomic variations among individuals returning to plain areas after exposure to high altitudes: a metabolomic analysis of human plasma samples with high-altitude de-acclimatization syndrome.

Background: High altitude de-acclimatization (HADA) is gradually becoming a public health concern as millions of individuals of different occupations migrate to high-altitude areas for work due to economic growth in plateau areas. HADA affects people who return to lower elevations after exposure to high altitudes. It causes significant physiological and functional changes that can negatively impact health and even endanger life. However, uncertainties persist about the detailed mechanisms underlying HADA. Methods: We established a population cohort of individuals with HADA and assessed variations in metabolite composition. Plasm samples of four groups, including subjects staying at plain (P) and high altitude (H) as well as subjects suffering from HADA syndrome with almost no reaction (r3) and mild-to-moderate reaction (R3) after returning to plain from high altitude, were collected and analyzed by Liquid Chromatography-Mass Spectrometry metabolomic. Multivariate statistical analyses were used to explore significant differences and potential clinical prospect of metabolites. Result: Although significantly different on current HADAS diagnostic symptom score, there were no differences in 17 usual clinical indices between r3 and R3. Further multivariate analyses showed isolated clustering distribution of the metabolites among the four groups, suggesting significant differences in their metabolic characteristics. Through K-means clustering analysis, we identified 235 metabolites that exhibited patterns of abundance change consistent with phenotype of HADA syndrome. Pathway enrichment analysis indicated a high influence of polyunsaturated fatty acids under high-altitude conditions. We compared the metabolites between R3 and r3 and found 107 metabolites with differential abundance involved in lipid metabolism and oxidation, suggesting their potential role in the regulation of oxidative stress homeostasis. Among them, four metabolites might play a key role in the occurrence of HADA, including 11-beta-hydroxyandrosterone-3-glucuronide, 5-methoxyindoleacetate, 9,10-epoxyoctadecenoic acid, and PysoPC (20:5). Conclusion: We observed the dynamic variation in the metabolic process of HADA. Levels of four metabolites, which might be provoking HADA mediated through lipid metabolism and oxidation, were expected to be explore prospective indices for HADA. Additionally, metabolomics was more efficient in identifying environmental risk factors than clinical examination when dramatic metabolic disturbances underlying the difference in symptoms were detected, providing new insights into the molecular mechanisms of HADAS.

Clinical Conundrum: Return to High Altitude After Cerebral Venous Sinus Thrombosis.

Luks, Andrew M., Thomas G. DeLoughery, Jeffrey H. Gertsch, and Suzy Stokes. Clinical conundrum: return to high altitude after cerebral venous sinus thrombosis. High Alt Med Biol. 00:00-00, 2024.

Prevalence and Risk Factors of Ocular Demodex at Ultra-High Altitude and Sea Level: A Cross-Sectional Study of Shigatse and Shanghai.

Purpose: Demodex infestation is a risk factor for several ocular surface diseases. However, the prevalence of ocular Demodex infection in the ultra-high altitude population is not clear. This study aimed to compare the prevalence and factors associated with Demodex in populations residing in ultra-high altitude region and sea level areas. Methods: Consecutive patients who visited Shigatse People's Hospital (> 4,000 m) and Shanghai Tongren Hospital (sea level) for eye complaints between January 2023 and January 2024 were included. Subjects were divided into ultra-high altitude and sea level groups. All subjects underwent eyelash epilation for ocular Demodex identification and counting. Demographic and lifestyle information was also collected. Results: A total of 517 subjects were eligible, including 255 subjects in the ultra-high-altitude group and 262 subjects in the sea level group. In the overall analysis, the prevalence of ocular Demodex infection was significantly different between the ultra-high-altitude and sea level groups (15.7% vs. 33.2%, P < 0.001). Multiple logistic regression showed that age, time spent outdoors, and makeup were associated with ocular Demodex infection in both groups. In addition, in the ultra-high-altitude group, people who wear sun hats outdoors were more likely to be infected with Demodex. Conclusion: The infection rate of ocular Demodex in the residents of ultra-high altitude area was significantly lower than that in the residents of sea level area, which may be related to lower ambient temperature, lower humidity, and higher solar radiation. Additionally, age, time spent outdoors, and makeup may be associated with ocular Demodex infection.

Effects of Naltrexone on Sleep Quality and Periodic Breathing at High Altitude.

Foster, Katharine, James D. Anholm, Gary Foster, Suman Thapamagar, and Prajan Subedi. Effects of naltrexone on sleep quality and periodic breathing at high altitude. High Alt Med Biol. 00:000-000, 2024. Objective: This study examined the effects of naltrexone on breathing and sleep at high altitude. Mu-opioid receptor (MOR) agonists have a depressive effect on respiration. Naltrexone is known to block the MOR. We hypothesized that MOR blockade with naltrexone would result in higher nocturnal oxygen saturations, fewer apneas, and improved sleep at high altitude. Methods: This double-blind, placebo-controlled, crossover study included nine healthy volunteers (four females, five males) aged 27.9 (4.6) (mean [standard deviation]) years. Two overnight trips spaced at least 2 weeks apart took participants from Loma Linda, CA (355 m) to the Barcroft Laboratory, CA (3,810 m) for each arm. Participants ingested either 50 mg naltrexone or matching placebo at bedtime. Sleep metrics were recorded using an ambulatory physiological sleep monitor (APSM). Subjective data were measured with the Groningen Sleep Quality Scale, Stanford Sleepiness Scale, and the 2018 Lake Louise Score (LLS) for acute mountain sickness (AMS). Results: Mean overnight SpO2 was lower after taking naltrexone, 81% (6) versus 83% (4) (mean difference 1.9% [2.1, 95% confidence interval or CI = 0.1-3.6, p = 0.040]). The lowest overnight SpO2 (nadir) was lower on naltrexone 70% (6) versus 74% (4) (dif. 4.6% [4.3], CI = 1.0-8.2, p = 0.020). Total sleep time and total apnea-hypopnea index were unchanged. Subjective sleep quality was significantly worse on naltrexone measured via the Groningen Sleep Quality Scale (p = 0.033) and Stanford Sleepiness Scale (p = 0.038). AMS measured via LLS was significantly worse while taking naltrexone (p = 0.025). Conclusion: Contrary to our hypothesis, this study demonstrated a significant decrease in nocturnal oxygen saturation, worse sleep quality, and AMS scores. Further characterization of the MOR's effects on sleep and AMS is needed to evaluate potential exacerbating mechanisms for AMS and poor sleep quality at altitude.

Preexisting Hyperuricemia Before High-Altitude Ascent is Associated with a Slower Recovery of Estimated Glomerular Filtration Rate Following Descent.

Zhao, Linggong, Yujie Huang, and Xiaoling Tan. Preexisting hyperuricemia before high-altitude ascent is associated with a slower recovery of estimated glomerular filtration rate following descent. High Alt Med Biol. 00:00-00, 2024. Objectives: Hypoxia at high altitudes results in elevated uric acid (UA) and reduced estimated glomerular filtration rate (eGFR). However, the impact of a prolonged high-altitude sojourn on UA levels and renal function in patients with preexisting hyperuricemia warrants further exploration. The study was to investigate the eGFR and related factors in patients with preexisting hyperuricemia following exposure to high altitude. Methods: The study included 345 participants, who worked at a high altitude for 1 year. Anthropometric and laboratory indices were collected before ascent (i.e., baseline), as well as 20 and 80 days after descent. The participants were categorized into individuals with hyperuricemia (HUA) or normal uric acid (NUA) group based on the presence or absence of hyperuricemia at baseline. Results: No difference in baseline eGFR was observed between the two groups before ascend or on day 20 after descent (p > 0.05). However, on day 80, eGFR of the HUA group was lower compared with the NUA group (p < 0.05). Correlations existed between post-descent eGFR levels and variables, including sampling time, UA levels, total and direct bilirubin, and baseline grouping. Conclusions: After high-altitude exposure, the recovery of eGFR was delayed in participants with preexisting hyperuricemia. Preexisting hyperuricemia and high-altitude hypoxia jointly contribute to renal impairment.

Case report: Dementia sensitivity to altitude changes and effective treatment with hyperbaric air and glutathione precursors.

A 78-year-old man with dementia experienced waxing and waning of symptoms with changes in altitude as he traveled from his home in the Rocky Mountains to lower elevations and back. To replicate the improvement in his symptoms with travel to lower elevations (higher pressure), the patient was treated with a near-identical repressurization in a hyperbaric chamber using compressed air. With four 1-h treatments at 1.3 Atmospheres Absolute (ATA) and concurrent administration of low-dose oral glutathione amino acid precursors, he recovered speech and showed improvement in activities of daily living. Regional broadcast media had documented his novel recovery. Nosocomial COVID-19 and withdrawal of hyperbaric air therapy led to patient demise 7 months after initiation of treatment. It is theorized that hyperbaric air therapy stimulated mitochondrial biochemical and physical changes, which led to clinical improvement.

Recent advances in predicting acute mountain sickness: from multidimensional cohort studies to cutting-edge model applications.

High-altitude illnesses, encompassing a spectrum of health threats including Acute Mountain Sickness (AMS), pose significant challenges to individuals exposed to high altitude environments, necessitating effective prophylaxis and immediate management. Given the variability in individual responses to these conditions, accurate prediction of high-altitude illnesses onset is of paramount importance. This review systematically consolidates recent advancements in research on predicting AMS by evaluating existing cohort data, predictive models, and methodologies, while also delving into the application of emerging technologies. Through a thorough analysis of scholarly literature, we discuss traditional prediction methods anchored in physiological parameters (e.g., heart rate, respiratory frequency, blood pressure) and biochemical markers, as well as the integration and utility of novel technologies such as biosensors, genetic testing, and artificial intelligence within high-altitude prediction research. While conventional pre-diction techniques have been extensively used, they are often constrained by limitations in accuracy, reliability, and multifactorial influences. The advent of these innovative technologies holds promise for more precise individual risk assessments and personalized preventive and therapeutic strategies across various forms of AMS. Future research endeavors must pivot decisively towards the meticulous identification and stringent validation of innovative predictive biomarkers and models. This strategic re-direction should catalyze intensified interdisciplinary cooperation to significantly deepen our mechanistic insights into the pathogenesis of AMS while refining existing prediction methodologies. These groundbreaking advancements harbor the potential to fundamentally transform preventive and therapeutic frameworks for high-altitude illnesses, ultimately securing augmented safety standards and wellbeing for individuals operating at elevated altitudes with far-reaching global implications.

Effectiveness of Continuous Positive Airway Pressure in Alleviating Hypoxemia and Improving Exertional Capacity at Altitude.

Strickland, Brian, Elan Small, Mary Ryan, and Ryan Paterson. Effectiveness of continuous positive airway pressure in alleviating hypoxemia and improving exertional capacity at altitude. High Alt Med Biol. 00:000-000, 2024. Introduction: Decreased oxygen saturation and exercise tolerance are commonly experienced at high altitude. Continuous positive airway pressure (CPAP) devices have become increasingly portable and battery powered, providing a potentially unique new therapeutic modality for treatment of altitude-related illnesses. This study evaluated the potential use of CPAP devices to improve and maintain oxygen saturation at altitude, both at rest and with exertion, to evaluate the feasibility of using this device at altitude. Methods: Subjects were taken to Mount Blue Sky and monitored while they hiked to the summit (4,350 m), maintaining a consistent level of exertion. Subjects hiked for 0.7 km both with and without CPAP set to 10 cmH2O pressure. Continuous vital signs were collected during the hike and recovery period. Results: All subjects completed the hike wearing CPAP devices at a vigorous level of exertion. Mean oxygen saturation of the CPAP group (M = 83.8%, SD = 3.72) was significantly higher than that of the control group during exertion (M = 78.7%, SD = 2.97); p = 0.005. Recovery after exertion was quicker in the CPAP group than the control group. Three subjects experienced claustrophobia requiring a brief pause, but were able to complete their exercise trial without removing equipment or experiencing adverse events. When pauses from claustrophobia were excluded, there was no difference in completion time between the groups (p = 0.06). Conclusion: CPAP reliably improved oxygen saturation at rest and during vigorous exertion at high altitude. Its ability to correct hypoxemia, even with physical exertion, may prove useful after further study as a portable self-carried device to prevent and treat altitude-related illness, or to improve safety in high-altitude rescues.

Selection signatures for high altitude adaptation in livestock: A review.

High altitude adapted livestock species (cattle, yak, goat, sheep, and horse) has critical role in the human socioeconomic sphere and acts as good source of animal source products including milk, meat, and leather, among other things. These species sustain production and reproduction even in harsh environments on account of adaptation resulting from continued evolution of beneficial traits. Selection pressure leads to various adaptive strategies in livestock whose footprints are evident at the different genomic sites as the "Selection Signature". Scrutiny of these signatures provides us crucial insight into the evolutionary process and domestication of livestock adapted to diverse climatic conditions. These signatures have the potential to change the sphere of animal breeding and further usher the selection programmes in right direction. Technological revolution and recent strides made in genomic studies has opened the routes for the identification of selection signatures. Numerous statistical approaches and bioinformatics tools have been developed to detect the selection signature. Consequently, studies across years have identified candidate genes under selection region found associated with numerous traits which have a say in adaptation to high-altitude environment. This makes it pertinent to have a better understanding about the selection signature, the ways to identify and how to utilize them for betterment of livestock populations as well as farmers. This review takes a closer look into the general concept, various methodologies, and bioinformatics tools commonly employed in selection signature studies and summarize the results of recent selection signature studies related to high-altitude adaptation in various livestock species. This review will serve as an informative and useful insight for researchers and students in the field of animal breeding and evolutionary biology.

Effect of Nitrate Supplementation on Oxygen Saturation Levels for Acute Mountain Sickness Prevention: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to systematically review the effect of nitrate supplementation on blood oxygen saturation. METHODS: We searched PubMed, Scopus, and Cochrane Library databases from their inception up to October 2022. Two reviewers independently conducted two stages of the screening process to include a randomized controlled trial with nitrate supplementation versus placebo intervention assessing oxygen saturation among lowlanders going to either real or simulated high altitude environments. We used the Cochrane Risk of Bias 2.0 tool to assess the risk of bias in the included studies. Fixed-effect model meta-analyses were conducted for laboratory-based studies. Random-effect meta-analyses were conducted for real-world studies. RESULTS: We found 7 trials that met the eligibility criteria. A meta-analysis of studies with some bias concerns showed an increase of 1.26% in the SpO2 with 44% I2 during submaximal exercise at simulated high altitudes (GRADE: low). On the contrary, a meta-analysis of studies without heterogeneity showed that nitrate supplementation aggravated oxygen saturation decline (-2.64%, p=0.03, GRADE: high) during rest in real high-altitude environments. A meta-analysis also showed that nitrate supplementation did not affect Acute Mountain Sickness (AMS) symptoms (GRADE: high). CONCLUSION: Our results suggest that nitrate supplementation did not provide benefits for AMS prevention during rest at high altitudes. The low-quality evidence showing small beneficial effects of nitrate supplementation during exercise calls for further studies.

Product of Traditional Chinese Medicine Longgui Yangxinwan Protects the Human Body from Altitude Sickness Damage by Reducing Oxidative Stress and Preventing Mitochondrial Dysfunction.

Yu Liu, Zhengyang Zhang, Yongting Luo, Peng An, Jingyi Qi, Xu Zhang, Shuaishuai Zhou, Yongzhi Li, Chong Xu, Junjie Luo, and Jiaping Wang. Product of traditional Chinese medicine longgui yangxinwan protects the human body from altitude sickness damage by reducing oxidative stress and preventing mitochondrial dysfunction. High Alt Med Biol. 00:00-00, 2024. Background: Plateau reaction, caused by high-altitude exposure, results in symptoms like headaches, dyspnea, palpitations, fatigue, shortness of breath, and insomnia due to reduced oxygen levels. Mitochondria are crucial for high-altitude acclimatization as they regulate oxygen metabolism and cellular energy, reducing oxidative stress and maintaining bodily functions. Methods: The study participants were randomly divided into placebo group, Rhodiola group and longgui yangxinwan (Original name: taikong yangxinwan) group, with 20 people in each group. Three groups of subjects were sampled at three time points (PI: pre-intervention; P-D1: high-altitude day 1; P-D7: high-altitude day 7), and blood pressure, blood oxygen, heart rate, hemoglobin, and red blood cell count were measured. The ATP content, mitochondrial DNA copy number, expression of mitochondria-related genes, reactive oxygen species (ROS), glutathione peroxidase (GSH-PX) and malondialdehyde (MDA) levels, and mitochondrial morphology were measured in blood at each time point. Results: Our study results demonstrate that longgui yangxinwan keeps the selected human physiological indicators stable and prevents mitochondrial dysfunction in the high altitude. Mechanically, longgui yangxinwan decreases the level of ROS in human serum, whereas increases the activity of the antioxidant enzyme GSH-PX. At high-altitude day 1 (P-D1) and high-altitude day 7 (P-D7), ROS in the placebo group were 1.5 and 2.2-fold higher than those of the longgui yangxinwan group, respectively. In addition, longgui yangxinwan enhances ATP production capacity, restores the levels of mitochondrial respiratory chain complexes, and effectively maintains mitochondrial morphology and integrity. At P-D1 and P-D7, the ATP levels in the longgui yangxinwan group were 19-fold and 26-fold higher than those in the placebo group, respectively. Conclusions: Our study highlights longgui yangxinwan as a potential drug for protecting humans from high-altitude damage by reducing oxidative stress and preventing mitochondrial dysfunction.

Local adaptation, plasticity, and evolved resistance to hypoxic cold stress in high-altitude deer mice.

A fundamental question in evolutionary biology concerns the relative contributions of phenotypic plasticity vs. local adaptation (genotypic specialization) in enabling wide-ranging species to inhabit diverse environmental conditions. Here we conduct a long-term hypoxia acclimation experiment to assess the relative roles of local adaptation and plasticity in enabling highland and lowland deer mice (Peromyscus maniculatus) to sustain aerobic thermogenesis at progressively increasing elevations. We assessed the relative physiological performance capacities of highland and lowland natives as they were exposed to progressive, stepwise increases in hypoxia, simulating the gradual ascent from sea level to an elevation of 6000 m. The final elevation of 6000 m far exceeds the highest attainable elevations within the species' range, and therefore tests the animals' ability to tolerate levels of hypoxia that surpass the prevailing conditions within their current distributional limits. Our results demonstrate that highland natives exhibit superior thermogenic capacities at the most severe levels of hypoxia, suggesting that the species' broad fundamental niche and its ability to inhabit such a broad range of elevational zones is attributable to a combination of genetically based local adaptation and plasticity. Transcriptomic and physiological measurements identify evolved changes in the acclimation response to hypoxia that contribute to the enhanced thermogenic capacity of highland natives.

The role of the heart in the evolution of aerobic performance.

Aerobic metabolism underlies vital traits such as locomotion and thermogenesis, and aerobic capacity influences fitness in many animals. The heart is a key determinant of aerobic capacity, but the relative influence of cardiac output versus other steps in the O2 transport pathway remains contentious. In this Commentary, we consider this issue by examining the mechanistic basis for adaptive increases in aerobic capacity (thermogenic V̇O2,max; also called summit metabolism) in deer mice (Peromyscus maniculatus) native to high altitude. Thermogenic V̇O2,max is increased by acclimation to cold hypoxia (simulating high-altitude conditions), and high-altitude populations generally have greater V̇O2,max than their low-altitude counterparts. This plastic and evolved variation in V̇O2,max is associated with corresponding variation in maximal cardiac output, along with variation in other traits across the O2 pathway (e.g. arterial O2 saturation, blood haemoglobin content and O2 affinity, tissue O2 extraction, tissue oxidative capacity). By applying fundamental principles of gas exchange, we show that the relative influence of cardiac output on V̇O2,max depends on the O2 diffusing capacity of thermogenic tissues (skeletal muscles and brown adipose tissues). Functional interactions between cardiac output and blood haemoglobin content determine circulatory O2 delivery and thus affect V̇O2,max, particularly in high-altitude environments where erythropoiesis can increase haematocrit and blood viscosity. There may also be functional linkages between cardiac output and tissue O2 diffusion due to the role of blood flow in determining capillary haematocrit and red blood cell flux. Therefore, the functional interactions between cardiac output and other traits in the O2 pathway underlie the adaptive evolution of aerobic capacities.

Death Risk Response of High-Altitude Resident Populations to COVID-19 Vaccine: A Retrospective Cohort Study.

Vásquez-Velásquez, Cinthya, Diego Fano-Sizgorich, and Gustavo F Gonzales. Death risk response of high-altitude resident populations to COVID-19 vaccine: Retrospective cohort study. High Alt Med Biol. 00:00-00, 2024. Background: Peru had one of the highest mortality rates caused by the coronavirus disease 2019 (COVID-19) pandemic worldwide. Vaccination significantly reduces mortality. However, the effectiveness of vaccination might differ at different altitudinal levels. The study aimed to evaluate the effect modification of altitude on the association between vaccination and COVID-19 mortality in Peru. Methodology: A retrospective cohort, using open access databases of deaths, COVID-19 cases, hospitalizations, and vaccination was obtained from the Peruvian Ministry of Health. Deaths due to COVID-19 were evaluated in vaccinated and nonvaccinated patients. Crude (RR) and adjusted relative risks (aRR) were calculated using generalized linear models of Poisson family with robust variances. Models were adjusted for age, sex, pandemic wave, and Human Development Index. To evaluate the interaction by altitude, a stratified analysis by this variable was performed. The variable altitude was categorized as, 0-499 m (828,298 cases), 500-1,499 m (64,735 cases), 1,500-2,499 m (106,572 cases), and ≥2,500 m (179,004 cases). The final sample studied included 1,362,350 cases. Results: The vaccine showed a considerable reduction of death risk with the second (aRR: 0.41, 95% confidence interval [CI]: 0.38-0.44) and third doses (aRR: 0.21, 95% CI: 0.20-0.23). In the adjusted and interaction model, it can be observed that medium and high altitude present a higher risk of death compared to sea level (aRR: 2.58 and 2.03, respectively). Likewise, the two doses' group presents an aRR:1.22 for medium altitude (1,500-2,499 m) and 1.6 for high altitude (≥2,500 m), compared with low-altitude population, suggesting that the action of vaccination at high altitude is altered by the effect of the altitude itself. Conclusions: Altitude might modify the protective effect of SARS-CoV-2 vaccine against COVID-19 death.

The impact of high-altitude and cold environment on brain and heart damage in rats with hemorrhagic shock.

BACKGROUND: Hemorrhagic shock (HS) causes severe organ damage, worsened by high-altitude conditions with lower oxygen and temperatures. Existing research lacks specific insights on brain and heart damage under these conditions. This study hypothesizes that high-altitude and cold (HAC) environments exacerbate HS-induced damage in the brain and heart, aiming to improve treatment strategies. MATERIALS AND METHODS: Twenty-four male Sprague-Dawley (SD) rats (200-250 g of weight) were randomly assigned into sham, HS + normal, HS + HAC (4,000 m), and HS + HAC (6,000 m). The HS model was established in SD rats (35% loss of total blood volume), and histopathological injuries of the brain and heart were detected using hematoxylin and eosin staining, Sirius red staining, and immunohistochemistry. Apoptosis of the brain and heart tissues was detected by terminal transferase-mediated dUTP nick end labeling (TUNEL) immunofluorescence staining. To determine the levels of tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), monocyte chemoattractant protein-1 (Mcp-1), BCL2-associated X (BAX), and myeloid cell leukemia-1 (Mcl-1) protein, western blotting assay was used. RESULTS: The HAC environment induced pathological damage to the brain and heart and aggravated the degree of cardiac fibrosis in HS rats. However, it did not cause apoptosis of the brain and heart. In addition, it upregulated TNF-α, IFN-γ, Mcp-1, and BAX protein levels, but downregulated Mcl-1 protein levels (P < 0.05). CONCLUSIONS: The HAC environment aggravated the degree of brain and heart damage in HS rats, which may be related to neuron nucleus pyknosis, myocardial fibrosis, and inflammatory and apoptosis activation.