Prevalence of Drug Use in Ultraendurance Athletes.

PURPOSE: In competitive sport, classic methods of measuring drug prevalence, such as doping controls or questionnaires, are challenging. Here we describe a novel urine sampling method to measure drug use in athletes. We hypothesize that the prevalence of drug use in ultramarathon runners is measured more accurately with our sampling method than randomized-response questionnaires. METHODS: Urine samples and associated demographic data were collected from male participants using blind, automated urinals at the start of ultramarathon races. Various nonprohibited and prohibited substances were subsequently screened. Concomitantly, 2931 male and female runners participating in the same ultramarathons completed an anonymized, randomized-response questionnaire regarding drug use. RESULTS: Among 412 individual urine samples, 205 (49.8%) contained at least one substance, and 16.3% of the samples contained one or more prohibited substances. Substances detected in urine included nonsteroid anti-inflammatory drugs (NSAID) (22.1%), acetaminophen (15.5%), opioids (6.6%), diuretics (4.9%), hypnotics (4.4%), glucocorticoids (2.7%), beta-2 agonists (2.2%), cannabinoids (1.9%), and stimulants (1.2%). None of the samples contained erythropoietin-receptor agonists or suspicious testosterone. Drug use was not associated with the participants' characteristics or ranking. Respondents to the questionnaire reported using acetaminophen (13.6%) and NSAID (12.9%); however, no prohibited substances were declared. CONCLUSIONS: There was a high prevalence of drug use among male ultramarathon runners, in particular, NSAID and painkillers; however, performance-enhancing drugs were marginally used. Blind urine sampling highlighted prohibited drug use not declared in questionnaires, and it is useful to assess the prevalence of drug use and/or doping in competitive athletes.

Impaired cerebrovascular CO2 reactivity at high altitude in prematurely born adults.

Premature birth impairs cardiac and ventilatory responses to both hypoxia and hypercapnia, but little is known about cerebrovascular responses. Both at sea level and after 2 days at high altitude (3375 m), 16 young preterm-born (gestational age, 29 ± 1 weeks) and 15 age-matched term-born (40 ± 0 weeks) adults were exposed to two consecutive 4 min bouts of hyperoxic hypercapnic conditions (3% CO2 -97% O2 ; 6% CO2 -94% O2 ), followed by two periods of voluntary hyperventilation-induced hypocapnia. We measured middle cerebral artery blood velocity, end-tidal CO2 , pulmonary ventilation, beat-by-beat mean arterial pressure and arterialized capillary blood gases. Baseline middle cerebral artery blood velocity increased at high altitude compared with sea level in term-born (+24 ± 39%, P = 0.036), but not in preterm-born (-4 ± 27%, P = 0.278) adults. The end-tidal CO2 , pulmonary ventilation and mean arterial pressure were similar between groups at sea level and high altitude. Hypocapnic cerebrovascular reactivity was higher at high altitude compared with sea level in term-born adults (+173 ± 326%, P = 0.026) but not in preterm-born adults (-21 ± 107%, P = 0.572). Hypercapnic reactivity was altered at altitude only in preterm-born adults (+125 ± 144%, P < 0.001). Collectively, at high altitude, term-born participants showed higher hypocapnic (P = 0.012) and lower hypercapnic (P = 0.020) CO2 reactivity compared with their preterm-born peers. In conclusion, exposure to high altitude revealed different cerebrovascular responses in preterm- compared with term-born adults, despite similar ventilatory responses. These findings suggest a blunted cerebrovascular response at high altitude in preterm-born adults, which might predispose these individuals to an increased risk of high-altitude illnesses. KEY POINTS: Cerebral haemodynamics and cerebrovascular reactivity in normoxia are known to be similar between term-born and prematurely born adults. In contrast, acute exposure to high altitude unveiled different cerebrovascular responses to hypoxia, hypercapnia and hypocapnia. In particular, cerebral vasodilatation was impaired in prematurely born adults, leading to an exaggerated cerebral vasoconstriction. Cardiovascular and ventilatory responses to both hypo- and hypercapnia at sea level and at high altitude were similar between control subjects and prematurely born adults. Other mechanisms might therefore underlie the observed blunted cerebral vasodilatory responses in preterm-born adults at high altitude.

Effects of Electrical Stimulation on Delayed Onset Muscle Soreness (DOMS): Evidences from Laboratory and In-Field Studies.

Intense, long exercise can increase oxidative stress, leading to higher levels of inflammatory mediators and muscle damage. At the same time, fatigue has been suggested as one of the factors giving rise to delayed-onset muscle soreness (DOMS). The aim of this study was to investigate the efficacy of a specific electrical stimulation (ES) treatment (without elicited muscular contraction) on two different scenarios: in the laboratory on eleven healthy volunteers (56.45 ± 4.87 years) after upper limbs eccentric exercise (Study 1) and in the field on fourteen ultra-endurance athletes (age 47.4 ± 10.2 year) after an ultra-running race (134 km, altitude difference of 10,970 m+) by lower exercising limbs (Study 2). Subjects were randomly assigned to two experimental tasks in cross-over: Active or Sham ES treatments. The ES efficacy was assessed by monitoring the oxy-inflammation status: Reactive Oxygen Species production, total antioxidant capacity, IL-6 cytokine levels, and lactate with micro-invasive measurements (capillary blood, urine) and scales for fatigue and recovery assessments. No significant differences (p > 0.05) were found in the time course of recovery and/or pre-post-race between Sham and Active groups in both study conditions. A subjective positive role of sham stimulation (VAS scores for muscle pain assessment) was reported. In conclusion, the effectiveness of ES in treating DOMS and its effects on muscle recovery remain still unclear.

Comparative Effectiveness of an Artificial Air Pocket Device to Delay Asphyxiation in Supine Individuals Critically Buried in Avalanche Debris.

Importance: Approximately 70% of individuals critically buried in avalanche debris die within 35 minutes as a result of asphyxial cardiac arrest. An artificial air-pocket device (AAPD) that separates inhaled air from exhaled air may delay the onset of severe hypoxemia and eventual asphyxia during snow burial. Objective: To investigate the efficacy of a new AAPD during snow burial in a supine position. Design, Setting, and Participants: This comparative effectiveness trial was performed in winter 2016 with data analysis in November 2016 and November 2022. Each trial used a simulated critical avalanche burial scenario, in which a trough was dug in a snow pile and an additional air pocket of 0.5 L volume was punched into the lateral wall for each control trial. All participants were buried in a supine position. Trials could be voluntarily terminated at any time, with a maximum length of 60 minutes; trials were automatically terminated if the participant's peripheral oxygen saturation (Spo2) dropped to less than 84%. Exposures: Each participant conducted 2 trials, one in which they breathed into the AAPD (intervention trial) and the other in which they breathed into the prepared air pocket (control trial). Main Outcomes and Measures: Measurements included Spo2, cerebral oxygenation, ventilatory parameters, respiratory gas concentrations, and visual-analogue scales. Kaplan-Meier survival curves and rank test for matched survival data were used to analyze the total burial time in each trial. Results: A total of 13 volunteers (9 men; mean [SD] age, 33 [8] years) were exposed to the intervention and control trials. Intervention trials were terminated less often (2 of 13 trials) as a result of hypoxemia than control trials (11 of 12 trials). Similarly, survival curves showed a longer duration of burial in the intervention compared with the control trials for the time to reach an Spo2 less than 84% (rank test for matched survival data: P = .003). The intervention trials, compared with the control trials, also had slower rates of decrease in fraction of inspired oxygen (mean [SD] rate, -0.8 [0.4] %/min vs -2.2 [1.2] %/min) and of increase in fraction of inspired carbon dioxide (mean [SD] rate, 0.5 [0.3] %/min vs 1.4 [0.6] %/min) and expired ventilation per minute (mean [SD] rate, 0.5 [1.0] L/min2 vs 3.9 [2.6] L/min2). Conclusions and Relevance: This comparative effectiveness trial found that the new AAPD was associated with delaying the development of hypoxemia and hypercapnia in supine participants in a critical burial scenario. Use of the AAPD may allow a longer burial time before asphyxial cardiac arrest, which might allow longer times for successful rescue by companions or by prehospital emergency medical services.

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

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

Pathophysiology and Therapy of High-Altitude Sickness: Practical Approach in Emergency and Critical Care.

High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability. The second section discusses the main high-altitude diseases, highlighting how environmental factors can lead to the loss of homeostasis, compromising important vital functions. Early recognition of clinical symptoms is important for the establishment of the correct therapy. The third section focuses on high-altitude pulmonary edema, which is one of the main high-altitude diseases. With a deeper understanding of the pathogenesis of high-altitude diseases, as well as a reasoned approach to environmental or physical factors, we examine the main high-altitude diseases. Such an approach is critical for the effective treatment of patients in a hostile environment, or treatment in the emergency room after exposure to extreme physical or environmental factors.

Kinetics of Cardiac Remodeling and Fibrosis Biomarkers During an Extreme Mountain Ultramarathon.

Objectives: The effects of ultra-distance on cardiac remodeling and fibrosis are unclear. Moreover, there are no data reporting the kinetics of cardiac alterations throughout the event and during recovery. Our aim was to investigate the kinetics of biological markers including new cardiac fibrosis biomarkers suppression of tumorigenicity 2 (ST2) and galectin-3 (Gal-3) during and after an extreme mountain ultramarathon. Methods: Fifty experienced runners participating in one of the most challenging mountain ultramarathons (330 km, D+ 25,000 m) were enrolled in our study. Blood samples were collected at four time points: before (Pre-), at 148 km (Mid-), at the finish line (Post-), and 3 days after the recovery period (Recov-). Results: The cardiac fibrosis biomarkers (ST2 and Gal-3) increased from Pre- to Mid-. During the second half, ST2 remained higher than pre-values as opposed to Gal-3. Necrosis, ischemia, and myocyte injury biomarkers increased until Mid- then decreased but remained higher at Recov- than Pre-values. Oxidative stress appeared at Mid-. Lipid peroxides remained higher at Recov- compared to Pre-. The maximal value in most of these biomarkers was observed at Mid- and not at Post-. Conclusions: The present study supports biphasic kinetics of cardiac fibrosis biomarkers, with a relative recovery during the second half of the event that seems specific to this extreme event. Overall, performing at such an extreme ultramarathon seems less deleterious for the heart than shorter events.

High-altitude mountain telemedicine.

INTRODUCTION: An innovative teleconsultation platform has been designed, developed and validated between summer 2017 and winter 2018, in five mountain huts and in three remote outpatient clinical centres of the Italian region Valle d'Aosta of the Mont Blanc massif area. METHODS: An ad-hoc videoconference system was developed within the framework of the e-Rés@MONT (Interreg ALCOTRA) European project, to tackle general health problems and high-altitude diseases (such as acute mountain sickness, high-altitude pulmonary and cerebral oedema). The system allows for contacting physicians at the main hospital in Aosta to perform a specific diagnosis and to give specific advice and therapy to the patients in an extreme environment out-hospital setting. At an altitude between 1500-3500 m, five trained nurses performed clinical evaluations (anamnesis, blood pressure, heart rate, oxygen saturation), electrocardiographic and echography monitoring on both tourists and residents as necessary; all of the collected data were sent to the physicians in Aosta. RESULTS: A total of 702 teleconsultation cases were performed: 333 dismissed (47%), 356 observed (51%) and 13 immediate interventions (2%). In 30 cases the physicians decided there was no need for helicopter and ambulance rescue intervention and hospital admissions. The main physiological measures, the classified pathologies, the severe cases and the cost savings are described in this article. DISCUSSION: The e-Rés@MONT teleconsultation platform has been discussed in terms of treated cases, feasibility, proactivity in reducing complexities, direct and indirect advantages, and diagnostics help; moreover, general and specific pros and cons have been debated, and future steps have been exposed.

Recommendations for traveling to altitude with neurological disorders.

BACKGROUND: Several neurological conditions might worsen with the exposure to high altitude (HA). The aim of this review was to summarize the available knowledge on the neurological HA illnesses and the risk for people with neurological disorders to attend HA locations. METHODS: A search of literature was conducted for several neurological disorders in PubMed and other databases since 1970. The neurological conditions searched were migraine, different cerebrovascular disease, intracranial space occupying mass, multiple sclerosis, peripheral neuropathies, neuromuscular disorders, epileptic seizures, delirium, dementia, and Parkinson's disease (PD). RESULTS: Attempts were made to classify the risk posed by each condition and to provide recommendations regarding medical evaluation and advice for or against traveling to altitude. Individual cases should be advised after careful examination and risk evaluation performed either in an outpatient mountain medicine service or by a physician with knowledge of HA risks. Preliminary diagnostic methods and anticipation of neurological complications are needed. CONCLUSIONS: Our recommendations suggest absolute contraindications to HA exposure for the following neurological conditions: (1) Unstable conditions-such as recent strokes, (2) Diabetic neuropathy, (3) Transient ischemic attack in the last month, (4) Brain tumors, and 5. Neuromuscular disorders with a decrease of forced vital capacity >60%. We consider the following relative contraindications where decision has to be made case by case: (1) Epilepsy based on recurrence of seizure and stabilization with the therapy, (2) PD (± obstructive sleep apnea syndrome-OSAS), (3) Mild Cognitive Impairment (± OSAS), and (4) Patent foramen ovale and migraine have to be considered risk factors for acute mountain sickness.

Validation of a Score for the Detection of Subjects with High Risk for Severe High-Altitude Illness.

PURPOSE: A decision tree based on a clinicophysiological score (severe high-altitude illness (SHAI) score) has been developed to detect subjects susceptible to SHAI. We aimed to validate this decision tree, to rationalize the prescription of acetazolamide (ACZ), and to specify the rule for a progressive acclimatization. METHODS: Data were obtained from 641 subjects in 15 European medical centers before and during a sojourn at high altitude. Depending on the value of the SHAI score, advice was given and ACZ was eventually prescribed. The outcome was the occurrence of SHAI at high altitude as a function of the SHAI score, ACZ prescription, and use and fulfillment of the acclimatization rule. RESULTS: The occurrence of SHAI was 22.6%, similar to what was observed 18 yr before (23.7%), whereas life-threatening forms of SHAI (high-altitude pulmonary and cerebral edema) were less frequent (2.6%-0.8%, P = 0.007). The negative predictive value of the decision tree based was 81%, suggesting that the procedure is efficient to detect subjects who will not suffer from SHAI, therefore limiting the use of ACZ. The maximal daily altitude gain that limits the occurrence of SHAI was established at 400 m. The occurrence of SHAI was reduced from 27% to 12% when the recommendations for ACZ use and 400-m daily altitude gain were respected (P < 0.001). CONCLUSIONS: This multicenter study confirmed the interest of the SHAI score in predicting the individual risk for SHAI. The conditions for an optimized acclimatization (400-m rule) were also specified, and we proposed a rational decision tree for the prescription of ACZ, adapted to each individual tolerance to hypoxia.

Tendon morphological changes after a prolonged ski race can be detected by ultrasound echo intensity.

BACKGROUND: Ultrasound imaging techniques have been used to assess the characteristics of skeletal muscles and tendons. Such techniques (gray scale analysis) allow qualitative evaluation and have been used recently to assess the internal structure of muscles and tendons by computer-aided gray scale analysis. We hypothesized that changes in the internal structure of the Achilles and patellar tendons after a ski mountaineering race competition could be detected with ultrasound. METHODS: Twenty athletes were recruited during the 19th Millet Tour du Rutor extreme, a three-day ski mountaineering competition. Ultrasound measurements of the Achilles and patellar tendons were carried out before the first race and immediately after each of the three competition days. Tendon thickness, cross-sectional area (CSA), and ultrasound gray scale analysis were calculated. RESULTS: Significant differences (p < 0.05) were observed between the pre- and post-race measurements for the Achilles tendon thickness and CSA, while no significant differences were noted for the patellar tendon thickness and CSA. However, gray scale analysis of both the Achilles and patellar tendons showed significantly higher post-race values, than the pre-race values (p < 0.05). CONCLUSIONS: Achilles and patellar tendons of healthy athletes are highly responsive to an acute increase in mechanical load. Those changes can be detected from classical (thickness and CSA) and innovative (gray scale) ultrasound-based parameters. TRIAL REGISTRATION: This study was approved by the Azienda USL Valle d'Aosta Ethics Committee (protocol no. 23/03/2018.0026243.I).

Acute Effects of Triathlon Race on Oxidative Stress Biomarkers.

The response to strenuous exercise was investigated by reactive oxygen species (ROS) production, oxidative damage, thiol redox status, and inflammation assessments in 32 enrolled triathlon athletes (41.9 ± 7.9 yrs) during Ironman® (IR), or half Ironman® (HIR) competition. In biological samples, inflammatory cytokines, aminothiols (glutathione (GSH), homocysteine (Hcy), cysteine (Cys), and cysteinylglycine (CysGly)), creatinine and neopterin, oxidative stress (OxS) biomarkers (protein carbonyl (PC), thiobarbituric acid-reactive substances (TBARS)), and ROS were assessed. Thirteen HIR and fourteen IR athletes finished the race. Postrace, ROS (HIR +20%; IR +28%; p < 0.0001), TBARS (HIR +57%; IR +101%), PC (HIR +101%; IR +130%) and urinary neopterin (HIR +19%, IR +27%) significantly (range p < 0.05-0.0001) increased. Moreover, HIR showed an increase in total Cys +28%, while IR showed total aminothiols, Cys, Hcy, CysGly, and GSH increase by +48, +30, +58, and +158%, respectively (range p < 0.05-0.0001). ROS production was significantly correlated with TBARS and PC (R 2 = 0.38 and R 2 = 0.40; p < 0.0001) and aminothiols levels (range R 2 = 0.17-0.47; range p < 0.01-0.0001). In particular, ROS was directly correlated with the athletes' age (R 2 = 0.19; p < 0.05), with ultraendurance years of training (R 2 = 0.18; p < 0.05) and the days/week training activity (R 2 = 0.16; p < 0.05). Finally, the days/week training activity (hours/in the last 2 weeks) was found inversely correlated with the IL-6 postrace (R 2 = -0.21; p < 0.01). A strenuous performance, the Ironman® distance triathlon competition, alters the oxidant/antioxidant balance through a great OxS response that is directly correlated to the inflammatory parameters; furthermore, the obtained data suggest that an appropriate training time has to be selected in order to achieve the lowest ROS production and IL-6 concentration at the same time.

[Work on a building site at high altitude: physiopathological features and entailments for the occupational medicine]. / Il lavoro in un cantiere in alta quota: generalità fisiopatologiche e analisi di una casistica occupazionale.

SUMMARY: Introduction. From a physiological perspective the high altitude is defined by altitudes higher than 3000 meters above sea level: at this altitude the atmospheric pressure is reduced to 525 mmHg and the partial pressure of Oxygen drops to 110 mmHg in the ambient air follows and 60 mmHg in the alveolar air. To stay at altitudes above 3000 m s.l.m. therefore places the human organism in front of a notable reduction of the functional respiratory reserve already in conditions of rest, leading to inevitable repercussions on the ability to sustain physical effort. Materials and methods. A population of 39 workers employed in the construction sector at a high altitude construction site (2200-3480 m) was examined. Data relating to sex, age, body mass index, smoking, residence altitude, mountaineering history (maximum altitude reached over a lifetime, frequency of ascents, time spent at high altitude, both for pleasure and for work) and sport practice were collected. Among them, for 25 workers the data of the ergometric tests in normobaric hypoxia (pO2, desaturation and peak values of heart rate, respiratory frequency, ventilation) conducted with simplified mode were collected. Purpose. The study aims to analyze the health of a group of workers exposed to the risk related to staying at high altitude in light of the indications of the scientific literature on health surveillance. Results. The data relating to the group of workers studied with regard to anamnestic data and to the results of ergospirometric examinations in hypoxic conditions are described. Conclusions. In working conditions at high altitude it is necessary to consider both the effect of high altitude in itself, similar to a sort of substantially unchangeable "background risk", and the ways in which high altitude interacts with other risk factors characteristic of the work site activity (which are the same as for any construction site activity that takes place at sea level), considering also the pathophysiological or frankly pathological conditions of which the worker is a carrier. This evaluation can be articulated on two levels: a first level concerning the suitability of the individual for access and the simple prolonged stay in altitude where the work activity will be performed; a second level regarding the suitability of the worker to carry out the work tasks required by the specific task in the particular environmental conditions.

Clinical recommendations for high altitude exposure of individuals with pre-existing cardiovascular conditions: A joint statement by the European Society of Cardiology, the Council on Hypertension of the European Society of Cardiology, the European Society of Hypertension, the International Society of Mountain Medicine, the Italian Society of Hypertension and the Italian Society of Mountain Medicine.

Take home figureAdapted from Bärtsch and Gibbs2 Physiological response to hypoxia. Life-sustaining oxygen delivery, in spite of a reduction in the partial pressure of inhaled oxygen between 25% and 60% (respectively at 2500 m and 8000 m), is ensured by an increase in pulmonary ventilation, an increase in cardiac output by increasing heart rate, changes in vascular tone, as well as an increase in haemoglobin concentration. BP, blood pressure; HR, heart rate; PaCO2, partial pressure of arterial carbon dioxide.

Air blood barrier phenotype correlates with alveolo-capillary O2 equilibration in hypobaric hypoxia.

The O2 diffusion limitation across the air blood barrier (DO2 and subcomponents Dm and Vc) was evaluated in 17 healthy participants exposed to hypobaric hypoxia (HA, 3840m, PIO2 ∼90mmHg). A 10% decrease in alveolar volume (VA) in all participants suggested the development of sub-clinical interstitial lung edema. In >80% of participants DO2/VA increased, reflecting an individual strategy to cope with the hypoxia stimulus by remodulating Vc or Dm. Opposite changes in Dm/Vc ratio were observed and participants decreasing Vc showed reduced alveolar blood capillary transit time. The interplay between diffusion and perfusion (cardiac output) was estimated in order to investigate the individual adaptive response to hypoxia. It appears remarkable that despite individual differences in the adaptive response to HA, diffusion limitation did not exceed ∼11% of the alveolar-venous PO2 gradient, revealing an admirable functional design of the air-blood barrier to defend the O2 diffusion/perfusion function when facing hypobaric hypoxia corresponding to 50mmHg decreased PAO2.

Enhanced Right-Chamber Remodeling in Endurance Ultra-Trail Athletes Compared to Marathon Runners Detected by Standard and Speckle-Tracking Echocardiography.

Background: Strenuous and endurance exercise training have been associated with morphological and functional heart remodeling. Two-dimensional speckle-tracking echocardiography (STE) is a novel technique that allows an accurate quantification of global myocardium deformation. Our aim was to evaluate together left and right cardiac remodeling in different long-distance running athletes: marathon runners (42 km) (M) and endurance mountain runners (>300 Km) (UT). Methods: A total of 92 athletes (70 males, 76%) including 47 M [age 45 ± 7 years; training: 18 (9-53) years*days/week], 45 UT [age 42 ± 9, training: 30 (15-66) years*days/week] underwent conventional echocardiography and STE (Beyond Diogenes 2.0, AMID) during the agonistic season. Results: Right ventricle (RV) end-diastolic area (p = 0.026), fractional area changing (FAC) (p = 0.008) and RV global longitudinal strain (GLS) were significantly increasedin UT athletes. Furthermore, UT showed larger right atrium (RA) volume (p = 0.03), reduced RA GLS and significantly increased RA global circumferential strain (GCS) compared to M. After adjustment for age, sex, and HR as covariates, UT showed a reduced RA GLS (OR 0.907; CI 0.856-0.961) and increased RV FAC (OR 1.172; CI: 1.044-1.317) compared to M. Conclusion: Athletes enrolled in UT endurance activities showed RV and RA morphological and functional remodeling to increased preload in comparison with M runners characterized by increased RV FAC and reduced RA GLS. Follow-up studies are needed to better assess the long-term clinical impact of these modifications. 2D STE is a useful tool for investigating the deformation dynamic in different sports specialties.

Neurosensory and Cognitive Modifications in Europe's Toughest RandoRaid Competition: the Transpyrénéa Extreme Study.

Introduction: Given the wide proliferation of ultra-long endurance races, it is important to understand the physiological response of the athletes to improve their safety. We evaluated the cognitive and neurosensory effects on ultra-endurance athletes during the Transpyrénéa (866 Km, 65,000 m positive slope), held on the French Pyrenees. Materials and Methods: 40 athletes were enrolled (age 43.8 ± 8.8 years; 36 males). Olfactory and cognitive tests were performed before the race (T0, n = 40), at 166 kms (T1, n = 28), at 418 kms (T2, n = 20), and after the race (T3, 866 kms, n = 13). The effect of dehydration and sleep deprivation on cognitive features were also studied. Results: Olfactory function decreased during the race (T0: 24.9 ± 4.3 vs. T3: 22.8 ± 3.5, z = -2.678, p = 0.007), language fluency increased (T0: 10.8 ± 2.9; T1: 11.4 ± 2.7; T2: 12.9 ± 2.8; T3: 12.9 ± 3.0; χ2 = 11.132, p = 0.011 for combined samples), whereas the Trail Making Test did not show any changes between pre- and post-race (T0 vs. T3 p = 0.697 for TMT-A, p = 0.977 for TMT-B). The mean aggregate sleeping time was 9.3 ± 5.4 h at T1, 22.4 ± 10.0 h at T2, 29.5 ± 20.5 h at T3, with a correlation with olfactory function (r = 0.644, p = 0.018), while Total Body Water (TBW) was not correlated with olfactory or cognitive scores. Conclusion: Physical activity and sleep restriction in ultra-endurance could transiently affect olfactory function, while verbal fluency improved, demonstrating a dissimilar mechanism of activation/deactivation in different cortical areas. Body water loss was uncorrelated to cognition. Further studies should clarify whether cognitive and sensory deficits occur even in absence of sleep restriction.

Correction: Shear-Wave Elastography Assessments of Quadriceps Stiffness Changes prior to, during and after Prolonged Exercise: A Longitudinal Study during an Extreme Mountain Ultra-Marathon.

[This corrects the article DOI: 10.1371/journal.pone.0161855.].

An Extreme Mountain Ultra-Marathon Decreases the Cost of Uphill Walking and Running.

Purpose: To examine the effects of the world's most challenging mountain ultramarathon (MUM, 330 km, cumulative elevation gain of +24,000 m) on the energy cost and kinematics of different uphill gaits. Methods: Before (PRE) and immediately after (POST) the competition, 19 male athletes performed three submaximal 5-min treadmill exercise trials in a randomized order: walking at 5 km·h-1, +20%; running at 6 km·h-1, +15%; and running at 8 km·h-1, +10%. During the three trials, energy cost was assessed using an indirect calorimetry system and spatiotemporal gait parameters were acquired with a floor-level high-density photoelectric cells system. Results: The average time of the study participants to complete the MUM was 129 h 43 min 48 s (range: 107 h 29 min 24 s to 144 h 21 min 0 s). Energy costs in walking (-11.5 ± 5.5%, P < 0.001), as well as in the first (-7.2 ± 3.1%, P = 0.01) and second (-7.0 ± 3.9%, P = 0.02) running condition decreased between PRE and POST, with a reduction both in the heart rate (-11.3, -10.0, and -9.3%, respectively) and oxygen uptake only for the walking condition (-6.5%). No consistent and significant changes in the kinematics variables were detected (P-values from 0.10 to 0.96). Conclusion: Though fatigued after completing the MUM, the subjects were still able to maintain their uphill locomotion patterns noted at PRE. The decrease (improvement) in the energy costs was likely due to the prolonged and repetitive walking/running, reflecting a generic improvement in the mechanical efficiency of locomotion after ~130 h of uphill locomotion rather than constraints imposed by the activity on the musculoskeletal structure and function.