Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.

Narcolepsy is a sleep disorder caused by deficiency of orexin signaling. However, the neural mechanisms by which deficient orexin signaling causes the abnormal rapid eye movement (REM) sleep characteristics of narcolepsy, such as cataplexy and frequent transitions to REM states, are not fully understood. Here, we determined the activity dynamics of orexin neurons during sleep that suppress the abnormal REM sleep architecture of narcolepsy. Orexin neurons were highly active during wakefulness, showed intermittent synchronous activity during non-REM (NREM) sleep, were quiescent prior to the transition from NREM to REM sleep, and a small subpopulation of these cells was active during REM sleep. Orexin neurons that lacked orexin peptides were less active during REM sleep and were mostly silent during cataplexy. Optogenetic inhibition of orexin neurons established that the activity dynamics of these cells during NREM sleep regulate NREM-REM sleep transitions. Inhibition of orexin neurons during REM sleep increased subsequent REM sleep in "orexin intact" mice and subsequent cataplexy in mice lacking orexin peptides, indicating that the activity of a subpopulation of orexin neurons during the preceding REM sleep suppresses subsequent REM sleep and cataplexy. Thus, these results identify how deficient orexin signaling during sleep results in the abnormal REM sleep architecture characteristic of narcolepsy.

Association of a third vaccination with antibody levels and side reactions in essential workers: A prospective cohort study.

OBJECTIVE: To evaluate the relationship between the change of titer and adverse events after the third vaccination for COVID-19 among healthcare workers. DESIGN AND SETTING: This was a prospective cohort study, and the follow-up period was from December 2021 to November 2023. PARTICIPANTS: A total of 392 healthcare workers aged over 20 years who worked at the facility and wished to have vaccine antibody titers measured participated in this study. EXPOSURES: A third dose of BNT162b2 COVID-19 vaccine was administered to healthcare workers working at the hospital, and we evaluated the changes in antibody titers before and after the vaccine, as well as adverse reactions after vaccination. MAIN OUTCOMES AND MEASURES: The primary endpoints were adverse reactions within 7 days after the third dose of COVID-19 vaccine and the rate of increase in COVID-19 vaccine antibody titer at 4 weeks. RESULTS: A total of 392 people participated in the study, of whom 358 participants had their antibody titers measured before and after the booster vaccination. The overall IgG geometric mean was 609 U/mL (561-663) before booster vaccination and increased to 18,735 U/mL (17,509-20,049) at 4 weeks after vaccination (p < 0.001). Multivariate analysis showed no statistically significant relationship between the primary endpoints, such as a change in antibody titer due to the presence of fever after vaccination or a change in antibody titer due to swelling at the vaccination site. Factors affecting the rate of increase in antibody titer, evaluated as secondary endpoints, were suggested to be age (1.02 (95 % confidence interval (CI): 1.01-1.03)) and hypertension (0.66 (95 % CI: 0.47-0.93)). CONCLUSIONS AND RELEVANCE: In relation to the booster effect of the third dose of COVID-19 vaccination, there was no statistically significant difference in the presence of fever or use of antipyretic or other drugs.

[Challenges, prevention, and countermeasures for social withdrawal (hikikomori) by age group].

　The term "hikikomori" was recognized by society between 1980 and 2000, when the term "NEET" also appeared and it was regarded as a problem of irresponsible youth. However, accumulation of surveys and research both in Japan and abroad, including those conducted by the Cabinet Office, has revealed that the reasons behind social withdrawal are not only limited to mental illness. There are many people who exhibit withdrawal because they are unable to establish relationships with the community and other people owing to various factors such as social systems, attachment formation, family background, and education. In other words, withdrawal is better described as a "symptom" or "condition" than a disease. Therefore, it is necessary to understand and analyze the diverse backgrounds and needs of individuals with withdrawal and confront them about their state. Currently, many hikikomori people with prolonged withdrawal are now in their 40s and 50s. With their parents' aging, there are cases where people with hikikomori and their families become socially isolated and are unable to make ends meet. It is undeniable that, until now, the society we live in as a whole has little interest in or understanding of hikikomori. In contrast, withdrawal among older adults (tojikomori), which has become a problem in the super-aging society. Tojikomori is defined as "going out less than once a week and not requiring nursing care", which is not equivalent with hikikomori. Owing to the decline in the frequency of going out among the elderly in the recent coronary crisis, the number of pre-frailty in older adults has become a nationwide problem.　Thus, both hikikomori and tojikomori are reversible conditions, and can be alleviated by providing necessary support. This paper summarizes the findings of the symposium "Challenges, Prevention, and Countermeasures for Social Withdrawal (Hikikomori) by Age Group" organized by the Committee on Mental Health and Suicide Prevention of the Japanese Society of Public Health at the 79th Annual Meeting of the Japanese Society of Public Health. This article is a compilation of findings that can benefit public health practitioners and researchers.

Testosterone improved erectile function by upregulating transcriptional expression of growth factors in late androgen replacement therapy model rats.

We previously showed that castration of rats reduced erectile function over time; when testosterone replacement therapy was started 4 weeks after castration, erectile function improved. In this study, we examined the mechanism of improvement in erectile function following testosterone replacement therapy in rats. Thirty 12-week-old rats were divided into castrated (Cast), castrated with subcutaneous administration of testosterone (Cast + T), and sham (Sham) groups. Erectile function and mRNA and protein expression were evaluated in the rats by using standard methods. To assess erectile function, we measured the intracavernosal pressure, mean arterial pressure, mRNA expression of endothelial growth factors, and protein expression of endothelial nitric oxide synthase (eNOS). The intracavernosal pressure/mean arterial pressure ratio was significantly lower in the Cast group, and testosterone administration significantly improved (P = 0.017). Compared to the Cast group, the Cast+T group exhibited significantly increased mRNA expressions of vascular endothelial growth factor A (VEGF-A), intercellular adhesion molecule 1 (ICAM-1), transforming growth factor-ß (TGF-ß), nerve growth factor (NGF), α-smooth muscle actin (α-SMA), caveolae associated protein 1 (Cavin-1), Cavin-2, Cavin-3, sirtuin 1 (Sirt-1), sphingosine-1-phosphate 1 (S1P1), S1P2, and S1P3 and eNOS protein expression. Testosterone replacement therapy improved erectile function in castrated rats by increasing growth factors and eNOS protein.

Evolution of global development cooperation: An analysis of aid flows with hierarchical stochastic block models.

Despite considerable scholarly attention on the institutional and normative aspects of development cooperation, its longitudinal dynamics unfolding at the global level have rarely been investigated. Focusing on aid, we examine the evolving global structure of development cooperation induced by aid flows in its entirety. Representing annual aid flows between donors and recipients from 1970 to 2013 as a series of networks, we apply hierarchical stochastic block models to extensive aid-flow data that cover not only the aid behavior of the major OECD donors but also that of other emerging donors, including China. Despite a considerable degree of external expansion and internal diversification of aid relations over the years, the analysis has uncovered a temporally persistent structure of aid networks. The latter comprises, on the one hand, a limited number of major donors with far-reaching resources and, on the other hand, a large number of mostly poor but globally well-connected recipients. The results cast doubt on the efficacy of recurrent efforts for "aid reform" in substantially changing the global aid flow pattern.

Acute Effect of Repeated Sprint Exercise With Blood Flow Restriction During Rest Periods on Muscle Oxygenation.

PURPOSE: This study aimed to examine the effect of applying BFR during rest periods of repeated cycling sprints on muscle oxygenation. METHODS: Seven active males performed 5 × 10-s maximal pedaling efforts with 40-s passive rest, with or without BFR application during rest period. BFR was applied for 30 s between sprints (between 5 and 35 s into rest) through a pneumatic pressure cuff inflated at 140 mmHg. Vastus lateralis muscle oxygenation was monitored using near-infrared spectroscopy. In addition, blood lactate concentration and heart rate were also evaluated. RESULTS: The BFR trial showed significantly lower oxyhemoglobin (oxy-Hb) and tissue saturation (StO2) levels than the CON trial (P < 0.05). However, power output and blood lactate concentration did not significantly differ between the two trials (P > 0.05). CONCLUSION: Applying BFR during rest periods of repeated cycling sprints decreased muscle oxygenation of active musculature, without interfering with power output during sprints.

Effects of Reduced Carbohydrate Intake after Sprint Exercise on Breath Acetone Level.

Assessment of breath acetone level may be an alternative procedure to evaluate change in fat metabolism. The purpose of the present study was to investigate the effect of insufficient carbohydrate (CHO) intake after sprint exercise on breath acetone level during post-exercise. Nine subjects conducted two trials, consisting of either reduced CHO trial (LOW trial) or normal CHO trial (NOR trial). In each trial, subjects visited to laboratory at 7:30 following an overnight fast to assess baseline breath acetone level. They commenced repeated sprint exercise from 17:00. After exercise, isoenergetic meals with different doses of CHO (LOW trial; 18% for CHO, 27% for protein, 55% for fat, NOR trial; 58% for CHO, 14% for protein, 28% for fat) were served. Breath acetone level was also monitored immediately before and after exercise, 1 h, 3 h, 4 h, and 15 h (on the following morning) after completing exercise. A significant higher breath acetone level was observed in LOW trial than in NOR trial 4 h after completion of exercise (NOR trial; 0.66 ppm, LOW trial; 0.9 ppm). However, breath acetone level did not differ on the following morning between two trials. Therefore, CHO intake following an exhaustive exercise affects breath acetone level during early phase of post-exercise.

Effects of electrolyzed hydrogen water ingestion during endurance exercise in a heated environment on body fluid balance and exercise performance.

Electrolyzed hydrogen water (EHW) is generated at a cathode. It contains many hydrogen molecules with high alkaline properties. The physiological effects of ingesting EHW during endurance exercise are unclear. The purpose of this study was to determine the effects of ingesting EHW during endurance exercise in a heated environment on body fluid balance and exercise performance. Twelve triathletes (20.0 ± 1.3 years, 171 ± 6 cm, 60.6 ± 3.9 kg, V̇O2max 67.1 ± 3.8 mL/kg/min) performed pedaling exercise for 60 min at 65% of V̇O2max consuming either purified water (CON trial) or EHW (EHW trial) and then conducted an incremental pedaling test. Blood parameters, tissue temperature, and respiratory variables were determined during 60 min of exercise. The time to exhaustion (TTE) during the incremental pedaling test was also determined. Body weights were 1.1 ± 0.4 kg lower after exercise, with no significant differences between trials. Plasma volume and serum osmolality and blood sodium and potassium concentrations significantly changed with exercise, but no significant differences were observed between trials. The pH, blood lactate and bicarbonate concentrations, and changes in skin and muscle temperature did not significantly differ between the two trials. Energy expenditure during exercise was significantly (P = 0.04) lower in the EHW trial (13.2 ± 0.5 kcal/min) than in the CON trial (13.7 ± 0.4 kcal/min). TTE did not significantly differ between the trials. In conclusion, EHW ingestion during endurance exercise in a heated environment decreased energy expenditure but did not affect body fluid balance or exercise performance. Abbreviations: CON: control trial; CV: coefficient of variation; EHW: electrolyzed hydrogen water; HR: heart rate; RPE: rating of perceived exertion; SE: standard error; TP: total protein; TTE: time to exhaustion.

Endocrine and Metabolic Responses to Endurance Exercise Under Hot and Hypoxic Conditions.

PURPOSE: We explored the effect of heat stress during an acute endurance exercise session in hypoxia on endocrine and metabolic responses. METHODS: A total of 12 healthy males cycled at a constant workload (60% of the power output associated with their maximal oxygen uptake under each respective condition) for 60 min in three different environments: exercise under hot and hypoxia (H+H; fraction of inspiratory oxygen or FiO2: 14.5%, 32°C), exercise under hypoxia (HYP; FiO2: 14.5%, 23°C), and exercise under normoxia (NOR; FiO2: 20.9%, 23°C). After completing the exercise, participants remained in the chamber for 3 h to evaluate metabolic and endocrine responses under each environment. Changes in muscle oxygenation (only during exercise), blood variables, arterial oxygen saturation, and muscle temperature were determined up to 3 h after exercise. RESULTS: Serum erythropoietin (EPO) level was increased to similar levels in both H+H and HYP at 3 h after exercise compared with before exercise (P < 0.05), whereas no significant increase was found under NOR. No significant difference between H+H and HYP was observed in the serum EPO level, blood lactate level, or muscle oxygenation at any time (P > 0.05). Exercise-induced serum growth hormone (GH) elevation was significantly greater in H+H compared with HYP (P < 0.05) and HYP showed significantly lower value than NOR (P < 0.05). Arterial oxygen saturation during exercise was significantly lower in H+H and HYP compared with NOR (P < 0.05). Furthermore, H+H showed higher value compared with HYP (P < 0.05). CONCLUSION: The serum EPO level increased significantly with endurance exercise in hypoxia. However, the addition of heat stress during endurance exercise in hypoxia did not augment the EPO response up to 3 h after completion of exercise. Exercise-induced GH elevation was significantly augmented when the hot exposure was combined during endurance exercise in hypoxia. Muscle oxygenation levels during endurance exercise did not differ significantly among the conditions. These findings suggest that combined hot and hypoxic stresses during endurance exercise caused some modifications of metabolic and endocrine regulations compared with the same exercise in hypoxia.

The relationships between three-axis accelerometer measures of physical activity and motor symptoms in patients with Parkinson's disease: a single-center pilot study.

BACKGROUND: Various wearable devices for objectively evaluating motor symptoms of patients with Parkinson's disease (PD) have been developed. Importantly, previous studies have suggested protective effects of physical activity in PD. However, the relationships between conventional clinical ratings for PD and three-axis accelerometer measures of physical activity (e.g., daily physical activity levels [PAL] or metabolic equivalents of task [METs]) are still unclear, particularly for METs. In the current study, we sought to elucidate these relationships on a daily basis, and to clarify optimal predictors for clinical states on a 30-min basis. METHODS: Patients who were hospitalized for adjustment of drugs or deep brain stimulation were enrolled. Using waist-worn three-axis accelerometers, PAL and METs parameter data were obtained and compared with UPDRS-3[On] and symptom diary data. We extracted data from the patients' best and worst days, defined by the best and worst UPDRS-3[On] scores, respectively. Thus, 22 data sets from 11 patients were extracted. We examined the correlations and produced scatter plots to represent the relationships, then investigated which METs parameters and activity patterns were the best predictors for "On" and "dyskinesia". RESULTS: The parameter "mean METs value within the 95-92.5 percentile range on a day (95-92.5 percentile value)" exhibited the strongest correlation with conventional daily clinical ratings (Rho: - 0.799 for UPDRS-3[On], 0.803 for On hours [p < 0.001]). Scatter plots suggested that PAL tended to have higher values in patients with involuntary movement. However, METs parameters focusing on higher METs seemed to alleviate this tendency. We clarified that "time over 2.0 METs" and "time over 1.5 METs" could be predictors for "On" and "dyskinesia" on a 30-min basis, respectively (AUROC: 0.779 and 0.959, 95% CI: 0.733-0.824 and 0.918-1.000). The specificity and sensitivity of the optimal activity pattern for "On" were 0.858 and 0.621. CONCLUSIONS: This study suggested feasible activity patterns and METs parameters for objective evaluation of motor symptoms on a 30-min or daily basis. Three-axis accelerometer measures focusing on higher METs may be appropriate for evaluating physical activity. Further larger-scale studies are necessary to clarify the validity, reliability, and clinical utility of these objective measures.

An integrated community mental healthcare program to reduce suicidal ideation and improve maternal mental health during the postnatal period: the findings from the Nagano trial.

BACKGROUND: During the perinatal period, suicides are more likely to occur in those with depression and who are not receiving active treatment at the time of death. Suicide is a common outcome in people with suicide ideation. We developed an intervention program taking care of comprehensive perinatal maternal mental healthcare to prevent suicide ideation. We hypothesized that our intervention program could reduce postnatal suicide ideation and improve maternal mental health. METHODS: We performed a controlled trial to examine the usual postnatal care plus a maternal suicide prevention program (the intervention group) compared with usual postnatal care alone, which comprised home visits by public health nurses without mental health screening (the control group) in Nagano city, Japan. In total, 464 women were included; 230 were allocated to the control group and 234 to the intervention group. The intervention had three components: 1) all the women received postnatal mental health screening by public health nurses who completed home visits during the neonatal period, 2) the intervention was administered by a multidisciplinary clinical network, and 3) systematic follow-up sheets were used to better understand bio-psycho-social characteristics of both the mothers and their infants and develop responsive care plans. We measured the participants' mental health at 3-4 months postpartum (T1) and 7-8 months postpartum (T2) using the Japanese version of the Edinburgh Postnatal Depression Scale (EPDS). RESULTS: Suicidal ideation was significantly lower in the intervention group compared with the control group at T1 (p = 0.014); however, this significant between-group difference did not continue to T2 (p = 0.111). We measured the intervention effects on maternal mental health using the total score of the EPDS, which was significantly improved in the intervention group compared with the control group at T1. Here, the significant difference continued to T2 (p = 0.049). CONCLUSIONS: Our results indicate that our program may reduce maternal suicidal ideation at 3-4 months postnatally and improve women's mental health during the postnatal periods of 3-4 to 7-8 months. Postnatal maternal mental healthcare, including services to reduce suicide ideation, should be included as an important component of general postnatal care. TRIAL REGISTRATION: Name of registry: A multidisciplinary intervention program for maternal mental health in perinatal periods. UMIN Clinical Trials Registry number: UMIN000033396 . Registration URL: https://upload.umin.ac.jp/cgibin/ctr/ctr_view_reg.cgi?recptno=R000038076 Registration date: July 15, 2018. Registration timing: retrospective.

Partial sleep deprivation after an acute exercise session does not augment hepcidin levels the following day.

The purpose of the present study was to determine the effects of partial sleep deprivation (PSD) after an exercise session in the evening on the endurance exercise-induced hepcidin response the following morning. Ten recreationally trained males participated under two different conditions. Each condition consisted of 2 consecutive days of training (days 1 and 2). On day 1, participants ran for 60 min at 75% of maximal oxygen uptake ( V˙ O2max ) followed by 100 drop jumps. Sleep duration at night was manipulated, with a normal length of sleep (CON condition, 23:00-07:00 hr) or a shortened length of sleep (PSD condition). On the morning of day 2, the participants ran for 60 min at 65% of V˙ O2max . Sleep duration was significantly shorter under the PSD condition (141.2 ± 13.3 min) than under the CON condition (469.0 ± 2.3 min, p < .0001). Serum hepcidin, plasma interleukin (IL)-6, serum haptoglobin, iron, and myoglobin levels did not differ significantly between the conditions (p > .05) on the morning (before exercise) of day 2. Additionally, the 3-hr postexercise levels for the hematological variables were not significantly different between the two conditions (p > .05). In conclusion, the present study demonstrated that a single night of PSD after an exercise session in the evening did not affect baseline serum hepcidin level the following morning. Moreover, a 60 min run the following morning increased serum hepcidin and plasma IL-6 levels significantly, but the exercise-induced elevations were not affected by PSD.

No effect of supplemented heat stress during an acute endurance exercise session in hypoxia on hepcidin regulation.

Hepcidin is a novel factor for iron deficiency in athletes, which is suggested to be regulated by interleukin-6 (IL-6) or erythropoietin (EPO). PURPOSE: The purpose of the present study was to compare endurance exercise-induced hepcidin elevation among "normoxia", "hypoxia" and "combined heat and hypoxia". METHODS: Twelve males (21.5 ± 0.3 years, 168.1 ± 1.2 cm, 63.6 ± 2.0 kg) participated in the present study. They performed 60 min of cycling at 60% of [Formula: see text] in either "heat and hypoxia" (HHYP; FiO2 14.5%, 32 °C), "hypoxia" (HYP; FiO2 14.5%, 23 °C) or "normoxia" (NOR; FiO2 20.9%, 23 °C). After completing the exercise, participants remained in the prescribed conditions for 3 h post-exercise. Blood samples were collected before, immediately and 3 h after exercise. RESULTS: Plasma IL-6 level significantly increased immediately after exercise (P < 0.05), with no significant difference among the trials. A significant elevation in serum EPO was observed 3 h after exercise in hypoxic trials (HHYP and HYP, P < 0.05), with no significant difference between HHYP and HYP. Serum hepcidin level increased 3 h after exercise in all trials (NOR, before 18.3 ± 3.9 and post180 31.2 ± 6.3 ng/mL; HYP, before 13.5 ± 2.5 and post180 23.3 ± 3.6 ng/mL, HHYP; before 15.8 ± 3.3 and post180 31.4 ± 5.3 ng/mL, P < 0.05). However, there was no significant difference among the trials during post-exercise. CONCLUSION: Endurance exercise in "combined heat and hypoxia" did not exacerbate exercise-induced hepcidin elevation compared with the same exercise in "hypoxia" or "normoxia".

Development and Practical Test of Quality Indicators for Palliative Care in Patients With Chronic Heart Failure.

BACKGROUND: Palliative care is highly relevant for patients with heart failure (HF), and there is a need for quantitative information on quality of care. Accordingly, this study aimed to develop a set of quality indicators (QIs) for palliative care of HF patients, and to conduct a practical pilot measurement of the proposed QIs in clinical practice.Methods and Results:We used a modified Delphi technique, a consensus method that involves a comprehensive literature review, face-to-face multidisciplinary panel meeting, and anonymous rating in 2 rounds. A 15-member multidisciplinary expert panel individually rated each potential indicator on a scale of 1 (lowest) to 9 (highest) for appropriateness. All indicators receiving a median score ≥7 without significant disagreement were included in the final set of QIs. Through the consensus-building process, 35 QIs were proposed for palliative care in HF patients. Practical measurement in HF patients (n=131) from 3 teaching hospitals revealed that all of the proposed QIs could be obtained retrospectively from medical records, and the following QIs had low performance (<10%): "Intervention by multidisciplinary team", "Opioid therapy for patients with refractory dyspnea", and "Screening for psychological symptoms". CONCLUSIONS: The first set of QIs for palliative care of HF patients was developed and could clarify quantitative information and might improve the quality of care.

Development and validation of support tools for advance care planning in patients with chronic heart failure.

BACKGROUND: Advance care planning (ACP) is recommended as part of the management of patients with heart failure (HF). AIMS: To develop and validate ACP support tools for patients with HF. METHODS: An ACP support tool was developed based on a systematic literature review. A multi-center, prospective before and after study was conducted to evaluate the usefulness of the support tool. This study included 21 patients with HF, 11 patients formed the control group and 10 patients were part of the intervention group who received ACP from medical staff using the ACP support tools developed for this study. Participants of the study were surveyed about their experience of ACP using a 6-point Likert scale. FINDINGS: All of the healthcare professionals (n=9) involved in the study found the ACP tool useful and about 90% of patients considered the support tool useful. The score for 'the patient did not feel anxious about the future after receiving ACP discussion' was significantly higher (3.5 [3.0, 4.0] vs 2.0 [1.0, 3.0]; P=0.04) in the intervention group that used the ACP tool. CONCLUSION: ACP support tools are useful to manage patients with HF and could enable effective ACP without increasing patient anxiety.

The Effects of Endurance Exercise in Hypoxia on Acid-Base Balance, Potassium Kinetics, and Exogenous Glucose Oxidation.

PURPOSE: To investigate the carbohydrate metabolism, acid-base balance, and potassium kinetics in response to exercise in moderate hypoxia among endurance athletes. METHODS: Nine trained endurance athletes [maximal oxygen uptake (VO2max): 62.5 ± 1.2 mL/kg/min] completed two different trials on different days: either exercise in moderate hypoxia [fraction of inspired oxygen (FiO2) = 14.5%, HYPO] or exercise in normoxia (FiO2 = 20.9%, NOR). They performed a high-intensity interval-type endurance exercise consisting of 10 × 3 min runs at 90% of VO2max with 60 s of running (active rest) at 50% of VO2max between sets in hypoxia (HYPO) or normoxia (NOR). Venous blood samples were obtained before exercise and during the post-exercise. The subjects consumed 13C-labeled glucose immediately before exercise, and we collected expired gas samples during exercise to determine the 13C-excretion (calculated as 13CO2/12CO2). RESULTS: The running velocities were significantly lower in HYPO (15.0 ± 0.2 km/h) than in NOR (16.4 ± 0.3 km/h, P < 0.0001). Despite the lower running velocity, we found a significantly greater exercise-induced blood lactate elevation in HYPO compared with in NOR (P = 0.002). The bicarbonate ion concentration (P = 0.002) and blood pH (P = 0.002) were significantly lower in HYPO than in NOR. There were no significant differences between the two trials regarding the exercise-induced blood potassium elevation (P = 0.87) or 13C-excretion (HYPO, 0.21 ± 0.02 mmol⋅39 min; NOR, 0.14 ± 0.03 mmol⋅39 min; P = 0.10). CONCLUSION: Endurance exercise in moderate hypoxia elicited a decline in blood pH. However, it did not augment the exercise-induced blood K+ elevation or exogenous glucose oxidation (13C-excretion) compared with the equivalent exercise in normoxia among endurance athletes. The findings suggest that endurance exercise in moderate hypoxia causes greater metabolic stress and similar exercise-induced elevation of blood K+ and exogenous glucose oxidation compared with the same exercise in normoxia, despite lower mechanical stress (i.e., lower running velocity).