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Extracellular vesicles (EVs) enriched with bioactive molecules have gained considerable attention in nanotechnology because they are critical to intercellular communication while maintaining low immunological impact. Among biological matrices, urine has emerged as a noninvasive source of extracellular-contained liquid biopsy, currently of interest as a readout for physiological adaptations. Therefore, we aimed to evaluate chronic adaptations of endurance sport practice in terms of urinary EV parameters and evaluated by food consumption assessment. Two balanced groups of 13 inactive controls vs. triathlon athletes were enrolled; their urinary EVs were obtained by differential ultracentrifugation and analyzed by dynamic light scattering and transmission electron and atomic force microscopy. The cargo was analyzed by means of purine and miRNA content through HPLC-UV and qRT-PCR. Specific urinary EV signatures differentiated inactive versus endurance-trained in terms of peculiar shape. Particularly, a spheroid shape, smaller size, and lower roughness characterize EVs from triathletes. Metabolic and regulatory miRNAs often associated with skeletal muscle (i.e., miR378a-5p, miR27a-3p, miR133a, and miR206) also accounted for a differential signature. These miRNAs and guanosine in urinary EVs can be used as a readout for metabolic status along with the shape and roughness of EVs, novel informative parameters that are rarely considered. The network models allow scholars to entangle nutritional and exercise factors related to EVs’ miRNA and purine content to depict metabolic signatures. All in all, multiplex biophysical and molecular analyses of urinary EVs may serve as promising prospects for research in exercise physiology.

Altitude hypoxia can impair sensory and cognitive functions, from causing slowed responses to sensory hallucinations. In a field study, we tested 12 expeditioners at varied altitudes (low: 1696 m; high: 4556 m) with a simple auditory detection task and a dichotic listening paradigm in which a voice was presented, lateralized, within a binaural white noise stream. Slower reaction times and a reduced right ear advantage might be expected at high (vs. low) altitude, due to hypoxia. The participants’ performances on both tasks did not differ between conditions, revealing that these functions are resistant to short-term hypoxia in young healthy adults.

Introduction: Since decades, the “Mozart effect” has been studied. However, the diverse effects of Mozart’s music components have not been yet defined. Authors aimed to identify a differential response to short-term exposure to Mozart’s music, or to its rhythmic signature only, on subjective and objective measures. Methods: The Mozart Sonata in A major K 331 (Mozart), the same piece consisting only of beat (Destructured), and duration-matched silence were administered to 25 healthy young adults, stood supine in a relaxing setting. The Italian Mood Scale questionnaire was administered before and after each listening. Heart rate variability (HRV) metrics were calculated from ECG recording, and breath flow was registered during experiments. Results: After Destructured, there was no change of fatigue and tension. After Mozart, fatigue was significantly reduced (and a tendency appeared for tension), whereas vigor was not. Breathing rate tended to be higher during Mozart. The nonlinear parameter HFD of HRV analysis, even though not significantly, was slightly lower during Destructured; Poincaré plots SD1 and SD2 tended to be lower during Mozart. Discussion/Conclusion: Mozart’s music may allow to maintain arousal during relaxing condition. Psychological response of music and physiological dynamics were not necessarily entangled. Musical pieces based on individual physiological signature may lead musical psychological interventions.

The relationship between prostatic chronic inflammation (PCI) and prostate cancer (PCa) is unclear and controversial. Some authors reported that a history of chronic prostatitis may be correlated with PCa induction, while others associate chronic inflammation with less aggressive disease or consider inflammation as a possible protective factor against PCa. Four different types of prostatitis are known: bacterial acute prostatic inflammation, bacterial chronic prostatic inflammation, abacterial prostatitis/chronic pelvic pain syndrome, and asymptomatic prostatic chronic inflammation. Prostatic inflammation is underestimated during daily clinical practice, and its presence and degree often go unmentioned in the pathology report of prostate biopsies. The goal of this report is to further our understanding of how PCI influences the biology of PCa. We investigated the main pathogenetic mechanisms responsible for prostatic inflammation, including the cellular response and inflammatory mediators to describe how inflammation modifies the prostatic environment and can lead to benign or malignant prostatic diseases. We found that prostatic inflammation might have a pivotal role in the pathogenesis of prostatic diseases. Details about PCI in all prostate biopsy reports should be mandatory. This will help us better understand the prostatic microenvironment pathways involved in PCa biology, and it will allow the development of specific risk stratification and a patient-tailored therapeutic approach to prostatic diseases.

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, η2p = 0.36; map task p = 0.016, η2p = 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, η2p = 0.57; map task 12.5 ± 1.8 seconds vs. 7.8 ± 0.6 seconds, p = 0.038, η2p = 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, η2p = 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.

Background Strength training as neuromuscular electrical stimulation (NMES) is effective in counteracting age-related postural impairments in elderly. However, it remains unknown whether training different muscle groups would entail in different adaptations. Aim To evaluate the effect of NMES training on balance function in healthy inactive elderly, targeting paravertebral muscles, in addition to thigh muscles. Methods Eleven healthy elderly were trained with NMES for 8 week allocated to combined training (CT: quadriceps and lumbar paraspinal muscles) or to quadriceps training (QT), after completing lifestyle questionnaire and spine morphology measurements. Functional balance, static stabilometry, and isometric strength tests were assessed before and after the training period. Results and conclusion The CT group showed a greater improve in static balance control, i.e., reducing the CEA of the CoP displacement from 99 ± 38 to 76 ± 42 mm2 (Cohen’s d = 0.947). Benefits for improving static balance through CT might be due to NMES training, which increases spinal stabilization.

Altitude hypoxia induces changes in iron homeostasis with serum ferritin (sFER) response being recently linked to erythropoiesis. The main aim of this study was to investigate sFER and Vitamin D (Vit D) response to hypobaric hypoxia, taking into account factors including nutrition and ethnic origin. As part of a "Kanchenjunga ExplorationPhysiology" project, 6 Italian trekkers and 6 Nepalese porters took part in a 19-days long altitude trek in the Himalayas self-recording daily food consumption. Blood samples were collected and analyzed before and after the trek for sFER and Vit D. A web-based system calculated the dietary intake, generating reports that were used for later statistical analyses. sFER decreased after the trek (on average by 26%

The Wingate anaerobic test measures the maximum anaerobic capacity of the lower limbs. The energy sources of Wingate test are dominated by anaerobic metabolism (~ 80%). Chronic high altitude exposure induces adaptations on skeletal muscle function and metabolism. Therefore, the study aim was to investigate possible changes in the energy system contribution to Wingate test before and after a high-altitude sojourn. Seven male climbers performed a Wingate test before and after a 43-day expedition in the Himalaya (23 days above 5.000 m). Mechanical parameters included: peak power (PP), average power (AP), minimum power (MP) and fatigue index (FI). The metabolic equivalents were calculated as aerobic contribution from O2 uptake during the 30-s exercise phase (WVO2), lactic and alactic anaerobic energy sources were determined from net lactate production (WLa) and the fast component of the kinetics of post-exercise oxygen uptake (WPCr), respectively. The total metabolic work (WTOT) was calculated as the sum of the three energy sources. PP and AP decreased from 7.3 ± 1.1 to 6.7 ± 1.1 W/kg and from 5.9 ± 0.7 to 5.4 ± 0.8 W/kg, respectively, while FI was unchanged. WTOT declined from 103.9 ± 28.7 to 83.8 ± 17.8 kJ. Relative aerobic contribution remained unchanged (19.9 ± 4.8% vs 18.3 ± 2.3%), while anaerobic lactic and alactic contributions decreased from 48.3 ± 11.7 to 43.1 ± 8.9% and increased from 31.8 ± 14.5 to 38.6 ± 7.4%, respectively. Chronic high altitude exposure induced a reduction in both mechanical and metabolic parameters of Wingate test. The anaerobic alactic relative contribution increased while the anaerobic lactic decreased, leaving unaffected the overall relative anaerobic contribution to Wingate test.

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.

The adaptation of olfaction to extreme environments is an area of limited understanding. This study aimed to get insights into the factors that constrain olfactory function at high altitudes. To this end, we compared the results of smell tests performed on the same subjects at low (665 m) and high altitude (4,780 m) during the "Kanchenjunga Exploration and Physiology" project in the Himalayas. The most distinct adaptive differences found at high altitude were reductions in the odor intensity, color-odor bimodal association, and memory, and increases in flavor perception. Physiological adaptations of the sense of smell resulting from exposure to hypoxia at altitude may have explanatory validity in unraveling the mechanisms that shape changes in olfactory function in the processes of aging and neurodegenerative diseases.

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.

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.

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°), 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.

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.

Altitude exposure affects hormonal homeostasis, but the adaptation of different populations is still not finely defined. This study aims to compare the mid-term effects of combining physical activity and altitude hypoxia on hormonal profiles in foreign trekkers coming from Italy versus indigenous Nepalese porters during a Himalayan trek. Participants (6 Italians and 6 Nepalese) completed a 300 km distance in 19 days of an accumulated altitude difference of 16,000 m, with an average daily walk of 6 h. The effect of high altitude on hormonal pathways was assessed by collecting blood samples the day before the expedition and the day after its completion. Foreign trekkers had an additional follow-up sample collected after 10 days. The findings revealed a different adaptation of thyroidal and gonadal axes to mid-term strenuous physical activity combined with high-altitude hypobaric hypoxia. The thyroid function shifted to the protective mechanism of low free triiodothyronine (FT3), whereas the gonadal axis was suppressed. The Italian trekkers and Nepalese porters had lower total testosterone and 17-β-estradiol levels after the expedition. At the follow-up, the Italians had increased testosterone values. Prolactin secretion decreased in the Italians but increased in the Nepalese. We conclude that exposure to high-altitude affects the hormonal axes. The effect seems notably pronounced for the hypothalamus-pituitary gonadal axis, suppressed after high-altitude exposure.

Objective: Occlusal disturbances affect human posture and sports performance. This study aimed to monitor biomechanical adaptations to personalized occlusal splints.Methods: Splints were customized...

Hypoxia alters micturition, which influences bladder function by involving different neurological and humoral systems. In this study we assessed the mid-term effects of altitude hypoxia on uroflowmetry in healthy male lowlander native Nepali porters and Italian trekkers, four each, who coattended a Himalayan expedition. All the participants completed a 19-day trek along a demanding route with ascent and descent at the Kanchenjunga Mountain. They underwent micturition and urodynamic analysis twice, at low altitude of 665 m a.s.l. and high altitude of 4,750 m a.s.l. Statistical comparisons considered the altitude effects (low vs. high) and ethnicity (Italian vs. Nepali). Food consumption was recorded, and water and energy intake were calculated. We found trends of borderline significance in the mean urinary flow rate (Qmean) (p = 0.058; effect size η2 p = 0.478) and in Qmax to the advantage of the Nepali. There was no evidence of differences when comparing time to Qmax and urine volume at Qmax and Qmean for altitude or altitude × ethnicity. In addition, there was a lonely female participant, who, analyzed as a case report, showed increased Qmean at high altitude. Older age mitigated while energy intake potentiated the ethnic differences noted in uroflowmetry. We conclude that altitude hypoxia rather inappreciably affects micturition in healthy men. However, a trend for possible ethnic differences raises worthy of note perspectives on adaptive ability of micturition. Also, dietary intake and age should be considered as confounding elements when evaluating micturition.

Altitude exposure affects hormonal homeostasis, but the adaptation of different populations is still not finely defined. This study aims to compare the mid-term effects of combining physical activity and altitude hypoxia on hormonal profiles in foreign trekkers coming from Italy versus indigenous Nepalese porters during a Himalayan trek. Participants (6 Italians and 6 Nepalese) completed a 300 km distance in 19 days of an accumulated altitude difference of 16,000 m, with an average daily walk of 6 h. The effect of high altitude on hormonal pathways was assessed by collecting blood samples the day before the expedition and the day after its completion. Foreign trekkers had an additional follow-up sample collected after 10 days. The findings revealed a different adaptation of thyroidal and gonadal axes to mid-term strenuous physical activity combined with high-altitude hypobaric hypoxia. The thyroid function shifted to the protective mechanism of low free triiodothyronine (FT3), whereas the gonadal axis was suppressed. The Italian trekkers and Nepalese porters had lower total testosterone and 17-β-estradiol levels after the expedition. At the follow-up, the Italians had increased testosterone values. Prolactin secretion decreased in the Italians but increased in the Nepalese. We conclude that exposure to high-altitude affects the hormonal axes. The effect seems notably pronounced for the hypothalamus-pituitary gonadal axis, suppressed after high-altitude exposure.

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.

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.