Oxidative Stress Reaction to Hypobaric-Hyperoxic Civilian Flight Conditions.

BACKGROUND: In military flight operations, during flights, fighter pilots constantly work under hyperoxic breathing conditions with supplemental oxygen in varying hypobaric environments. These conditions are suspected to cause oxidative stress to neuronal organ tissues. For civilian flight operations, the Federal Aviation Administration (FAA) also recommends supplemental oxygen for flying under hypobaric conditions equivalent to higher than 3048 m altitude, and has made it mandatory for conditions equivalent to more than 3657 m altitude. AIM: We hypothesized that hypobaric-hyperoxic civilian commercial and private flight conditions with supplemental oxygen in a flight simulation in a hypobaric chamber at 2500 m and 4500 m equivalent altitude would cause significant oxidative stress in healthy individuals. METHODS: Twelve healthy, COVID-19-vaccinated (third portion of vaccination 15 months before study onset) subjects (six male, six female, mean age 35.7 years) from a larger cohort were selected to perform a 3 h flight simulation in a hypobaric chamber with increasing supplemental oxygen levels (35%, 50%, 60%, and 100% fraction of inspired oxygen, FiO2, via venturi valve-equipped face mask), switching back and forth between simulated altitudes of 2500 m and 4500 m. Arterial blood pressure and oxygen saturation were constantly measured via radial catheter and blood samples for blood gases taken from the catheter at each altitude and oxygen level. Additional blood samples from the arterial catheter at baseline and 60% oxygen at both altitudes were centrifuged inside the chamber and the serum was frozen instantly at -21 °C for later analysis of the oxidative stress markers malondialdehyde low-density lipoprotein (M-LDL) and glutathione-peroxidase 1 (GPX1) via the ELISA test. RESULTS: Eleven subjects finished the study without adverse events. Whereas the partial pressure of oxygen (PO2) levels increased in the mean with increasing oxygen levels from baseline 96.2 mm mercury (mmHg) to 160.9 mmHg at 2500 m altitude and 60% FiO2 and 113.2 mmHg at 4500 m altitude and 60% FiO2, there was no significant increase in both oxidative markers from baseline to 60% FiO2 at these simulated altitudes. Some individuals had a slight increase, whereas some showed no increase at all or even a slight decrease. A moderate correlation (Pearson correlation coefficient 0.55) existed between subject age and glutathione peroxidase levels at 60% FiO2 at 4500 m altitude. CONCLUSION: Supplemental oxygen of 60% FiO2 in a flight simulation, compared to flying in cabin pressure levels equivalent to 2500 m-4500 m altitude, does not lead to a significant increase or decrease in the oxidative stress markers M-LDL and GPX1 in the serum of arterial blood.

Influence of nutrition and food on sleep-is there evidence?

BACKGROUND: The influence of sleep disorders on metabolism, especially concerning obesity and diabetes, as well as obesity and obstructive sleep apnea, has been widely investigated. However, the effect of nutrition and the intake of certain foods on sleep has only recently gained attention. In recent years, there have been publications on intake of certain foods and certain diets regarding their influence on sleep, as well as activity of adipocytes and their effect on production of sleep hormones. METHODS: Following PRISMA guidelines, we performed a PubMed search using the key words "sleep," "sleep disorders," "nutrition," "food," and "food intake" published from 2012 to 2022. We excluded by consensus all articles with diets and exercise programs or bariatric surgery for weight loss to treat sleep apnea, all articles on connections between sleep disorders and metabolic disorders, and articles concerning the influence of drugs on neuroactive substances. RESULTS: Of the 4155 publications revealed, 988 had nutrition, metabolism, and sleep as the primary topic of research. Of these 988 publications, only 26 fulfilled the content requirements concerning the influence of certain food and diets on sleep or sleep disorders, including the influence of the gastrointestinal system and adipocytes on sleep hormones. None of the investigations revealed clear evidence of an effect of a certain diet or food on sleep. Epidemiologic surveys suggest that shortened or fragmented sleep and chronotype in adults influence nutrition and fat metabolism. Additionally, there is evidence that adipocyte signaling influences neuronal mediators and hormones of the sleep-wake cycle. CONCLUSION: There is no evidence of a direct influence of certain nutrition or food intake on sleep. Obesity via adipocyte signaling may influence the sleep-wake cycle, though the molecular research on this topic is based on animal studies.

The Effects of Napping on Wakefulness and Endurance Performance in Athletes: A Randomized Crossover Study.

Background: Athletes often experience poor sleep quality due to stress, altitude exposure, travel across different time zones, and pre-competition nervousness. Coaches use daytime naps to counteract the negative effects of fragmented nighttime sleep. Napping before competitions has also been used to enhance performance in athletes without sleep problems, with mixed results in previous studies, particularly for endurance performance. Thus, we investigated the effects of napping after partial sleep deprivation (PSD) on endurance performance and wakefulness in athletes. Methods: We recruited 12 healthy and trained participants (seven female and five male) for a randomized crossover study design. The participants underwent two test sessions: a five-hour night of sleep without a nap (noNap) and a five-hour night of sleep with a 30-min nap opportunity (Nap30). Participants recorded their sleep-wake rhythm one week before and during the study using the Consensus Sleep Diary-Core and the Morningness-Eveningness Questionnaire to examine their circadian rhythm type. We quantified PSD and the nap with pupillography (pupil unrest index, PUI), a subjective level of sleepiness questionnaire (Karolinska Sleepiness Scale, KSS), and polysomnography. After each night, participants performed a maximal cycling ergometry test to determine time to exhaustion (TTE) and maximal oxygen uptake (VO 2max). Results: Participants had an average sleep duration of 7.2 ± 0.7 h and were identified as moderately morning types (n = 5), neither type (n = 5), and moderately evening types (n = 2). There was a significant difference in both sleepiness parameters between the two conditions, with the PUI (p = 0.015) and KSS (p ≤ 0.01) significantly decreased at 5 h and nap compared with only 5 h of sleep. The PUI (p ≤ 0.01) and KSS (p ≤ 0.01) decreased significantly from before to after the nap. However, there was no significant difference in physical exercise test results between the conditions for TTE (p = 0.367) or VO 2max (p = 0.308). Conclusions: Our results suggest that napping after light PSD does not significantly influence endurance performance. We conclude that aerobic performance is a multidimensional construct, and napping after PSD may not enhance it. However, napping is an effective method to increase wakefulness and vigilance, which can be beneficial for sports competitions.

The Effects of Exercise Therapy Moderated by Sex in Rehabilitation of COVID-19.

Standardized exercise therapy programs in pulmonary rehabilitation have been shown to improve physical performance and lung function parameters in post-acute COVID-19 patients. However, it has not been investigated if these positive effects are equally beneficial for both sexes. The purpose of this study was to analyze outcomes of a pulmonary rehabilitation program with respect to sex differences, in order to identify sex-specific pulmonary rehabilitation requirements. Data of 233 post-acute COVID-19 patients (40.4% females) were analyzed before and after a three-week standardized pulmonary rehabilitation program. Lung function parameters were assessed using body-plethysmography and functional exercise capacity was measured by the Six-Minute Walk Test. At post-rehabilitation, females showed a significantly smaller improvement in maximal inspiration capacity and forced expiratory volume (F=5.86, ω2=.02; p<0.05) than males. Exercise capacity improvements between men and women did not differ statistically. Females made greater progress towards reference values of exercise capacity (T(231)=-3.04; p<0.01) and forced expiratory volume in the first second (T(231)=2.83; p<0.01) than males. Sex differences in the improvement of lung function parameters seem to exist and should be considered when personalizing standardized exercise therapies in pulmonary rehabilitation.

Weight Loss and Fat Metabolism during Multi-Day High-Altitude Sojourns: A Hypothesis Based on Adipocyte Signaling.

Several publications and random observations have reported weight loss in high-altitude sojourners of both sexes. This could be a result of multiple adaptations, which hypoxia and mountaineering provoke on a cellular and organic level. Several publications have discussed the effect on appetite-regulating hormones to be one of the main contributing factors. We aimed to review the available data and show the current state of knowledge regarding nutritional aspects in high altitude with a special focus on fatty dietary forms. To reach this aim we conducted a literature search via PubMed according to the PRISMA 2020 protocol to identify relevant studies. We found that very few studies cover this field with scientifically satisfying evidence. For final analysis, reviews as well as papers that were not clearly related to the topic were excluded. Six articles were included discussing hormonal influences and the impact of exercise on appetite regulation as well as genetic factors altering metabolic processes at altitude. Leptin expression seems to be the biggest contributor to appetite reduction at altitude with an initial increase followed by a decrease in the course of time at high altitude. Its expression is greatly dependent on the amount of white adipose tissue. Since the expression of leptin is associated with an increased ß-oxidation of fatty acids, a high-fat diet could be advantageous at a certain time point in the course of high-altitude sojourns.

Expiratory Peak Flow and Minute Ventilation Are Significantly Increased at High Altitude versus Simulated Altitude in Normobaria.

Simulated altitude (normobaric hypoxia, NH) is used to study physiologic hypoxia responses of altitude. However, several publications show differences in physiological responses between NH and hypobaric conditions at altitude (hypobaric hypoxia, HH). The causality for these differences is controversially discussed. One theory is that the lower air density and environmental pressure in HH compared to NH lead to lower alveolar pressure and therefore lower oxygen diffusion in the lung. We hypothesized that, if this theory is correct, due to physical laws (Hagen-Poiseuille, Boyle), resistance respectively air compression (Boyle) at expiration should be lower, expiratory flow higher, and therefore peak flow and maximum expiratory flow (MEF) 75-50 increased in hypobaric hypoxia (HH) vs. normobaric hypoxia (NH). To prove the hypothesis of differences in respiratory flow as a result of lower alveolar pressure between HH and NH, we performed spirography in NH at different simulated altitudes and the corresponding altitudes in HH. In a cross over study, 6 healthy subjects (2 f/4 m, 28.3 ± 8.2 years, BMI: 23.2 ± 1.9) performed spirography as part of spiroergometry in a normobaric hypoxic room at a simulated altitude of 2800 m and after a seven-hour hike on a treadmill (average incline 14%, average walking speed 1.6 km/h) to the simulated summit of Mauna Kea at 4200 m. After a two-month washout, we repeated the spirometry in HH on the start and top of the Mauna Kea hiking trail, HI/USA. Comparison of NH (simulated 4200 m) and HH at 4200 m resulted in increased pulmonary ventilation during exercise (VE) (11.5%, p < 0.01), breathing-frequency (7.8%, p < 0.01), peak expiratory flow PEF (13.4%, p = 0.028), and MEF50 (15.9%, p = 0.028) in HH compared to NH, whereas VO2max decreased by 2%. At 2800 m, differences were only trendy, and at no altitude were differences in volume parameters. Spirography expresses higher mid expiratory flows and peak flows in HH vs. NH. This supports the theory of lower alveolar and small airway pressure due to a lower air density resulting in a lower resistance.

Differential neural response to psychoanalytic intervention techniques during structural interviewing: A single-case analysis using EEG.

Background: Previous studies detected changes in the electroencephalographic (EEG) signal as an effect of psychoanalytic interventions. However, no study has investigated neural correlates of specific psychoanalytic interventions in the EEG power spectrum yet. In the present case study, we contrasted three types of interventions (clarification, confrontation, and interpretation) and a neutral control condition during a structural psychoanalytic interview conducted while EEG was recorded. Methods: A 27-year-old male patient diagnosed with major depressive disorder and borderline personality disorder with recurrent suicidal and self-injurious behavior underwent a structural interview while recording EEG. Two independent experts selected by consensus the characteristic episodes of the four conditions (clarification, confrontation, interpretation, and neutral control) within the interview, which were included in the EEG analyses. Fast Fourier transformation (FFT) was applied to subsegments of the intervention type to analyze the EEG power spectra. Alpha and beta power from central, frontal, and parietal sites were considered in linear mixed-effects models with segments as a random factor with maximum-likelihood estimates due to the lack of balance in the length of the interview segments. Results: The interventions "interpretation" and "confrontation" showed a significantly lower alpha power compared with the control condition in the central electrodes. In the frontal and parietal sites of the alpha power and all beta power sites, the omnibus tests (full model/model without intervention) and comparisons relative to control conditions showed no significant overall result or failed significance after alpha error correction. Conclusion: Incisive interventions, such as confrontation with discrepancies and interpretation of unconscious intrapsychic conflicts, may have provoked temporary emotional lability, leading to a change in psychic processing akin to interference from external stimuli. This conclusion is consistent with the finding that interpretations, which are potentially the most concise interventions, had the strongest effects on alpha power. Using EEG during therapeutic psychoanalytic intervention techniques might be a helpful tool to evaluate differential responses to the psychotherapeutic process on a neural level. However, this single-case result has to be replicated in a larger sample and does not allow generalizations.

Extreme sports performance for more than a week with severely fractured sleep.

PURPOSE: Severely fractured sleep is mostly portrayed negatively, but investigations in extreme sports show that humans can maintain performance with a minimum of sleep. With two cases of long-lasting extreme sports performances, we demonstrate that severely fragmented sleep does not necessarily lead to a deterioration of physical and cognitive performance. METHODS: We performed continuous polysomnography on a 34 year-old skier for 11 days and nights during a world record attempt in long-term downhill skiing and monitored a 32 year-old cyclist during the Race Across America for 8.5 days via sleep and activity logs. RESULTS: The skier slept fractured fashion in 15-16 naps with a daily average of 6 h consisting of 77% in sleep stage 1 and 2, 11% in stage 3, and 13% in stage REM. The cyclist slept a total of 7 h and 52 min in 8.5 days, split up into 11 short naps and 6 sleep periods. The average duration of napping was 8.8 min and of sleep 64.2 min. CONCLUSIONS: These two cases demonstrate that outstanding performances are possible with severely fractured sleep and/or sleep deprivation. In well-trained athletes, breaking new recordsis possible despite extreme sleep habits.

Assessment of sleep and sleep disorders in geriatric patients.

Sufficient and refreshing sleep is important for good health, physical and cognitive functioning as well as quality of life. An assessment of sleep quality and sleep disorders is therefore mandatory in geriatric patients. Despite a variety of clinical assessment tools for screening and diagnosing sleep disorders, only some of them have been validated in older subjects and nearly none in geriatric patients or in individuals with dementia. Therefore, the aim of this review is to present a concise overview of assessment tools for sleep disorders that are widely used in sleep medicine and to briefly discuss the suitability and limitations in geriatric patients and subjects with dementia.

Cultural adaptation and evaluation of the measurement properties of the Berlin Questionnaire for Brazil.

OBJECTIVE: to produce the Brazilian version of the Berlin Questionnaire (BQ) with evidence of reliability and validity. METHOD: The cultural adaptation was carried out in the following stages: translation, synthesis of translations, back-translation, evaluation by an expert committee and pre-test with 30 participants. Next, the psychometric properties were evaluated with 104 participants who answered the Brazilian version of the BQ and underwent polysomnography (PSG). They also completed a sociodemographic and clinical characterization instrument and the Epworth Sleepiness Scale. Reliability was assessed concerning homogeneity of the items (internal consistency), and criterion validity was tested by comparing the Brazilian version of the BQ with the apnea and hypopnea index (AHI) obtained through PSG. RESULTS: The Brazilian version of the BQ presented evidence of semantic-idiomatic, conceptual and cultural equivalence, with good acceptability and feasibility. The findings demonstrated the reliability of the measure (Cronbach's alpha 0.74). The instrument presented a sensitivity of 81.3%, 86.2%, and 93.8%, and specificity of 82.5%, 54.7% and 50.0% for the risk stratification of obstructive sleep apnea according to the AHI ≥5, ≥15 and ≥ 30 events per hour, respectively. It should be emphasized that the BQ is a screening instrument for obstructive sleep apnea (OSA) and should be combined with a clinical evaluation and later confirmed with PSG. CONCLUSION: The Brazilian version of the Berlin Questionnaire was reliable and valid in the study population.

Periodic breathing in healthy young adults in normobaric hypoxia equivalent to 3500 m, 4500 m, and 5500 m altitude.

PURPOSE: The occurrence of periodic breathing (PB) at high altitude during sleep and the quality of sleep are individually different and influenced by multiple factors including sex. Although poor sleep quality at high altitude might not be directly linked to oxygen desaturations, the PB upsurge at high altitude leads to significant oscillations in oxygen saturation. METHODS: Thirty-three students were recruited. Participants were randomly assigned to three groups (A, B, C) sleeping one full night in a dormitory with normobaric hypoxia at a FIO2 of 14.29% (A), a FIO2 of 12.47% (B), or a FIO2 of 10.82% (C). Full polysomnography was performed in each participant. RESULTS: Mean total sleeping time decreased significantly with increasing hypoxia (p < 0.001). Respiratory events changed from central hypopneas to central apneas (CA) with increasing hypoxia: CA = 17.8%, 50.0%, 92.2% of AHI (37.96 events per hour (n/h), 68.55 n/h, 93.44 n/h). AHI (p = 0.014) and time duration of respiratory events (p = 0.003) were significantly different between sexes, both greater in men. REM sleep was reduced. CONCLUSIONS: Men tend to be more prone to PB in normobaric hypoxia. Further research should implicate a longer acclimatization period around simulated 4500 m in order to find out if the exponential increase in PB between 4500 m and 5500 m could be shifted to lower hypoxic levels, i.e., higher altitudes.

Adiponectin, Leptin and Visfatin in Hypoxia and its Effect for Weight Loss in Obesity.

Rationale: Hypoxia induces leptin gene expression in human adipocytes via hypoxia-inducible factors (HIF-α/ß). Under ambient moderate hypoxia, leptin in adipocytes is elevated for at least 14 days. Leptin is supposedly involved in the reduced food intake, increased utilization of fatty acids for energy production and possible weight loss observed at high altitudes. Literature on adiponectin and visfatin in high altitude is inconsistent with reports of elevated levels and non-elevated levels. Exercise in hypoxia studies in obese subjects have shown a significant weight loss after up to 3 weeks, but it is unclear if this effect holds up for longer time periods. Therefore, we aimed to investigate 32 obese subjects completing 52 exercise and rest sessions within 8 months at either moderate or sham hypoxia and to analyze leptin, adiponectin, and visfatin mRNA-expression at different time points of exposure. Methods: Abdominal subcutaneous fat biopsies were taken from 32 obese subjects before, after 3 months and after 8 months of intervention. Subjects were randomly divided into two groups and exercised at moderate intensity at two different study sites twice a week. The IG was exposed to normobaric hypoxia (FiO2: 14.0 ± 0.2%,) at exercise and at rest (FiO2: 12.0 ± 0.2%) and the CG to sham hypoxia. Quantitative real-time polymerase chain reaction (qPCR) was used in order to determine mRNA-levels of leptin, adiponectin, and visfatin. Results: No differences in leptin levels after 3 and 8 months compared to baseline and between groups were found. There was no significant difference regarding adiponectin or visfatin at any time point compared to baseline in the hypoxia group, but an increase after 3 months was seen in the control group at normoxia compared to the hypoxia group (adiponectin: p = 0.029 and visfatin: p = 0.014). Conclusion: In this first several months' duration randomized sham controlled hypoxia exercise and rest study with obese subjects, we found no time extended leptin mRNA-expression in subjects under hypoxia after 3 and 8 months compared to baseline levels. Moderate exercise in normoxia not in hypoxia leads to elevated adiponectin and visfatin levels after 3 months.

Sleep medicine is coming of age in military medicine : Report from the Military Health System Research Symposium (2017) in Kissimmee, Florida.

In August 2017, the US Military Health System held its sixth annual Research Symposium for medical researchers from the US Army, Navy, Air Force, and Public Health Service. The symposium provides a collaborative environment for academia, industry, and military researchers who address advancement in areas of Combat Casualty Care, Military Operational Medicine, Clinical and Rehabilitative Medicine, and Military Infectious Diseases. This year, Sleep Medicine received substantial attention with presentations scattered throughout the program, poster presentations as well as a scheduled breakout session with podium presentations. A brief description of the breakout session follows.

The Linkage between Breast Cancer, Hypoxia, and Adipose Tissue.

OBJECTIVE: The development of breast cancer cells is linked to hypoxia. The hypoxia-induced factor HIF-1α influences metastasis through neovascularization. Hypoxia seems to decrease the responsiveness to hormonal treatment due to loss of estrogen receptors (ERs). Obesity is discussed to increase hypoxia in adipocytes, which promotes a favorable environment for tumor cells in mammary fat tissue, whereas, tumor cells profit from good oxygen supply and are influenced by its deprivation as target regions within tumors show. This review gives an overview of the current state on research of hypoxia and breast cancer in human adipose tissue. METHODS: A systematic literature search was conducted on PubMed (2000-2016) by applying hypoxia and/or adipocytes and breast cancer as keywords. Review articles were excluded as well as languages other than English or German. There was no restriction regarding the study design or type of breast cancer. A total of 35 papers were found. Eight studies were excluded due to missing at least two of the three keywords. One paper was removed due to Russian language, and one was dismissed due to lack of adherence. Seven papers were identified as reviews. After applying exclusion criteria, 18 articles were eligible for inclusion. RESULTS: Two articles describe the impairment of mammary epithelial cell polarization through hypoxic preconditioning. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α which causes the loss of ER α protein as stated in four articles. Four articles analyzed that increased activation of HIF's induces a series of transcriptions resulting in tumor angiogenesis. HIF inhibition, especially when combined with cytotoxic chemotherapy, holds strong potential for tumor suppression as stated in further four articles. In two articles there is evidence of a strong connection between hypoxia, oxidative stress and a poor prognosis for breast cancer via HIF regulated pathways. Acute hypoxia seems to normalize the microenvironment in breast cancer tissue and has proven to affect tumor growth positively as covered in two articles. CONCLUSION: This review indicates that the development of breast cancer is influenced by hypoxia. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α.

Endurance Training in Normobaric Hypoxia Imposes Less Physical Stress for Geriatric Rehabilitation.

Rationale: Evidence suggests that training in hypoxia can be very effective even while requiring less physical effort. We therefore aimed to measure the effect of endurance training under hypoxic conditions on pulmonary and cardiovascular parameters in an elderly population undergoing inpatient rehabilitation. Methods: Forty patients over age 65 years with multiple co-morbid conditions were recruited during a 3-week stay in a geriatric rehabilitation center. Using a randomized, single-blinded, placebo-controlled design, patients were assigned to a hypoxic (HG) or normoxic (NG) group. HG patients completed seven training sessions of 30 min duration on a treadmill in a normobaric chamber with inspired oxygen fraction (FiO2) of 15.27%, with 10-30 min active training. Training was conducted with target heart rate at 80% of peak oxygen consumption (VO2-peak). NG group performed similar training in sham hypoxia (room air or FiO2 = 20.94%). At pre- and post-test completion, measures included: (1) cycle ergometry with ECG monitoring and measurement of VO2-peak, and (2) echocardiography for ejection fraction. Results: The physical effort required of patients to reach target heart rate was reduced significantly (-28%, p = 0.043) in the HG compared to NG. Cardiopulmonary parameters showed no differences between groups. Conclusion: Endurance training at 3,000 meters elevation imposes less stress on the locomotor systems while resulting in a similar physiological strain (i.e., heart rate). Hypoxic training holds promise for successful geriatric rehabilitation by being more accommodating to physical limitations in geriatric patients. Trial registration: Registration at DRKS. (Approval No. 359/12, Trial No. DRKS00005241).

Sleep in older adults and in subjects with dementia.

The neuronal structures for the regulation of sleep and wakefulness are located in the brain. This complex network is vulnerable to numerous factors, most importantly neurodegenerative diseases and drugs. The macrostructure and microstructure of sleep change with age. These changes are more pronounced in subjects with dementia. Sleep disorders in subjects with dementia may be independent of dementia or caused by dementia. Furthermore, epidemiological studies reveal that sleep disorders per se may induce dementia by reduction of cerebral clearance of beta-amyloids. The population attributable risk (PAR) of sleep disturbances to the incidence of dementia is estimated to be about 15%; therefore, management of sleep disturbances in older adults and subjects with dementia gives the opportunity of an impact on incidence and course of dementia. Sleep history should be taken from each individual and obvious sleep disturbances, especially sleep apnea, should be managed according to current guidelines. Future studies that concern the incidence and the management of dementia must take into account sleep and sleep disturbances.