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Chronic mountain sickness (CMS) is a high-altitude (HA) maladaptation syndrome characterised by elevated systemic oxidative-nitrosative stress (OXNOS) due to a free radical-mediated reduction in vascular nitric oxide (NO) bioavailability. To better define underlying mechanisms and vascular consequences, this study compared healthy male lowlanders (80 m, n = 10) against age/sex-matched highlanders born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 10) and without (CMS-, n = 10) CMS. Cephalic venous blood was assayed using electron paramagnetic resonance spectroscopy and reductive ozone-based chemiluminescence. Nutritional intake was assessed via dietary recall. Systemic vascular function and structure were assessed via flow-mediated dilatation, aortic pulse wave velocity and carotid intima-media thickness using duplex ultrasound and applanation tonometry. Basal systemic OXNOS was permanently elevated in highlanders (P =0.001 vs. lowlanders) and further exaggerated in CMS+, reflected by increased hydroxyl radical spin adduct formation (P =0.001 vs. CMS-) subsequent to liberation of free 'catalytic' iron consistent with a Fenton and/or nucleophilic addition mechanism(s). This was accompanied by elevated global protein carbonylation (P = 0.046 vs. CMS-) and corresponding reduction in plasma nitrite (P =0.001 vs. lowlanders). Dietary intake of vitamins C and E, carotene, magnesium and retinol were lower in highlanders and especially deficient in CMS + due to reduced consumption of fruit and vegetables (P =0.001 to 0.028 vs. lowlanders/CMS-). Systemic vascular function and structure were also impaired in highlanders (P =0.001 to 0.040 vs. lowlanders) with more marked dysfunction observed in CMS+ (P = 0.035 to 0.043 vs. CMS-) in direct proportion to systemic OXNOS (r = -0.692 to 0.595, P =0.001 to 0.045). Collectively, these findings suggest that lifelong exposure to iron-catalysed systemic OXNOS, compounded by a dietary deficiency of antioxidant micronutrients, likely contributes to the systemic vascular complications and increased morbidity/mortality in CMS+. TRIAL REGISTRY: ClinicalTrials.gov; No: NCT01182792; URL: www.clinicaltrials.gov.

Background The most important determinant of long-term survival in patients with idiopathic pulmonary fibrosis is the right ventricular (RV) adaptation to the increased pulmonary vascular resistance. Our aim was to explore RV contractile reserve during stress echocardiography in early-stage IPF. Methods Fifty early-stage patients with IPF and 50 healthy control patients underwent rest and stress echocardiography, including RV two-dimensional speckle tracking echocardiography. At peak exertion, blood gas analysis and spirometry were also assessed. Results At rest, RV diameters were mildly increased in IPF; however, although RV conventional systolic function indexes were similar between the IPF and control groups, RV global longitudinal strain and RV lateral wall longitudinal strain (LWLS) were significantly reduced in the IPF cohort. During physical exercise, patients with IPF showed a reduced exercise tolerance with lower maximal workload (P o 2; P Conclusions RV myocardial dysfunction is already present at rest in early-stage IPF and worsens during exertion as detected by two-dimensional speckle-tracking echocardiography. The RV altered contractile reserve appears to be related to reduced exercise tolerability and impaired pulmonary hemodynamic.

Purpose High altitude results in lower barometric pressure and hence partial pressure of O2 decrease can lead to several molecular and cellular changes, such as generation of reactive oxygen species (ROS). Electron Paramagnetic Resonance technique was adopted in the field, to evaluate the effects of acute and sub-acute hypobaric hypoxia (HH) on ROS production by micro-invasive method. Biological biomarkers, indicators of oxidative stress, renal function and inflammation were investigated too. Methods Fourteen lowlander subjects (mean age 27.3 ± 5.9 years) were exposed to HH at 3269 m s.l. ROS production, related oxidative damage to cellular components, systemic inflammatory response and renal function were determined through blood and urine profile performed at 1st, 2nd, 4th, 7th, and 14th days during sojourn. Results Kinetics of changes during HH exposition showed out significant (range p < 0.05-0.0001) increases that at max corresponds to 38% for ROS production rate, 140% for protein carbonyl, 44% for lipid peroxidation, 42% for DNA damage, 200% for inflammatory cytokines and modifications in renal function (assessed by neopterin concentration: 48%). Conversely, antioxidant capacity significantly (p < 0.0001) decreased - 17% at max. Conclusion This 14 days in-field study describes changes of oxidative-stress biomarkers during HH exposure in lowlanders. The results show an overproduction of ROS and consequent oxidative damage to protein, lipids and DNA with a decrease in antioxidant capacity and the involvement of inflammatory status and a transient renal dysfunction. Exposure at high altitude induces a hypoxic condition during acute and sub-acute phases accompanied by molecular adaptation mechanism indicating acclimatization.

The Mountain Activities Neuro-behavioural Research Programme is a research project born in the 2 nd Unit of Psychiatry, Department of Clinical and Experimental Medicine at the University of Pisa to investigate the effects of altitude on the mental and neuro-behavioural aspects of people performing activities in mountainous areas.In this study, after elaborating a standardised data collection form, based on traditional psychopathology notions, to classify the misperceptions reported by the athletes taking part, we investigated the various types of these misperceptions in 21 athletes (including only one female), with a mean age of 44.90 ± 8.51 (min 33 and max 58).The athletes reported different kinds of misperceptions. It was possible to highlight three different clusters of athletes, based on the similarities between the kinds of misperceptions reported in each cluster: (a) anomalies in the intrinsic characteristics of perceptions (i.e. depersonalisation and derealisation), (b) illusions and (c) hallucinations.This study supports the concept that anomalous perceptual experiences may occur independently of the context of psychiatric or neurological disorders. The chance of observing hallucinatory phenomena outside the context of psychiatric disorders and in extreme environmental conditions among ultra-trail runners may offer a unique opportunity to those intending to study psychopathological conditions in a 'para-physiological' context.

The coronavirus disease 2019 (COVID-19) pandemic is overwhelming healthcare systems worldwide. There is no evidence from randomised clinical trials that any potential therapy improves outcome in COVID-19 pneumonia, and therapeutic strategies have been based on a progressively increasing knowledge of the clinical presentation of the disease. Some clinicians have found the clinical features of COVID-19 pneumonia to be similar to high-altitude pulmonary oedema (HAPE) [1], and such theory has been amplified via social media. We question this relationship., COVID-19 pneumonia is a viral infection; high-altitude pulmonary oedema is a non-cardiogenic oedema. Some clinicians have found the clinical features similar. It is important to clarify such misconceptions to prevent erroneous treatment strategies https://bit.ly/2KOBi3F

Purpose: This study was a quality-control study of resting and exercise echocardiography (EDE) variables measured by 19 echocardiography laboratories with proven experience participating in the RIGHT Heart International NETwork. Methods: All participating investigators reported the requested variables from ten randomly selected exercise stress tests. Intraclass correlation coefficients (ICC) were calculated to evaluate the inter-observer agreement with the core laboratory. Inter-observer variability of resting and peak exercise tricuspid regurgitation velocity (TRV), right ventricular outflow tract acceleration time (RVOT Act), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler tricuspid lateral annular systolic velocity (S’), right ventricular fractional area change (RV FAC), left ventricular outflow tract velocity time integral (LVOT VTI), mitral inflow pulsed wave Doppler velocity (E), diastolic mitral annular velocity by TDI (e’) and left ventricular ejection fraction (LVEF) was measured. Results: The accuracy of 19 investigators for all variables ranged from 99.7% to 100%. ICC was > 0.80 for all observers. Inter-observer variability for resting and exercise variables was for TRV = 3.8 to 2.4%, E = 5.7 to 8.3%, e’ = 6 to 6.5%, RVOT Act = 9.7 to 12, LVOT VTI = 7.4 to 9.6%, S’= 2.9 to 2.9% and TAPSE = 5.3 to 8%. Moderate inter-observer variability was found for resting and peak exercise RV FAC (15 to 16%). LVEF revealed lower resting and peak exercise variability of 7.6 and 9%. Conclusions: When performed in expert centers EDE is a reproducible tool for the assessment of the right heart and the pulmonary circulation

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 (R2=0.38 and R2=0.40; p<0.0001) and aminothiols levels (range R2=0.17-0.47; range p<0.01-0.0001). In particular, ROS was directly correlated with the athletes’ age (R2=0.19; p<0.05), with ultraendurance years of training (R2=0.18; p<0.05) and the days/week training activity (R2=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 (R2=‐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.

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.

KEY POINTS: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. We examined if exaggerated oxidative‐inflammatory‐nitrosative stress (OXINOS) and corresponding decrease in vascular nitric oxide bioavailability in patients with CMS (CMS+) is associated with impaired cerebrovascular function and adverse neurological outcome. Systemic OXINOS was markedly elevated in CMS+ compared to healthy HA (CMS−) and low‐altitude controls. OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. These findings are the first to suggest that a physiological continuum exists for hypoxaemia‐induced systemic OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of more specialist neurological assessment and targeted support. ABSTRACT: Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. The present cross‐sectional study examined to what extent exaggerated systemic oxidative‐inflammatory‐nitrosative stress (OXINOS), defined by an increase in free radical formation and corresponding decrease in vascular nitric oxide (NO) bioavailability, is associated with impaired cerebrovascular function, accelerated cognitive decline and depression in CMS. Venous blood was obtained from healthy male lowlanders (80 m, n = 17), and age‐ and gender‐matched HA dwellers born and bred in La Paz, Bolivia (3600 m) with (CMS+, n = 23) and without (CMS−, n = 14) CMS. We sampled blood for oxidative (electron paramagnetic resonance spectroscopy, HPLC), nitrosative (ozone‐based chemiluminescence) and inflammatory (fluorescence) biomarkers. We employed transcranial Doppler ultrasound to measure cerebral blood flow (CBF) and reactivity. We utilised psychometric tests and validated questionnaires to assess cognition and depression. Highlanders exhibited elevated systemic OXINOS (P < 0.05 vs. lowlanders) that was especially exaggerated in the more hypoxaemic CMS+ patients (P < 0.05 vs. CMS−). OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and, in CMS+, symptoms of depression. Collectively, these findings are the first to suggest that a physiological continuum exists for hypoxaemia‐induced OXINOS in HA dwellers that when excessive is associated with accelerated cognitive decline and depression, helping identify those in need of specialist neurological assessment and support.

OBJECTIVES The aim of this study was to evaluate the acute effects of participation in an Ironman distance triathlon competition on arterial function by ultrasound, in relation to cardiac function and body water content. METHODS Twenty-eight male triathletes participating in an Ironman distance competition underwent carotid, femoral, and cardiac ultrasound examinations. Moreover, the presence of extravascular lung water was identified by lung echo B-lines (echogenic coherent wedge-shaped signal with a narrow origin from the hyperechoic pleural line) at rest and within 20 minutes of arrival. RESULTS At the end of the competition, athletes showed an increased heart rate (mean ± SD, from 60.2 ± 13.1 to 82.8 ± 15.6 beats/min; P .05) in the presence of negligible dehydration (total body water from 48.0 ± 4.0 to 46.5 ± 3.9 kg; P > .05). Cardiac output increased (from 5.5 ± 1.2 to 6.7 ± 2.4 L/min; P .05) and unchanged left ventricular elastance (from 1.52 ± 0.48 to 1.39 ± 0.48 mm Hg/mL/m2 ; P > .05). The mean carotid diameter increased (from 7.19 ± 0.65 to 7.61 ± 0.76 mm; P .05). Carotid intima-media thickness was significantly reduced (from 537 ± 70 to 495 ± 70 μm; P

The Right Heart International Network is a multicenter international study aiming to prospectively collect exercise Doppler echocardiography tests of the right heart pulmonary circulation unit (RHPCU) in large cohorts of healthy subjects, elite athletes, and individuals at risk of or with overt pulmonary hypertension. It is going to provide standardization of exercise stress echocardiography of RHPCU and explore the full physiopathologic response.

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.

Various lung ultrasound (LUS) scanning modalities have been proposed for the detection of B-lines, also referred to as ultrasound lung comets , which are an important indication of extravascular lung water at rest and after exercise stress echo (ESE). The aim of our study was to assess the lung water spatial distribution ( comet map ) at rest and after ESE. We performed LUS at rest and immediately after semi-supine ESE in 135 patients (45 women, 90 men; age 62 ± 12 y, resting left ventricular ejection fraction = 41 ± 13%) with known or suspected heart failure or coronary artery disease. B-lines were measured by scanning 28 intercostal spaces (ISs) on the antero-lateral chest, 2nd–5th IS, along with the midaxillary (MA), anterior axillary (AA), mid-clavicular (MC) and parasternal (PS) lines. Complete 28-region, 16-region (3rd and 4th IS), 8-region (3rd IS), 4-region (3rd IS, only AA and MA) and 1-region (left 3rd IS, MA) scans were analyzed. In each space, the B-lines were counted from 0 = black lung to 10 = white lung. Interpretable images were obtained in all spaces (feasibility = 100 %). B-lines (>0 in at least 1 space) were present at ESE in 93 patients (69%) and absent in 42. More B-lines were found in the 3rd IS and along AA and MA lines. The B-line cumulative distribution was symmetric at rest (right/left = 1.10) and asymmetric with left lung predominance during stress (right/left = 0.67). The correlation of per-patient B-line number between 28-S and 16-S (R 2 = 0.9478), 8-S (R 2 = 0.9478) and 4-S scan (R 2 = 0.9146) was excellent, but only good with 1-S (R 2 = 0.8101). The average imaging and online analysis time were 5 s per space. In conclusion, during ESE, the comet map of lung water accumulation follows a predictable spatial pattern with wet spots preferentially aligned with the third IS and along the AA and MA lines. The time-saving 4-region scan is especially convenient during stress, simply dismissing dry regions and focusing on wet regions alone.

Decrease in SpO2 at HA is the main cause of acute mountain sickness (AMS) and development of interstitial lung edema. Aim: to evaluate the effect of a respiratory training (RT) on SpO2, AMS and interstitial lung edema during the ascent to Regina Margherita Hut (4559 m). 16 subjects (12 M, 4 F) age 22-61 yrs, performed an 8 weeks RT, taught and supervised by Apnea Academy’s instructors: 30 min/day; a sequence of inspiratory and expiratory apnea of the same duration plus 3 sets of 5 minutes of ventilation with maximal inspiration and expiration. At the end of the 8 weeks they reached a village at 1635 m and were randomized in trial (T) and control (C) group. Day 1: walk to 3498 m; Day 2: to 4167 m; Day 3: to Regina Margherita Hut and back to 1635 m. T stopped every 3 hours to perform RT. Both groups during the climb underwent: 24h SpO2 monitoring, Lake Louise Scoring System (LLS) for the diagnosis of AMS, lung ultrasound analysis to assess the presence of B lines (sign of interstitial lung edema). Results: (ANOVA repeated measures): SpO2 was significantly higher in T during both the climb and the nights through all 3 days (p Conclusion: Respiratory exercises performed during HA ascent, helps to maintain a better SpO2 during the climb and the sleep. The better oxygenation reduces the evidence of B lines after a long exposure. This is the first step of assessment of a new way to counteract HA hypoxia.

OBJECTIVES: The aim of this study was to evaluate the acute effects of participation in an Ironman distance triathlon competition on arterial function by ultrasound, in relation to cardiac function and body water content. METHODS: Twenty-eight male triathletes participating in an Ironman distance competition underwent carotid, femoral, and cardiac ultrasound examinations. Moreover, the presence of extravascular lung water was identified by lung echo B-lines (echogenic coherent wedge-shaped signal with a narrow origin from the hyperechoic pleural line) at rest and within 20 minutes of arrival. RESULTS: At the end of the competition, athletes showed an increased heart rate (mean ± SD, from 60.2 ± 13.1 to 82.8 ± 15.6 beats/min; P < .0001) and unchanged mean blood pressure (from 93 ± 14 to 91 ± 10 mm Hg; P > .05) in the presence of negligible dehydration (total body water from 48.0 ± 4.0 to 46.5 ± 3.9 kg; P > .05). Cardiac output increased (from 5.5 ± 1.2 to 6.7 ± 2.4 L/min; P < .05) in the presence of an unchanged stroke volume (from 64 ± 14 to 59 ± 16 mL; P > .05) and unchanged left ventricular elastance (from 1.52 ± 0.48 to 1.39 ± 0.48 mm Hg/mL/m2 ; P > .05). The mean carotid diameter increased (from 7.19 ± 0.65 to 7.61 ± 0.76 mm; P < .05), whereas the mean femoral diameter was unchanged at the end of the competition (from 10.41 ± 0.83 to 10.49 ± 0.82 mm; P > .05). Carotid intima-media thickness was significantly reduced (from 537 ± 70 to 495 ± 70 ?m; P < .05), whereas B-lines increased significantly after the competition (from 1 [0-4] to 12 [5-23]; P < .0001). CONCLUSIONS: These data suggest different acute functional adaptation in central arteries with respect to peripheral leg vessels.

International audience; Chronic mountain sickness (CMS) is a maladaptation syndrome encountered at high-altitude (HA) characterised by severe hypoxaemia that carries a higher risk of stroke and migraine and is associated with increased morbidity and mortality. The present cross-sectional study examined to what extent exaggerated systemic oxidative-nitrosative-inflammatory stress (OXINOS), defined by an increase in free radical formation and corresponding decrease in vascular nitric oxide (NO) bioavailability, is associated with impaired cerebrovascular function, accelerated cognitive decline and depression in CMS. Venous blood was obtained from healthy male lowlanders (80m,n= 17), and age and gender-matched HAdwellers born and bred in La Paz, Bolivia (3,600 m) with (CMS+, n= 23) and without (CMS-, n= 14) CMS. We sampled blood for oxidative (electron paramagnetic resonance spectroscopy, HPLC), nitrosative (ozone-based chemiluminescence), and inflammatory (fluorescence) biomarkers. We employed transcranial Doppler ultrasound to measure cerebral blood flow (CBF) and reactivity. We utilised psychometric tests and validated questionnaires to assess cognition and depression. Highlanders exhibited elevated systemic OXINOS (P< 0.05 vs. lowlanders) that was especially exaggerated in the more hypoxaemic CMS+ patients (P< 0.05 vs. CMS-). OXINOS was associated with blunted cerebral perfusion and vasoreactivity to hypercapnia, impaired cognition and in CMS+, symptoms of depression. Collectively, these findings are the first to suggest that a physiological continuum exists for hypoxaemia-induced OXINOS in HA dwellers that when excessive,is associated with accelerated cognitive decline and depression, helping identify those in need of specialist neurological assessment and support.

Changes in barometric pressure characterize both high altitude and the underwater world. These changes have a significant impact on the body’s pulmonary physiology and can affect both mountain climbers and divers. In both of these conditions, the organism must use compensatory mechanisms to adapt to the different environmental conditions. In this chapter, the environmental characteristics of altitude and underwater and their effects on the respiratory system are discussed. The body’s compensatory responses at high altitude, primarily the ventilatory response, are discussed. A section is devoted to the maladaptive response (i.e. high-altitude pulmonary oedema) and its prevention and treatment. Next, we consider the safety of high-altitude travel in patients with chronic respiratory disease, primarily chronic obstructive pulmonary disease, asthma and cystic fibrosis. In the second part of the chapter, the physiology and pathophysiology of the hyperbaric and diving environments, especially those involving the respiratory system, are described. A paragraph is dedicated to fitness for immersion, especially for the most common chronic respiratory diseases, such as asthma and COPD. In the last part of the chapter, we discuss lung interstitial oedema, its development in extreme environments or after strenuous exercise, and the diagnostic methods.

Background: Increasing evidence links meteorological characteristics and air pollution to physiological responses during sports activities in urban areas with different traffic levels. Objective: The main objective of the Smart Healthy ENV (SHE, “Smart Monitoring Integrated System For A Healthy Urban Environment In Smart Cities”) project was to identify the specific responses of a group of volunteers during physical activity, by monitoring their heart rates and collecting breath samples, combined with data on meteorological determinants and pollution substances obtained through fixed sensor nodes placed along city routes and remotely connected to a dedicated data acquisition server. Methods: Monitoring stations were placed along two urban routes in Pisa, each two km long, with one located within the park beside the Arno river (green route) and the other in a crowded traffic zone (red route). Our sample participants were engaged in sports activities (N = 15, with different levels of ability) and were monitored through wearable sensors. They were first asked to walk back and forth (4 km) and then to run the same route. The experimental sessions were conducted over one day per route. A breath sample was also collected before each test. A questionnaire concerning temperature and fatigue perception was administered for all of the steps of the study over the two days. Results: The heart rates of the participants were monitored in the baseline condition, during walking, and while running, and were correlated with meteorological and pollutant data and with breath composition. Changes in the heart rates and breath composition were detected during the experimental sessions. These variations were related to the physical activity and to the meteorological conditions and air pollution levels. Conclusions: The SHE project can be considered a proof-of-concept study aimed at monitoring physiological and environmental variables during physical activity in urban areas, and can be used in future studies to provide useful information to those involved in sports and the broader community.

Chronic mountain sickness (CMS) is often associated with vascular dysfunction, but the underlying mechanism is unknown. Sleep-disordered breathing (SDB) frequently occurs at high altitude. At low altitude, SDB causes vascular dysfunction. Moreover, in SDB, transient elevations of right-sided cardiac pressure may cause right-to-left shunting in the presence of a patent foramen ovale (PFO) and, in turn, further aggravate hypoxemia and pulmonary hypertension. We speculated that SDB and nocturnal hypoxemia are more pronounced in patients with CMS compared with healthy high-altitude dwellers, and are related to vascular dysfunction.We performed overnight sleep recordings, and measured systemic and pulmonary artery pressure in 23 patients with CMS (mean ± SD age, 52.8 ± 9.8 y) and 12 healthy control subjects (47.8 ± 7.8 y) at 3,600 m. In a subgroup of 15 subjects with SDB, we assessed the presence of a PFO with transesophageal echocardiography.The major new findings were that in patients with CMS, (1) SDB and nocturnal hypoxemia was more severe (P.01) than in control subjects (apnea-hypopnea index [AHI], 38.9 ± 25.5 vs 14.3 ± 7.8 number of events per hour [nb/h]; arterial oxygen saturation, 80.2% ± 3.6% vs 86.8% ± 1.7%, CMS vs control group), and (2) AHI was directly correlated with systemic blood pressure (r = 0.5216; P = .001) and pulmonary artery pressure (r = 0.4497; P = .024). PFO was associated with more severe SDB (AHI, 48.8 ± 24.7 vs 14.8 ± 7.3 nb/h; P = .013, PFO vs no PFO) and hypoxemia.SDB and nocturnal hypoxemia are more severe in patients with CMS than in control subjects and are associated with systemic and pulmonary vascular dysfunction. The presence of a PFO appeared to further aggravate SDB. Closure of the PFO may improve SDB, hypoxemia, and vascular dysfunction in patients with CMS.ClinicalTrials.gov; No.: NCT01182792; URL: www.clinicaltrials.gov.

Background Exposure to indoor biomass fuel smoke is associated with increased morbidity and mortality. The aim of this study is to evaluate the association between exposure to indoor biomass burning and early pulmonary and cardiovascular damage. Methods The indoor levels of particulate matter (PM) [PM10, PM2.5] and black carbon (BC) were monitored in 32 houses in a Himalayan village. Seventy-eight subjects were submitted to spirometry and cardiovascular evaluation [carotid to femoral pulse wave velocity (PWV) and echocardiography]. Results Peak indoor BC concentration up to 100 ?g m-3 and PM10 - PM2.5 up to 1945-592 ?g m-3 were measured. We found a non-reversible bronchial obstruction in 18% of subjects >=40 yr; mean forced expiratory flow between 25% and 75% of the forced vital capacity (FEF25-75) 30 yr. In multiple variable analysis, BC remained an independent predictor of PWV (? = 0.556,p = .001), and TPR (? = 0.366;p = .018). Conclusions Indoor pollution exposure is associated to early pulmonary and cardiovascular damages, more evident for longer duration and higher intensity exposure.

Most healthy subjects can develop a subclinical interstitial pulmonary edema that is a complex and multifactor phenomenon, still with unanswered questions, and might be one line of defense against the development of severe symptomatic lung edema. Whether the acute, reversible increase in lung fluid content is really an innocent and benign part of the adaptation to extreme physiologic condition or rather the clinically relevant marker of an individual vulnerability to life-threatening high altitude pulmonary edema remains to be established in future studies. Thus the question if encouraging more conservative habits to climb is right or not remains open.

Objective The negative effect of sepsis on the myocardium affects its electric functionality. This study aims to evaluate the incidence of atrial fibrillation (AF) in patients with septic shock, and the mortality rate of patients with AF versus patients that maintained sinus rhythm (SR). Methods This is a one-year observational prospective pilot study. It was conducted at the Department of Anaesthesia and Intensive Care of Pisa University. Patients with septic shock were enrolled in this study. They were divided in two groups based on the occurrence of AF while in the ICU. Data were collected at admission and after 72 hours, and the data consisted of anamnesis, vital parameters, blood results and severity score. Results Out of 27 patients, 9 developed AF during the first 72 hours. At admission and at 72 hours, SOFA was statistically higher in the patients with AF (p=0.012 and p=0.002, respectively). In the AF group, the overall mortality was 66.7%, whereas, it was 11.1% (p=0.006) in the patients with SR. Age, rhythm and noradrenaline dosage were univariate predictors of total mortality. Conclusion In patients with septic shock, AF has a high incidence, and it correlated with a worse outcome. Patients with higher SOFA score are at a greater risk of developing arrhythmia.

Household air pollution (HAP) from biomass fuel smoke is a major health risk, especially in developing countries. The ventilation of buildings and the type of fume discharge could also affect HAP. The present study aims to investigate the impact of stove type and kitchen characteristics on levels of pollutants. In particular, we investigated the potential geometric ventilation of buildings using geometric ventilation index (GVI), the presence of chimneys, the type of fuel and the environmental carbon monoxide level (a marker of indoor pollution) in the households of four Sherpa villages located in a mountain region of Nepal at altitudes between 2500 and 3900 m. We analysed 114 buildings (76 private residences and 38 lodges that accommodate tourists). Lodges had a more effective discharge system and a higher GVI, which had an inverse, significant correlation with indoor CO levels (r = 0.52). The level of indoor CO was more than 50% higher in private residences than in lodges. In the univariate analysis, only the absence of a chimney was associated with higher indoor CO (OR 3.4 (CL95%, 1.2–10.0), p = 0.02). We conclude that the adoption of chimneys and sealed stoves with exhaust pipes should be the first measure taken to reduce pollutants inside the households of high mountain regions until a switch to clean fuels can be achieved.

It is well established that physical exercise induces reactive oxygen species production, while physical training increases antioxidant defense systems thereby reducing exercise-induced oxidative stress. However, intense physical exercise, competition, and training such as those imposed on high-level athletes may lead to increased oxidative stress implicating an overtraining condition. In the present study, the effects of training and competition load on oxidative stress, redox and antioxidant status, and cell damage markers have been studied on high-level players in different sports (i.e., 15 ultra-endurance and 12 long-distance runners, and 12 junior professional rugby players) during a competitive season. Oxidative damage plasmatic markers, including protein carbonyls (PC) and thiobarbituric acid-reactive substances (TBARS), total antioxidant capacity (TAC), and amino-thiols redox status were assessed at three critical time points of the season: T0, the beginning; T1, the top; T2, the end. Seasonal variations of all the investigated parameters were observed. With respect to the basal level T0 (0.69 ± 0.14), significant increases of PC concentration (nmol/mg protein) at T1 (1.08 ± 0.36, p < 0.001) and T2 (1.04 ± 0.27, p < 0.01), as well as of TBARS concentration (µM, T0: 6.11 ± 1.11) at T2 (8.09 ± 1.07, p < 0.0001) and T1 (6.77 ± 1.22, p < 0.01) were measured in ultra-endurance athletes. PC was found significantly increased in rugby players too (T0: 0.76 ± 0.26 vs. T2: 1.19 ± 0.34; p

Background: Dementia has been recently viewed as a predominantly vascular disorder. Indeed, reduced brain NO availability causes increased ß-amyloid deposition by several mechanisms, including hypoperfusion. Purpose: To investigate the relationship between cerebral blood flow in the hippocampal and parahippocampal regions (CBF-hipp and CBF-parahipp), crucial areas for memory and processing of non-verbal/spatial information, and systemic endothelial function in individuals with mild cognitive impairment (MCI), a subclinical condition predisposing to dementia. Methods: CBF-hipp and CBF-parahipp were evaluated by magnetic resonance imaging (arterial spin labeling, GE HDxt 1.5 T Signa Neuro-optimized System) and systemic endothelial function by flow-mediated dilation (FMD) in the brachial artery. Results: Complete data about CBF and FMD at enrollment were available for 66 individuals with MCI and 32 without (non-MCI). The two groups were matched for age (75 ± 5 vs 74 ± 5 years, p = 0.22), sex (men 45 vs 50%, p = 0.18) and mean BP (96 ± 10 vs 97 ± 9 mmHg, p = 0.41). FMD was significantly lower in MCI than in non-MCI (2.93 ± 2.18 vs 3.74 ± 2.03%, p = 0.02); CBF-hipp (64.3 ± 9.43 vs 69.5 ± 7.03 ml/100 gr/min, p = 0.002) and CBF-parahipp (66.3 ± 8.02 vs 70.0 ± 8.12 ml/100 gr/min, p = 0.002) were significantly lower in MCI as well. Among MCI, FMD was significantly correlated with CBF-parahipp (r = 0.26, p = 0.03) and CBF-hipp (r = 0.32, p = 0.009). In multiple regression models, including age, sex, mean BP, BMI, brachial artery diameter as confounders, FMD remained an independent determinant of CBF-parahipp (beta = 0.93, r2 = 0.063, p = 0.04) and CBF-hipp (beta = 1.31, r2 = 0.089, p = 0.01). Nor CBF-parahipp (r = −0.13, p = 0.48) neither CBF-hipp (r = 0.05, p = 0.80) were correlated with FMD in non-MCI group. Conclusions: An independent association between hippocampal and parahippocampal CBF and systemic endothelial function is present in individuals with MCI.

Telomere shortening is considered a cellular marker of health status and biological ageing. Exercise may influence the health and lifespan of an individual by affecting telomere length (TL). However, it is unclear whether different endurance exercise levels may have beneficial or detrimental effects on biological aging. The aims of the study were to assess both chronic and acute effects of endurance training on TL after an exceptional and extreme trail race. TL was assessed in 20 endurance athletes (17 males; age = 45.4 ± 9.2 years) and 42 age- and gender-matched sedentary controls (32 males; age = 45.9 ± 9.5 years) with quantitative real-time PCR at baseline conditions. Of the 20 runners enrolled in the 'Tor des Géants ®' ultra-distance trail race, 15 athletes (12 males; age = 47.2 ± 8.5 years) were re-evaluated at the intermediate point and 14 athletes (11 males; age = 47.1 ± 8.8 years) completed the competition and were analysed at the final point. Comparison between the two groups (endurance athletes vs. sedentary controls) revealed a significant difference in TL (1.28 ± 0.4 vs. 1.02 ± 0.3, P = 0.005). TL was better preserved in elder endurance runners compared with the same age control group (1.3 ± 0.27 vs. 0.91 ± 0.21, P = 0.003). TL was significantly reduced at the intermediate (0.88 ± 0.36 vs. 1.11 ± 0.34, P = 0.002) and final point compared with baseline measurements (0.86 ± 0.4 vs. 1.11 ± 0.34, P = 0.0006) for athletes engaged in the ultra-marathon race. Our data suggest that chronic endurance training may provide protective effects on TL attenuating biological aging. Conversely, acute exposure to an ultra-distance endurance trail race implies telomere shortening probably caused by oxidative DNA damage.

Background Intense physical stress might promote inflammatory responses, whereas a regular physical exercise has positive influence. Little is known on the acute metabolic and inflammatory responses to different levels of strenuous exercise in trained athletes. Aim To compare the short-term effect of two different ultra-endurance competitions on the inflammatory profile in male triathletes. Methods We studied 14 Ironman (IR) and 13 Half Ironman (HIR) before and after their own specific race. We assessed body composition and measured blood cells, lipids, iron metabolism and plasma levels of some acute-phase cytokines and inflammatory markers. Results After the race, IR showed reduced total body water and fat-free mass, not related with the duration of exercise, and increased white cells and platelets; high-density lipoprotein levels also increased. IR, but not HIR, showed reduced iron levels, increased ferritin and transferrin, reduced % saturated transferrin. HIR showed higher basal interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-10, IL-1β than IR; however, the post-performance rise was greater in IR. Irisin increased only in HIR and osteocalcin decreased in IR. In the whole study group, delta of white blood cells was directly related with delta of monocyte chemoattractant protein 1, and Δ ferritin was inversely related with Δosteocalcin. Conclusions A single ultra-endurance competition induces an inflammatory response depending on the duration of physical effort, with increased acute-phase cytokines, and an altered iron metabolism. Irisin, whose biological meaning is still uncertain, seems to be associated with acute variations of some metabolic parameters.

Wearable sensors currently represent a non-invasive way of monitoring health-related parameters, quite useful for both self-assessment and naturalistic studies. The autonomic imbalance experienced by athletes engaged in strenuous physical exercises could be also seen through this minimally obtrusive approach, possibly opening the field to a variety of novel investigations. Here, 41 athletes, taking part to two of the most strenuous ultra-trail competitions in Europe were assessed in terms of autonomic evaluation before, during and after the race, through a minimally invasive ECG system based on a fitness-like chest strap. Results showed an increased sympathetic activity both before and after the race, whereas vagal tone appeared increased during the race. Having proven the good feasibility of the proposed approach in such field, further investigations are needed to clarify the scientific basis explaining such modifications.

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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.

Ujka, Kristian, Rosa Maria Bruno, Luca Bastiani, Eva Bernardi, Paolo Sdringola, Nenad Dikic, Bikash Basyal, Sanjeeb Sundarshan Bhandari, Buddha Basnyat, Annalisa Cogo, and Lorenza Pratali. Relationship between occupational physical activity and subclinical vascular damage in moderate-altitude dwellers. High Alt Med Biol. 18:249-257, 2017.Occupational physical activity (OPA) has been associated with increased cardiovascular (CV) events. The aim of this study was to investigate the association between OPA and markers of subclinical vascular damage among a moderate-altitude population living in the rural village of Chaurikharka (Nepal; 2600 m sea level).Seventy-two individuals (age 42 ± 15 years, ranges 15-85 years, 23 men) were enrolled. Physical activity (PA) was evaluated using the International Physical Activity Questionnaire (IPAQ). Carotid-femoral pulse wave velocity (PWV), carotid ultrasound assessment, and flow-mediated dilation (FMD) were performed.OPA was 9860 ± 5385 Metabolic Equivalent of Task (MET)-minutes/week, representing 77% of total energy expenditure, with 97% of the population performing high-intensity PA. In the univariate analysis, OPA was significantly associated with PWV (β = 0.474, p = 0.001) and carotid stiffness (CS) (β = 0.29, p = 0.019). In the multivariate analysis, including age, sex, oxygen saturation, mean blood pressure, low-density lipoprotein (LDL), and OPA, OPA remained an independent predictor of PWV (β = 0.403, p = 0.001) but not of CS (β = 0.028, p = 0.8). OPA remained an independent predictor of PWV independently from the Framingham risk score (FRS).High-intensity OPA shows a positive, independent association with aortic stiffness in Himalayan moderate-altitude dwellers. This study suggests how vigorous OPA performed in moderate altitude may be a CV risk factor.

Age-related cognitive impairment and dementia are an increasing societal burden. Epidemiological studies indicate that lifestyle factors, e.g. physical, cognitive and social activities, correlate with reduced dementia risk; moreover, positive effects on cognition of physical/cognitive training have been found in cognitively unimpaired elders. Less is known about effectiveness and action mechanisms of physical/cognitive training in elders already suffering from Mild Cognitive Impairment (MCI), a population at high risk for dementia. We assessed in 113 MCI subjects aged 65–89 years, the efficacy of combined physical-cognitive training on cognitive decline, Gray Matter (GM) volume loss and Cerebral Blood Flow (CBF) in hippocampus and parahippocampal areas, and on brain-blood-oxygenation-level-dependent (BOLD) activity elicited by a cognitive task, measured by ADAS-Cog scale, Magnetic Resonance Imaging (MRI), Arterial Spin Labeling (ASL) and fMRI, respectively, before and after 7 months of training vs. usual life. Cognitive status significantly decreased in MCI-no training and significantly increased in MCI-training subjects; training increased parahippocampal CBF, but no effect on GM volume loss was evident; BOLD activity increase, indicative of neural efficiency decline, was found only in MCI-no training subjects. These results show that a non pharmacological, multicomponent intervention improves cognitive status and indicators of brain health in MCI subjects.