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The study investigated the effect of prolonged hypoxia on central [i.e., cardiovascular oxygen delivery (QaO2)] and peripheral (i.e., O2 utilization) determinants of oxidative metabolism response during exercise in humans. To this aim, seven male mountaineers were examined before and immediately after the Himalayan Expedition Interamnia 8000-Manaslu 2008, lasting 43 days, among which, 23 days were above 5,000 m. The subjects showed a decrease in body weight (P < 0.05) and of power output during a Wingate Anaerobic test (P < 0.05) and an increase of thigh cross-sectional area (P < 0.05). Absolute maximal O2 uptake (VO2max) did not change. The mean response time of 402 kinetics at the onset of step submaximal cycling exercise was reduced significantly from 53.8 s ± 10.9 to 39.8 s ± 10.9 (P < 0.05), whereas that of QaO2 was not. Analysis of single fibers dissected from vastus lateralis biopsies revealed that the expression of slow isoforms of both heavy and light myosin subunits increased, whereas that of fast isoforms decreased. Unloaded shortening velocity of fibers was decreased significantly. In summary, independent findings converge in indicating that adaptation to chronic hypoxia brings about a fast-to-slow transition of muscle fibers, resulting in a faster activation of the mitochondrial oxidative metabolism. These results indicate that a prolonged and active sojourn in hypoxia may induce muscular ultrastructural and functional changes similar to those observed after aerobic training. [ABSTRACT FROM AUTHOR]

Background: The environment can alter the homeostasis of humans and human microbiota. Oral health is influenced by high altitude through symptoms of periodontitis, barodontalgia, dental barotrauma, and a decrease in salivary flow. Microbiota and inflammatory state are connected in the oral cavity. This study aimed to explore the effect of acute high-altitude exposure on the salivary microbiome and inflammatory indicators. Methods: Fifteen healthy expeditioners were subjected to oral examination, recording the plaque index (PII), gingival index (GI), the simplified oral hygiene index (OHI-S), and the number of teeth; unstimulated saliva samples were collected at an altitude of 1191 m (T1) and 4556 m (T2). TNF-α, sICAM1, ROS, and the oral bacterial species Porphyromonas gingivalis ( Pg ) and Fusobacterium nucleatum ( Fn ) were quantified. Results: At T2, slCAM, TNF, and ROS increased by 85.5% (IQR 74%), 84% (IQR 409.25%), and 53.5% (IQR 68%), respectively, while Pg decreased by 92.43% (IQR 102.5%). The decrease in Pg was greater in the presence of low OHI-S. The increase in slCAM1 correlated with the reduction in Fn . Individuals with high GI and OHI-S had a limited increase in TNF-α at T2. Conclusion: Short-term exposures can affect the concentration of pathogenic periodontal bacteria and promote local inflammation.

Background and Objectives : This study aimed to compare the effects and safety of boldine combined with Phyllanthus niruri and Ononis spinosa plus tamsulosin vs. tamsulosin alone in medical expulsive therapy (MET) for distal ureteral calculi. Materials and Methods : This retrospective cohort study was conducted on 159 renal colic patients with distal ureteric stones (≤10 mm). Patients aged between 18 and 70 years or older with distal ureteral (below the sacroiliac joint) stones ≤10 mm (defined by the largest diameter in three planes) confirmed by urinary ultrasonography and/or native computed tomography (CT). Patients were divided into two groups: A and B. Patients in Group A received tamsulosin 0.4 mg plus boldine combined with Phyllanthus niruri and Ononis spinosa , while those in Group B received tamsulosin 0.4 mg. The rate of stone expulsion, duration of stone expulsion, the dose and the duration of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesic use, and adverse effects of drugs were recorded. Results : No differences were reported in demographic profiles between the two groups. The stone expulsion rate in Group A (84.8%) was higher in comparison to Group B (52.5%); the mean time of stone expulsion was 16.33 ± 4.75 days in Group A and 19.33 ± 6.42 days in Group B. The mean requirement time of analgesia was significantly less in Group A, 2.42 ± 2.56, than in Group B, 6.25 ± 3.05. Drug-related adverse effects (headache, dizziness, nausea, vomiting, postural hypotension, backache, and running nose) were comparable between the two groups. Conclusions : Tamsulosin plus boldine combined with Phyllanthus niruri and Ononis spinosa as medical expulsion therapy is more effective for distal ureteric stones with less need for analgesics and a shorter stone expulsion time than tamsulosin alone.

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers.

Objective: Occlusal disturbances affect human posture and sports performance. This study aimed to monitor biomechanical adaptations to personalized occlusal splints., Methods: Splints were customized based on stabilometry, thermography, sEMG, and kinesiography, and administered to three triathlon athletes. They were evaluated during a 4-month period, using isokinetic indexes, running kinematics and anaerobic outputs., Results: Individuality emerged as a key factor driving type, quantity, quality, and time trajectories of adaptations. The use of instrumental and clinical tests allowed the detection of static balance and biting function improvements, but not necessarily parallel to sports performance improvements., Conclusion: The authors argue that strength and kinematic imbalances are joint and task-specific and support the use of multi-stage monitoring of the biomechanical effect of mouthpieces. Kinematics of cycling and running may be widely assessed with ecological and inexpensive methods. Strength imbalances need to be continuously monitored due to the high informative value to injury prevention.

We read the comment by Šarabon and Sašek (Eur J Transl Myol 11846, 2023 doi: 10.4081/ejtm.2023.11846) on our study on the electromyographic results during squat at high-altitude. Their highlighting of the factors that may have biased our results is commendable, despite they criticized our work as if it were a controlled laboratory study. We considered the limitations and argued our interpretation with caution. We found no changes in median frequency, frequency's slope and conduction velocity of EMG signals at high altitude, and a slight decrease of root mean square. We argued that our results may have been due to a preventative mechanism that compensates for relatively greater effort during a fatiguing strength test involving large muscle masses, or to cumulative exertional stress on the muscles. The authors of the comment themselves somehow agree with these interpretations. Guidelines for collecting, reporting and interpreting data from EMG to obtain original information on the neuromuscular system should be integrated with the effort to maintain as much as possible those field conditions that offer unique opportunities.

Reports of electromyography during hypoxic exercise are contrasting, due to protocol and muscle diversity. This work aimed to investigate alterations in muscle activation and myoelectrical fatigue during exercise at high-altitude in those muscles primarily involved in trekking. Twelve young adults balanced by gender and age were tested at low (1,667 m) and high (4,554 m, "Capanna Margherita", Italy) altitude, during an isometric squat lasting 60 seconds. High-density surface electromyography was performed from the quadriceps of right limb. The root mean square (RMS), median frequency with its slope, and muscle fiber conduction velocity (MFCV) were computed. Neither males nor females showed changes in median frequency (Med: 36.13 vs 35.63 Hz) and its slope (Med: -9 vs -12 degree) in response to high-altitude trekking, despite a great inter-individual heterogeneity, nor differences were found for MFCV. RMS was not significantly equivalent, with greater values at low altitude (0.385 ± 0.104 mV) than high altitude (0.346 ± 0.090 mV). Unexpected results can be due either to a postural compensation of the whole body compensating for a relatively greater effort or to the inability to support muscle activation after repeated physical efforts.  Interesting results may emerge by measuring simultaneously electromyography, muscle oxygenation and kinematics comparing trekking at normoxia vs hypoxia.

This review summarises key aspects of the first reproductive and developmental systems Science Community White Paper, supported by the European Space Agency (ESA). Current knowledge regarding human development and reproduction in space is mapped to the roadmap. It acknowledges that sex and gender have implications on all physiological systems, however, gender identity falls outside the scope of the document included in the white paper collection supported by ESA. The ESA SciSpacE white papers on human developmental and reproductive functions in space aim to reflect on the implications of space travel on the male and female reproductive systems, including the hypothalamic-pituitary-gonadal (HPG) reproductive hormone axis, and considerations for conception, gestation and birth. Finally, parallels are drawn as to how this may impact society as a whole on Earth., (© 2023. The Author(s).)

Many authors described negative but reversible effects of high-altitude hypoxic exposure on animal and human fertility in terms of sperm concentration, function, and biochemical alterations. The aim of this study was to evaluate the acute and chronic effects of high-altitude exposure on classical sperm parameters, redox status, and membrane composition in a group of travellers. Five healthy Italian males, all lowlanders not accustomed to the altitude, were evaluated after 19 days-trekking through low, moderate, and high altitudes in the Himalayas. Sperm samples were collected before (Pre), 10 days after (Post), and 70 days after the end of the expedition (Follow-up). Sperm concentration, cholesterol and oxysterol membrane content, and redox status were measured. Hypoxic trek led to a significant reduction in sperm concentration (p < 0.001, η2p = 0.91), with a reduction from Pre to Post (71.33 ± 38.81 to 60.65 ± 34.63 × 106/mL) and a further reduction at Follow-up (to 37.13 ± 39.17 × 106/mL). The seminal volume was significantly affected by the hypoxic trek (p = 0.001, η2p = 0.75) with a significant reduction from Pre to Post (2.86 ± 0.75 to 1.68 ± 0.49 mL) and with partial recovery at Follow-up (to 2.46 ± 0.45 mL). Moreover, subjects had an increase in ROS production (+86%), and a decrease in antioxidant capacity (−37%) in the Post period with partial recovery at Follow-up. These results integrated the hormonal response on thyroid function, hypothalamus−pituitary−gonadal axis, and the prolactin/cortisol pathways previously reported. An uncontrolled ROS production, rather than a compromised antioxidant activity, was likely the cause of impaired sperm quality. The reduction in fertility status observed in this study may lie in an evolutionary Darwinian explanation, i.e., limiting reproduction due to the “adaptive disadvantage” offered by the combined stressors of high-altitude hypoxia and daily physical exercise.

Human postmortem skeletal muscles are a unique source of satellite cells for skeletal muscle regenerative studies. Presomite and somite satellite cells obtained by postmortem muscles have been established as populations of human skeletal muscle precursor cells able to proliferate and differentiate in vitro . It is extremely interesting to have access to a large amount of postmortem human skeletal muscle precursor cells, especially from craniofacial as well as limb skeletal muscles in order to evaluate their potential application not only for the fundamental understanding of muscle physiology and diseases but also for drug testing in a challenging 3D-shaping muscles like skeletal muscle microphysiological systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pietrangelo, Demontis, Santangelo, Pini, Bonelli, Rosato, Roberti, Locatelli, Tartaglia, Marramiero, Verratti, Bondi, Fulle, D’Aloja and D’Ovidio.)

Committeri Giorgia, Danilo Bondi, Carlo Sestieri, Ginevra Di Matteo, Claudia Piervincenzi, Christian Doria, Roberto Ruffini, Antonello Baldassarre, Tiziana Pietrangelo, Rosamaria Sepe, Riccardo Navarra, Piero Chiacchiaretta, Antonio Ferretti, and Vittore Verratti. Neuropsychological and neuroimaging correlates of high-altitude hypoxia trekking during the "Gokyo Khumbu/Ama Dablam" expedition. High Alt Med Biol . 23:57-68, 2022. Background: Altitude hypoxia exposure may produce cognitive detrimental adaptations and damage to the brain. We aimed at investigating the effects of trekking and hypoxia on neuropsychological and neuroimaging measures. Methods: We recruited two balanced groups of healthy adults, trekkers ( n  = 12, 6 F and 6 M, trekking in altitude hypoxia) and controls (gender- and age-matched), who were tested before (baseline), during (5,000 m, after 9 days of trekking), and after the expedition for state anxiety, depression, verbal fluency, verbal short-term memory, and working memory. Personality and trait anxiety were also assessed at a baseline level. Neuroimaging measures of cerebral perfusion (arterial spin labeling), white-matter microstructural integrity (diffusion tensor imaging), and resting-state functional connectivity (functional magnetic resonance imaging) were assessed before and after the expedition in the group of trekkers. Results: At baseline, the trekkers showed lower trait anxiety ( p  = 0.003) and conscientiousness ( p  = 0.03) than the control group. State anxiety was lower in the trekkers throughout the study ( p  < 0.001), and state anxiety and depression decreased at the end of the study in both groups ( p  = 0.043 and p  = 0.007, respectively). Verbal fluency increased at the end of the study in both groups ( p  < 0.001), whereas verbal short-term memory and working memory performance did not change. No significant differences between before and after the expedition were found for neuroimaging measures. Conclusions: We argue that the observed differences in the neuropsychological measures mainly reflect aspecific familiarity and learning effects due to the repeated execution of the same questionnaires and task. The present results thus suggest that detrimental effects on neuropsychological and neuroimaging measures do not necessarily occur as a consequence of short-term exposure to altitude hypoxia up to 5,000 m, especially in the absence of altitude sickness.

High-altitude locations are fascinating for investigating biological and physiological responses in humans. In this work, we studied the high-altitude response in the plasma and urine of six healthy adult trekkers, who participated in a trek in Nepal that covered 300 km in 19 days along a route in the Kanchenjunga Mountain and up to a maximum altitude of 5140 m. Post-trek results showed an unbalance in redox status, with an upregulation of ROS (+19%), NOx (+28%), neopterin (+50%), and pro-inflammatory prostanoids, such as PGE 2 (+120%) and 15-deoxy-delta12,14-PGJ 2 (+233%). The isoprostane 15-F 2t -IsoP was associated with low levels of TAC (-18%), amino-thiols, omega-3 PUFAs, and anti-inflammatory CYP450 EPA-derived mediators, such as DiHETEs. The deterioration of antioxidant systems paves the way to the overload of redox and inflammative markers, as triggered by the combined physical and hypoxic stressors. Our data underline the link between oxidative stress and inflammation, which is related to the concept of OxInflammation into the altitude hypoxia fashion.

Altitude hypoxia exposure results in increased sympathetic activity and heart rate due to several mechanisms. Recent studies have contested the validity of heart rate variability (HRV) analysis on sympathetic activity measurement. But the plethora of HRV metrics may provide meaningful insights, particularly if linked with cardiovascular and autonomic nervous system parameters. However, the population-specific nature of HRV and cardiorespiratory response to altitude hypoxia are still missing. Six Italian trekkers and six Nepalese porters completed 300 km of a Himalayan trek. The ECG analysis was conducted at baseline, and before ( bBC ) and after ( aBC ) the high-altitude (HA) circuit. Urine was collected before and after the expedition in Italians, for assessing catecholamines. Heart rate increased with altitude significantly ( p < 0.001) in the Italian group; systolic ( p = 0.030) and diastolic ( p = 0.012) blood pressure, and mean arterial pressure ( p = 0.004) increased with altitude. Instead, pulse pressure did not change, although the Nepalese group showed lower baseline values than the Italians. As expected, peripheral oxygen saturation decreased with altitude ( p < 0.001), independently of the ethnic groups. Nepalese had a higher respiratory rate ( p = 0.007), independent of altitude. The cardiac vagal index increased at altitude, from baseline to bBC ( p = 0.008). Higuchi fractal dimension (HFD) showed higher basal values in the Nepalese group ( p = 0.041), and a tendency for the highest values at bBC . Regarding the urinary catecholamine response, exposure to HA increased urinary levels, particularly of norepinephrine ( p = 0.005, d = 1.623). Our findings suggest a better cardiovascular resilience of the Nepalese group when compared with Italians, which might be due to an intrinsic adaptation to HA, resulting from their job., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Verratti, Tonacci, Bondi, Chiavaroli, Ferrante, Brunetti, Crisafulli and Cerretelli.)

Background: Penile curvature (PC) can be surgically corrected by plication techniques or Nesbit corporoplasty. These shortening techniques can be complicated by post-operative: penile shortening, recurrent PC, palpable suture knots and erectile dysfunction. Furthermore, Nesbit procedures require the use of a penile tourniquet to avoid intraoperative bleeding. This observational study aims to assess the results of Nesbit modified corporoplasty, avoiding intraoperative use of tourniquet without risk of bleeding. The objective is to reduce penile ischemic anatomical and functional damages such as long-term erectile dysfunction., Methods: Between January 2010 and March 2019, a total of 64 patients with congenital penile curvature (CPC) and Peyronie's disease (PD) underwent surgical correction with a Nesbit modified technique first time described by Rolle et al. , with minimal technical differences. The operation notes were retrospectively reviewed. In particular, we evaluated pre- and post-operative erectile functions using IIEF-5 score, penile Doppler ultrasonography and overall patient satisfaction., Results: During operations, no intraoperative bleeding was noted, and no short-term complications such as hematomas or neurovascular bundle lesions were reported. At 6 months, no palpable subcutaneous indurations and no sensory change were detected. Post-operative penile shortening was reported in 38 (59.4%) patients (mean 0.83±0.79 cm), but it did not influence the high overall satisfaction rate of 91.4%. Only 2 patients reported a slightly partial recurrence of curvature (<15%) with no need for a redo surgery. Mean IIEF-5 score increased from 17.1±5.2 to 20.8±3.9 at 6 months and 21.8±3.4 at 12 months (P<0.001 in both cases). Mean PSV also significantly increased at the end of follow-up (28.5±6.1 at baseline vs. 31.0±7.1 at 12 months, P=0.03)., Conclusions: Considering the optimal results in terms of erectile functions increasing and absence of PC recurrence (>15°), we think that Nesbit modified corporoplasty without tourniquet application during reconstruction is a safe and effective surgical procedure for all kind of shortening corporoplasty to reduce the time of penile ischemia, preventing even serious consequences for the normal physiology of erection., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1338). The authors have no conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)

Bondi, Danilo, Vittore Verratti, Raffaella Nori, Laura Piccardi, Giulia Prete, Tiziana Pietrangelo, and Luca Tommasi. Spatial abilities at high altitude: Exploring the role of cultural strategies and hypoxia. High Alt Med Biol . 22: 157-165, 2021. Background: Over the past couple of decades, the number of people of different cultures traveling to places of high altitude (HA) increased. At HA, a decline in cognitive abilities has been described, including spatial skills. However, it is still unknown whether people accustomed to hypobaric hypoxia are less susceptible to cognitive decline. Method: We aimed to determine if three ethnic groups would show any difference in the performance of spatial abilities. Italian trekkers (46.20 ± 15.83 years), Nepalese porters (30.33 ± 8.55 years), and lowlander and highlander Sherpas (30.33 ± 8.55 and 37.00 ± 16.51 years) were tested with a building photograph recognition, a map orienting, and a mental rotation task during a Himalayan expedition. Accuracy and response times were collected at low altitude (LA) and HA. Results: Nepalese performed the worst (photograph task: p  = 0.015, η 2 p  = 0.36; map task: p  = 0.016, η 2 p  = 0.36), but the difference was mitigated after correcting for length of schooling. Participants took more time to respond at LA than in HA condition (photograph task: 24.0 ± 15.3 seconds vs. 12.7 ± 6.3 seconds, p  = 0.008, η 2 p  = 0.57; map task: 12.5 ± 1.8 seconds vs. 7.8 ± 0.6 seconds, p  = 0.038, η 2 p  = 0.40). In the map task, participants performed with greater accuracy at LA (5.1 ± 0.4 vs. 4.4 ± 0.4 number of correct responses, p  = 0.006, η 2 p  = 0.59). Conclusions: Altitude hypoxia elicited impairments in cognitive spatial tasks. This may be due to the inability to acquire new unfamiliar patterns, and to the difficulty in managing a high cognitive workload. The ethnic differences were ascribed to schooling, even we consider the different system of reference usually exploited in each culture (egocentric: dependent, or allocentric: independent from the personal viewpoint), and that Westerners are more likely to focus on specific details of the scene. Further studies should investigate the diverse strategies to complete spatial tasks.

High-altitude exposure leads to many physiological challenges, such as weight loss and dehydration. However, little attention has been posed to the role of nutrition and ethnic differences. Aiming to fulfill this gap, five Italian trekkers and seven Nepalese porters, all males, recorded their diet in diaries during a Himalayan expedition (19 days), and the average daily intake of micro and macro-nutrients were calculated. Bioimpedance analysis was performed five times during the trek; muscle ultrasound was performed before and after the expedition, only for the Italians. The Nepalese group consumed a lot of rice and only Italians consumed cheese. Water intake was slightly over 3000 g/d for both groups. Nepalese diet had a higher density of dietary fibre and lower density of riboflavin, vitamins A, K, and B12. Intake of calcium was lower than recommended levels. Body mass index, waist circumference, fat-free mass, and total body water decreased in both groups, whereas resistance (Rz) increased. Italians reactance (Xc) increased at day 9, whereas that of Nepalese occurred at days 5, 9, and 16. The cross-sectional area of the Vastus lateralis was reduced after the expedition. Specific nutritional and food-related risk factors guidance is needed for diverse expedition groups. Loss of muscle mass and balance of fluids both deserve a particular focus as concerns altitude expeditions.

Global Proprioceptive Resonance (GPR) is a recently developed approach conceived to solicit the various cutaneous mechanoreceptors, through application of mechanical multifocal vibration at low amplitude and at definite body sites, limiting the stimulation of the profound structures. This interventional study evaluated the effects of GPR on cardiorespiratory function during the post-exertional recovery period. A group of volunteers involved in Triathlon (a multisport discipline consisting of sequential swim, cycle, and run disciplines higly demanding in terms of metabolic engagment), underwent two maximal incremental exercise tests until exhaustion followed alternatively to (a) a 13 minutes section of GPR or (b) a standard low intensity exercise acute trend of the same duration. These effects of these two approaches were compared in terms of recovery of: heart rate (HR), respiratory rate (RR), peripheral oxygen saturation (SpO2) and venous lactate concentration (Lac). The physiological parameters (HR, RR, SpO2 and Lac) recorded in the pre-exertion session showed similar values between the 40 volunteers while several differences were recorded in the post-exertion phase. After 6 min of GPR recovery it was recorded a drop in RR below baseline (19.4±4.15 min-1 vs. 12.2± 0.4 min-1; p<0.001) coupled with an increase in peripheral oxygen saturation above the baseline (GPR: 99.0%±0.16% vs. 96.6%±0.77%, p<0.001). Moreover, the most striking result was the drop in lactate concentration measured after 13 min of GPR recovery: 84.5±3.5% in GPR vs 2.9±7.6% reduction in standard recovery (p<0.001). Notably no differences were recorded recovery of heart rate. GPR has promising effects on post-exercise recovery on RR, SpO2 and lactate level on young athletes., Competing Interests: We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

Altitude ascending represents an intriguing experimental model reproducing physiological and pathophysiological conditions sharing hypoxemia as the denominator. The aim of the present study was to investigate fractional oxygen extraction and blood dynamics in response to hypobaric hypoxia and to acute resistance exercises, taking into account several factors including different ethnic origin and muscle groups. As part of the "Kanchenjunga Exploration & Physiology" project, six Italian trekkers and six Nepalese porters took part in a high altitude trek in the Himalayas. The measurements were carried out at low (1,450 m) and high altitude (HA; 4,780 m). Near-infrared spectroscopy (NIRS)-derived parameters, i.e., Tot-Hb and tissue saturation index (TSI), were gathered at rest and after bouts of 3-min resistive exercise, both in the quadriceps and in the forearm muscles. TSI decreased with altitude, particularly in forearm muscles (from 66.9 to 57.3%), whereas the decrement was less in the quadriceps (from 62.5 to 57.2%); Nepalese porters were characterized by greater values in thigh TSI than Italian trekkers. Tot-Hb was increased after exercise. At altitude, such increase appeared to be higher in the quadriceps. This effect might be a consequence of the long-term adaptive memory due to the frequent exposures to altitude. Although speculative, we suggest a long-term adaptation of the Nepalese porters due to improved oxygenation of muscles frequently undergoing hypoxic exercise. Muscle structure, individual factors, and altitude exposure time should be taken into account to move on the knowledge of oxygen delivery and utilization at altitude., (Copyright © 2020 Verratti, Bondi, Mulliri, Ghiani, Crisafulli, Pietrangelo, Marinozzi and Cerretelli.)

Loss of muscle mass of the lower limbs and of the spine extensors markedly impairs locomotor ability and spine stability in old age. In this study, we investigated whether 8 w of neuromuscular electrical stimulation (NMES) improves size and architecture of the lumbar multifidus (LM) and vastus lateralis (VL) along with locomotor ability in healthy older individuals. Eight volunteers (aged 65 ≥ years) performed NMES 3 times/week. Eight sex- and age-matched individuals served as controls. Functional tests (Timed Up and Go test (TUG) and Five Times Sit-to-Stand Test (FTSST)), VL muscle architecture (muscle thickness (MT), pennation angle (PA), and fiber length (FL)), along with VL cross-sectional area (CSA) and both sides of LM were measured before and after by ultrasound. By the end of the training period, MT and CSA of VL increased by 8.6% and 11.4%, respectively. No significant increases were observed in FL and PA. LM CSA increased by 5.6% (left) and 7.1% (right). Interestingly, all VL architectural parameters significantly decreased in the control group. The combined NMES had a large significant effect on TUG (r = 0.50, p = 0.046). These results extend previous findings on the hypertrophic effects of NMES training, suggesting to be a useful mean for combating age-related sarcopenia.

The study aimed at exploring the mechanisms behind blood pressure and heart rate changes upon acute altitude exposure utilizing urinary excretion of biochemical factors involved in cardiovascular regulation. The study was conducted on 12 lowlander native male mountain climbers, living at sea level, exposed to altitudes ranging from 1800 to 5147 m above sea level over 4 days, during their ascent to Mount Ararat (Turkey). Blood pressure (measured by oscillometric method), heart rate, and blood oxygen saturation (SpO 2 ) were recorded at rest (on awakening before food intake), in hypoxic conditions at 4200 m and at sea level before and after the altitude expedition. In the same study conditions (ie before-during-after the expedition), first-voided urinary samples were collected and assayed for 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) and asymmetric dimethylarginine (ADMA) determination. Heart rate, and systolic and diastolic blood pressures were higher (P < .05) at high altitude than at the sea level. Furthermore, both urinary 8-iso-PGF 2α and ADMA were significantly elevated (P < .01) at high altitude and returned to normal levels soon after returning to sea level. A 4-day exposure to high-altitude hypoxia induced a temporary increase in blood pressure and heart rate, confirming previous findings. Blood pressure increase at high altitude was associated with significantly enhanced production of biochemical mediators such as 8-iso-PGF2α, catecholamines, and ADMA, although we could not demonstrate a direct link between these parallel significant changes probably due to the forcefully limited sample size of our study, carried out in challenging environmental conditions at very high altitude., (©2020 Wiley Periodicals LLC.)

Background: Previous studies have shown that music preferences are influenced by cultural "rules", and some others have suggested a universal preference for some features over others., Methods: We investigated cultural differences on the "consonance effect", consisting in higher pleasantness judgments for consonant compared to dissonant chords-according to the Western definition of music: Italian and Himalayan participants were asked to express pleasantness judgments for consonant and dissonant chords. An Italian and a Nepalese sample were tested both at 1,450 m and at 4,750 m of altitude, with the further aim to evaluate the effect of hypoxia on this task. A third sample consisted of two subgroups of Sherpas: lowlanders (1,450 m of altitude), often exposed to Western music, and highlanders (3,427 m of altitude), less exposed to Western music. All Sherpas were tested where they lived., Results: Independently from the altitude, results confirmed the consonance effect in the Italian sample, and the absence of such effect in the Nepalese sample. Lowlander Sherpas revealed the consonance effect, but highlander Sherpas did not show this effect., Conclusions: Results of this pilot study show that neither hypoxia (altitude), nor demographic features (age, schooling, or playing music), nor ethnicity per se influence the consonance effect. We conclude that music preferences are attributable to music exposure., Competing Interests: Luca Tommasi is an Academic Editor for PeerJ, (© 2020 Prete et al.)

Biopsy of human skeletal muscle tissue is a widely used method in many research studies, where 'the tiny percutaneous needle biopsy' (TPNB) is one of the relatively simplest and safest procedures currently available. By using and contrasting ultrasound images of vastus lateralis of young and elderly subjects, this work highlights further the safety aspects of TPNB and stresses the importance of prior ultrasound evaluation of muscle depth and thickness in order to prevent wrong muscle group or tissue sampling in subsequent laboratory analyses., Competing Interests: Conflict of interest The authors declare they have no financial, personal, or other conflicts of interest.We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The study was approved by the Ethics Committee of “G. d’Annunzio” University (protocol n. 16/2019) and was in accordance to the Declaration of Helsinki.

Skeletal muscle aging is a multifactorial process strictly related to progressive weakness. One of the results that were focused on was the fiber phenotype modification and their loss. The physiological muscle recruitment to contraction, basically prosecuted under volitional control, can also be engaged by means of Neuromuscular Electrical Stimulation (NMES). Knowing that the NMES is effective in improving muscle strength in active healthy elderly, the aim was to investigate which physiological modifications were able to produce in the Vastus lateralis muscle and the pathways involved. It was found that NMES increased the cross sectional area and the isometric strength of type II myofibers together with the activated myogenic pathway in order to shift glycolytic toward the oxidative phenotype II myofibers, at a molecular level and with an increase of maximal voluntary contraction (MVC) at a functional level. Using the TaqMan low density array on 48 different genes, we found that NMES specific gene regulation highlighted: (i) increased protein synthesis with respect to protein degradation; (ii) the activation of an apoptotic pathway involved in the differentiation process; (iii) increased regeneration signals; (iv) oxidative enzyme regulation. These pathways were validated via confirmatory RT-PCR for genes involved in the regeneration process as well as Myosin isoforms. We also investigated the oxidative stress status analyzing superoxide anion levels, the protein expression of two different superoxide dismutase and the activity of both catalase and superoxide anion dismutase, being two main antioxidant enzymes. In conclusion, data demonstrates that NMES is effective in producing physiological adaptation on Vastus Lateralis of active healthy elderly as well as providing new insights for further research on elderly who experienced muscle detriment for periodic or permanent immobility., (Copyright © 2019 Mancinelli, Toniolo, Di Filippo, Doria, Marrone, Maroni, Verratti, Bondi, Maccatrozzo, Pietrangelo and Fulle.)

Exposure to high altitude is one of the most widely used models to study the adaptive response to hypoxia in humans. However, little is known about the related effects on micturition. The present study addresses the adaptive urinary responses in four healthy adult lowlanders, comparing urodynamic indexes at Kathmandu [1,450 m above sea level (a.s.l.); K 1450 ] and during a sojourn in Namche Bazar (3,500 m a.s.l.; NB 3500 ). The urodynamic testing consisted of cistomanometry and bladder pressure/flow measurements. Anthropometrics, electrocardiographic, and peripheral capillary oxygen saturation data were also collected. The main findings consisted of significant reductions in bladder power at maximum urine flow by ~30%, bladder contractility index by 13%, and infused volume both at first (by 57%) and urgency sensation (by 14%) to urinate, indicating a reduced cystometric capacity, at NB 3500 . In addition to the urinary changes, we found that oxygen saturation, body mass index, body surface area, and median RR time were all significantly reduced at altitude. We submit that the hypoxia-related parasympathetic inhibition could be the underlying mechanism of both urodynamic and heart rate adaptive responses to high-altitude exposure. Moreover, increased diuresis and faster bladder filling at altitude may trigger the anticipation of being able to void, a common cause of urgency. We believe that the present pilot study represents an original approach to the study of urinary physiology at altitude.

Global Proprioceptive Resonance (GPR) is a recently developed approach conceived to solicit the various cutaneous mechanoreceptors, through application of mechanical multifocal vibration at low amplitude and at definite body sites, limiting the stimulation of the profound structures. This interventional study evaluated the effects of GPR on cardiorespiratory function during the post-exertional recovery period. A group of volunteers involved in Triathlon (a multisport discipline consisting of sequential swim, cycle, and run disciplines higly demanding in terms of metabolic engagment), underwent two maximal incremental exercise tests until exhaustion followed alternatively to (a) a 13 minutes section of GPR or (b) a standard low intensity exercise acute trend of the same duration. These effects of these two approaches were compared in terms of recovery of: heart rate (HR), respiratory rate (RR), peripheral oxygen saturation (SpO2) and venous lactate concentration (Lac). The physiological parameters (HR, RR, SpO2 and Lac) recorded in the pre-exertion session showed similar values between the 40 volunteers while several differences were recorded in the post-exertion phase. After 6 min of GPR recovery it was recorded a drop in RR below baseline (19.4±4.15 min-1 vs. 12.2± 0.4 min-1; p<0.001) coupled with an increase in peripheral oxygen saturation above the baseline (GPR: 99.0%±0.16% vs. 96.6%±0.77%, p<0.001). Moreover, the most striking result was the drop in lactate concentration measured after 13 min of GPR recovery: 84.5±3.5% in GPR vs 2.9±7.6% reduction in standard recovery (p<0.001). Notably no differences were recorded recovery of heart rate. GPR has promising effects on post-exercise recovery on RR, SpO2 and lactate level on young athletes., Competing Interests: We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines.

The phenomenon of strength gain is highly relevant for sarcopenia and clinical aspect linked to aging. Recent advancements drive the interest toward the exercise-related cross-talk between distant tissues. We demonstrated the cross-talk between lower and upper limbs, we named the Bottom-Up Rise Strength Transfer (BURST), mainly linked to endurance training. In our opinion, this effect can be mainly related to systemic factors, likely circulating myokines and extracellular vesicles (recently defined in terms of "exerkines" and "exersomes") whit an eventual concomitant reduction of a sub-clinical chronic inflammation. The neuronal mechanisms, even if to our sight less likely involved in this adaptation, need to be deeply investigated. Further studies are needed to better characterize the exercise-related BURST, concerning the specificity of different protocols and the underlying physiological mechanisms.

Altitude hypoxia is often associated with impairment of human reproduction. In this study, hormones and macrophage migration inhibitory factor (MIF, a proinflammatory cytokine with key roles in human reproduction) were determined in seven regularly menstruating, lowlander native women living at sea level participating in 14 days of trekking at moderate and high altitude. Blood and saliva samples were collected from each subject at high altitude (5050 m a.s.l. [above sea level]), and at sea level before and after the expedition. Testosterone level was lowered by high altitude and was restored after the end of the expedition, while progesterone decreased significantly in all participants at the end of the expedition, although most of the participants were in the luteal phase. The salivary concentration of MIF decreased greatly at altitude, but its levels were completely restored after the return to sea level. Our findings showed high sensitivity and rapid changes in the determined parameters in response to the high-altitude hypoxic environment, particularly MIF., (© 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)

The aim of this study was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 wk of NMES were allowed to proliferate to provide myogenic populations of adult stem cells [myogenic precursor cells (MPCs)]. These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca 2+ concentrations, and their expression of myogenic regulatory factors ( PAX3, PAX7, MYF5, MYOD , and MYOG ) and micro-RNAs (miR-1, miR-133a/b, and miR-206). The oxidative status of these MPCs was evaluated through superoxide anion production and superoxide dismutase and glutathione peroxidase activities. On dissected single skeletal myofibers, the nuclei were counted to determine the myonuclear density, the fiber phenotype, cross-sectional area, and tension developed. The MPCs obtained after NMES showed increased proliferation rates along with increased cytoplasmic free Ca 2+ concentrations and gene expression of MYOD and MYOG on MPCs. Muscle-specific miR-1, miR-133a/b, and miR-206 were upregulated. This NMES significantly reduced superoxide anion production, along with a trend to reduction of superoxide dismutase activity. The NMES-dependent stimulation of muscle regeneration enhanced satellite cell fusion with mature skeletal fibers. NMES improved the regenerative capacity of skeletal muscle in elderly subjects. Accordingly, the skeletal muscle strength and mobility of NMES-stimulated elderly subjects significantly improved. NMES may thus be further considered for clinical or ageing populations. NEW & NOTEWORTHY The neuromuscular electrical stimulation (NMES) effect on skeletal muscle regeneration was assessed in healthy elderly subjects for the first time. NMES improved the regenerative capacity of skeletal muscle through increased myogenic precursor cell proliferation and fusion with mature myofibers. The increased cytoplasmic free Ca 2+ concentration along with MYOD , MYOG , and micro-RNA upregulation could be related to reduced O 2 ·- production, which, in turn, favors myogenic regeneration. Accordingly, the skeletal muscle strength of NMES-stimulated lower limbs of healthy elderly subjects improved along with their mobility., (Copyright © 2017 the American Physiological Society.)

There is scientific evidence to suggest a correlation between hypoxia and the physiology of micturition. During a Himalayan Scientific and Mountaineering Expedition, we performed tests to investigate the functional interactions between altitude hypoxia and uroflowmetry parameters in women. The tests were carried out in seven women (36.3 ± 7.1 yr) from normoxic [1,340 meters above sea level (m a.s.l.)] to hypoxic conditions (up to 5,050 m a.s.l.) and during the return descent. The following measures were determined: uroflowmetry parameters and saturation of peripheral oxygen (SpO2 ). As expected, SpO2 decreased from 97.7 to 77.8% with increasing altitude. Micturition flow time, flow volume, and voiding time increased with altitude (P < 0.04 for all), indicating a negative correlation with SpO2 In conclusion, in young adult women, micturition physiological parameters were affected during adaptation to hypoxia; the correlation with SpO2 strongly suggests a role of hypoxia in these changes. These data could help to support the design of new strategies for both prevention and medical treatment. An example of the latter might be hyperbaric oxygen therapy, which in some studies has proved able to reduce the symptoms in patients with hypoxic bladder., (Copyright © 2016 the American Physiological Society.)

Aim: The aim of this study was to determine whether a 14-day trekking expeditions, in high altitude hypoxic environment, triggers redox disturbance at the level of satellite cells (adult stem cells) in young women., Methods: We collected muscle biopsies from Vastus Lateralis muscle for both single fiber analysis and satellite cells isolation. The samples collected before (PRE-Hypoxia) and after (POST-Hypoxia) the trekking in the Himalayas were compared. Satellite cells were investigated for oxidative stress (oxidant production, antioxidant enzyme activity, and lipid damage), mitochondrial potential variation, gene profile of HIF, and myogenic transcription factors (Pax7, MyoD, myogenin), and miRNA expression (miR-1, miR-133, miR-206)., Results: The nuclear domain analysis showed a significant fusion and consequent reduction of the Pax7(+) satellite cells in the single mature fibers. The POST-Hypoxia myoblasts obtained by two out of six volunteers showed high superoxide anion production and lipid peroxidation along with impaired dismutase and catalase and mitochondrial potential. The transcription profile and miRNA expression were different for oxidized and non-oxidized cells., Conclusions: The present study supports the phenomenon of hypobaric-hypoxia-induced oxidative stress and its role in the impairment of the regenerative capacity of satellite cells derived from the V. Lateralis muscle of young adult female subjects.

Difficulties in handwriting are often reported in children with developmental coordination disorder, and they represent an important element in the diagnosis. The present study was aimed at investigating the relation between motor coordination and handwriting skills, and to identify differences in handwriting between children without and with coordination difficulties. In particular, we asked whether visual-spatial skills have a role as mediating variables between motor coordination and handwriting. We assessed motor coordination as well as graphic abilities in children aged 7-10 years. Moreover, we evaluated their visual-motor integration, visual-spatial skills, and other cognitive abilities (memory and planning). We found no relation between motor coordination and handwriting skills, while visual-spatial skills (measured by a visual-constructive task) were related with both. Our conclusion is that visual-spatial skills are involved both in general motor coordination and in handwriting, but the relationship involves different aspects in the two cases.

Objective: To explore the effect of physical exercise at high altitudes (HA) on male reproductive system., Design: Prospective study., Setting: Andrology Clinic, University of L'Aquila, Italy., Patient(s): Seven male mountaineers involved in an expedition at 5,900 m., Intervention(s): Semen analysis, sperm DNA fragmentation with flow cytometry, and reproductive hormone levels., Main Outcome Measure(s): Hormone levels were evaluated at sea level (SL) at baseline (SL-pre), after 22 days of exercise at HA (intermediate), and after 10 days upon reaching SL (SL-post). Sperm parameters, percentage of sperm with fragmented DNA, and body composition measures were evaluated at SL-pre and at SL-post., Result(s): A reduction of sperm concentration, of body mass index (BMI), of waist circumference, and of percentage of body fat was observed at SL-post compared with SL-pre values. Increased levels of FSH and PRL were observed at the intermediate point, and normalized at SL-post, whereas T was higher at SL-post compared with SL-pre levels., Conclusion(s): Physical exercise at HA is associated with a testicular dysfunction leading to a reduced sperm concentration probably through an altered spermiation. The improved body composition after physical exercise might explain the higher T levels observed after the expedition., (Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Recent studies underscore the importance of oxygen supply in bladder cancer. Tumour growth stimulates the production of vasoactive factors to increase oxygen delivery to tissues by vasodilatation. Any vasoconstrictor mediator could impair this vasodilatation reducing the oxygen supply. 8-Iso-PGF2 alpha is a potent vasoconstrictor agent. The aim of this work is to determine 8-Iso-PGF2 alpha release in healthy bladder mucosa and in superficial bladder cancer in order to investigate a pathophysiological vasoconstrictor answer of the superficial bladder cancer. The study was conducted on a sample of 12 patients; for every subject studied 8-Iso-PGF2 alpha release was assayed in healthy bladder mucosa and in superficial bladder tumour. 8-Iso-PGF2 alpha release was significantly reduced (p less than 0.001) in superficial bladder cancer compared with healthy bladder mucosa. The inhibition of the production of a powerful vasoconstrictor such as 8-Iso-PGF2 alpha in the vascular homeostatic mechanism of bladder cancer can represent a response of the tumor tending to contrast an antagonist effect of vasodilatation and the necessary to support the oxygen supply.

Depending on the absolute altitude and the duration of exposure, a high altitude environment induces various cellular effects that are strictly related to changes in oxidative balance. In this study, we used in vitro isolated peripheral blood lymphocytes as biosensors to test the effect of hypobaric hypoxia on seven climbers by measuring the functional activity of these cells. Our data revealed that a 21-day exposure to high altitude (5000 m) (1) increased intracellular Ca(2+) concentration, (2) caused a significant decrease in mitochondrial membrane potential, and (3) despite possible transient increases in intracellular levels of reactive oxygen species, did not significantly change the antioxidant and/or oxidative damage-related status in lymphocytes and serum, assessed by measuring Trolox-equivalent antioxidant capacity, glutathione peroxidase activity, vitamin levels, and oxidatively modified proteins and lipids. Overall, these results suggest that high altitude might cause an impairment in adaptive antioxidant responses. This, in turn, could increase the risk of oxidative-stress-induced cellular damage. In addition, this study corroborates the use of peripheral blood lymphocytes as an easily handled model for monitoring adaptive response to environmental challenge.

Hypoxia transiently increases transcription of the gene encoding heme oxygenase-1 (HO-1) and potently activates production of endothelin-1 (ET-1), the latter of which plays a central role in cellular adaptation to hypoxia. The ventilatory response to hypoxia attenuates with aging, and decreased responsiveness to hypoxia is seen in the aged vs. young rats, suggesting that the functionality of the oxygen-sensitive mechanism is age-dependent. In the present study, we examined the effects of aging on the expression of HO-1 and ET-1 in the carotid body, which is a small cluster of chemoreceptors and supporting cells that measure changes in the composition of arterial blood flowing through it. Our results revealed that HO-1 and ET-1 were expressed in carotid bodies of both young and old rats, although less so in the old ones. Exposure to chronic intermittent hypoxia significantly increased both HO-1 and ET-1 immunoreactivity in both young and old carotid body tissues, with the persisting age-dependent inequality to the disadvantage of old age. Considering that ET-1 is capable of enhancing intermittent hypoxia-induced chemosensory responses by the carotid body, our results suggest that decreased induction of ET-1 and HO-1 during aging could form the basis for age-related reductions in chemosensory discharge.