New opportunities at the next-generation neutrino experiments I: BSM neutrino physics and dark matter.

The combination of the high intensity proton beam facilities and massive detectors for precision measurements of neutrino oscillation parameters including the charge-parity violating (CPV) phase will open the door to help make beyond the standard model (BSM) physics reachable even in low energy regimes in the accelerator-based experiments. Large-mass detectors with highly precise tracking and energy measurements, excellent timing resolution, and low energy thresholds will enable the searches for BSM phenomena from cosmogenic origin, as well. Therefore, it is also conceivable that BSM topics in the next-generation neutrino experiments could be the dominant physics topics in the foreseeable future, as the precision of the neutrino oscillation parameter and CPV measurements continue to improve.This paper provides a review of the current landscape of BSM theory in neutrino experiments in two selected areas of the BSM topics-dark matter and neutrino related BSM-and summarizes the current results from existing neutrino experiments to set benchmarks for both theory and experiment. This paper then provides a review of upcoming neutrino experiments throughout the next 10 to 15 year time scale and their capabilities to set the foundation for potential reach in BSM physics in the two aforementioned themes. An important outcome of this paper is to ensure theoretical and simulation tools exist to carry out studies of these new areas of physics, from the first day of the experiments, such as Deep Underground Neutrino Experiment in the U.S. and Hyper-Kamiokande Experiment in Japan.

Serum lipidomics reveals early differential effects of gastric bypass compared with banding on phospholipids and sphingolipids independent of differences in weight loss.

BACKGROUND/OBJECTIVES: Circulating phospholipids and sphingolipids are implicated in obesity-related comorbidities such as insulin resistance and cardiovascular disease. How bariatric surgery affects these important lipid markers is poorly understood. We sought to determine whether Roux-en-Y gastric bypass (RYGB), which is associated with greater metabolic improvement, differentially affects the phosphosphingolipidome compared with adjustable gastric banding (AGB). SUBJECTS/METHODS: Fasting sera were available from 59 obese women (body mass index range 37-51 kg m-2; n=37 RYGB and 22 AGB) before surgery, then at 1 (21 RYGB, 12 AGB) and 3 months follow-up (19 RYGB, 12 AGB). HPLC-MS/MS was used to quantify 131 lipids from nine structural classes. DXA measurements and laboratory parameters were also obtained. The associations between lipids and clinical measurements were studied with P-values adjusted for the false discovery rate (FDR). RESULTS: Both surgical procedures rapidly induced weight loss and improved clinical profiles, with RYGB producing better improvements in fat mass, and serum total cholesterol, low-density lipoprotein-cholesterol (LDL-C) and orosomucoid (FDR <10%). Ninety-three (of 131) lipids were altered by surgery-the majority decreasing-with 29 lipids differentially affected by RYGB during the study period. The differential effect of the surgeries remained statistically significant for 20 of these lipids after adjusting for differences in weight loss between surgery types. The RYGB signature consisted of phosphatidylcholine species not exceeding 36 carbons, and ceramides and sphingomyelins containing C22 to C25 fatty acids. RYGB also led to a sustained increase in unsaturated ceramide and sphingomyelin species. The RYGB-specific lipid changes were associated with decreases in body weight, total and LDL-C, orosomucoid and increased HOMA-S (FDR <10%). CONCLUSIONS: Concomitant with greater metabolic improvement, RYGB induced early and sustained changes in phosphatidylcholines, sphingomyelins and ceramides that were independent of greater weight loss. These data suggest that RYGB may specifically alter sphingolipid metabolism, which, in part, could explain the better metabolic outcomes of this surgical procedure.

[What's new in gynecology and obstetrics]. / Gynécotogie et obstétrique.

Because of the lack of screening methods, ovarian cancer remains one of the major causes of mortality in gynecological oncology. Prevention by salpingectomy, based on a concept about the origin of serous carcinoma, may be proven effective in the future. Regarding cervical cancer, screening methods are improving and the benefit of HPV-HR testing has been recently demonstrated. Metabolic requirements and exercise are modified during pregnancy. Present recommendations are for pregnant women to practice regular moderate exercise, as in a non-pregnant population. This guideline, despite being reasonable, is not based on strong evidence. A randomised trial is ongoing in our Department to evaluate the effects of exercise in women with gestational diabetes.

Equal BMD after daily or triweekly exercise in growing rats.

The purpose of this study was to examine the efficacy of continuous resistance training (3 days/wk) compared to interrupted resistance training where 20-24 h separated an exercise bout (i. e. 6 days/wk) for enhancing bone mineral density (BMD) in growing male rats. The total volume of work performed per week between the two resistance training programs was equivalent by design. Young male rats were randomly divided into Control (Con, n=9), 3 days/wk resistance trained group (RT3, n=9), and 6 days/wk resistance trained group (RT6, n=9). The RT3 and RT6 groups were conditioned to climb a vertical ladder with weights appended to their tail for a total of 6 wks. After 6 wks, BMD (assessed via DXA) from the left tibia was significantly greater for RT3 (0.242+/-0.004 g/cm (2)) and RT6 (0.244+/-0.004 g/cm (2)) compared to Con (0.226+/-0.003 g/cm (2)). Further, serum osteocalcin (oc, in ng/ml) was significantly greater for RT3 (75.8+/-4.4) and RT6 (73.5+/-3.8) compared to Con (53.4+/-2.4). There was no significant difference in BMD or serum OC between RT3 and RT6 groups. The results indicate that both resistance training programs were equally effective in elevating bone mineral density in young, growing rats.

Interrupted resistance training and BMD in growing rats.

A resistance training program, where the exercise was uninterrupted (UT, i.e. continuous repetitions) was compared against another resistance training program where the exercise was interrupted (IT, i.e. 2 exercise sessions during a training day) for enhancing bone modeling and bone mineral density (BMD) in maturating animals. The total volume of work performed between the two resistance training programs was equivalent by design. Young male rats (approximately 8 weeks old) were randomly divided into Control (Con, n=8), UT (n=8) and IT (n=7) resistance trained groups. The UT and IT groups were conditioned to climb a vertical ladder with weights appended to their tail 3 days/week for 6 weeks. After the 6 week training regimen (Mean+/-SD), tibial BMD (assessed via DXA) was significantly greater for UT (0.237+/-0.008 g/cm(2)) and IT (0.238+/-0.005 g/cm(2)) compared to Con (0.223+/-0.004 g/cm(2)). Further, serum osteocalcin (OC) was significantly greater for UT (45.65+/-2.83 ng/ml) and IT (46.33+/-4.60 ng/ml) compared to Con (37.86+/-4.04 ng/ml). There was no significant difference in BMD or serum OC between UT and IT groups. The results indicate that both resistance training programs were equally effective in elevating BMD in growing animals.

[Serious and sometimes fatal consequences of high-altitude pulmonary oedema]. / Ernstige en soms fatale gevolgen van hoogtelongoedeem.

Three women aged 25, 34 and 22 years respectively, experienced high-altitude pulmonary oedema during a climbing holiday. The first patient presented with complaints arising from a fast ascent to high altitude and was treated with acetazolamide and rapid descent. She recovered without any complications. The second patient developed symptoms during the night, which were not recognised as high-altitude pulmonary oedema. The next morning she died while being transported down on a stretcher without having received any medication or oxygen. The third case was not a specific presentation of high-altitude pulmonary oedema but autopsy revealed pulmonary oedema. This woman had already been higher up on the mountain before she developed complications. The cases illustrate the seriousness of this avoidable form of high altitude illness. The current Dutch national guidelines advise against the use of medication by lay people. A revision is warranted: travellers to high altitude should be encouraged to carry acetazolamide, nifedipine and corticosteroids on the trip. Travel guides ought to be trained to use these drugs. In addition climbing travellers should be encouraged to adopt appropriate preventive behaviour and to start descending as soon as signs of high-altitude pulmonary oedema develop.

Wide-pulse-high-frequency neuromuscular electrical stimulation in cerebral palsy.

OBJECTIVE: The present study assesses whether wide-pulse-high-frequency (WPHF) neuromuscular electrical stimulation (NMES) could result in extra-force production in cerebral palsy (CP) patients as previously observed in healthy individuals. METHODS: Ten CP and 10 age- and sex-matched control participants underwent plantar flexors NMES. Two to three 10-s WPHF (frequency: 100 Hz, pulse duration: 1 ms) and conventional (CONV, frequency 25 Hz, pulse duration: 50 µs) trains as well as two to three burst-like stimulation trains (2s at 25 Hz, 2s at 100 Hz, 2s at 25 Hz; pulse duration: 1 ms) were evoked. Resting soleus and gastrocnemii maximal H-reflex amplitude (Hmax) was normalized by maximal M-wave amplitude (Mmax) to quantify α-motoneuron modulation. RESULTS: Similar Hmax/Mmax ratio was found in CP and control participants. Extra-force generation was observed both in CP (+18 ± 74%) and control individuals (+94 ± 124%) during WPHF (p<0.05). Similar extra-forces were found during burst-like stimulations in both groups (+108 ± 110% in CP and +65 ± 85% in controls, p>0.05). CONCLUSION: Although the mechanisms underlying extra-force production may differ between WPHF and burst-like NMES, similar increases were observed in patients with CP and healthy controls. SIGNIFICANCE: Development of extra-forces in response to WPHF NMES evoked at low stimulation intensity might open new possibilities in neuromuscular rehabilitation.

In search for better pharmacological prophylaxis for acute mountain sickness: looking in other directions.

Despite decades of research, the exact pathogenic mechanisms underlying acute mountain sickness (AMS) are still poorly understood. This fact frustrates the search for novel pharmacological prophylaxis for AMS. The prevailing view is that AMS results from an insufficient physiological response to hypoxia and that prophylaxis should aim at stimulating the response. Starting off from the opposite hypothesis that AMS may be caused by an initial excessive response to hypoxia, we suggest that directly or indirectly blunting-specific parts of the response might provide promising research alternatives. This reasoning is based on the observations that (i) humans, once acclimatized, can climb Mt Everest experiencing arterial partial oxygen pressures (PaO2) as low as 25 mmHg without AMS symptoms; (ii) paradoxically, AMS usually develops at much higher PaO2 levels; and (iii) several biomarkers, suggesting initial activation of specific pathways at such PaO2, are correlated with AMS. Apart from looking for substances that stimulate certain hypoxia triggered effects, such as the ventilatory response to hypoxia, we suggest to also investigate pharmacological means aiming at blunting certain other specific hypoxia-activated pathways, or stimulating their agonists, in the quest for better pharmacological prophylaxis for AMS.

Contractile properties and fiber type distribution of quadriceps muscles in adults with childhood-onset growth hormone deficiency.

Adults with GH deficiency (GHD) report weakness and fatigability. The origin of such symptoms is still debated. This work aimed to clarify whether weakness and fatigability depend on impairment of skeletal muscle contractile capacity. Five males with childhood-onset GHD (age +/- SE, 29.6 +/- 1.9) and 13 age- and sex-matched controls were enrolled in the study. Quadriceps muscle cross-sectional area (CSA), strength, twitch characteristics, and fatigue index of voluntary and electrically evoked contractions were determined in vivo in all subjects. Fiber type distribution and CSA of identified types of skeletal fibers were determined on needle biopsy samples of the vastus lateralis muscle of all subjects. Fiber type distribution was assessed on the basis of myosin heavy chain (MHC) isoform composition determined by electrophoresis on polyacrylamide gels. Fiber CSA was determined on cross-cryosections of fiber bundles immunostained by monoclonal antibodies against MHC isoforms. Absolute values of strength and fiber CSA of quadriceps were significantly lower in patients affected by GHD than in controls. However, once strength and fiber CSA were normalized for quadriceps CSA and subject height, respectively, differences disappeared. No difference was found between GHD patients and controls for quadriceps muscle twitch characteristics, fatigue index, and fiber type distribution. The results reported here suggest that weakness and fatigability in childhood-onset GHD do not have a skeletal muscle origin.

Muscle structure and performance capacity of Himalayan Sherpas.

The ultrastructure of the vastus lateralis muscle of Sherpas from Nepal [5 males; age 28 +/- 2.8 (SD) yr, indirect maximal O2 consumption 48.5 +/- 5.4 ml.kg(-1).min(-1)] was assessed and compared with those of sedentary lowlanders and of Caucasian climbers before and after high-altitude exposure. The mean cross-sectional area of the fibers was 3,186 +/- 521 microns2, i.e., similar to those of Caucasian elite high-altitude climbers (3,108 +/- 303 microns2) and a group of climbers after a 6- to 8-wk sojourn at 5,000-8,600 m (3,360 +/- 580 microns2) but significantly (P less than 0.05) smaller than that of unacclimatized climbers (4,170 +/- 710 microns2) and slightly, although not significantly, lower than that of sedentary lowlanders (3,640 +/- 260 microns2). The number of capillaries per square millimeter of muscle cross section was 467 +/- 22, not significantly smaller than those of climbers on return from a Himalayan expedition (538 +/- 89) and elite high-altitude climbers (542 +/- 127) but significantly (P less than 0.05) greater than that of sedentary lowlanders (387 +/- 25). The volume density of mitochondria was 3.96 +/- 0.54%, significantly (P less than 0.05) less than the values found for any other investigated group, including sedentary subjects at sea level (4.74 +/- 0.30%). It is concluded that Sherpas, like acclimatized Caucasian climbers, are characterized by 1) facilitated convective and diffusive muscle O2 flow conditions and 2) a higher maximal O2 consumption-to-mitochondrial volume ratio than lowlanders despite a reduced mitochondrial volume density.

Breath-by-breath assessment of alveolar gas stores and exchange.

The volume of O(2) exchanged at the mouth during a breath (Vo(2,m)) is equal to that taken up by pulmonary capillaries (Vo(2,A)) only if lung O(2) stores are constant. The latter change if either end-expiratory lung volume (EELV), or alveolar O(2) fraction (Fa(O(2))) change. Measuring this requires breath-by-breath (BbB) measurement of absolute EELV, for which we used optoelectronic plethysmography combined with measurement of O(2) fraction at the mouth to measure Vo(2,A) = Vo(2,m) - (DeltaEELV x Fa(O(2)) + EELV x DeltaFa(O(2))), and divided by respiratory cycle time to obtain BbB O(2) consumption (Vo(2)) in seven healthy men during incremental exercise and recovery. To synchronize O(2) and volume signals, we measured gas transit time from mouthpiece to O(2) meter and compared Vo(2) measured during steady-state exercise by using expired gas collection with the mean BbB measurement over the same time period. In one subject, we adjusted the instrumental response time by 20-ms increments to maximize the agreement between the two Vo(2) measurements. We then applied the same total time delay (transit time plus instrumental delay = 660 ms) to all other subjects. The comparison of pooled data from all subjects revealed r(2) = 0.990, percent error = 0.039 +/- 1.61 SE, and slope = 1.02 +/- 0.015 (SE). During recovery, increases in EELV introduced systematic errors in Vo(2) if measured without taking DeltaEELV x Ca(O(2))+EELV x DeltaFa(O(2)) into account. We conclude that optoelectronic plethysmography can be used to measure BbB Vo(2) accurately when studying BbB gas exchange in conditions when EELV changes, as during on- and off-transients.

Maximal lactic capacity at altitude: effect of bicarbonate loading.

The aim of the present study was to test the hypothesis that the net maximal blood lactate accumulation ([La]max) during heavy exercise in lowlanders acclimatized to chronic hypoxia may be limited by the reduced bicarbonate stores. Six men [age 32 +/- 4 (SD) yr] performed supramaximal exercise until voluntary exhaustion at sea level (204 +/- 54 W) and after sojourning for 1 mo at 5,050 m (175 +/- 23 W), without (C) and with (B) oral sodium-bicarbonate loading (0.3 g/kg body wt). Exhaustion time, arterial blood lactate concentration, arterial pH (pHa), arterial PCO2, and intramuscular pH were measured at rest and after exercise. At sea level, exhaustion time increased from 6.5 +/- 2.8 min in C to 7.5 +/- 2.7 min in B (P < 0.05). At altitude, exhaustion times were similar to the sea level C values and the same in C and B. At sea level, resting pHa increased from 7.41 +/- 0.02 in C to 7.46 +/- 0.03 in B (P < 0.001); the corresponding values at altitude were 7.46 +/- 0.04 and 7.55 +/- 0.03 (P < 0.001). Postexercise pHa at sea level was 7.22 +/- 0.02 in C and 7.25 +/- 0.08 in B (NS). After exercise at altitude, pHa was 7.32 +/- 0.04 and 7.44 +/- 0.03 in C and B, respectively (P < 0.001). [La]max increased from 12.86 +/- 1.45 mM in C to 16.63 +/- 1.76 mM in B (P < 0.01) at sea level and from 6.85 +/- 1.40 mM in C to 7.95 +/- 1.74 mM in B (NS) at altitude.(ABSTRACT TRUNCATED AT 250 WORDS)

Protein absorption and energy digestibility at high altitude.

To test the hypothesis that malabsorption of dietary protein is partly responsible for the weight loss observed during prolonged altitude exposure, six healthy male subjects [31.8 +/- 4.5 (SD) yr] received 15N-labeled soya protein by mouth and [15N]glycine intravenously at 122 and 5,000 m. From the subsequent 4-day total urine and fecal pools, the different fractions of the administered 15N were determined by mass spectrometry. Weight and skinfold thickness were measured at the beginning and end of the altitude exposure. In addition, the overall digestible energy of the diet at altitude was assessed by a 3-day diet control and adiabatic bomb calorimetric assessment of the energy content of the corresponding fecal pool. The average decrease of the subjects' weight during altitude exposure was 3%. Loss of fat mass at altitude estimated from the skinfold measurements was 9%. Protein absorption, calculated as 100--[fecal excretion of 15N after ingestion of 15N soya protein (% of dose given)--fecal excretion of 15N after injection of 15N glycine (% of dose given)], was not significantly impaired at altitude compared with sea level (96 vs. 97%, respectively), and overall digestible energy at altitude, calculated as 100--percent undigested gross energy in the feces, amounted to 96%. It is concluded that, at least up to an altitude of 5,000 m, malabsorption does not play a role in altitude-related weight loss.

Human intramuscular temperature and heat flow transients at rest.

A general model for heat exchange, comprising the major models in the literature, was developed. Temperature changes as a function of space and time were determined in six resting humans (age 32.7 +/- 4.5 yr) during temperature transients by magnetic resonance imaging (MRI), so that the exact solution of the model was obtained. These results allowed application of the model, e.g., the analysis of transient muscle heat flow changes, which could not be assessed by previous steady-state analyses. A microthermocouple was inserted in muscle vastus lateralis 2-3 cm below the skin surface. The measured temperature was used for calibrating the pixel intensity of a temporal series of transaxial magnetic resonance images obtained with a spin echo sequence around the microthermocouple position. After muscle temperature was increased by immersion in a controlled water bath, MRI acquisition was performed while muscle temperature was decreasing. Temperature maps relative to space and time inside a homogeneous region of interest were reconstructed by neural networks, showing specific temperature patterns. Subsequently calculated heat flows (with negative sign) appeared to increase linearly as temperature decreased, until a maximum was attained at a critical temperature, below which dramatic consistent heat flow changes were found. In conclusion, MRI is indeed a powerful technique, useful to study the determinants of muscle temperature and heat flow changes in space and time.

Respiratory effort sensation during exercise with induced expiratory-flow limitation in healthy humans.

Nine healthy subjects (age 31 +/- 4 yr) exercised with and without expiratory-flow limitation (maximal flow approximately 1 l/s). We monitored flow, end-tidal PCO2, esophageal (Pes) and gastric pressures, changes in end-expiratory lung volume, and perception (sensation) of difficulty in breathing. Subjects cycled at increasing intensity (+25 W/30 s) until symptom limitation. During the flow-limited run, exercise performance was limited in all subjects by maximum sensation. Sensation was equally determined by inspiratory and expiratory pressure changes. In both runs, 90% of the variance in sensation could be explained by the Pes swings (difference between peak inspiratory and peak expiratory Pes). End-tidal PCO2 did not explain any variance in sensation in the control run and added only 3% to the explained variance in the flow-limited run. We conclude that in healthy subjects, during normal as well as expiratory flow-limited exercise, the pleural pressure generation of the expiratory muscles is equally related to the perception of difficulty in breathing as that of the inspiratory muscles.

Twitch transdiaphragmatic pressure depends critically on thoracoabdominal configuration.

We measured the effect of thoracoabdominal configuration on twitch transdiaphragmatic pressure (Pdi, t) in response to supramaximal, transcutaneous, bilateral phrenic nerve shocks in three thin normal men. Pdi, t was measured as a function of lung volume (VL) in the relaxation configuration, at functional residual capacity (FRC), and at the same end-tidal VL 1) during relaxation; 2) with the abdomen (Ab) expanded and the rib cage (RC) in its relaxed FRC configuration; 3) with RC expanded and Ab in its relaxed FRC configuration; and 4) in configuration 3 with an active transdiaphragmatic pressure similar to that required to produce configuration 2. In increasing VL from FRC to configuration 1, Pdi, t decreased by 3.6 cmH(2)O; to configuration 2 by 14.8 cmH(2)O; to configuration 3 by 3.7 cmH(2)O; and to configuration 4 by 2.7 cmH(2)O. We argue that changes in velocity of shortening and radius of curvature are unlikely to account for these effects and suggest that changes in diaphragmatic fiber length (L(di)) are primarily responsible. If so, equivolume displacements of Ab and RC change L(di) in a ratio of approximately 4:1. We conclude that Pdi, t is exquisitely sensitive to abdominal displacements that must be rigorously controlled if Pdi, t is to be used to assess diaphragmatic contractility.

Fatigue and exhaustion in chronic hypobaric hypoxia: influence of exercising muscle mass.

Exhaustive dynamic exercise with large muscle groups in chronic hypobaric hypoxia may be limited by central (nervous) rather than peripheral (metabolic) fatigue. Six males [32 +/- 4 (SD) yr] at sea level (SL) and after 1-mo acclimatization at 5,050 m (HA) performed exhaustive dynamic forearm exercise at a constant absolute load, requiring regional maximum aerobic power at SL, and exhaustive cycle exercise at prevailing maximal O2 uptake (HA approximately equal to 80% SL). Exhaustion time (t(ex)), blood O2 saturation (SaO2), and heart rate (HR) were measured during each exercise bout. Before and after both arm and leg exercise, lactate concentration ([La]), PO2, PCO2, and pH were measured in arterialized blood samples. Integrated electromyogram activity (IEMG) and mean (MPF) and centroid (CPF) power frequencies of the EMG power spectrum during exercise were calculated for forearm flexors and vastus lateralis muscle. t(ex) for forearm exercise at the same absolute load was the same at SL and HA. Similar increases of IEMG (+214% at SL vs. +172% at HA) and decreases of CPF (-13% at SL vs. -16% at HA) and MPF (-22% at SL vs. -21% at HA) were observed. By contrast, at HA, for similar t(ex), leg exercise had to be performed at the same relative (i.e., prevailing maximal O2 uptake) but lower absolute load (approximately equal to 80% of SL).(ABSTRACT TRUNCATED AT 250 WORDS)

Energy balance at high altitude of 6,542 m.

Weight loss due to malnutrition and possibly intestinal malabsorption is a well-known phenomenon in high-altitude climbers. Up to approximately 5,000 m, energy balance may be attained and intestinal energy digestibility remains normal. To see whether 1) energy balance may also be attained at 6,542 m and, if not, 2) whether decreased energy digestibility would play a significant role in the energy deficit, energy intake (EI), energy expenditure, body composition, and energy digestibility of 10 subjects (4 women, 6 men; 27-44 yr) were assessed during a 21-day sojourn on the summit of Mt. Sajama, Bolivia (6,542 m). EI was measured during two 3-day intervals: EI1 (days 7-9) and EI2 (days 17-19). Total fecal energy loss during EI1 was calculated from fecal energy measured by bomb calorimetry. Average daily metabolic rate (ADMR) at altitude was measured in six subjects (2 women, 4 men) using doubly labeled water over a 10-day interval (days 9-19). Basal metabolic rate was measured before and after the expedition by respiratory gas analysis. Body composition was estimated from skinfolds and body mass before and during the altitude sojourn. Subjects were in negative energy balance throughout the observation period (EI1-ADMR = -2.9 +/- 1.8 MJ/day and EI2-ADMR = -2.3 +/- 1.8 MJ/day based on a gross energy digestibility of 95%). The activity level, expressed as ADMR to basal metabolic rate, was 1.56-2.39. The loss of fat mass (3.7 +/- 1.5 kg) represented 74 +/- 15% of the loss of body mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Energy expenditure climbing Mt. Everest.

Weight loss is a well-known phenomenon at high altitude. It is not clear whether the negative energy balance is due to anorexia only or an increased energy expenditure as well. The objective of this study was to gain insight into this matter by measuring simultaneously energy intake, energy expenditure, and body composition during an expedition to Mt. Everest. Subjects were two women and three men between 31 and 42 yr of age. Two subjects were observed during preparation at high altitude, including a 4-day stay in the Alps (4,260 m), and subsequently during four daytime stays in a hypobaric chamber (5,600-7,000 m). Observations at high altitude on Mt. Everest covered a 7- to 10-day interval just before the summit was reached in three subjects and included the summit (8,872 m) in a fourth. Energy intake (EI) was measured with a dietary record, average daily metabolic rate (ADMR) with doubly labeled water, and resting metabolic rate (RMR) with respiratory gas analysis. Body composition was measured before and after the interval from body mass, skinfold thickness, and total body water. Subjects were in negative energy balance (-5.7 +/- 1.9 MJ/day) in both situations, during the preparation in the Alps and on Mt. Everest. The loss of fat mass over the observation intervals was 1.4 +/- 0.7 kg, on average two-thirds of the weight loss (2.2 +/- 1.5 kg), and was significantly correlated with the energy deficit (r = 0.84, P < 0.05). EI on Mt. Everest was 9-13% lower than during the preparation in the Alps.(ABSTRACT TRUNCATED AT 250 WORDS)

Maximal rate of blood lactate accumulation during exercise at altitude in humans.

The lower peak lactate accumulation in blood ([La(b)]p) at altitude may be associated with a reduced maximal glycolytic flux. Based on certain assumptions, the latter can be indirectly evaluated in vivo, during short supramaximal exercises, by measuring the maximal rate of lactate accumulation in blood (delta [La(b)]max). delta [La(b)]max was determined on six white subjects at sea level (SL1), after approximately 1 wk (Alt1) and 4 wk (Alt2) of a 35-day sojourn at 5,050 m, and 1 wk after return to sea level (SL2). The subjects performed exercises of increasing duration (5, 15, 25, 35, 45 s or until exhaustion) on a bicycle ergometer at loads = 200% of the individual Wmax. The latter was previously determined in each condition as the greatest work rate that could be sustained for 2-4 min during an incremental exercise. Net [La(b)] accumulation (delta [La(b)]) was measured after each exercise bout. delta [La(b)] resulted to be linearly related to exercise duration. The slopes of the individual delta [La(b)] vs. exercise duration lines were taken as delta [La(b)]max. Exhaustion times were approximately 30-45 s in all conditions. [La(b)]p (in mM) during recovery after the exhaustive load was higher at SL1 (10.22 +/- 1.09; means +/- SD) than at Alt1 (5.08 +/- 0.82), Alt2 (8.13 +/- 2.67), and SL2 (8.18 +/- 1.43). delta [La(b)]max was lower at Alt1 (0.09 +/- 0.02) and at Alt2 (0.17 +/- 0.05) than at SL1 (0.25 +/- 0.05) and SL2 (0.23 +/- 0.06). Both [La(b)]p and delta [La(b)]max increased during acclimatization.(ABSTRACT TRUNCATED AT 250 WORDS)