Mateikaitė-Pipirienė, Kastė, Dominique Jean, Peter Paal, Lenka Horakova, Susi Kriemler, Alison J. Rosier, Marija Andjelkovic, Beth A. Beidleman, Mia Derstine, Jacqueline Pichler Hefti, David Hillebrandt, and Linda E. Keyes for the UIAA MedCom writing group on Women's Health in the Mountains. Menopause and high altitude: A scoping review-UIAA Medical Commission Recommendations. High Alt Med Biol. 25:1-8, 2024. Background: Older people are an important fraction of mountain travelers and climbers, many of them postmenopausal women. The aim of this work was to review health issues that older and postmenopausal women may experience at high altitude, including susceptibility to high-altitude illness. Methods: We performed a scoping review for the UIAA Medical Commission series on Women's Health in the mountains. We searched PubMed and Cochrane libraries and performed an additional manual search. The primary search focused on articles assessing lowland women sojourning at high altitude. Results: We screened 7,165 potential articles. The search revealed three relevant articles, and the manual search another seven articles and one abstract. Seven assessed menopausal low-altitude residents during a high-altitude sojourn or performing hypoxic tests. Four assessed high-altitude residents. We summarize the results of these 11 studies. Conclusions: Data are limited on the effects of high altitude on postmenopausal women. The effects of short-term, high-altitude exposure on menopause symptoms are unknown. Menopause has minimal effect on the physiological responses to hypoxia in physically fit women and does not increase the risk of acute mountain sickness. Postmenopausal women have an increased risk of urinary tract infections, which may be exacerbated during mountain travel. More research is needed on the physiology and performance of older women at high altitude.
BACKGROUND: The optimal dose of dexamethasone for severe/critical COVID-19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID-19 and hypoxia. METHODS: We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethasone in adults with COVID-19 and hypoxia. The primary outcome was mortality at 1 month. Secondary outcomes were mortality closest to 90 days; days alive without life support; and the occurrence of serious adverse events/reactions (SAEs/SARs) closest to 1 month. We assessed the risk of bias using the Cochrane RoB2 tool, risk of random errors using trial sequential analysis, and certainty of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We included eight trials (2478 participants), of which four (1293 participants) had low risk of bias. Higher doses of dexamethasone probably resulted in little to no difference in mortality at 1 month (relative risk [RR] 0.97, 95% CI: 0.79-1.19), mortality closest to Day 90 (RR 1.01, 95% CI: 0.86-1.20), and SAEs/SARs (RR 1.00, 95% CI: 0.97-1.02). Higher doses of dexamethasone probably increased the number of days alive without invasive mechanical ventilation and circulatory support but had no effect on days alive without renal replacement therapy. CONCLUSIONS: Based on low to moderate certainty evidence, higher versus standard doses of dexamethasone probably result in little to no difference in mortality, SAEs/SARs, and days alive without renal replacement therapy, but probably increase the number of days alive without invasive mechanical ventilation and circulatory support.
- MeSH
- COVID-19 * MeSH
- dexamethason škodlivé účinky MeSH
- dospělí MeSH
- farmakoterapie COVID-19 MeSH
- hypoxie MeSH
- lidé MeSH
- pacienti MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
Visual loss in acute optic neuritis is typically attributed to axonal conduction block due to inflammatory demyelination, but the mechanisms remain unclear. Recent research has highlighted tissue hypoxia as an important cause of neurological deficits and tissue damage in both multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) and, here, we examine whether the optic nerves are hypoxic in experimental optic neuritis induced in Dark Agouti rats. At both the first and second peaks of disease expression, inflamed optic nerves labelled significantly for tissue hypoxia (namely, positive for hypoxia inducible factor-1α (HIF1α) and intravenously administered pimonidazole). Acutely inflamed nerves were also labelled significantly for innate markers of oxidative and nitrative stress and damage, including superoxide, nitric oxide and 3-nitrotyrosine. The density and diameter of capillaries were also increased. We conclude that in acute optic neuritis, the optic nerves are hypoxic and come under oxidative and nitrative stress and damage. Tissue hypoxia can cause mitochondrial failure and thus explains visual loss due to axonal conduction block. Tissue hypoxia can also induce a damaging oxidative and nitrative environment. The findings indicate that treatment to prevent tissue hypoxia in acute optic neuritis may help to restore vision and protect from damaging reactive oxygen and nitrogen species.
- MeSH
- encefalomyelitida autoimunitní experimentální * metabolismus MeSH
- hypoxie metabolismus MeSH
- imunologické faktory metabolismus MeSH
- krysa rodu rattus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nervus opticus metabolismus MeSH
- zánět zrakového nervu * metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: This randomised study in preterm infants on non-invasive respiratory support investigated the effectiveness of automated oxygen control (A-FiO2) in keeping the oxygen saturation (SpO2) within a target range (TR) during a 28-day period compared with manual titration (M-FiO2). DESIGN: A single-centre randomised control trial. SETTING: A level III neonatal intensive care unit. PATIENTS: Preterm infants (<28 weeks' gestation) on non-invasive respiratory support. INTERVENTIONS: A-FiO2 versus M-FiO2 control. METHODS: Main outcomes were the proportion of time spent and median area of episodes in the TR, hyperoxaemia, hypoxaemia and the trend over 28 days using a linear random intercept model. RESULTS: 23 preterm infants (median gestation 25.7 weeks; birth weight 820 g) were randomised. Compared with M-FiO2, the time spent within TR was higher in the A-FiO2 group (68.7% vs 48.0%, p<0.001). Infants in the A-FiO2 group spent less time in hyperoxaemia (13.8% vs 37.7%, p<0.001), but no difference was found in hypoxaemia. The time-based analyses showed that the A-FiO2 efficacy may differ over time, especially for hypoxaemia. Compared with the M-FiO2 group, the A-FiO2 group had a larger intercept but with an inversed slope for the daily median area below the TR (intercept 70.1 vs 36.3; estimate/day -0.70 vs 0.69, p<0.001). CONCLUSION: A-FiO2 control was superior to manual control in keeping preterm infants on non-invasive respiratory support in a prespecified TR over a period of 28 days. This improvement may come at the expense of increased time below the TR in the first days after initiating A-FiO2 control. TRIAL REGISTRATION NUMBER: NTR6731.
- MeSH
- hypoxie prevence a kontrola MeSH
- klinické křížové studie MeSH
- kojenec MeSH
- kyslík * MeSH
- lidé MeSH
- novorozenec nedonošený * MeSH
- novorozenec MeSH
- porodní hmotnost MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: Blood bicarbonate concentration plays an important role for obstructive sleep apnea (OSA) patients to maintain acid-base balance. We investigated the association between arterial standard bicarbonate ([HCO3-]) and nocturnal hypoxia as well as comorbid hypertension in OSA. METHODS: A cross-sectional analysis of 3329 patients in the European Sleep Apnea Database (ESADA) was performed. Arterial blood gas analysis and lung function test were performed in conjunction with polysomnographic sleep studies. The 4% oxygen desaturation index (ODI), mean and minimum oxygen saturation (SpO2), and percentage of time with SpO2 below 90% (T90%) were used to reflect nocturnal hypoxic burden. Arterial hypertension was defined as a physician diagnosis of hypertension with ongoing antihypertensive medication. Hypertensive patients with SBP/DBP below or above 140/90 mmHg were classified as controlled-, uncontrolled hypertension, respectively. RESULTS: The [HCO3-] level was normal in most patients (average 24.0 ± 2.5 mmol/L). ODI, T90% increased whereas mean and minimum SpO2 decreased across [HCO3-] tertiles (ANOVA, p = 0.030, <0.001, <0.001, and <0.001, respectively). [HCO3-] was independently associated with ODI, mean SpO2, minimum SpO2, and T90% after adjusting for confounders (β value [95%CI]: 1.21 [0.88-1.54], -0.16 [-0.20 to -0.11], -0.51 [-0.64 to -0.37], 1.76 [1.48-2.04], respectively, all p < 0.001). 1 mmol/L elevation of [HCO3-] was associated with a 4% increased odds of uncontrolled hypertension (OR: 1.04 [1.01-1.08], p = 0.013). CONCLUSION: We first demonstrated an independent association between [HCO3-] and nocturnal hypoxic burden as well as uncontrolled hypertension in OSA patients. Bicarbonate levels as an adjunctive measure provide insight into the pathophysiology of hypertension in OSA.
- MeSH
- hydrogenuhličitany MeSH
- hypertenze * epidemiologie komplikace MeSH
- hypoxie komplikace MeSH
- kyslík MeSH
- lidé MeSH
- obstrukční spánková apnoe * MeSH
- průřezové studie MeSH
- syndromy spánkové apnoe * komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
TP53 gene abnormalities represent the most important biomarker in chronic lymphocytic leukemia (CLL). Altered protein modifications could also influence p53 function, even in the wild-type protein. We assessed the impact of p53 protein phosphorylations on p53 functions as an alternative inactivation mechanism. We studied p53 phospho-profiles induced by DNA-damaging agents (fludarabine, doxorubicin) in 71 TP53-intact primary CLL samples. Doxorubicin induced two distinct phospho-profiles: profile I (heavily phosphorylated) and profile II (hypophosphorylated). Profile II samples were less capable of activating p53 target genes upon doxorubicin exposure, resembling TP53-mutant samples at the transcriptomic level, whereas standard p53 signaling was triggered in profile I. ATM locus defects were more common in profile II. The samples also differed in the basal activity of the hypoxia pathway: the highest level was detected in TP53-mutant samples, followed by profile II and profile I. Our study suggests that wild-type TP53 CLL cells with less phosphorylated p53 show TP53-mutant-like behavior after DNA damage. p53 hypophosphorylation and the related lower ability to respond to DNA damage are linked to ATM locus defects and the higher basal activity of the hypoxia pathway.
- MeSH
- ATM protein genetika metabolismus MeSH
- chronická lymfatická leukemie * genetika MeSH
- doxorubicin farmakologie MeSH
- fosforylace MeSH
- geny p53 MeSH
- hypoxie genetika MeSH
- lidé MeSH
- nádorový supresorový protein p53 * metabolismus MeSH
- poškození DNA MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Mycotoxins induce oxidative stress, hypoxia, and cause immunosuppressive effects. Moreover, emerging evidence show that mycotoxins have a potential of inducing cellular senescence, which are involved in their immunomodulatory effects. Mycotoxins upregulate the expression of senescence markers γ-H2AX, senescence-associated β-galactosidase, p53, p16, and senescence-associated secretory phenotype (SASP) inflammatory factors. Moreover, mycotoxins cause senescence-associated cell cycle arrest by diminishing cyclin D1 and Cdk4 pathways, as well as increasing the expression of p53, p21, and CDK6. Mycotoxins may induce cellular senescence by activating reactive oxygen species (ROS)-induced oxidative stress. In addition, hypoxia acts as a double-edged sword on cell senescence; it could both act as the stress-induced senescence and also hinder the onset of cellular senescence. The SASP inflammatory factors have the ability to induce an immunosuppressive environment, while mycotoxins directly cause immunosuppression. Therefore, there is a potential relationship between mycotoxins and cellular senescence that synergistically cause immunosuppression. However, most of the current studies have involved the effect of mycotoxins on cell cycle arrest, but only limited in-depth research has been carried out to link the occurrence of this condition (cell cycle arrest) with cellular senescence.
- MeSH
- hypoxie MeSH
- imunosupresivní léčba MeSH
- lidé MeSH
- nádorový supresorový protein p53 * metabolismus MeSH
- oxidační stres MeSH
- stárnutí buněk * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Although smartwatches are not considered medical devices, experimental validation of their accuracy in detecting hypoxemia is necessary due to their potential use in monitoring conditions manifested by a prolonged decrease in peripheral blood oxygen saturation (SpO2), such as chronic obstructive pulmonary disease, sleep apnea syndrome, and COVID-19, or at high altitudes, e.g., during sport climbing, where the use of finger-sensor-based pulse oximeters may be limited. The aim of this study was to experimentally compare the accuracy of SpO2 measurement of popular smartwatches with a clinically used pulse oximeter according to the requirements of ISO 80601-2-61. Each of the 18 young and healthy participants underwent the experimental assessment three times in randomized order-wearing Apple Watch 8, Samsung Galaxy Watch 5, or Withings ScanWatch-resulting in 54 individual experimental assessments and complete datasets. The accuracy of the SpO2 measurements was compared to that of the Radical-7 (Masimo Corporation, Irvine, CA, USA) during short-term hypoxemia induced by consecutive inhalation of three prepared gas mixtures with reduced oxygen concentrations (14%, 12%, and 10%). All three smartwatch models met the maximum acceptable root-mean-square deviation (≤4%) from the reference measurement at both normal oxygen levels and induced desaturation with SpO2 less than 90%. Apple Watch 8 reached the highest reliability due to its lowest mean bias and root-mean-square deviation, highest Pearson correlation coefficient, and accuracy in detecting hypoxemia. Our findings support the use of smartwatches to reliably detect hypoxemia in situations where the use of standard finger pulse oximeters may be limited.
- MeSH
- chronická obstrukční plicní nemoc * MeSH
- hypoxie diagnóza MeSH
- kyslík MeSH
- lidé MeSH
- oxymetrie * metody MeSH
- reprodukovatelnost výsledků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Farrerol (FA) is a traditional Chinese herbal medicine known for its anti-inflammatory and anti-oxidative properties in various diseases. Ferroptosis is an iron-dependent oxidative stress-induced cell death. It is characterized by lipid peroxidation and glutathione depletion and is involved in neuronal injury. However, the role of FA in inhibiting ferroptosis in hypoxic-ischemic encephalopathy (HIE) and its underlying mechanisms are not yet completely elucidated. This study aimed to investigate whether FA could mediate ferroptosis and explore its function and molecular mechanism in HIE. A neonatal rat model of HIE was used, and rats were treated with FA, ML385 (a specific inhibitor of nuclear factor erythroid 2-related factor 2 [Nrf2]), or a combination of both. Neurological deficits, infarction volume, brain water content, pathological changes, and iron ion accumulation in the brain tissues were measured using the Zea-Longa scoring system and triphenyl tetrazolium chloride (TTC), hematoxylin-eosin (HE), and Perls' staining. The expression levels of GSH-Px, MDA, SOD, and ROS in brain tissues were also evaluated. Western blot analysis was performed to analyze the expression of the Nrf2 pathway and ferroptosis-related proteins. The results showed that FA administration significantly reduced neuronal damage, infarct volume, cerebral edema, and iron ion accumulation and inhibited MDA and ROS levels while promoting GSH-Px and SOD levels. FA also increased the expression levels of glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), Nrf2, and HO-1. Moreover, the combination of ML385 and FA in HIE abolished the FA protective effects. Therefore, the study concludes that FA exerts a neuroprotective effect after HIE by inhibiting oxidative stress and ferroptosis via the Nrf2 signaling pathway.
- MeSH
- faktor 2 související s NF-E2 MeSH
- ferroptóza * MeSH
- glutathion MeSH
- krysa rodu rattus MeSH
- mozková hypoxie a ischemie * farmakoterapie MeSH
- novorozená zvířata MeSH
- reaktivní formy kyslíku MeSH
- superoxiddismutasa MeSH
- železo MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF THE STUDY Articular cartilage injury is a common disease in daily life, with a high incidence. The aim of this study was to investigate the effect and mechanism of miRNA-140-3p in bone mesenchymal stem cells (BMSCs)-derived exosomes under hypoxia on inflammatory articular chondrocytes. MATERIAL AND METHODS To simulate the pathological status of arthritis, rat chondrocytes were used to establish the osteoarthritis (OA) model by IL-1β (10 μg/ml) as a modulating in vitro, and exosomes were isolated by differential ultra-high speed centrifugation. The cell counting kit-8, wound healing and flow cytometry assays were utilized to assess proliferation, migration and apoptosis of chondrocytes, respectively. Lipogenic and chondrogenic differentiation of chondrocytes were detected by oil red O staining and toluidine blue staining individually. The expressions of miR-140-3p and chondrocyte-specific gene mRNA were investigated using qRT-PCR. Western blot was applied to assess chondrocyte associated proteins and BMSC-Exo surface protein markers, and immunohistochemistry was adopted to detect the staining of collagen I and II. RESULTS Under scanning electronic microscope, the shape of exosomes was almost round. Exosome treatment prominently impaired the inhibition of chondrocytes' proliferative and migrative ability by IL-1β. It was found hypoxia had a more marked impact on proliferation, expression of collagen II and apoptosis in OA chondrocytes than normoxia, as well as a stronger effect on weakening adipose differentiation and enhancing chondrogenic differentiation in inflammatory chondrocytes. Furthermore, incubation with BMSC-Exo overexpressing miR-140-3p can remarkably increase the survival rate and migration in inflammatory chondrocytes. In addition, overexpression of miR-140-3p was found to enhance the chondrogenic differentiation of inflammatory chondrocytes. Furthermore, we found that the healing effect of exosomes on inflammatory chondrocytes under hypoxic conditions was produced by a rise in miR-140-3p expression within them and that hypoxia-mediated upregulation of miR-140-3p expression occurred through HIF-1α. CONCLUSIONS Under hypoxia, BMSC-Exo enhanced the chondrogenic phenotype, increased the viability of inflammatory chondrocytes. The overexpression of miR-140-3p in BMSC-Exo is beneficial to protect joints and delaying the pathogenesis in OA. Key words: HIF-1α, apoptosis, lipogenic differentiation, chondrogenic differentiation.
- MeSH
- antiflogistika MeSH
- exozómy * genetika MeSH
- hypoxie MeSH
- krysa rodu rattus MeSH
- mikro RNA * genetika MeSH
- osteoartróza * genetika terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
