Ventilatory responses to independent and combined hypoxia, hypercapnia and hypobaria in healthy pre-term-born adults.

Pre-term birth is associated with physiological sequelae that persist into adulthood. In particular, modulated ventilatory responsiveness to hypoxia and hypercapnia has been observed in this population. Whether pre-term birth per se causes these effects remains unclear. Therefore, we aimed to assess pulmonary ventilation and blood gases under various environmental conditions, comparing 17 healthy prematurely born individuals (mean ± SD; gestational age, 28 ± 2 weeks; age, 21 ± 4 years; peak oxygen uptake, 48.1 ± 11.2 ml kg <sup>-1</sup> min <sup>-1</sup> ) with 16 well-matched adults born at term (gestational age, 40 ± 1 weeks; age, 22 ± 2 years; peak oxygen uptake, 51.2 ± 7.7 ml kg <sup>-1</sup> min <sup>-1</sup> ). Participants were exposed to seven combinations of hypoxia/hypobaria (equivalent to ∼3375 m) and/or hypercapnia (3% CO <sub>2</sub> ), at rest for 6 min. Pulmonary ventilation, pulse oxygen saturation and the arterial partial pressures of O <sub>2</sub> and CO <sub>2</sub> were similar in pre-term and full-term individuals under all conditions. Higher ventilation in hypoxia compared to normoxia was only observed at terrestrial altitude, despite an equivalent (normobaric) hypoxic stimulus administered at sea level (0.138 ). Assessment of oscillations in key variables revealed that combined hypoxic hypercapnia induced greater underlying fluctuations in ventilation in pre-term individuals only. In general, higher pulse oxygen saturation fluctuations were observed with hypoxia, and lower fluctuations in end-tidal CO <sub>2</sub> with hypercapnia, despite similar ventilatory oscillations observed between conditions. These findings suggest that healthy prematurely born adults display similar overall ventilation to their term-born counterparts under various environmental stressors, but that combined ventilatory stimuli could induce an irregular underlying ventilatory pattern. Moreover, barometric pressure may be an important factor when assessing ventilatory responsiveness to moderate hypoxic stimuli. KEY POINTS: Evidence exists for unique pulmonary and respiratory function under hypoxic conditions in adult survivors of pre-term birth. Whether pre-term birth per se causes these differences requires a comparison of conventionally healthy prematurely born adults with an appropriately matched sample of term-born individuals. According to the present data, there is no difference between healthy pre-term and well-matched term-born individuals in the magnitude of pulmonary ventilation or arterial blood gases during independent and combined hypobaria, hypoxia and hypercapnia. Terrestrial altitude (hypobaria) was necessary to induce differences in ventilation between normoxia and a hypoxic stimulus equivalent to ∼3375 m of altitude. Furthermore, peak power in pulse oxygen saturation was similar between hypobaric normoxia and normobaric hypoxia. The observed similarities between groups suggest that ventilatory regulation under various environmental stimuli is not impaired by pre-term birth per se. Instead, an integrated combination of neonatal treatment strategies and cardiorespiratory fitness/disease status might underlie previously observed chemosensitivity impairments

Microvascular and oxidative stress responses to acute high-altitude exposure in prematurely born adults.

Premature birth is associated with endothelial and mitochondrial dysfunction, and chronic oxidative stress, which might impair the physiological responses to acute altitude exposure. We assessed peripheral and oxidative stress responses to acute high-altitude exposure in preterm adults compared to term born controls. Post-occlusive skeletal muscle microvascular reactivity and oxidative capacity from the muscle oxygen consumption recovery rate constant (k) were determined by Near-Infrared Spectroscopy in the vastus lateralis of seventeen preterm and seventeen term born adults. Measurements were performed at sea-level and within 1 h of arrival at high-altitude (3375 m). Plasma markers of pro/antioxidant balance were assessed in both conditions. Upon acute altitude exposure, compared to sea-level, preterm participants exhibited a lower reperfusion rate (7 ± 31% vs. 30 ± 30%, p = 0.046) at microvascular level, but higher k (6 ± 32% vs. -15 ± 21%, p = 0.039), than their term born peers. The altitude-induced increases in plasma advanced oxidation protein products and catalase were higher (35 ± 61% vs. -13 ± 48% and 67 ± 64% vs. 15 ± 61%, p = 0.034 and p = 0.010, respectively) and in xanthine oxidase were lower (29 ± 82% vs. 159 ± 162%, p = 0.030) in preterm compared to term born adults. In conclusion, the blunted microvascular responsiveness, larger increases in oxidative stress and skeletal muscle oxidative capacity may compromise altitude acclimatization in healthy adults born preterm

Difference in expiratory flow limitations development in normoxia and hypoxia in healthy individuals.

The present study investigated the maintenance/repeatability of expiratory flow limitation (EFL) between normoxia and hypoxia. Fifty-one healthy active individuals (27 men and 24 women) performed a lung function test and a maximal incremental cycling test in both normoxia and hypoxia (inspired oxygen fraction = 0.14) on two separate visits. During exercise in normoxia, 28 participants exhibited EFL (55 %). In hypoxia, another cohort of 28 participants exhibited EFL. The two groups only partly overlapped. Individuals with EFL only in normoxia reported lower maximal ventilation values in hypoxia than in normoxia (n=5; -13.5 ± 7.8 %) compared to their counterparts with EFL only in hypoxia (n=5; +6.7 ± 6.3 %) or without EFL (n=18; +5.1 ± 10.3 %) (p=0.004 and p<0.001, respectively). EFL development may be induced by different mechanisms in hypoxia vs. normoxia since the individuals who exhibited flow limitation were not the same between the two environmental conditions. This change seems influenced by the magnitude of the maximal ventilation change

Oxidative stress and nitric oxide metabolism responses during prolonged high-altitude exposure in preterm born adults.

Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm (gestational age ≤ 32 weeks) and their term-born (gestational age ≥ 38 weeks) counterparts. Resting venous blood was obtained in normoxia (prior to altitude exposure), immediately upon arrival to altitude, and the following 3 mornings. Antioxidant (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and ferric reducing antioxidant power (FRAP)), pro-oxidant (xanthine oxidase (XO) and myeloperoxidase (MPO)) enzyme activity, oxidative stress markers (advanced oxidation protein product (AOPP) and malondialdehyde (MDA)), nitric oxide (NO) metabolites (nitrites, nitrates, and total nitrite and nitrate (NOx)), and nitrotyrosine were measured in plasma. SOD increased only in the preterm group (p < 0.05). Catalase increased at arrival in preterm group (p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely (arrival and Day 1) in control group. MPO increased in both groups throughout the 3 days (p < 0.05). AOPP only increased at arrival in the preterm (p < 0.05) whereas it decreased at arrival up to Day 3 (p < 0.05) for control. MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups (p < 0.05). Nitrites increased on Day 3 (p < 0.05) in control group and decreased on Day 1 (p < 0.05) in preterm group. These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals. These findings lend further support to the potential hypoxic preconditioning effect of preterm birth

Challenges and opportunities in many-core computing,”

With increasing use of computers that employ many independent processing units, commercial and technical-scientific software, as well as general-purpose operating systems, will have to undergo fundamental changes. By John L. Manferdelli, Naga K. Govindaraju, and Chris Crall ABSTRACT | In this paper, we present some of the challenges and opportunities in software development based on the current hardware trends and the impact of massive parallelism on both the software and hardware industry. We indicate some of the approaches that can enable software development to effectively exploit the many-core architectures. Some of these include encapsulating domain-specific knowledge in reusable components, such as libraries, integrating concurrency with languages, and supporting explicit declarations to help compilers and operating system schedulers. Tighter interaction between software and underlying hardware is required to build scalable and portable applications with predictable performance and higher power-efficiency. Overall, many-core computing provides us opportunities to enable new application scenarios that support enhanced functionality and a richer experience for the user on commodity hardware

Diversity of oat varieties in eliciting the early inflammatory events in celiac disease

Purpose Celiac disease (CD) is an autoimmune enteropathy, triggered by dietary gluten. The only treatment is a strict gluten-free diet. Oats are included in the list of gluten-free ingredients by European Regulation, but the safety of oats in CD is still a matter of debate. The present study examined the capability of different oat cultivars of activating the gliadin-induced transglutaminase-2 (TG2)-dependent events in some in vitro models of CD. In addition, we compared this capability with the electrophoresis pattern of peptic\u2013tryptic digests of the proteins of the oat cultivars. Methods K562(S) cells agglutination, transepithelial electrical resistance of T84-cell monolayers, intracellular levels of TG2 and phosphorylated form of protein 42\u201344 in T84 cells were the early gliadin-dependent events studied. Results The results showed that the Nave oat cultivar elicited these events, whereas Irina and Potenza varieties did not. The ability of a cultivar to activate the above-described events was associated with the electrophoretic pattern of oat proteins and their reactivity to anti-gliadin antibodies. Conclusion We found significant differences among oat cultivars in eliciting the TG2-mediated events of CD inflammation. Therefore, the safety of an oat cultivar in CD might be screened in vitro by means of biochemical and biological assays, before starting a clinical trial to definitely assess its safety

Recommendations for Women in Mountain Sports and Hypoxia Training/Conditioning.

The (patho-)physiological responses to hypoxia are highly heterogeneous between individuals. In this review, we focused on the roles of sex differences, which emerge as important factors in the regulation of the body's reaction to hypoxia. Several aspects should be considered for future research on hypoxia-related sex differences, particularly altitude training and clinical applications of hypoxia, as these will affect the selection of the optimal dose regarding safety and efficiency. There are several implications, but there are no practical recommendations if/how women should behave differently from men to optimise the benefits or minimise the risks of these hypoxia-related practices. Here, we evaluate the scarce scientific evidence of distinct (patho)physiological responses and adaptations to high altitude/hypoxia, biomechanical/anatomical differences in uphill/downhill locomotion, which is highly relevant for exercising in mountainous environments, and potentially differential effects of altitude training in women. Based on these factors, we derive sex-specific recommendations for mountain sports and intermittent hypoxia conditioning: (1) Although higher vulnerabilities of women to acute mountain sickness have not been unambiguously shown, sex-dependent physiological reactions to hypoxia may contribute to an increased acute mountain sickness vulnerability in some women. Adequate acclimatisation, slow ascent speed and/or preventive medication (e.g. acetazolamide) are solutions. (2) Targeted training of the respiratory musculature could be a valuable preparation for altitude training in women. (3) Sex hormones influence hypoxia responses and hormonal-cycle and/or menstrual-cycle phases therefore may be factors in acclimatisation to altitude and efficiency of altitude training. As many of the recommendations or observations of the present work remain partly speculative, we join previous calls for further quality research on female athletes in sports to be extended to the field of altitude and hypoxia

Women at Altitude: Sex-Related Physiological Responses to Exercise in Hypoxia.

Sex differences in physiological responses to various stressors, including exercise, have been well documented. However, the specific impact of these differences on exposure to hypoxia, both at rest and during exercise, has remained underexplored. Many studies on the physiological responses to hypoxia have either excluded women or included only a limited number without analyzing sex-related differences. To address this gap, this comprehensive review conducted an extensive literature search to examine changes in physiological functions related to oxygen transport and consumption in hypoxic conditions. The review encompasses various aspects, including ventilatory responses, cardiovascular adjustments, hematological alterations, muscle metabolism shifts, and autonomic function modifications. Furthermore, it delves into the influence of sex hormones, which evolve throughout life, encompassing considerations related to the menstrual cycle and menopause. Among these physiological functions, the ventilatory response to exercise emerges as one of the most sex-sensitive factors that may modify reactions to hypoxia. While no significant sex-based differences were observed in cardiac hemodynamic changes during hypoxia, there is evidence of greater vascular reactivity in women, particularly at rest or when combined with exercise. Consequently, a diffusive mechanism appears to be implicated in sex-related variations in responses to hypoxia. Despite well-established sex disparities in hematological parameters, both acute and chronic hematological responses to hypoxia do not seem to differ significantly between sexes. However, it is important to note that these responses are sensitive to fluctuations in sex hormones, and further investigation is needed to elucidate the impact of the menstrual cycle and menopause on physiological responses to hypoxia