The Dewey Monitor: Pulse Oximetry can Warn of Hypoxia in an Immersed Rebreather Diver in Multiple Scenarios.

Divers who wish to prolong their time underwater while carrying less equipment often use devices called rebreathers, which recycle the gas expired after each breath instead of discarding it as bubbles. However, rebreathers' need to replace oxygen used by breathing creates a failure mechanism that can and frequently does lead to hypoxia, loss of consciousness, and death. The purpose of this study was to determine whether a pulse oximeter could provide a useful amount of warning time to a diver with a rebreather after failure of the oxygen addition mechanism. Twenty-eight volunteer human subjects breathed on a mixed-gas rebreather in which the oxygen addition system had been disabled. The subjects were immersed in water in four separate environmental scenarios, including cold and warm water, and monitored using pulse oximeters placed at multiple locations. Pulse oximeters placed on the forehead and clipped on the nasal ala provided a mean of 32 s (±10 s SD) of warning time to divers with falling oxygen levels, prior to risk of loss of consciousness. These devices, if configured for underwater use, could provide a practical and inexpensive alarm system to warn of impending loss of consciousness in a manner that is redundant to the rebreather.

Dietary ω-3 polyunsaturated fatty acids are protective for myopia.

Myopia is a leading cause of visual impairment and blindness worldwide. However, a safe and accessible approach for myopia control and prevention is currently unavailable. Here, we investigated the therapeutic effect of dietary supplements of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) on myopia progression in animal models and on decreases in choroidal blood perfusion (ChBP) caused by near work, a risk factor for myopia in young adults. We demonstrated that daily gavage of ω-3 PUFAs (300 mg docosahexaenoic acid [DHA] plus 60 mg eicosapentaenoic acid [EPA]) significantly attenuated the development of form deprivation myopia in guinea pigs and mice, as well as of lens-induced myopia in guinea pigs. Peribulbar injections of DHA also inhibited myopia progression in form-deprived guinea pigs. The suppression of myopia in guinea pigs was accompanied by inhibition of the "ChBP reduction-scleral hypoxia cascade." Additionally, treatment with DHA or EPA antagonized hypoxia-induced myofibroblast transdifferentiation in cultured human scleral fibroblasts. In human subjects, oral administration of ω-3 PUFAs partially alleviated the near-work-induced decreases in ChBP. Therefore, evidence from these animal and human studies suggests ω-3 PUFAs are potential and readily available candidates for myopia control.

Highland mate: Edible and functional foods in traditional medicine for the prevention and treatment of hypoxia-related symptoms.

The highlands evoke both fascination and awe. Regardless of the reason to live in the highlands, symptoms related to altitude sickness are unbearable because of low atmospheric pressure, low oxygen concentration, strong ultraviolet radiation, cold, and psychological factors. Food and herbal medicines and/or health-care foods have protected highland dwellers owing to their multisystem regulation. These versatile products combine health-care properties with medical values by enhancing immunity, relieving physical fatigue, improving sleep, and augmenting hypoxia tolerance, with rare side effects. We therefore aimed to provide a more comprehensive analysis of these nutraceuticals, which can be used to prevent and treat symptoms of altitude hypoxia in the Chinese market. Finally, we dissect a new perspective for their promotion and development from molecular aspects.

Preclinical Investigation of Trifluoperazine as a Novel Therapeutic Agent for the Treatment of Pulmonary Arterial Hypertension.

Trifluoperazine (TFP), an antipsychotic drug approved by the Food and Drug Administration, has been show to exhibit anti-cancer effects. Pulmonary arterial hypertension (PAH) is a devastating disease characterized by a progressive obliteration of small pulmonary arteries (PAs) due to exaggerated proliferation and resistance to apoptosis of PA smooth muscle cells (PASMCs). However, the therapeutic potential of TFP for correcting the cancer-like phenotype of PAH-PASMCs and improving PAH in animal models remains unknown. PASMCs isolated from PAH patients were exposed to different concentrations of TFP before assessments of cell proliferation and apoptosis. The in vivo therapeutic potential of TFP was tested in two preclinical models with established PAH, namely the monocrotaline and sugen/hypoxia-induced rat models. Assessments of hemodynamics by right heart catheterization and histopathology were conducted. TFP showed strong anti-survival and anti-proliferative effects on cultured PAH-PASMCs. Exposure to TFP was associated with downregulation of AKT activity and nuclear translocation of forkhead box protein O3 (FOXO3). In both preclinical models, TFP significantly lowered the right ventricular systolic pressure and total pulmonary resistance and improved cardiac function. Consistently, TFP reduced the medial wall thickness of distal PAs. Overall, our data indicate that TFP could have beneficial effects in PAH and support the view that seeking new uses for old drugs may represent a fruitful approach.

Pathogenesis-directed therapy of 2019 novel coronavirus disease.

The 2019 novel coronavirus disease (COVID-19) now is considered a global public health emergency. One of the unprecedented challenges is defining the optimal therapy for those patients with severe pneumonia and systemic manifestations of COVID-19. The optimal therapy should be largely based on the pathogenesis of infections caused by this novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the onset of COVID-19, there have been many prepublications and publications reviewing the therapy of COVID-19 as well as many prepublications and publications reviewing the pathogenesis of SARS-CoV-2. However, there have been no comprehensive reviews that link COVID-19 therapies to the pathogenic mechanisms of SARS-CoV-2. To link COVID-19 therapies to pathogenic mechanisms of SARS-CoV-2, we performed a comprehensive search through MEDLINE, PubMed, medRxiv, EMBASE, Scopus, Google Scholar, and Web of Science using the following keywords: COVID-19, SARS-CoV-2, novel 2019 coronavirus, pathology, pathologic, pathogenesis, pathophysiology, coronavirus pneumonia, coronavirus infection, coronavirus pulmonary infection, coronavirus cardiovascular infection, coronavirus gastroenteritis, coronavirus autopsy findings, viral sepsis, endotheliitis, thrombosis, coagulation abnormalities, immunology, humeral immunity, cellular immunity, inflammation, cytokine storm, superantigen, therapy, treatment, therapeutics, immune-based therapeutics, antiviral agents, respiratory therapy, oxygen therapy, anticoagulation therapy, adjuvant therapy, and preventative therapy. Opinions expressed in this review also are based on personal experience as clinicians, authors, peer reviewers, and editors. This narrative review linking COVID-19 therapies with pathogenic mechanisms of SARS-CoV-2 has resulted in six major therapeutic goals for COVID-19 therapy based on the pathogenic mechanisms of SARS-CoV-2. These goals are listed below: 1. The first goal is identifying COVID-19 patients that require both testing and therapy. This is best accomplished with a COVID-19 molecular test from symptomatic patients as well as determining the oxygen saturation in such patients with a pulse oximeter. Whether a symptomatic respiratory illness is COVID-19, influenza, or another respiratory pathogen, an oxygen saturation less than 90% means that the patient requires medical assistance. 2. The second goal is to correct the hypoxia. This goal generally requires hospitalization for oxygen therapy; other respiratory-directed therapies such as prone positioning or mechanical ventilation are often used in the attempt to correct hypoxemia due to COVID-19. 3. The third goal is to reduce the viral load of SARS-CoV-2. Ideally, there would be an oral antiviral agent available such as seen with the use of oseltamivir phosphate for influenza. This oral antiviral agent should be taken early in the course of SARS-CoV-2 infection. Such an oral agent is not available yet. Currently, two options are available for reducing the viral load of SARS-CoV-2. These are post-Covid-19 plasma with a high neutralizing antibody titer against SARS-CoV-2 or intravenous remdesivir; both options require hospitalization. 4. The fourth goal is to identify and address the hyperinflammation phase often seen in hospitalized COVID-19 patients. Currently, fever with an elevated C-reactive protein is useful for diagnosing this hyperinflammation syndrome. Low-dose dexamethasone therapy currently is the best therapeutic approach. 5. The fifth goal is to identify and address the hypercoagulability phase seen in many hospitalized COVID-19 patients. Patients who would benefit from anticoagulation therapy can be identified by a marked increase in d-dimer and prothrombin time with a decrease in fibrinogen. To correct this disseminated intravascular coagulation-like phase, anticoagulation therapy with low molecular weight heparin is preferred. Anticoagulation therapy with unfractionated heparin is preferred in COVID-19 patients with acute kidney injuries. 6. The last goal is prophylaxis for persons who are not yet infected. Potential supplements include vitamin D and zinc. Although the data for such supplements is not extremely strong, it can be argued that almost 50% of the population worldwide has a vitamin D deficiency. Correcting this deficiency would be beneficial regardless of any impact of COVID-19. Similarly, zinc is an important supplement that is important in one's diet regardless of any effect on SARS-CoV-2. As emerging therapies are found to be more effective against the SARS-CoV-2 pathogenic mechanisms identified, they can be substituted for those therapies presented in this review.

Randomised controlled trial for high-dose intravenous zinc as adjunctive therapy in SARS-CoV-2 (COVID-19) positive critically ill patients: trial protocol.

INTRODUCTION: SARS-CoV-2 (COVID-19) has caused an international pandemic of respiratory illness, resulting in significant healthcare and economic turmoil. To date, no robust vaccine or treatment has been identified. Elemental zinc has previously been demonstrated to have beneficial effects on coronaviruses and other viral respiratory infections due to its effect on RNA polymerase. Additionally, zinc has well-demonstrated protective effects against hypoxic injury-a clear mechanism of end-organ injury in respiratory distress syndrome. We aimed to assess the effect of high-dose intravenous zinc (HDIVZn) on SARS-CoV-2 infection. The end of study analyses will evaluate the reduction of impact of oxygen saturations or requirement of oxygen supplementation. METHODS AND ANALYSIS: We designed a double-blind randomised controlled trial of daily HDIVZn (0.5 mg/kg) versus placebo. Primary outcome measures are lowest oxygen saturation (or greatest level of supplemental oxygenation) for non-ventilated patients and worst PaO2/FiO2 for ventilated patients. Following power calculations, 60 hospitalised patients and 100 ventilated patients will be recruited to demonstrate a 20% difference. The duration of follow-up is up to the point of discharge. ETHICS AND DISSEMINATION: Ethical approval was obtained through the independent Human Research Ethics Committee. Participant recruitment will commence in May 2020. Results will be published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: ACTRN126200000454976.

Mechanism and effects of fructose diphosphate on anti-hypoxia fatigue and learning memory ability.

This study aims to investigate the mechanisms through which fructose diphosphate (FDP) causes anti-hypoxia and anti-fatigue effects and improves learning and memory. Mice were divided into three groups: low-dose FDP (FDP-L), high-dose FDP (FDP-H), and a control group. Acute toxic hypoxia induced by carbon monoxide, sodium nitrite, and potassium cyanide and acute cerebral ischemic hypoxia were used to investigate the anti-hypoxia ability of FDP. The tests of rod-rotating, mouse tail suspension, and swimming endurance were used to explore the anti-fatigue effects of FDP. The Morris water maze experiment was used to determine the impact of FDP on learning and memory ability. Poisoning-induced hypoxic tests showed that mouse survival time was significantly prolonged in the FDP-L and FDP-H groups compared with the control group (p < 0.05). In the exhaustive swimming test, FDP significantly shortened struggling time and prolonged the time of mass-loaded swimming; the rod-rotating test showed that endurance time was significantly prolonged by using FDP (p < 0.05). FDP significantly decreased lactate and urea nitrogen levels and increased hepatic and muscle glycogen and glucose transporter-4 and Na+-K+-ATPase (p < 0.05). To conclude, FDP enhances hypoxia tolerance and fatigue resistance and improves learning and memory ability through regulating glucose and energy metabolism.

Influence of muscle oxygenation and nitrate-rich beetroot juice supplementation on O2 uptake kinetics and exercise tolerance.

We tested the hypothesis that acute supplementation with nitrate (NO3-)-rich beetroot juice (BR) would improve quadriceps muscle oxygenation, pulmonary oxygen uptake (V˙O2) kinetics and exercise tolerance (Tlim) in normoxia and that these improvements would be augmented in hypoxia and attenuated in hyperoxia. In a randomised, double-blind, cross-over study, ten healthy males completed two-step cycle tests to Tlim following acute consumption of 210 mL BR (18.6 mmol NO3-) or NO3--depleted beetroot juice placebo (PL; 0.12 mmol NO3-). These tests were completed in normobaric normoxia [fraction of inspired oxygen (FIO2): 21%], hypoxia (FIO2: 15%) and hyperoxia (FIO2: 40%). Pulmonary V˙O2 and quadriceps tissue oxygenation index (TOI), derived from multi-channel near-infrared spectroscopy, were measured during all trials. Plasma [nitrite] was higher in all BR compared to all PL trials (P < 0.05). Quadriceps TOI was higher in normoxia compared to hypoxia (P < 0.05) and higher in hyperoxia compared to hypoxia and normoxia (P < 0.05). Tlim was improved after BR compared to PL ingestion in the hypoxic trials (250 ± 44 vs. 231 ± 41 s; P = 0.006; d = 1.13), with the magnitude of improvement being negatively correlated with quadriceps TOI at Tlim (r = -0.78; P < 0.05). Tlim was not improved following BR ingestion in normoxia (BR: 364 ± 98 vs. PL: 344 ± 78 s; P = 0.087, d = 0.61) or hyperoxia (BR: 492 ± 212 vs. PL: 472 ± 196 s; P = 0.273, d = 0.37). BR ingestion increased peak V˙O2 in hypoxia (P < 0.05), but not normoxia or hyperoxia (P > 0.05). These findings indicate that BR supplementation is more likely to improve Tlim and peak V˙O2 in situations when skeletal muscle is more hypoxic.

Health professionals' views of newborn pulse oximetry screening in a midwifery-led maternity setting. "It's a good thing to do, but fund it!"

OBJECTIVE: To understand from health professionals who care for newborns their views on the introduction of pulse oximetry screening for the detection of hypoxaemia in a midwifery-led maternity setting. Although oximetry screening for newborns is internationally accepted, national screening is not yet introduced in New Zealand. In this context, we drew on maternity carers' reflections during a feasibility study of oximetry screening to provide perspectives on barriers and enablers to universal screening. METHODS: Data were generated from nine focus groups during five months of 2018 in two north island regions of New Zealand. Participants' (n = 45) opinions about the use of oximetry screening in newborns were analysed thematically using an inductive approach. FINDINGS: Overall, participants stated pulse oximetry screening was easy to do, non-invasive, and worthwhile. Midwives were reassured by screening that provided evidence of either a healthy baby or a need for urgent review. From participants' reports, we identified three themes: (1) oximetry screening for newborns is reassuring, practical and worthwhile; (2) midwifery services workload expectations and under-resourcing will hinder universal screening, and (3) location of the baby at the time of screening could impede universal access. CONCLUSION AND IMPLICATIONS FOR PRACTICE: Midwives viewed implementing a national pulse oximetry screening programme as sensible but problematic unless resourced and funded appropriately. Policymakers should view the concerns of midwives about human and physical resources as significant and account for the need to resource this screening programme appropriately as a priority before implementation.

Effectiveness of an Electronic Partogram: A Mixed-Method, Quasi-Experimental Study Among Skilled Birth Attendants in Kenya.

BACKGROUND: Timely identification and management of intrapartum complications could significantly reduce maternal deaths, intrapartum stillbirths, and newborn deaths due to hypoxia. The World Health Organization (WHO) identifies monitoring of labor using the paper partograph as a high-priority intervention for identifying abnormities in labor and fetal well-being. This article describes a mixed-method, quasi-experimental study to assess the effectiveness of an Android tablet-based electronic, labor clinical decision-support application (ePartogram) in limited-resource settings. METHODS: The study, conducted in Kenya from October 2016 to May 2017, allocated 12 hospitals and health centers to an intervention (ePartogram) or comparison (paper partograph) group. Skilled birth attendants (SBAs) in both groups received a 2-day refresher training in labor management and partograph use. The intervention group received an additional 1-day orientation on use and care of the Android-based ePartogram app. All outcomes except one compare post-ePartogram intervention versus paper partograph controls. The exception is outcome of early perinatal mortality pre- and post-ePartogram introduction in intervention sites compared to control sites. We used log binomial regression to analyze the primary outcome of the study, suboptimal fetal outcomes. We also analyzed for secondary outcomes (SBAs performing recommended actions), and conducted in-depth interviews with facility in-charges and SBAs to ascertain acceptability and adoptability of the ePartogram. RESULTS: We compared data from 842 clients in active labor using ePartograms with data from 1,042 clients monitored using a paper partograph. SBAs using ePartograms were more likely than those using paper partographs to take action to maintain normal labor, such as ambulation, feeding, and fluid intake, and to address abnormal measurements of fetal well-being (14.7% versus 5.3%, adjusted relative risk=4.00, 95% confidence interval [CI]=1.95-8.19). Use of the ePartogram was associated with a 56% (95% CI=27%-73%) lower likelihood of suboptimal fetal outcomes than the paper partograph. Users of the ePartogram were more likely to be compliant with routine labor observations. SBAs stated that the technology was easy to use but raised concerns about its use at high-volume sites. Further research is needed to evaluate costs and benefit and to incorporate recent WHO guidance on labor management. CONCLUSION: ePartogram use was associated with improvements in adherence to recommendations for routine labor care and a reduction in adverse fetal outcomes, with providers reporting adoptability without undue effort. Continued development of the ePartogram, including incorporating new clinical rules from the 2018 WHO recommendations on intrapartum care, will improve labor monitoring and quality care at all health system levels.

Influence of the TLR4-mediated p38MAPK signaling pathway on chronic intermittent hypoxic-induced rat's oxidative stress and inflammatory cytokines in rats.

OBJECTIVE: To investigate the influence of the TOLL-like receptor 4 (TLR4)-mediated p38MAPK signaling pathway on chronic intermittent hypoxic (CIH)-induced oxidative stress and inflammatory cytokines in rats. MATERIALS AND METHODS: A total of 120 healthy male Sprague Dawley (SD) rats, aged between 8-10 weeks, were randomly divided into 9 groups (normoxia control group, CIH 2 weeks group, CIH 4 weeks group, CIH 6 weeks group, CIH 8 weeks group, CIH 6 weeks + p38MAPK receptor inhibit group, CIH 6 weeks + Tempol group, CIH 8 weeks + p38MAPK receptor inhibitor group and CIH 8 weeks + Tempol group). The expression of TLR4 and p38MAPK in the adipose tissue was evaluated, as well as the level of serum oxidative stress markers (SOD, TRx-1, MDA) and inflammatory cytokines (adiponectin, TNF-α, hsCRP and IL-6). RT-PCR and Western-blot were conducted to detect the expression of TLR4 and p38MAPK mRNA. RESULTS: With increased hypoxia, the levels of SOD and adiponectin in the serum of the CIH group decreased significantly, and the levels of TNF-α, hsCRP, IL-8 and IL-6 in serum increased significantly. After the intervention of antioxidant Tempol and p38MAPK inhibitor SB203580, SOD increased significantly but with significant MDA reduction. The levels of TNF-α, hsCRP, IL-8 and IL-6 in serum significantly decreased. The results of RT-PCR and Western-Blot indicated that the P-p38 and TLR4 proteins related to the MAPK pathway were expressed in rat adipose tissue. With the hypoxia intensity, expression of P-p38 decreased after initially increasing. The expression of TLR4 showed a continuously growing trend. After Tempol treatment, the expression of p38MAPK protein decreased, and the expression of TLR4 did not change significantly, indicating the inhibiting effect of Tempol on p38MAPK, without a significant inhibiting effect on TLR4. CONCLUSIONS: The TLR4-mediated p38MAPK signaling pathway was active in adipose tissue and the expression of the corresponding molecules increased as the duration of intermittent hypoxia increased. The expression of TLR4 and p38MAPK components regulated the level of oxidative stress and inflammatory cytokines; the application of p38MAPK inhibitors and antioxidant free radical scavengers improved the levels of oxidative stress and inflammatory cytokines.

Muscle oxygenation profiles between active and inactive muscles with nitrate supplementation under hypoxic exercise.

Whether dietary nitrate supplementation improves exercise performance or not is still controversial. While redistribution of sufficient oxygen from inactive to active muscles is essential for optimal exercise performance, no study investigated the effects of nitrate supplementation on muscle oxygenation profiles between active and inactive muscles. Nine healthy males performed 25 min of submaximal (heart rate ~140 bpm; EXsub) and incremental cycling (EXmax) until exhaustion under three conditions: (A) normoxia without drink; (B) hypoxia (FiO2 = 13.95%) with placebo (PL); and (c) hypoxia with beetroot juice (BR). PL and BR were provided for 4 days. Oxygenated and deoxygenated hemoglobin (HbO2 and HHb) were measured in vastus lateralis (active) and biceps brachii (inactive) muscles, and the oxygen saturation of skeletal muscle (StO2; HbO2/total Hb) were calculated. During EXsub, BR suppressed the HHb increases in active muscles during the last 5 min of exercise. During EXmax, time to exhaustion with BR (513 ± 24 sec) was significantly longer than with PL (490 ± 39 sec, P < 0.05). In active muscles, BR suppressed the HHb increases at moderate work rates during EXmax compared to PL (P < 0.05). In addition, BR supplementation was associated with greater reductions in HbO2 and StO2 at higher work rates in inactive muscles during EXmax Collectively, these findings indicate that short-term dietary nitrate supplementation improved hypoxic exercise tolerance, perhaps, due to suppressed increases in HHb in active muscles at moderate work rates. Moreover, nitrate supplementation caused greater reductions in oxygenation in inactive muscle at higher work rates during hypoxic exercise.

Physiological and performance effects of nitrate supplementation during roller-skiing in normoxia and normobaric hypoxia.

The present study examined the effects of acute nitrate (NO3-) supplementation ingested in the form of concentrated beetroot juice on cross-country roller-ski performance in normoxia (N) and normobaric hypoxia (H). Eight competitive cross-country skiers (five males: age 22 ± 3 years, V·O2max 71.5 ± 4.7 mL kg-1·min-1; three females: age 21 ± 1 years, V·O2max 58.4 ± 2.5 mL kg-1·min-1) were supplemented with a single dose of NO3--rich beetroot juice (BRJ, ∼13 mmol NO3-) or a NO3--depleted placebo (PL, ∼0 mmol NO3-) and performed 2 x 6-min submaximal exercise bouts and a 1000-m time-trial (TT) on a treadmill in N (20.9% O2) or H (16.8% O2). The four experimental trials were presented in a randomised, counter-balanced order. Plasma NO3- and nitrite concentrations were significantly higher following BRJ compared to PL (both p < 0.001). However, respiratory variables, heart rate, blood lactate concentration, ratings of perceived exertion, and near-infrared spectroscopy-derived measures of muscle tissue oxygenation during submaximal exercise were not significantly different between BRJ and PL (all p > 0.05). Likewise, time to complete the TT was unaffected by supplementation in both N and H (p > 0.05). In conclusion, an acute dose of ∼13 mmol NO3- does not affect physiological or performance responses to submaximal or maximal treadmill roller-skiing in competitive cross-country skiers exercising in N and H.

Dietary fish oil delays hypoxic skeletal muscle fatigue and enhances caffeine-stimulated contractile recovery in the rat in vivo hindlimb.

Oxygen efficiency influences skeletal muscle contractile function during physiological hypoxia. Dietary fish oil, providing docosahexaenoic acid (DHA), reduces the oxygen cost of muscle contraction. This study used an autologous perfused rat hindlimb model to examine the effects of a fish oil diet on skeletal muscle fatigue during an acute hypoxic challenge. Male Wistar rats were fed a diet rich in saturated fat (SF), long-chain (LC) n-6 polyunsaturated fatty acids (n-6 PUFA), or LC n-3 PUFA DHA from fish oil (FO) (8 weeks). During anaesthetised and ventilated conditions (normoxia 21% O2 (SaO2-98%) and hypoxia 14% O2 (SaO2-89%)) the hindlimb was perfused at a constant flow and the gastrocnemius-plantaris-soleus muscle bundle was stimulated via sciatic nerve (2 Hz, 6-12V, 0.05 ms) to established fatigue. Caffeine (2.5, 5, 10 mM) was supplied to the contracting muscle bundle via the arterial cannula to assess force recovery. Hypoxia, independent of diet, attenuated maximal twitch tension (normoxia: 82 ± 8; hypoxia: 41 ± 2 g·g-1 tissue w.w.). However, rats fed FO sustained higher peak twitch tension compared with the SF and n-6 PUFA groups (P < 0.05), and the time to decline to 50% of maximum twitch tension was extended (SF: 546 ± 58; n-6 PUFA: 522 ± 58; FO: 792 ± 96 s; P < 0.05). In addition, caffeine-stimulated skeletal muscle contractile recovery was enhanced in the FO-fed animals (SF: 41 ± 3; n-6 PUFA: 40 ± 4; FO: 52 ± 7% recovery; P < 0.05). These results support a physiological role of DHA in skeletal muscle membranes when exposed to low-oxygen stress that is consistent with the attenuation of muscle fatigue under physiologically normoxic conditions.

Advanced Uses of Pulse Oximetry for Monitoring Mechanically Ventilated Patients.

Pulse oximetry is an undisputable standard of care in clinical monitoring. It combines a spectrometer to detect hypoxemia with a plethysmograph for the diagnosis, monitoring, and follow-up of cardiovascular diseases. These pulse oximetry capabilities are extremely useful for assessing the respiratory and circulatory status and for monitoring of mechanically ventilated patients. On the one hand, the key spectrography-derived function of pulse oximetry is to evaluate a patient's gas exchange that results from a particular ventilatory treatment by continuously and noninvasively measuring arterial hemoglobin saturation (SpO2). This information helps to maintain patients above the hypoxemic levels, leading to appropriate ventilator settings and inspired oxygen fractions. However, whenever higher than normal oxygen fractions are used, SpO2 can mask existing oxygenation defects in ventilated patients. This limitation, resulting from the S shape of the oxyhemoglobin saturation curve, can be overcome by reducing the oxygen fraction delivered to the patient in a controlled and stepwise manner. This results in a SpO2/FIO2 diagram, which allows a rough characterization of a patient's gas exchange, shunt, and the amount of lung area with a low ventilation/perfusion ratio without the need of blood sampling. On the other hand, the photoplethysmography-derived oximeter function has barely been exploited for the purpose of monitoring hemodynamics in mechanically ventilated patients. The analysis of the photoplethysmography contour provides useful real-time and noninvasive information about the interaction of heart and lungs during positive pressure ventilation. These hemodynamic monitoring capabilities are related to both the assessment of preload dependency-mainly by analyzing the breath-by-breath variation of the photoplethysmographic signals-and the analysis of arterial impedance, which examines the changes in the plethysmographic amplitude, contour, and derived indexes. In this article, we present and describe these extended monitoring capabilities and propose a more holistic monitoring concept that takes advantage of these advanced uses of pulse oximetry in the monitoring of ventilated patients. Today's monitors need to be improved if such novel functionalities were to be offered for clinical use. Future developments and clinical evaluations are needed to establish the true potential of these advanced monitoring uses of pulse oximetry.

Dietary Recommendations for Cyclists during Altitude Training.

The concept of altitude or hypoxic training is a common practice in cycling. However, several strategies for training regimens have been proposed, like "live high, train high" (LH-TH), "live high, train low" (LH-TL) or "intermittent hypoxic training" (IHT). Each of them combines the effect of acclimatization and different training protocols that require specific nutrition. An appropriate nutrition strategy and adequate hydration can help athletes achieve their fitness and performance goals in this unfriendly environment. In this review, the physiological stress of altitude exposure and training will be discussed, with specific nutrition recommendations for athletes training under such conditions. However, there is little research about the nutrition demands of athletes who train at moderate altitude. Our review considers energetic demands and body mass or body composition changes due to altitude training, including respiratory and urinary water loss under these conditions. Carbohydrate intake recommendations and hydration status are discussed in detail, while iron storage and metabolism is also considered. Last, but not least the risk of increased oxidative stress under hypoxic conditions and antioxidant supplementation suggestions are presented.

S1P prophylaxis mitigates acute hypobaric hypoxia-induced molecular, biochemical, and metabolic disturbances: A preclinical report.

Sphingosine-1-phosphate (S1P) is emerging to have hypoxic preconditioning potential in various preclinical studies. The study aims to evaluate the preclinical preconditioning efficacy of exogenously administered S1P against acute hypobaric hypoxia (HH)-induced pathological disturbances. Male Sprague Dawley rats (200 ± 20 g) were preconditioned with 1, 10, and 100 µg/kg body weight (b.w.) S1P (i.v.) for three consecutive days. On the third day, S1P preconditioned animals, along with hypoxia control animals, were exposed to HH equivalent to 7,620 m (280 mm Hg) for 6 h. Postexposure status of cardiac energy production, circulatory vasoactive mediators, pulmonary and cerebral oxidative damage, and inflammation were assessed. HH exposure led to cardiac energy deficit indicated by low ATP levels and pronounced AMPK activation levels, raised circulatory levels of brain natriuretic peptide and endothelin-1 with respect to total nitrate (NOx), redox imbalance, inflammation, and alterations in NOx levels in the pulmonary and cerebral tissues. These pathological precursors have been routinely reported to be coincident with high-altitude diseases. Preconditioning with S1P, especially 1 µg/kg b.w. dose, was seen to reverse the manifestation of these pathological disturbances. The protective efficacy could be attributed, at least in part, to enhanced activity of cardioprotective protein kinase C and activation of small GTPase Rac1, which led to further induction of hypoxia-adaptive molecular mediators: hypoxia-inducible factor (HIF)-1α and Hsp70. This is a first such report, to the best of our knowledge, elucidating the mechanism of exogenous S1P-mediated HIF-1α/Hsp70 induction. Conclusively, systemic preconditioning with 1 µg/kg b.w. S1P in rats protects against acute HH-induced pathological disturbances. © 2016 IUBMB Life 68(5):365-375, 2016.

α-tocopherol supplementation prevents lead acetate and hypoxia-induced hepatic dysfunction.

OBJECTIVE: Lead (Pb) is a long-known poison of environment and industrial origin. Its prolonged exposure affects cellular material and alters cellular genetics and produces oxidative damages. In this study, we investigated the exposure of chronic sustained hypoxia or lead acetate alone or in combination with or without supplementation of α-tocopherol on hepatic oxidative and nitrosative stress in rats. MATERIALS AND METHODS: The rats weighing 165 ± 5 g were exposed to chronic sustained hypoxia (10% oxygen) or lead acetate (25 mg/kg of body weight, intraperitoneally) alone or in combination with or without supplementation of α-tocopherol (10 mg/100 g b.wt, intramuscularly). The body weight of all the rats was recorded on the day 1 of the treatment and the day of sacrifice. Serum lipid profile was estimated by using a biochemical analyzer. Oxidant and enzymatic antioxidants status was evaluated by using spectrophotometer. Serum levels of hypoxia inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) were measured by using ELISA technique. Histopathological assessments of hepatic tissue were also done. RESULTS: Exposure of both lead and hypoxia showed decreased body weight, altered serum lipid profile, oxidant and enzymatic antioxidants status, serum HIF-1α and VEGF concentrations. Simultaneous α-tocopherol supplementation showed beneficial effects to all these alterations. Histopathological observations also showed hepatic degenerative changes after lead or hypoxia exposure either alone or in combination, but remarkable improvement has been noticed after α-tocopherol supplementation. CONCLUSION: Supplementation of α-tocopherol is beneficial to counter both lead acetate and hypoxia induced hepatic cytotoxicities possibly by reducing oxidative and nitrosative stress.

Preoperative inspiratory muscular training to prevent postoperative hypoxemia in morbidly obese patients undergoing laparoscopic bariatric surgery. A randomized clinical trial.

BACKGROUND: Morbidly obese patients show an increased risk of postoperative hypoxemia and pulmonary complications when compared with normal weight subjects. The purpose of this study was to determine the effects of preoperative inspiratory muscular training (IMT) on postoperative arterial oxygenation in morbidly obese patients submitted to laparoscopic bariatric surgery. METHODS: Forty-four morbidly obese patients were randomly assigned to receive either preoperative usual care (control group, n = 21) or preoperative IMT (trained group, n = 23) for a month prior to the date of surgery. Data on oxygenation (PaO2/FiO2 ratio) were obtained at 1 h and at 12 h after surgery (PACU 1 h and PACU 12 h, respectively). Data on maximum static inspiratory pressure (MIP) were obtained before and after the training period, and at postanesthesia care unit (PACU) 12-h time point. RESULTS: PaO2/FiO2 was significantly higher in the trained group than in the control group, both at PACU 1 h (305.2 ± 77.6 vs. 248.8 ± 53.8, P = 0.008) and at PACU 12 h (333.5 ± 59.6 vs. 289.7 ± 79.6, P = 0.044). As a consequence, the percentage of patients with relative hypoxemia (PaO2/FiO2 lower than 300 mmHg) at the time of PACU discharge was higher in the control group (57 vs. 17 %, P: 0.006). MIP was significantly higher in the trained group compared with the control group at the preoperative time point (89.87 ± 19.00 vs. 77.00 ± 21.20 cm H2O, P = 0.04). CONCLUSIONS: Preoperative IMT improved postoperative oxygenation and increased inspiratory muscular strength in morbidly obese patients submitted to laparoscopic bariatric surgery.

Antihypoxic activities of the golden Chanterelle Mushroom, Cantharellus cibarius (higher Basidiomycetes).

Cantharellus cibarius is an edible mushroom with worldwide distribution. Because of its good radical scavenging and strong iron-chelating activity, this mushroom was nominated for assay of antihypoxic activity. Protective effects of Chanterelle extract against hypoxia-induced lethality in mice were evaluated by 3 experimental models of hypoxia: asphyctic, hemic, and circulatory. Antihypoxic activity was especially pronounced in the hemic model. The effect was dose dependent. C. cibarius extract (600 mg kg-1) kept the mice alive for 10.07 ± 1.18 min. It significantly (P < 0.0001) and dose dependently prolonged survival time compared to control group (7.00 ± 0.63 min). Extract at 300 mg kg-1 prolonged survival time to 9.94 ± 0.87 min, which was statistically significant (P < 0.0001) compared to control group. In circulatory model, C. cibarius extract (600 mg kg-1) was effective. It prolonged latency for death significantly with regard to the control group (15.18 ± 4.21 vs. 9.84 ± 0.75 min; P < 0.001). At 300 mg kg-1, the extract also prolonged survival time (13.57 ± 0.87 min), and this effect was also statistically significant compared to the control group (P < 0.01). Extract showed no activity in the asphyctic model. Mice in the control group died of hypoxia in 28.20 ± 3.27 min. Extract (600 mg kg-1) prolonged latency for death, but this activity was not statistically significant (P < 0.05). Phenytoin prolonged latency for death to 55.00 ± 6.05 min (P < 0.0001).