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Several benefits can be acquired through physical exercise. Different classes of biomolecules are responsible for the cross-talk between distant organs. The secretome of skeletal muscles, and more widely the field of organokines, is ever-expanding. “Exerkine” has emerged as the umbrella term covering any humoral factors secreted into circulation by tissues in response to exercise. This review aims at describing the most interesting exerkines discovered in the last 3 years, which are paving the way for both physiological novel insights and potential medical strategies. The five exerkines identified all play a significant role in the healthy effect of exercise. Specifically: miR-1192, released by muscles and myocardium into circulation, by modulating cardioprotective effect in trained mice; miR-342-5p, located into exosomes from vascular endothelial cells, also a cardioprotective miRNA in trained young humans; apelin, released by muscles into circulation, involved in anti-inflammatory pathways and muscle regenerative capacity in rats; GDF-15, released into circulation from yet unknown source, whose effects can be observed on multiple organs in young men after a single bout of exercise; oxytocin, released by myoblasts and myotubes, with autocrine and paracrine functions in myotubes. The systemic transport by vesicles and the crosstalk between distant organs deserve a deep investigation. Sources, targets, transport mechanisms, biological roles, population samples, frequency, intensity, time and type of exercise should be considered for the characterization of existing and novel exerkines. The “exercise is medicine” framework should include exerkines in favor of novel insights for public health.

A complex balanced equilibrium of the bacterial ecosystems exists in the oral cavity that can be altered by tobacco smoking, psychological stressors, bad dietary habit, and chronic periodontitis. Oral dysbiosis can promote the onset and progression of oral squamous cell carcinoma (OSCC) through the release of toxins and bacterial metabolites, stimulating local and systemic inflammation, and altering the host immune response. During the process of carcinogenesis, the composition of the bacterial community changes qualitatively and quantitatively. Bacterial profiles are characterized by targeted sequencing of the 16S rRNA gene in tissue and saliva samples in patients with OSCC. Capnocytophaga gingivalis, Prevotella melaninogenica, Streptococcus mitis, Fusobacterium periodonticum, Prevotella tannerae, and Prevotella intermedia are the significantly increased bacteria in salivary samples. These have a potential diagnostic application to predict oral cancer through noninvasive salivary screenings. Oral lactic acid bacteria, which are commonly used as probiotic therapy against various disorders, are valuable adjuvants to improve the response to OSCC therapy.

Exposure to high-altitude hypoxia leads to complex physiological and molecular adaptations, particularly in skeletal muscle. MicroRNAs (miRNAs), including muscle-enriched (myomiRNAs) and hypoxia-responsive (hypoxamiRNAs), play critical roles in regulating these responses. We investigated miRNA expression changes in the skeletal muscle of healthy, non-smoking Italian adults (mean age 36.7 ± 12.4 years) participating in the Himalayan expedition “Lobuche Peak—Pyramid Exploration & Physiology” conducted in the Sagaramāthā (Mount Everest) National Park, Nepal. The peak overnight stay altitude was ≈5000 m at the Pyramid International Laboratory—Observatory. Muscle biopsies were taken before and after the expedition from Vastus lateralis, at one-third of the distance from the upper margin of the rotula to the anterior superior iliac spine. Small RNA sequencing was used to profile differentially expressed miRNAs. Several miRNAs were differentially expressed (exploratory analysis), suggesting potential involvement in hypoxia-related adaptation. These encompass both canonical myomiRNAs (e.g., miR-206, miR-486-5p) and hypoxamiRNAs (e.g., miR-378a-5p, miR-199a-3p, let-7b-5p). In enrichment analysis, we found several connections between miRNAs and pathways that may play a role in physiological regeneration or differentiation in muscle cells. Among functions, focal adhesion (p-value = 0.001), regulation of actin cytoskeleton (p-value = 0.026), Rap-1 (p-value = 0.007), cAMP (p-value = 0.017), MAPK (p-value = 0.019), and Hippo (p-value = <0.001) signaling pathways were predicted to be the most targeted. These findings provide preliminary insights into physiological adaptation, requiring confirmation in larger and controlled cohorts.

Usually, settings of normobaric hypoxia underestimate the environmental hypoxia they are supposed to reproduce. The likely steady state of water vapour pressure within the human airways keeps the partial pressure of inspired oxygen very close to the assumed value, but this does not apply to the calculation of environmental hypoxia or experimental settings with other species. Additionally, in confined spaces, the CO 2 can exceed permissible exposure limits unless sufficient ventilation is calculated and required. The conversion of parts per million (ppm) to milligrams per metre cubed in dry air is facilitated by the general formula: , thus overcoming the common assumptions of dry air at 1 atm and 25°C. The use of spot values (i.e., single measurements taken at a specific point in time), especially those of oxyhaemoglobin saturation, should be avoided, given the significance of physiological fluctuations. By considering the assumptions of simulated altitude hypoxia, the calculations or estimations of the amount of carbon dioxide in the inspired air in confined spaces, and the avoidance of spot values, the physiological response will be more valid and informative. What is the central question of this study? What are the biases that affect normobaric hypoxia studies? What is the main finding and its importance? Although current estimates are acceptable for inhaled oxygen, they do not accurately account for environmental oxygen. Carbon dioxide overexposure is possible, but its levels are not necessarily monitored. The practices for taking spot measurements or averaging data from continuous monitoring do not account for physiological fluctuations or the variability inherent in continuous monitoring.

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.

Children are not fully able to associate severity and injury probability with cognitive, emotional, and social factors. This study focused on physical risk-taking by exploring the associations between risk propensity and physical balance during the developmental age. Specifically, sixteen girls aged 58 to 108 months (≈ 5 to 9 years), of whom 43.75% normal-weighted and all were active in rhythmic gymnastics, were subjected to a combination of physical tests (i.e., static and dynamic) and questionnaires to evaluate balance, sensation seeking, and risk propensity, respectively. Our results showed that the better the static balance, the higher the sensation seeking and risk propensity, while age had a negligible effect on these associations. Our study suggested that balance affects propensity towards risky behaviors in children.

The dynamics of physiological systems are impacted by both exercise and hypoxia. Network models can be used to map the interactions between various physiological components in environmental physiology and exercise using the concepts of information theory. This cross‐over study compared three normobaric conditions: control, simulated altitude of 2500 m (fraction of inspired oxygen: FiO2 ${F_{{\\mathrm{i}}{{\\mathrm{O}}_2}}}$≈ 15.1%) and 3500 m (FiO2 ${F_{{\\mathrm{i}}{{\\mathrm{O}}_2}}}$≈ 13.5%), and rest vs. isometric exercise through the lens of network physiology. The 12 participants (6 M and 6 F; 22.25 ± 2.42 years; 23.01 ± 3.24 kg/m2) spent ∼30 min in a tent coupled to an altitude simulator, whose last 3 min consisted of a series of nine unilateral isometric maximal contractions of quadriceps. A metabolic system in breath‐by‐breath mode was used to register cardiorespiratory variables. In‐degree, out‐degree, and transfer entropy (TE) were computed to capture the information flow between variables. A weighted Jaccard Similarity Index was used to assess network similarities. The increase of V̇O2 ${\\dot V_{{{\\mathrm{O}}_2}}}$in exercise over rest was slightly more prominent during hypoxia (P = 0.054, η2p = 0.232). Normoxia–hypoxia networks were more similar during resting than exercise. Rest–exercise networks were less similar to each other during simulated altitude of ∼2500 m (P = 0.008, η2p = 0.353). Neither TE during rest nor during exercise nor the SpO2 ${S_{{\\mathrm{p}}{{\\mathrm{O}}_2}}}$ /FiO2 ${F_{{\\mathrm{i}}{{\\mathrm{O}}_2}}}$ratio significantly predicted the occurrence of symptoms. Unexpectedly, compared to mild‐grade hypoxia, low‐grade hypoxia induced more changes in physiological connectivity, with the majority of the connections converging on putative hidden nodes that we suggest are oxygen delivery‐dependent. Network approaches could offer new developments in exercise and environmental physiology. What is the central question of this study? Can network models reveal original findings on how physiological systems are interconnected integrated stressors exposure to hypoxia and exercise? What is the main finding and its importance? The low‐grade hypoxia promoted changes in physiological interconnectedness more than mild grade hypoxia; physical effort triggers physiological variability differentially across hypoxic conditions.

Research indicates that the performance is enhanced in situations involving rapid movements at high altitude. However, maintaining equilibrium and walking economically in low‐oxygen conditions are often impaired. The objective of this study was to evaluate the impact of trekking at high altitudes on static balance, vertical jump, gait, and maximal strength symmetry by using portable technologies. Fifteen healthy travelers (eight men and seven women, aged 41.67 ± 14.71 years) completed a high‐altitude trekking expedition up to 5000 m and were tested for one‐leg standing balance, gait, repeated counter‐movement jumps, and symmetry of maximum plantar flexion strength of the ankle at peak altitude (HA) and at low altitude (before and after the high‐altitude trek, LApre and LApost). The strategy developed for balance maintenance was focused on sagittal tilt. Gait analysis revealed an increase in hip range of motion in the sagittal and transverse planes at HA. Jump height increased from LApre to HA and LApost, while maximal strength symmetry exhibited non‐homogeneous inter‐individual changes. The observed increments in vertical jump were attributed to the beneficial effect of trekking, rather than to reduced air density. The use of portable instruments represents a significant advancement for research into motor control and physical performance at high altitude.

Prior investigations concerning finishers of the Tor des Géants (TDG) have demonstrated oxi‐inflammatory response. MicroRNAs (miRNAs) have been identified as prospective biomarkers for oxi‐inflammatory and stress responses. This study addressed the acute responses concerning salivary miRNAs, circulating redox markers and urinary exercise‐induced markers during the 2019 TDG. It included seven healthy male participants who successfully completed the race. Biological specimens (blood, saliva, and urine) were collected 1–2 days prior to the race and immediately post‐completion, to assess redox system and glycemia from capillary blood, creatinine and neopterin concentrations from urine, and salivary hsa‐miR‐210 and hsa‐miR‐21. Circulating reactive oxygen species production increased, whereas total antioxidant capacity remained stable. Urinary creatinine and neopterin increased subsequent to the race. Nevertheless, salivary expression levels for both miR‐21 and miR‐210 displayed heterogeneity among participants. Variations in miR‐210 were significantly correlated with changes in heart rate. The extreme mountain ultramarathon incited cumulative stress reflective of muscle damage and immune response activation. Salivary miR‐21 and miR‐210 did not demonstrate acute alterations, indicating that they may not serve as highly responsive markers for the combined hypoxia‐strenuous exercise stressor; this finding may suggest the existence of adaptive mechanisms in finishers that facilitate their capacity to manage extreme challenges.

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. 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. 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. 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.