Journal Description
Physiologia
Physiologia
is an international, peer-reviewed, open access journal on physiology published quarterly online by MDPI.
- Open Access free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within ESCI (Web of Science), AGRIS, and other databases.
- Journal Rank: JCR - Q2 (Physiology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 18.5 days after submission; acceptance to publication is undertaken in 3.8 days (median values for papers published in this journal in the first half of 2025).
- Recognition of Reviewers: APC discount vouchers, optional signed peer review and reviewer names are published annually in the journal.
- Physiologia is a companion journal of Life.
Impact Factor:
2.3 (2024);
5-Year Impact Factor:
2.3 (2024)
Latest Articles
Real-Time Electroencephalography-Guided Binaural Beat Audio Enhances Relaxation and Cognitive Performance: A Randomized, Double-Blind, Sham-Controlled Repeated-Measures Crossover Trial
Physiologia 2025, 5(4), 44; https://doi.org/10.3390/physiologia5040044 (registering DOI) - 24 Oct 2025
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Background/Objectives: Binaural beat audio has gained popularity as a non-invasive tool to promote relaxation and enhance cognitive performance, though empirical support has been inconsistent. We developed a novel algorithm integrating real-time electroencephalography (EEG) feedback to dynamically tailor binaural beats to induce relaxed brain
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Background/Objectives: Binaural beat audio has gained popularity as a non-invasive tool to promote relaxation and enhance cognitive performance, though empirical support has been inconsistent. We developed a novel algorithm integrating real-time electroencephalography (EEG) feedback to dynamically tailor binaural beats to induce relaxed brain states. This study aimed to examine the efficacy and feasibility of this algorithm in a clinical trial. Methods: In a randomized, double-blinded, sham-controlled crossover trial, 25 healthy adults completed two 30 min sessions (EEG-guided intervention versus sham). EEG (Fp1) was recorded using a consumer-grade single-electrode headset, with auditory stimulation adjusted in real time based on EEG data. Outcomes included EEG frequency profiles, stop signal reaction time (SSRT), and novelty encoding task performance. Results: The intervention rapidly reduced dominant EEG frequency in all participants, with 100% achieving <8 Hz and 96% achieving <4 Hz within median 7.4 and 9.0 min, respectively. Compared to the sham, the intervention was associated with an faster novelty encoding reaction time (p = 0.039, dz = −0.225) and trends towards improved SSRT (p = 0.098, dz = −0.209), increased boundary separation in stop trials (p = 0.065, dz = 0.350), and improved inhibitory drift rate (p = 0.067, dz = 0.452) within the limits of the exploratory nature of these findings. Twenty-four (96%) participants reached a target level of <4 Hz with the intervention, while none reached this level with the sham. Conclusions: Real-time EEG-guided binaural beats may rapidly induce low-frequency brain states while potentially preserving or enhancing aspects of executive function. These findings support the feasibility of personalized, closed-loop auditory entrainment for promoting “relaxed alertness.” The results are preliminary and hypothesis-generating, warranting larger, multi-channel EEG studies in ecologically valid contexts.
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Open AccessBrief Report
The Effects of Spermidine on Functional and Transcriptomic Markers in Human Primary Keratinocytes
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Derick A. Anglin, Madison L. Mattingly, Nicholas J. Kontos and Michael D. Roberts
Physiologia 2025, 5(4), 43; https://doi.org/10.3390/physiologia5040043 - 15 Oct 2025
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Recent enthusiasm has surrounded the homeostatic roles that polyamines have in a variety of cell types. Thus, the purpose of this exploratory in vitro study was to determine how spermidine (SPD), a polyamine commonly consumed as a nutritional supplement, affected general markers of
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Recent enthusiasm has surrounded the homeostatic roles that polyamines have in a variety of cell types. Thus, the purpose of this exploratory in vitro study was to determine how spermidine (SPD), a polyamine commonly consumed as a nutritional supplement, affected general markers of cellular health and function in human primary epidermal keratinocytes. Commercial HEKa cells were seeded onto either six-well (transcriptomics and immunoblotting) or 96-well culture plates (viability, ATP, and JC-1 assays) and cultured to ~90+% confluency through complete growth media (CGM) changes every 48 h. Once cells reached this level of growth, treatments included either CGM + phosphate-buffered saline (PBS control, or CTL), CGM + 1 µM SPD, and CGM + 10 µM SPD for either 6 or 24 h depending upon the outcome being assessed. Cellular ATP levels were not significantly affected by 1 µM or 10 µM SPD treatments lasting 24 h. However, cell counts were 9% greater (p = 0.007) when comparing 24 h 10 µM versus CTL treatments indicating increased cell viability. Transcriptomic analyses indicated that 6 h treatments with 10 µM SPD significantly altered 162 transcripts versus non-treated CTL cells (65 up-regulated and 97 down-regulated, p < 0.01). Four pathways were predicted to be enriched based on differential gene expression including protein deubiquitination (GO:0016579), membrane lipid biosynthesis (GO:0046467), DNA metabolic process (GO:0006259), and cell cycle process (GO:0022402). Additionally, the HR gene (essential for keratinocyte hair follicle formation) was significantly up-regulated at the mRNA level with 6 h 10 µM SPD, and immunoblotting confirmed a 96% increase in protein levels with 24 h 10 µM SPD treatments, albeit this did not reach statistical significance (p = 0.102). Pan-keratin protein content was also 60% greater in the 1 µM and 10 µM 24 h treatments than CTL (p ≤ 0.029). Finally, although select markers of mitochondrial content and biogenesis were not significantly altered with 6 h and 24 h treatments, mitochondrial membrane potential (an aspect of mitochondrial function) was 84% greater with 24 h 1 µM versus CTL (p < 0.001). In conclusion, these preliminary screening experiments in unperturbed human keratinocytes suggest that exogenous SPD positively affects various aspects of homeostasis by stimulating transcriptomic and functional alterations (e.g., increased cell viability and enhanced keratinocyte protein levels).
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Open AccessArticle
Objective Evaluation of Fatigue-Associated Facial Expressions Using Measurements of Eye-Opening Degree, Motion Capture, and Heart Rate Variability Spectrum Analysis
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Yoshinao Nagashima, Kouichi Takamoto, Makiko Hiraishi, Etsuro Hori, Kiyoshi Kataoka and Hisao Nishijo
Physiologia 2025, 5(4), 42; https://doi.org/10.3390/physiologia5040042 - 14 Oct 2025
Abstract
Background/Objectives: This study aimed to objectively assess fatigue levels using facial expressions. Methods: This study included 25 female nurses aged between 30 and 50 years. We compared their subjective and objective fatigue levels after a night shift, when accumulated fatigue was assumed, with
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Background/Objectives: This study aimed to objectively assess fatigue levels using facial expressions. Methods: This study included 25 female nurses aged between 30 and 50 years. We compared their subjective and objective fatigue levels after a night shift, when accumulated fatigue was assumed, with those after a day off, when recovery was expected. Fatigue levels were subjectively assessed using questionnaires and were also quantified by the Visual Analog Scale (VAS). Objective evaluations included (1) the degree of eye-opening, (2) the maximum distance and speed of facial skin movement by tracking changes in coordinate values of facial markers on the skin during intentional smiling, and (3) analysis of high-frequency (HF) components and the low frequency-to-high frequency (LF/HF) ratio in heart rate variability (HRV). Results: After a night shift, compared to after a day off, subjective assessments of mental and physical fatigue in the questionnaires and VAS values of own fatigue were significantly elevated. Concurrently, objective evaluations revealed that the degree of eye-opening, along with the maximum movement distance and speed of the lower eyelid, cheek, and mouth corners during intentional smiling, were significantly reduced. Furthermore, the HF component, an index of parasympathetic activity, significantly decreased, whereas the LF/HF ratio, an index of sympathetic activity, significantly increased. Additionally, significant correlations were observed between subjective VAS estimation of fatigue levels and each objective parameter examined. Conclusions: Measuring facial parameters is an effective method for objectively assessing facial expressions of fatigue, and these changes are mediated through reduced parasympathetic nervous activity and increased sympathetic nervous activity during fatigue.
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(This article belongs to the Special Issue Feature Papers in Human Physiology—3rd Edition)
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Open AccessArticle
Emotional Salience of Evolutionary and Modern Disgust-Relevant Threats Measured Through Electrodermal Activity
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Tereza Hladíková, Iveta Štolhoferová, Daniel Frynta and Eva Landová
Physiologia 2025, 5(4), 41; https://doi.org/10.3390/physiologia5040041 - 11 Oct 2025
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Background: The study of psychophysiological responses to disgust-evoking stimuli has long been neglected in favour of other emotional stimuli, especially those evoking fear. While the basic cascade of responses to a frightening stimulus is relatively well-understood, psychophysiological responses to disgust-related threats, such as
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Background: The study of psychophysiological responses to disgust-evoking stimuli has long been neglected in favour of other emotional stimuli, especially those evoking fear. While the basic cascade of responses to a frightening stimulus is relatively well-understood, psychophysiological responses to disgust-related threats, such as parasites or rotten food, are scarcely studied. Methods: Here, we aimed to assess skin resistance (SR) change as a measure of electrodermal response to visual cues that signal the presence of disgust-relevant threats. To this aim, we recruited 123 participants and presented them with one of the following varieties of disgust-relevant threats: disgust-evoking animals (e.g., parasites, worms), spoiled food, threat of pandemic, or pollution and toxicity. The latter two represented modern threats to test whether also these modern stimuli can initiate immediate automatic reaction. Results: We found significant differences between the categories: Participants responded with the highest probability to disgust-evoking animals (38%) and sneezing (52%), suggesting that only ancestral cues of pathogen disgust trigger automatic physiological response. Moreover, we found significant inter-sexual differences: women exhibited more SR change responses than men, and the amplitude of these responses was overall larger. Finally, we report a weak effect of subjectively perceived disgust intensity on reactivity to threat stimuli. Conclusions: We discuss heterogeneity of disgust-relevant threats, their adequate behavioural responses, and subsequent heterogeneity of respective SR responses. We conclude that large interindividual variability might eclipse systematic differences between participants with high or low sensitivity to disgust, and that subjectively perceived intensity of disgust is only a weak predictor of electrodermal response to its elicitor.
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Open AccessArticle
Effects of Acute Morning Melatonin Supplementation Versus Placebo on Cardiometabolic Responses to High-Intensity Interval Exercise: A Randomized Crossover Trial in Active Men
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Naiara Ribeiro Almeida, Diego Alves dos Santos, Kaio Lages dos Santos, Diego Ignácio Valenzuela Pérez, Felipe J. Aidar, Walesca Agda Silva Miranda, Bianca Miarka, Andreia Cristiane Carrenho Queiroz and Ciro José Brito
Physiologia 2025, 5(4), 40; https://doi.org/10.3390/physiologia5040040 - 9 Oct 2025
Abstract
Aims: The present study evaluated the acute morning effect of melatonin supplementation (5 mg) on cardiometabolic responses. Methods: For this purpose, 12 physically active men (22.1 ± 1.3 years; 1.7 ± 01 m; 74.7 ± 12.1 kg; 24.3 ± 2.7 m/kg2;
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Aims: The present study evaluated the acute morning effect of melatonin supplementation (5 mg) on cardiometabolic responses. Methods: For this purpose, 12 physically active men (22.1 ± 1.3 years; 1.7 ± 01 m; 74.7 ± 12.1 kg; 24.3 ± 2.7 m/kg2; VO2max: 46.9 ± 2.3 mL/kg/min; 17.3 ± 5.2%F) were measured in a double-blind crossover protocol, where participants were measured before, during, and after a high-intensity interval exercise (HIIE) protocol [4 × 4 min at 95% of maximum heart rate (HRmax) with a 3 min interval at 60–70% of HRmax] followed by 30 min of recovery. At rest, the following variables were measured: HR, systolic blood pressure (SBP), diastolic blood pressure (DBP), lactate, and maximum oxygen consumption (VO2max). At the end of each stage and interval, VO2, respiratory exchange ratio (RER), and HR were measured. During recovery, VO2, VCO2, RER, SBP, DBP, and HR were measured. Results: Melatonin significantly enhanced recovery metabolism, as evidenced by increased VO2 at Interval 3 (+2.2 mL/kg/min, p = 0.03, d = 0.69) and 5 min postexercise (+2.4 mL/kg/min, p = 0.02, d = 0.81). The RER was higher during Sprint 4 (+0.08, p = 0.01, d = 0.84), indicating greater carbohydrate reliance. Cardiovascular recovery was also improved, with a reduced HR at 30 min (−5 bpm, p = 0.04, d = 0.66) and lower SBP at 15 min (−8 mmHg, p = 0.02, d = 0.75). Lactate concentration at 30 min was lower with melatonin (−0.7 mmol/L, p = 0.03, d = 0.72). No significant effects were observed at rest or during early exercise. Conclusions: Acute morning melatonin intake may amplify metabolic responses to HIIE while facilitating cardiometabolic recovery. This dual-phase action may benefit athletes aiming to optimize energy expenditure, fat metabolism, and recovery during early-day training.
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(This article belongs to the Special Issue Exercise Physiology and Biochemistry: 3rd Edition)
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Open AccessArticle
Effects of Respiratory Muscle Training on Performance and Inspiratory Strength in Female CrossFit Athletes: A Randomized Controlled Trial
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Juliana Andrade Assis, Lúcio Marques Vieira-Souza, Diego Valenzuela Pérez, Cristiano Diniz da Silva, Carlos Fuentes Veliz, Naiara Ribeiro Almeida, Bianca Miarka, Otávio Toledo Nóbrega and Ciro José Brito
Physiologia 2025, 5(4), 39; https://doi.org/10.3390/physiologia5040039 - 6 Oct 2025
Abstract
Background: The high-intensity demands of CrossFit induce respiratory muscle fatigue, potentially impairing performance via the metaboreflex. Respiratory muscle training (RMT) may mitigate this effect, but evidence in female athletes remains limited. Objective: We aimed to investigate the effects of RMT on sport-specific performance
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Background: The high-intensity demands of CrossFit induce respiratory muscle fatigue, potentially impairing performance via the metaboreflex. Respiratory muscle training (RMT) may mitigate this effect, but evidence in female athletes remains limited. Objective: We aimed to investigate the effects of RMT on sport-specific performance and maximal inspiratory pressure (PIMAX) in recreational female CrossFit practitioners. Design: We conducted a parallel-group randomized controlled trial. Setting: The study was conducted in a CrossFit-affiliated gym. Participants: We recruited twenty-nine recreational female practitioners (age: 30.3 ± 7.9 years) with ≥1 year of uninterrupted training who were free from respiratory diseases. Interventions: Participants were randomized to a CrossFit-only group (n = 14) or CrossFit + RMT group (n = 15). Both trained 5 days/week for 6 weeks; the RMT group additionally performed 30 inspiratory efforts at 50% of PIMAX, 5 days/week, with weekly load adjustment. Main Outcome Measures: Primary: Sport-specific performance (total repetitions in a 10-min AMRAP [As Many Rounds As Possible] test). Secondary: PIMAX (cmH2O). Measurements were taken pre- and post-intervention. Results: Baseline performance and PIMAX were similar between groups. After 6 weeks, the CrossFit + RMT group improved in performance more (Δ = +10.5 ± 10.7 reps, p = 0.03, ηp2 = 0.168) than the CrossFit-only group (Δ = +2.3 ± 8.1). PIMAX gains were also greater with RMT (Δ = +19.6 ± 8.4 cmH2O, p = 0.043, ηp2 = 0.148) vs. control (Δ = +10.1 ± 9.7). No adverse events occurred. Conclusions: Adding RMT to CrossFit training enhanced sport-specific performance and inspiratory strength in recreational female practitioners more than CrossFit alone. RMT appears to be a safe and effective complementary strategy for high-intensity functional training.
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(This article belongs to the Special Issue Exercise Physiology and Biochemistry: 3rd Edition)
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Open AccessArticle
Analysis of the Physiological Characteristics of Elite Male and Female Junior Rowers During Extreme Exercise
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István Barthalos, Zoltán Alföldi, Imre Soós, Anna Horváth Pápai, Ádám Balog, László Suszter and Ferenc Ihász
Physiologia 2025, 5(4), 38; https://doi.org/10.3390/physiologia5040038 - 3 Oct 2025
Abstract
Background: Rowing is a highly demanding endurance sport, requiring simultaneous work of approximately 70% of the body’s muscle mass and the combined contribution of aerobic and anaerobic energy systems. Objective: This study aimed to analyze the cardiorespiratory responses and performance characteristics of elite
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Background: Rowing is a highly demanding endurance sport, requiring simultaneous work of approximately 70% of the body’s muscle mass and the combined contribution of aerobic and anaerobic energy systems. Objective: This study aimed to analyze the cardiorespiratory responses and performance characteristics of elite junior male and female rowers during maximal effort over 2000 m on a rowing ergometer. Methods: Fifteen junior rowers (six males aged 15–17 and nine females aged 15–18) participated in the study. Anthropometric data (body height, weight, and body surface area) were recorded. All participants performed a maximal 2000 m test on a Concept2 D-model ergometer. Throughout the test, oxygen uptake (VO2), carbon dioxide production (VCO2), heart rate, and ventilation parameters were continuously measured. Performance and physiological data were analyzed in three intensity zones, defined by ventilatory thresholds (VT1–VT3), as well as at peak exercise. Results: Significant anthropometric differences were observed between genders. In terms of performance, males completed the 2000 m test significantly faster than females (208.83 ± 87.66 s vs. 333.78 ± 97.51 s, p = 0.0253). Relative VO2 at peak exercise was higher in males (58.73 ± 5.25 mL·kg−1·min−1) than females (48.32 ± 6.09 mL·kg−1·min−1, p = 0.0046). In most cardiorespiratory parameters, males outperformed females significantly, except for heart rate and ventilatory equivalents. Ranking analysis revealed that higher VO2max values were generally associated with a better placement in both genders, though this relationship was not perfectly linear. Performance time was negatively correlated with VO2Peak (r = −0.8286; p < 0.001), rVO2Peak (r = −0.6781; p < 0.01), and O2PPeak (r = −0.7729; p < 0.01). Conclusions: The findings confirm significant gender differences in anthropometric and cardiorespiratory characteristics of elite junior rowers and reinforce VO2max as a key determinant of performance. Yet, deviations from a direct VO2max–rank correlation highlight the influence of tactical, psychological, and biomechanical factors. Future research should provide practical recommendations for monitoring performance and tailoring training to optimize adaptation and long-term athlete development.
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(This article belongs to the Special Issue Exercise Physiology and Biochemistry: 3rd Edition)
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Open AccessReview
The Serotonergic System and Its Role in Thermoregulation
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Andrei-Ionuţ Negoiţă, Bogdan Amuzescu, Dan Florin Mihăilescu and Cristina Bordea
Physiologia 2025, 5(4), 37; https://doi.org/10.3390/physiologia5040037 - 1 Oct 2025
Abstract
Serotonin (5-hydroxytryptamine—5-HT) is an important neurotransmitter that exerts a remarkably large array of biological roles in the central nervous system and at the body level. It is involved in generating emotions, being a natural mood stabilizer; it reduces depression, anxiety, modulates sleep, and
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Serotonin (5-hydroxytryptamine—5-HT) is an important neurotransmitter that exerts a remarkably large array of biological roles in the central nervous system and at the body level. It is involved in generating emotions, being a natural mood stabilizer; it reduces depression, anxiety, modulates sleep, and has many other effects. It is also involved in fetal and postnatal brain development. This variety of biological effects, particularly in the central nervous system, with influence on behavior and cognitive functions, relies on a large number of pre- and postsynaptic serotonin receptor (5-HTR) isoforms spread throughout the brain. They can be grouped in seven large families and include over 18 subtypes, identified based on gene sequences, expression patterns, and pharmacological responses. While in vertebrates these receptors have been properly characterized and described, their correspondents in invertebrates have been far less explored, despite the assumption that they may have similar properties to those described in vertebrates. This paper summarizes the current knowledge in several important areas that together define the entire scope of serotonin receptor research, with a particular emphasis on the role of serotonergic central pathways and circuitry in thermoregulation and correlations with neurologic and psychiatric pathology.
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(This article belongs to the Special Issue Feature Papers in Human Physiology—3rd Edition)
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Environmental Hydrogen Concentration as a Novel Factor Determining Changes in Redox Potential
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Teruo Kiyama
Physiologia 2025, 5(4), 36; https://doi.org/10.3390/physiologia5040036 - 23 Sep 2025
Abstract
Intracellular oxidation–reduction (redox) potential is a key factor regulating various physiological phenomena in the cell. Monitoring this potential change is therefore important for understanding physiological homeostasis in cells. Herein, we propose a new approach for the real-time, non-invasive estimation of the redox potential
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Intracellular oxidation–reduction (redox) potential is a key factor regulating various physiological phenomena in the cell. Monitoring this potential change is therefore important for understanding physiological homeostasis in cells. Herein, we propose a new approach for the real-time, non-invasive estimation of the redox potential impacting biological metabolism and reactive oxygen species generation. Enzymes, specifically oxidoreductases, play a crucial role in catalyzing redox reactions by facilitating the transfer of electrons and hydrogen atoms between molecules. The redox potential of substrates, such as nicotinamide adenine dinucleotide, is determined by the ratio of its oxidized and reduced forms, while that of enzymes, such as succinate dehydrogenase, is determined using the reference electrode in protein-film voltammetry. Although the standard hydrogen electrode potential is defined as zero under standard conditions, the electrode potential of a reversible hydrogen electrode changes according to the ratio of the hydrogen ions (H+) and hydrogen gas (H2) in the biological fluids, as a reference electrode. The pH is maintained at 7.4 ± 0.1 in the arterial blood and the H2 that produced by the gut microbiota is measured in the endo-tidal breath for clinical diagnosis. The H2 in the endo-tidal breath equilibrates arterial blood during gas exchange in the lungs, as well as in whole-body tissues, due to the systemic circulation. In this study, H2 can be measured in the environmental gas compared to the atmosphere, and may serve as a novel factor for redox potential changes in redox enzymes, impacting biological metabolism and reactive oxygen species generation.
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(This article belongs to the Special Issue Feature Papers in Human Physiology—3rd Edition)
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Open AccessArticle
An Inconvenient Truth: Transdermal Buffering Lotions Appear to Offer No Significant Performance Improvement
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Christopher R. Harnish, Matthew E. Holman and Michael L. Bruneau, Jr.
Physiologia 2025, 5(3), 35; https://doi.org/10.3390/physiologia5030035 - 17 Sep 2025
Abstract
Background/Objectives: Transdermal bicarbonate (TBC) or carnosine (TC) have been sold as a convenient ergogenic aid, though little evidence supports these claims. The purpose of this study was to investigate if TBC or TC would improve high-intensity endurance cycling. Methods: Data were
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Background/Objectives: Transdermal bicarbonate (TBC) or carnosine (TC) have been sold as a convenient ergogenic aid, though little evidence supports these claims. The purpose of this study was to investigate if TBC or TC would improve high-intensity endurance cycling. Methods: Data were collected remotely using Zwift online platform. Fifteen cyclists completed four trials comprising five 9.1 km laps: warm-up lap, three interval laps (3 × 900 m hills, and 3 × 300 m sprints), and a 9.1 km time trial (TT) lap. A familiarization (FAM) trial followed by three randomized trials using a TBC, TC, or placebo (PLAC) lotion were completed. Trial data were assessed using general linear models to compare differences between conditions across cycling trials (p < 0.05). Results: Mean ± SD. 60 min mean max power (MMP60) was 2.9 ± 0.9 W/kg and ranged from 1.3 to 4.1 W/kg for participants. Exercise trials were 89.8 ± 17.0 min long. Laps 2–4 were ridden at 86.4 ± 7.3% and hill climbs at 131.6 ± 21.1% of MMP60, while sprints averaged 83.2 ± 17.7% of 30 s mean max power (MMP30s) and the TT ridden at 95.4 ± 8.7% of 20 min mean max power (MMP20). FAM trials were significantly lower (p < 0.05) in all power output measures, except TC sprints, and no heart rate or rating of perceived exertion differences. Similarly, there were no statistical differences in performance between any condition trials or placebo trial, but TBC hill climb power was significantly higher (p = 0.038) than TC trials. Conclusions: There are no apparent ergogenic benefits from TBC or TC during high intensity cycling performance.
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(This article belongs to the Section Exercise Physiology)
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Open AccessReview
The Cardiovascular Physiology of Glucagon-like Peptide-1 Receptor Agonists: From Macro-Level Outcomes to Micro-Level Mechanisms
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Masab Mansoor
Physiologia 2025, 5(3), 34; https://doi.org/10.3390/physiologia5030034 - 16 Sep 2025
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have instigated a paradigm shift in the management of cardiometabolic disease. Initially developed for glycemic control in type 2 diabetes, their therapeutic role has expanded dramatically following the demonstration of robust cardiovascular benefits in large-scale clinical trials.
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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have instigated a paradigm shift in the management of cardiometabolic disease. Initially developed for glycemic control in type 2 diabetes, their therapeutic role has expanded dramatically following the demonstration of robust cardiovascular benefits in large-scale clinical trials. This review provides a comprehensive synthesis of the physiological mechanisms underlying the cardioprotective effects of GLP-1 RAs, moving beyond the clinical outcomes to explore the cellular and molecular pathways involved. This review systematically deconstructs the effects of this drug class on the vasculature, where they mitigate atherosclerosis by improving endothelial function, attenuating vascular inflammation and oxidative stress, and favorably modulating plaque composition. The review delves into the complex and controversial effects on the myocardium, addressing the debate over GLP-1 receptor expression and detailing the interplay of direct and indirect actions on cardiomyocyte metabolism, ion homeostasis, and fibrosis. A central focus is the differential impact of GLP-1 RAs on heart failure (HF) phenotypes, clarifying their established benefits in HF with preserved ejection fraction (HFpEF), largely through targeting obesity and inflammation, whilst their role in the setting of HF with reduced ejection fraction (HFrEF) remains to be definitively determined. By integrating evidence from landmark trials with cutting-edge mechanistic studies, this review illuminates how GLP-1 RAs exert their profound cardiovascular effects and identifies critical unanswered questions that will shape the future of cardiometabolic medicine.
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(This article belongs to the Special Issue Advances in Cardiac Physiology and Pathophysiology)
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Open AccessSystematic Review
Occupational Therapy Interventions for Fall Prevention in Older Adults: A Systematic Review of Multimodal Strategies
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Alejandro Caña-Pino and Lucía Pesado-Fernández
Physiologia 2025, 5(3), 33; https://doi.org/10.3390/physiologia5030033 - 15 Sep 2025
Abstract
Background: Falls are a leading cause of morbidity and loss of independence among older adults, and occupational therapy (OT) offers a unique, multidimensional approach to fall prevention. This systematic review evaluates the effectiveness of OT-based interventions for improving balance, mobility, functional performance, and
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Background: Falls are a leading cause of morbidity and loss of independence among older adults, and occupational therapy (OT) offers a unique, multidimensional approach to fall prevention. This systematic review evaluates the effectiveness of OT-based interventions for improving balance, mobility, functional performance, and psychological outcomes related to fall risk in older adults. Methods: This review followed PRISMA (2020) guidelines. A comprehensive search of PubMed, Scopus, Dialnet, and OTseeker was conducted from March to May 2025. The inclusion criteria targeted studies involving non-pharmacological, OT-led interventions in adults aged ≥65. Seventeen studies were selected, including randomized controlled trials, pilot studies, and quasi-experimental designs. The data extraction and quality appraisal were performed independently by two reviewers. Results: The included interventions varied among exercise-based programs (e.g., Tai Chi, Pilates), virtual reality training, home safety modifications, cognitive–behavioral therapy, and wearable technologies. Most of the studies reported significant improvements in postural balance, fear of falling, and functional independence. Environmental adaptations and educational strategies also yielded positive outcomes. However, a real-world fall incidence reduction was inconsistently reported, and the methodological heterogeneity limited the meta-analytic synthesis. Conclusions: Occupational therapy contributes significantly to fall prevention through multimodal, person-centered strategies that integrate physical, cognitive, and environmental components. Future research should aim to standardize the outcome measures, include high-risk populations, and assess the long-term efficacy and cost-effectiveness of OT-led programs.
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(This article belongs to the Special Issue Resistance Training Is Medicine)
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Open AccessArticle
Combined Systemic and Cutaneous Ovalbumin–Aluminum Sensitization Triggers Thermal Hyperalgesia, Spinal Gliosis, and Nociceptive Nerve Fibers Sprouting in Mice
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Gabriel Siquier-Dameto, Javier Gimeno-Beltrán, Gilberto Bellia, Pere Boadas-Vaello and Enrique Verdú
Physiologia 2025, 5(3), 32; https://doi.org/10.3390/physiologia5030032 - 11 Sep 2025
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Background/Objectives: This study investigates whether systemic ovalbumin–aluminum sensitization followed by cutaneous challenge induces thermal hyperalgesia and spinal cord gliosis in mice. Methods: Adult female ICR-CD1 mice received ovalbumin–aluminum salt solution intraperitoneally on days 0, 7 and 14, and subcutaneously with daily
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Background/Objectives: This study investigates whether systemic ovalbumin–aluminum sensitization followed by cutaneous challenge induces thermal hyperalgesia and spinal cord gliosis in mice. Methods: Adult female ICR-CD1 mice received ovalbumin–aluminum salt solution intraperitoneally on days 0, 7 and 14, and subcutaneously with daily skin application via brush during days 15–21, 28–35 and 42–49. Control animals received saline. Plantar thermal hyperalgesia was assessed on days 21, 35 and 49. On day 49, tissues (dorsal skin, spinal cord, footpads) were harvested after perfusion and processed histologically to detect mast cells, astrocytes, microglia, afferent fibers and intraepidermal nerve profiles. Results: Ovalbumin-treated mice displayed thermal hyperalgesia, increased astrogliosis, and reactive microglia in the spinal cord, and expanded CGRP- and IB4-immunoreactive fiber areas. In footpads, CGRP-positive intraepidermal nerve profile density was elevated, and dorsal skin showed increased mast cell density compared to controls. Conclusions: Combined systemic and cutaneous ovalbumin–aluminum sensitization induces skin inflammation, spinal gliosis, and nociceptive fiber sprouting in both central and peripheral sites, which likely contribute to the observed thermal hyperalgesia.
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Open AccessSystematic Review
Systematic Review of the Role of Kv4.x Potassium Channels in Neurodegenerative Diseases: Implications for Neuronal Excitability and Therapeutic Modulation
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Bárbara Teruel-Peña, Piedad Gómez-Torres, Sergio Galarreta-Aperte, Nora Suleiman-Martos, Isabel Prieto, Manuel Ramírez-Sánchez, Carmen M. Fernández-Martos and Germán Domínguez-Vías
Physiologia 2025, 5(3), 31; https://doi.org/10.3390/physiologia5030031 - 10 Sep 2025
Abstract
Background/Objectives: The voltage-gated potassium channels of the Kv4 family (Kv4.1, Kv4.2, Kv4.3) regulate neuronal excitability and synaptic integration. The dysregulation of these channels has been linked to neurodegenerative diseases, such as Alzheimer’s disease (AD), spinocerebellar ataxias, amyotrophic lateral sclerosis (ALS), prion diseases, and
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Background/Objectives: The voltage-gated potassium channels of the Kv4 family (Kv4.1, Kv4.2, Kv4.3) regulate neuronal excitability and synaptic integration. The dysregulation of these channels has been linked to neurodegenerative diseases, such as Alzheimer’s disease (AD), spinocerebellar ataxias, amyotrophic lateral sclerosis (ALS), prion diseases, and Parkinson’s disease (PD). Current evidence is scattered across diverse models, and a systematic synthesis is lacking. This review seeks to compile and analyze data on Kv4 channel alterations in neurodegeneration, focusing on genetic variants, functional changes, and phenotypic consequences. Methods: A systematic search was conducted for peer-reviewed studies, including human participants, human-derived cell models, and relevant animal models. Studies were considered eligible if they investigated Kv4.1–Kv4.3 (encoded by gene encoding the Kv4.1-Kv4.3 α-subunit of voltage-gated A-type potassium channels (KCND1-KCND3)) expression, function, or genetic variants, as well as associated auxiliary subunits such as DPP6 (dipeptidyl peptidase–like protein 6) and KChIP2 (Kv channel–interacting protein 2), in neurodegenerative diseases. Both observational and experimental designs were considered. Data extraction included disease type, model, Kv4 subunit, functional or genetic findings, and key outcomes. Risk of bias was assessed in all included studies. Results: Kv4 channels exhibit significant functional and expression changes in various neurodegenerative diseases. In AD and prionopathies, reduced Kv4.1- and Kv4.2-mediated currents contribute to neuronal hyperexcitability. In spinocerebellar ataxias, KCND3 mutations cause loss- or gain-of-function phenotypes in Kv4.3, disrupting cerebellar signaling. In models of ALS and PD, Kv4 dysfunction correlates with altered neuronal excitability and can be modulated pharmacologically. Subunit modulators such as DPP6 and KChIP2 influence channel function and could represent therapeutic targets. Conclusions: Kv4 channels are crucial for neuronal excitability in multiple neurodegenerative contexts. Dysregulation through genetic or pathological mechanisms contributes to functional deficits, highlighting Kv4 channels as promising targets for interventions aimed at restoring electrical homeostasis and mitigating early neuronal dysfunction.
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(This article belongs to the Special Issue Feature Papers in Human Physiology—3rd Edition)
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Cardiovascular and Respiratory Adaptations During Pregnancy and Exercise in Pregnancy
by
Manuela Filipec and Marinela Jadanec Đurin
Physiologia 2025, 5(3), 30; https://doi.org/10.3390/physiologia5030030 - 6 Sep 2025
Abstract
During pregnancy, physiological adaptations occur in the respiratory and cardiovascular systems to support the increased metabolic needs of both mother and fetus. Key respiratory changes include mechanical adjustments of the chest wall and diaphragm to accommodate the growing uterus; decreases in functional residual
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During pregnancy, physiological adaptations occur in the respiratory and cardiovascular systems to support the increased metabolic needs of both mother and fetus. Key respiratory changes include mechanical adjustments of the chest wall and diaphragm to accommodate the growing uterus; decreases in functional residual capacity and its components—expiratory reserve volume and residual volume—with minimal or no change in total lung capacity; and an increase in minute ventilation. Major cardiovascular adaptations involve elevated cardiac output, stroke volume and heart rate, and decreased mean arterial pressure and systemic vascular resistance. During exercise in pregnancy, there is an increase in ventilation, alveolar diffusion, elevated oxygen consumption, greater carbon dioxide production and changes in respiratory volumes and capacities, as well as increases in cardiac output, stroke volume and heart rate. Understanding these normal physiological changes during pregnancy and exercise in pregnancy is essential for healthcare providers to develop and adapt exercise programs according to the gestational age and physical fitness level of the pregnant woman.
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(This article belongs to the Section Exercise Physiology)
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Effect of Foot Type on Plantar Pressure Distribution in Healthy Mexicans: Static and Dynamic Pressure Analysis
by
Jorge Armando Ramos-Frutos, Diego Oliva, Israel Miguel-Andres, Didier Samayoa-Ochoa, Jesús Salvador Jaime-Ferrer, Luis Angel Ortiz-Lango and Agustín Vidal Lesso
Physiologia 2025, 5(3), 29; https://doi.org/10.3390/physiologia5030029 - 4 Sep 2025
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Background: Plantar pressure distribution is a valuable tool for studying how the ground reaction forces are transmitted from the feet to the body and for detecting abnormalities in foot biomechanics. Objectives: The objective of this study was to determine the effect
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Background: Plantar pressure distribution is a valuable tool for studying how the ground reaction forces are transmitted from the feet to the body and for detecting abnormalities in foot biomechanics. Objectives: The objective of this study was to determine the effect of the foot type (normal foot, flatfoot, and cavus foot) on plantar pressure distribution in healthy Mexican men and women aged from 3 to 74 years. Methods: A database of the plantar pressure distribution under dynamic and static conditions for both feet was studied using descriptive statistics, regression analysis, and statistical factorial design. The database contained images of the soles of the feet and pressure distribution of 996 persons between 3 and 74 years old (53.9% females and 46.1% males). Two different conditions were evaluated; the first was in a static condition, and the second was during walking. The Chippaux–Smirak Index (CSI) was used to classify the type of feet. Results: In the left foot, a linear regression analysis of the soles of the feet shows that the prevalence of flatfoot (p-value = 3.45 × E−5) decreased with age, while the normal foot (p-value = 7.39 × E−5) increased. When people are standing (static), the hindfoot (55.64 ± 18.80%) presents more pressure than the forefoot (45.18 ± 19.50%), while in dynamic, the forefoot (55.95 ± 13.36%) supports more pressure than the hindfoot (44.05 ± 13.36%). Similar behavior occurs in the right foot. A statistical factorial design ANOVA shows that the plantar pressure in the forefoot and hindfoot regions is significantly different (p < 0.05). Conclusions: The prevalence of flatfoot decreased with age, while the proportion of normal foot type increased. Under static conditions, the hindfoot bore more load than the forefoot, whereas under dynamic conditions, the forefoot bore more load than the hindfoot. This research contributes to generating a comprehensive database of reference values of the plantar pressure of different foot types in a Mexican population; this will be useful to podiatrists, clinicians, and physiotherapists for the analysis or treatment of abnormal foot postures.
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Tears and Saliva as Biological Matrices for Vitamin D and Glucose Assessment: A Pilot Study
by
Pedro Henrique A. Reis, Giovanna K. Jorge, Edimar C. Pereira, Lai Yu Tsun, Thais M. Gascón, Beatriz da C. A. Alves, Glaucia L. da Veiga, Samantha S. de Carvalho, Renato G. Cerquinho Leça, Vagner L. Lima and Fernando L. A. Fonseca
Physiologia 2025, 5(3), 28; https://doi.org/10.3390/physiologia5030028 - 29 Aug 2025
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Background: Several studies have established correlations between low serum levels of vitamin D and various pathologies, such as diabetes mellitus and its complications. However, few studies analyze its levels in matrices other than blood plasma, such as tears and saliva. In this study,
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Background: Several studies have established correlations between low serum levels of vitamin D and various pathologies, such as diabetes mellitus and its complications. However, few studies analyze its levels in matrices other than blood plasma, such as tears and saliva. In this study, we aimed to demonstrate the feasibility of using tears and saliva as alternative biological matrices for laboratory assessment of vitamin D and glucose concentration in individuals with type II diabetes mellitus and healthy individuals, using the electrochemiluminescence method. Methods: This study included volunteers with type II diabetes and healthy controls, excluding those with certain comorbidities or a BMI ≥ 40. Blood, tear, and saliva samples were taken after 3 h of fasting for biochemical analysis of fasting glucose and vitamin D. Statistical analysis was conducted using GraphPad Prism® 8.0—with Pearson and other tests to evaluate correlations—at a significance level of 5% and test power > 95%. Results: A negative correlation between serum vitamin D values and those found in saliva (p = 0.041) was found, as well as a positive correlation between serum glucose values and those found in tears (p = 0.0254). Conclusions: Tears and saliva samples can be used as proxies for venous blood samples in specific situations, such as studying blood glucose levels and vitamin D levels. However, expanding the sample size is essential to confirm the correlation and develop an accurate equation for estimating serum levels of these markers using these alternative matrices.
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Outcome Analysis of Intensive Pulmonary Rehabilitation in Patients with COPD Exacerbation and Acute Respiratory Failure: A Single-Center Audit Aligned with Italian National Guidelines
by
Luigi Di Lorenzo, Andrea Esposito, Nicola Pirraglia, Chiara Capaldi, Gianleno De Vita and Carmine D’Avanzo
Physiologia 2025, 5(3), 27; https://doi.org/10.3390/physiologia5030027 - 27 Aug 2025
Abstract
Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and acute respiratory failure (ARF) are leading causes of hospitalization and functional decline in Italy, posing a significant burden on the healthcare system. In 2024, new national guidelines mandated the use of Intensive Care
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Background: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and acute respiratory failure (ARF) are leading causes of hospitalization and functional decline in Italy, posing a significant burden on the healthcare system. In 2024, new national guidelines mandated the use of Intensive Care Rehabilitation Units (ICRUs) within MDC4 to provide structured post-acute respiratory rehabilitation. Objective: This study aimed to evaluate functional outcomes in patients with AECOPD and ARF treated in a single ICRU, assessing the effectiveness of guideline-based rehabilitation protocols. Methods: A retrospective audit was conducted on patients admitted in 2024 to a dedicated ICRU. Functional outcomes were assessed using the Barthel Index, Six-Minute Walking Test (6MWT), and Rehabilitation Complexity Index (RCI-e13). Correlation analyses were performed to explore relationships between baseline status, rehabilitation progression, and discharge outcomes. Results: Thirty-six patients were included. Significant improvements were observed across all scales from admission to discharge. The Barthel Index showed a strong positive correlation between initial and final scores (r = 0.72), while the 6MWT indicated a similarly robust correlation (r = 0.73). Greater functional gains were noted among patients with lower baseline scores, especially in mobility. The RCI-e13 reflected decreased clinical complexity by discharge, with moderate correlations to baseline severity. Age moderately correlated with length of stay (r = 0.30), but not with outcome scores. Conclusions: The implementation of early, intensive rehabilitation in an ICRU setting—aligned with Italy’s 2024 national guidelines—led to measurable functional improvements in patients with AECOPD and ARF. These findings support the utility of structured outcome monitoring and reinforce the role of ICRUs in optimizing post-acute care pathways within respiratory rehabilitation services.
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(This article belongs to the Special Issue Feature Papers in Human Physiology—3rd Edition)
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Flywheel Resistance Training in Female Futsal Players: Muscle Power Asymmetries and Injury Risk Implications
by
Daniele Pereira da Silva Araújo, Pablo Augusto Garcia Agostinho, Suene Franciele Nunes Chaves, Rafael de Freitas Ferreira, Juliana Souza Valente, Claudia Eliza Patrocínio de Oliveira and Osvaldo Costa Moreira
Physiologia 2025, 5(3), 26; https://doi.org/10.3390/physiologia5030026 - 25 Aug 2025
Cited by 1
Abstract
Introduction: Women’s futsal demands strength, agility, speed, and endurance, involving sprints, dribbling, and rapid directional changes. In this context, the hamstring/quadriceps (H/Q) strength ratio and bilateral muscle asymmetries are recognized as risk factors for lower limb injuries and may also impact athletic performance.
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Introduction: Women’s futsal demands strength, agility, speed, and endurance, involving sprints, dribbling, and rapid directional changes. In this context, the hamstring/quadriceps (H/Q) strength ratio and bilateral muscle asymmetries are recognized as risk factors for lower limb injuries and may also impact athletic performance. Objective: This study aimed to analyze power output in two inertial flywheel resistance exercises and identify muscle imbalances in the lower limbs of female university futsal players. Methods: Twelve athletes (22.9 ± 2.3 years; 163 ± 6.8 cm; 60.9 ± 9.9 kg; 22.8 ± 3.1 kg/m2; ≥9 years of experience) participated in the study. They performed 2 sets of 8 unilateral knee flexion and extension repetitions per limb, following a warm-up of 20 bodyweight squats. Power output was assessed using a multi-joint isoinertial device (Physical Solutions, SP, Brazil). Data were analyzed using mean and standard deviation, with significance set at α = 0.05. Results: Eccentric power was significantly higher in both exercises and limbs (EJPD = 0.003; EJPE = 0.006; FJPD < 0.001; FJPE < 0.001). An imbalance in the H/Q ratio was observed: concentric right = 50.38% ± 14.67; left = 42.46% ± 9.24; eccentric right = 56.71% ± 15.56; left = 58.38% ± 21.06. The right limb showed a greater concentric imbalance (p = 0.016). Conclusions: Eccentric power was higher in both exercises without inter-limb differences. An H/Q imbalance was detected, with greater asymmetry in the right leg for concentric power. Coaches are encouraged to prioritize eccentric training to address these imbalances.
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(This article belongs to the Special Issue Exercise Physiology and Biochemistry: 2nd Edition)
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Effects of Contrast Potentiation on Endurance Performance and Cardiovascular Parameters in Elite Female Soccer Players
by
Dawid Koźlenia, Mikołaj Boros and Rafał Szafraniec
Physiologia 2025, 5(3), 25; https://doi.org/10.3390/physiologia5030025 - 12 Aug 2025
Abstract
Background/Objectives: The aim of this study was to investigate the acute effect of isometric and plyometric combined activation prior to the endurance performance assessed with the 30-15 Intermittent Fitness Test (30-15 IFT) and cardiovascular parameters. Methods: In this crossover study the
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Background/Objectives: The aim of this study was to investigate the acute effect of isometric and plyometric combined activation prior to the endurance performance assessed with the 30-15 Intermittent Fitness Test (30-15 IFT) and cardiovascular parameters. Methods: In this crossover study the data of 14 elite female soccer players aged 22.1 ± 2.9 years were assessed. The conditioning activity (CA) consisted of three sets of five seconds of maximal mid-thigh pull (IMPT), and peak force was measured, and four countermovement jumps were performed. Contact time, jump height, and reactive strength index (RSI) were assessed. Ninety seconds of rest between the sets was performed. Then, 7 min after the CA, the 30-15 IFT was performed. Results: One-way repeated measures (RM) ANOVA showed that performance during the CA did not decrease; what is more, it improved in RSI (p < 0.01). Further, paired samples t-test showed that the performance in the IFT did not change, whereas training impulse (TRIMP) was increased after CA (p = 0.039, ES = 0.61), thus the Bayesian paired test yielded only anecdotal evidence in favor of the alternative hypothesis (BF10 = 1.92; error = 2%). Conclusions: The improvement in CA suggests potentiation rather than fatigue. However, the unchanged performance alongside a modest TRIMP increase should be interpreted with caution, as TRIMP alone provides a limited assessment of physiological cost. Therefore, while the applied protocol did not enhance endurance performance, further research using multiple physiological markers is needed to clarify its impact on internal load and overall efficacy.
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(This article belongs to the Section Exercise Physiology)
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