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20 pages, 1012 KB  
Review
The Effectiveness of NIRS-Based Wearable Devices in Estimating Physical Activity Intensity in Patients with Chronic Non-Communicable Diseases: A Structured Narrative Review
by Raúl Caulier-Cisterna, Andrés Vega-Moraga, Daniel Ramos-López and Felipe Contreras-Briceño
Med. Sci. 2026, 14(2), 317; https://doi.org/10.3390/medsci14020317 (registering DOI) - 15 Jun 2026
Abstract
Background: Near-infrared spectroscopy (NIRS)-based wearable devices offer non-invasive, continuous monitoring of muscle oxygenation, providing direct microvascular and metabolic information that complements indirect indices of intensity such as heart rate and accelerometry. Their clinical applicability in chronic non-communicable diseases (NCDs) remains under active [...] Read more.
Background: Near-infrared spectroscopy (NIRS)-based wearable devices offer non-invasive, continuous monitoring of muscle oxygenation, providing direct microvascular and metabolic information that complements indirect indices of intensity such as heart rate and accelerometry. Their clinical applicability in chronic non-communicable diseases (NCDs) remains under active development. Methods: A structured narrative review was conducted in PubMed, Scopus, Web of Science, and IEEE Xplore (January 2010–January 2026) using pre-specified search strings combining NIRS, muscle oxygenation, SmO2, StO2, wearable, exercise intensity, ventilatory/lactate threshold, and individual chronic disease terms. Eligible studies addressed technical validation of wearable NIRS, NIRS-derived exercise intensity estimation, clinical applications in NCDs, or rehabilitation implementation. Evidence was synthesized thematically; quality of validation studies was appraised against AMSTAR-2-informed, COSMIN-informed, or Cochrane RoB-2 criteria. Results: Wearable continuous-wave NIRS shows acceptable concurrent validity with frequency-domain laboratory systems (r = 0.79; range 0.69–0.88; ±8% SmO2 agreement in 95% of measurements) and good test–retest reliability for moderate-to-severe domains (ICC 0.72–0.91). NIRS-derived breakpoints align more reliably with the second ventilatory/lactate threshold (ICC = 0.80) than with the first (ICC = 0.53), constraining its use for prescribing lower-intensity domains. In chronic obstructive pulmonary disease, peripheral arterial disease, chronic respiratory failure and selected cardiovascular conditions, wearable NIRS detects disease-specific patterns of muscle deoxygenation and post-exercise reoxygenation that track responses to rehabilitation. Conclusions: Current evidence supports wearable NIRS as a complementary, intensity-aware monitoring tool—particularly for delineating the heavy/severe-intensity boundary and detecting peripheral metabolic limitations—rather than as a stand-alone replacement for ventilatory or lactate thresholds. Because much of the evidence derives from small, single-sex or athlete-only cohorts, these findings should be regarded as a promising basis requiring further validation in broader NCD populations. Implementation in NCDs requires standardized placement and calibration protocols, sex- and body composition-stratified reference values, motion-artifact mitigation, and adequately powered longitudinal trials in clinical populations. Full article
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12 pages, 1034 KB  
Article
Acute Effects of Exercise Across Individualized Intensity Zones on Multidimensional Soccer Shooting Performance
by Wenkang Peng, Dayu Zhuang, Yingzhe Song, Dantang Wang, João Paulo Vilas-Boas and João Ribeiro
Appl. Sci. 2026, 16(11), 5228; https://doi.org/10.3390/app16115228 - 23 May 2026
Viewed by 251
Abstract
This study examined whether acute exercise performed within individualized physiological intensity zones affects multidimensional soccer shooting performance. Twenty male collegiate soccer players completed a Yo-Yo Intermittent Recovery Test Level 1 with portable gas analysis to determine the ventilatory threshold (VT) and respiratory compensation [...] Read more.
This study examined whether acute exercise performed within individualized physiological intensity zones affects multidimensional soccer shooting performance. Twenty male collegiate soccer players completed a Yo-Yo Intermittent Recovery Test Level 1 with portable gas analysis to determine the ventilatory threshold (VT) and respiratory compensation point (RCP). Three individualized zones were defined: Low (<VT), Moderate (VT–RCP), and High (>RCP). In a randomized design, players completed three 3 min shuttle-running bouts, each followed immediately by the 356 Soccer Shooting Test. Ball velocity (BV), shooting accuracy (SA), and shooting quality (SQ) were analyzed using repeated-measures ANOVA. Exercise condition significantly affected SA (p = 0.013) and SQ (p = 0.007), but not BV (p = 0.216). Bonferroni-adjusted comparisons showed that SA and SQ were lower in High than in Low, whereas no pairwise BV comparison reached significance. A sensitivity analysis using all ten recorded attempts rather than the original best-seven scoring approach showed an overall condition effect for BV without a significant pairwise comparison, retained overall effects for SA and SQ, and showed that the Low–High contrast remained robust only for SQ. Baseline comparisons were not significant. These findings indicate condition-specific shooting responses, with the clearest evidence for lower SQ after High compared with Low, supportive evidence for lower SA, and no significant primary condition effect for BV. Full article
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17 pages, 588 KB  
Article
Assessment of Maropitant Citrate Effectiveness as an Intraoperative Analgesic Through Monitoring Parasympathetic Tone Activity in Female Dogs Undergoing Ovariohysterectomy
by Areli Ramírez-Castillo, Claudia Interlandi, Agatha Elisa Miranda Cortés, Navid Ziaei-Darounkolaei, Alejandro Casas-Alvarado, Alejandro Jiménez-Yedra and Ismael Hernández-Avalos
Vet. Sci. 2026, 13(5), 463; https://doi.org/10.3390/vetsci13050463 - 10 May 2026
Viewed by 1545
Abstract
Maropitant has been proposed as an adjunct for pain relief in dogs undergoing surgeries like ovariohysterectomy (OVH), but its effectiveness has not yet been definitively proven. This study aimed to assess the intraoperative analgesic effect of intravenously administered maropitant citrate at a constant [...] Read more.
Maropitant has been proposed as an adjunct for pain relief in dogs undergoing surgeries like ovariohysterectomy (OVH), but its effectiveness has not yet been definitively proven. This study aimed to assess the intraoperative analgesic effect of intravenously administered maropitant citrate at a constant rate infusion through monitoring parasympathetic tone activity in female dogs undergoing OVH. Thirty healthy females of various breeds, with an average age of 3.8 ± 2.7 years, an average weight of 16.75 ± 10.68 kg, were randomly assigned to two treatment groups. The group receiving maropitant (GMaro, n = 15) was given a 1 mg kg−1 maropitant bolus intravenously (IV), followed by a continuous infusion of 100 mcg kg−1 min−1. The lidocaine group (GLido, n = 15) received a 2 mg/kg lidocaine IV bolus, with subsequent infusion at 50 mcg kg−1 min−1. Cardiorespiratory variables and the PTA index were evaluated at 11 anesthetic time points. Overall, cardiovascular variables such as Heart Rate (HR) and systolic arterial pressure (SAP) significantly decreased during anesthesia induction in the GMaro (p = 0.0001; p = 0.01, respectively) and in GLido (p = 0.01). Differences between groups during induction were observed in HR (p = 0.03), SAP (p = 0.04), and mean arterial pressure (MAP) (p = 0.03). MAP showed significant changes from baseline at the start of surgery and during clamping in both GMaro (p = 0.03) and GLido (p = 0.003). Regarding ventilatory variables—pulse oximetry (SpO2), respiratory rate (RR), inspired oxygen fraction (FiO2), end-tidal CO2 (EtCO2)—no group differences were found, but RR (GMaro; p = 0.001, GLido; p = 0.0001) and SpO2 (GMaro; p = 0.004, GLido; p = 0.04) differed significantly from baseline due to the controlled clinical setting. During anesthesia maintenance, end-tidal isoflurane (ETIso) increased significantly in the GLido (p = 0.009), with no difference between groups (p = 0.94). Finally, only the PTA energy variable showed a significant decrease in the GMaro (p = 0.0006), and a significant difference in this parameter was observed during right ovarian pedicle manipulation between groups (p = 0.02). In conclusion, continuous intravenous infusion of maropitant citrate at 100 mcg kg−1 h−1 effectively reduced the sympathetic response related to nociception, similar to lidocaine, in healthy female dogs undergoing OVH. Full article
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16 pages, 578 KB  
Review
Resting and Exercise Lactate Dynamics in Heart Failure: Guiding Therapeutic Optimization
by Aurora Ferro, Andrea Segreti, Nardi Tetaj, Martina Ciancio, Simone Pasquale Crispino, Riccardo Cricco, Chiara Fossati, Fabio Pigozzi and Francesco Grigioni
Biomedicines 2026, 14(4), 884; https://doi.org/10.3390/biomedicines14040884 - 13 Apr 2026
Viewed by 715
Abstract
In heart failure (HF), elevated blood lactate levels, particularly during exercise or in advanced disease stages, reflect impaired tissue perfusion and altered metabolic regulation. Beyond its traditional role as a marker of anaerobic metabolism, lactate has emerged as a dynamic indicator of metabolic [...] Read more.
In heart failure (HF), elevated blood lactate levels, particularly during exercise or in advanced disease stages, reflect impaired tissue perfusion and altered metabolic regulation. Beyond its traditional role as a marker of anaerobic metabolism, lactate has emerged as a dynamic indicator of metabolic reserve and ventilatory control. This narrative review summarizes current evidence on lactate dynamics at rest and during exercise, highlighting their pathophysiological and clinical relevance. In HF patients, exercise-induced lactate accumulation occurs earlier and at lower workloads, reflecting impaired oxidative capacity and reduced peripheral oxygen utilization. This phenomenon is closely associated with ventilatory inefficiency, as demonstrated by the relationship between lactate levels and the VE/VCO2 slope during cardiopulmonary exercise testing (CPET). Emerging data suggest that lactate is not only a marker of disease severity but also a potential mediator of chemoreflex activation and abnormal ventilatory responses. Furthermore, both pharmacologic and non-pharmacologic interventions may influence lactate production and utilization, supporting its role as a potential tool for therapeutic monitoring. Overall, the integration of lactate assessment, particularly during exercise, into clinical evaluation may provide additional insight into disease mechanisms, improve risk stratification, and contribute to personalized therapeutic optimization in patients with HF. Full article
(This article belongs to the Special Issue Advances in Airway Inflammation and Lung Dysfunction)
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18 pages, 3674 KB  
Article
Surface Electromyography Reveals Subject-Specific Alterations in Lumbar Flexion–Relaxation Following Prolonged Cycling in Pain-Free Road Cyclists
by David Arriagada-Tarifeño, Natalia Belmar, Maricel Cabezas, Javiera Ceballos, Nicole Cedeño, Iver Cristi-Sánchez, Nicolás Casanova, Sebastián Chávez and Britam Gómez
Sensors 2026, 26(7), 2214; https://doi.org/10.3390/s26072214 - 3 Apr 2026
Viewed by 647
Abstract
Low back pain is common in road cyclists and has been associated with prolonged lumbar flexion during cycling. The flexion–relaxation (FR) phenomenon reflects neuromuscular control of the lumbar spine, but its response to prolonged cycling under physiologically individualized conditions remains unclear. Thirty-one pain-free [...] Read more.
Low back pain is common in road cyclists and has been associated with prolonged lumbar flexion during cycling. The flexion–relaxation (FR) phenomenon reflects neuromuscular control of the lumbar spine, but its response to prolonged cycling under physiologically individualized conditions remains unclear. Thirty-one pain-free road cyclists completed a laboratory protocol in which exercise intensity was prescribed at 50% of the range between the first and second ventilatory thresholds (VT1 and VT2). Surface electromyography (sEMG) was recorded during trunk flexion extension tasks performed before and after a 60 min cycling trial. FR responses were characterized at both the individual and group levels using the flexion–relaxation ratio (FRR), descriptive classification of altered patterns, and exploratory estimates of mean change, effect size, and 95% confidence intervals. Four cyclists (12.9%; 95% CI: 3.6–29.8%) exhibited altered FR responses: three showed persistent alterations already present before cycling, and one showed an exercise-associated alteration. Group-level changes were minimal (effect sizes: −0.20 to 0.04). These findings suggest that prolonged cycling under controlled physiological load primarily reveals heterogeneous subject-specific neuromuscular patterns rather than a uniform average response. FR assessment using sEMG may therefore be useful as a complementary tool for identifying individual neuromuscular behavior in pain-free cyclists. Full article
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8 pages, 878 KB  
Case Report
PHOX2B Tyr14Ter Mutation Might Be Associated with Sustained Diurnal Hypertension: Case Report and Review of the Literature
by Fabio Antonelli, Simona Sottili, Maria Giovanna Paglietti, Alessandro Onofri, Renato Cutrera, Martina Mazzoni, Alessandro Rossi, Pierluigi Vuilleumier and Annalisa Allegorico
Children 2026, 13(3), 425; https://doi.org/10.3390/children13030425 - 19 Mar 2026
Viewed by 479
Abstract
Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by an impaired ventilatory response to hypercapnia and hypoxia, particularly during sleep, and frequently associated with autonomic dysfunction. It is caused by pathogenic variants in the PHOX2B gene. Although CCHS is typically [...] Read more.
Introduction: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by an impaired ventilatory response to hypercapnia and hypoxia, particularly during sleep, and frequently associated with autonomic dysfunction. It is caused by pathogenic variants in the PHOX2B gene. Although CCHS is typically diagnosed in the neonatal period, milder forms may present later in infancy or childhood, often triggered by respiratory infections. Case presentation: We report the case of 16-month-old male diagnosed with CCHS following an episode of hypoxemic–hypercapnic respiratory failure during respiratory syncytial virus (RSV) infection. His medical history included neonatal respiratory distress requiring oxygen therapy and recurrent wheezing. At 15 months, he developed acute respiratory distress with severe hypercapnia (PaCO2 70 mmHg), requiring admission to the Pediatric Intensive Care Unit and invasive mechanical ventilation. Persistent sleep-related hypercapnia and hypoxemia prompted evaluation for central hypoventilation, confirmed by means of transcutaneous capnography and nocturnal pulse oximetry. Genetic testing revealed a de novo nonsense mutation in exon 1 of PHOX2B (p.Tyr14Ter). Brain magnetic resonance imaging showed diffuse white matter changes suggestive of gliosis. Further investigations identified early-onset systemic hypertension, requiring antihypertensive therapy. The patient was discharged on nocturnal non-invasive ventilation and enrolled in a neurodevelopmental rehabilitation program. Conclusions: This case highlights the phenotypic variability of CCHS and the importance of considering this diagnosis in children presenting with unexplained hypercapnia and sleep-related hypoxemia. It underscores the need for comprehensive autonomic evaluation, including blood pressure monitoring. The p.Tyr14Ter variant may allow partial protein function, potentially accounting for the relatively mild phenotype. Full article
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16 pages, 384 KB  
Article
Real-World Impact of Initial Dual Bronchodilation on Exercise Physiological Response and Health-Related Quality of Life in Newly Diagnosed, Treatment-Naïve Chronic Obstructive Pulmonary Disease
by Ieva Dimiene, Deimante Hoppenot, Airidas Rimkunas, Neringa Vaguliene, Kristina Bieksiene, Marius Zemaitis, Kestutis Malakauskas and Skaidrius Miliauskas
Medicina 2026, 62(3), 531; https://doi.org/10.3390/medicina62030531 - 12 Mar 2026
Viewed by 575
Abstract
Background and Objectives: Dual bronchodilation in chronic obstructive pulmonary disease (COPD) has demonstrated beneficial effects on health-related quality of life (HRQoL) and exercise-related outcomes. Real-world evidence in treatment-naïve COPD remains limited. Materials and Methods: Forty-six COPD patients and 23 age-, gender-, BMI-, [...] Read more.
Background and Objectives: Dual bronchodilation in chronic obstructive pulmonary disease (COPD) has demonstrated beneficial effects on health-related quality of life (HRQoL) and exercise-related outcomes. Real-world evidence in treatment-naïve COPD remains limited. Materials and Methods: Forty-six COPD patients and 23 age-, gender-, BMI-, and cardiovascular comorbidity–matched controls underwent spirometry, plethysmography, symptom-limited incremental cardiopulmonary exercise testing (CPET), and the 36-item Short-Form Health Survey (SF-36). Following baseline assessment, COPD patients received tiotropium/olodaterol as part of routine practice. Thirty-two patients underwent repeated examinations at 12 weeks. Baseline differences between the COPD and control groups were assessed, and longitudinal changes in pulmonary function, CPET, and SF-36 were evaluated in COPD patients. Results: Compared with controls, COPD patients had lower peak oxygen uptake (VO2; 17.4 ± 4.4 vs. 22.8 ± 4.5 mL/kg/min, p < 0.001) and oxygen pulse (11.5 ± 3.5 vs. 14.0 ± 2.4 mL/beat, p = 0.003), failed to reach 80% of predicted values, and exhibited worse ventilatory efficiency (p < 0.001). SF-36 scores in the COPD group were lower across all domains. After 12 weeks of tiotropium/olodaterol, pulmonary function improved significantly. CPET was performed at comparable efforts at both visits. Peak VO2 increased from 70 ± 15 to 75 ± 16% predicted (p = 0.044), and peak oxygen pulse from 74 ± 16 to 79 ± 16% predicted (p = 0.015). VE/MVV decreased from 0.77 ± 0.23 to 0.69 ± 0.15 (p = 0.03). Higher baseline VE/MVV predicted a larger improvement after treatment (B = 0.71, p < 0.001), while beta-blocker use had no effect on the change of VE/MVV. SF-36 physical functioning and health change scores improved (both p < 0.01). Conclusions: At diagnosis, COPD was associated with impaired exercise physiology and reduced HRQoL. Dual bronchodilation improved exercise responses and perceived physical functioning. Beta-blocker use was not associated with changes in breathing reserve, supporting the use of cardioselective agents when indicated. Full article
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12 pages, 633 KB  
Article
Comparison of Ventilatory and Metabolic Demands Across Percentage-Based Heart Rate Zones in Firefighters
by Benjamin J. Mendelson, David J. Cornell, Scott D. Brau, Nathan T. Ebersole, Robert J. Flees and Kyle T. Ebersole
J. Funct. Morphol. Kinesiol. 2026, 11(1), 102; https://doi.org/10.3390/jfmk11010102 - 28 Feb 2026
Viewed by 2603
Abstract
Background: The purpose was to determine the ventilatory and metabolic demands in percentage-based heart rate (HR) zones in active-duty firefighters. Methods: Male career firefighters (n = 48, 38.17 ± 9.02 years, 1.79 ± 0.05 m, 88.27 ± 12.50 kg) completed a maximal [...] Read more.
Background: The purpose was to determine the ventilatory and metabolic demands in percentage-based heart rate (HR) zones in active-duty firefighters. Methods: Male career firefighters (n = 48, 38.17 ± 9.02 years, 1.79 ± 0.05 m, 88.27 ± 12.50 kg) completed a maximal treadmill test while wearing chest strap monitors to measure physiological responses corresponding to Zone 1 (50–59%), Zone 2 (60–69%), Zone 3 (70–79%), Zone 4 (80–89%), and Zone 5 (90–100%) based on age-predicted maximal HR. Aerobic capacity (VO2PEAK, mL·kg−1·min−1), average minute ventilation (VE, L·min−1), and respiratory exchange ratio (RER) in each zone was measured via indirect calorimetry. Linear mixed models determined significant differences in VE, RER, and time in zone (min). Results: Significant relationships emerged between VO2PEAK and average RER in Zone 5 (r = −0.33) and time in Zone 3 (r = 0.45), Zone 4 (r = 0.41), and Zone 5 (r = 0.41). A significant HR zone effect emerged in VE (F = 516.01, p < 0.001) indicating that VE increased as zone intensity increased. After controlling for VO2PEAK, a significant HR zone effect emerged in RER (F = 11.90, p < 0.001), indicating that average RER increased as zone intensity increased. No HR zone effect was found for time in zone (F = 1.18 p = 0.332) after controlling for VO2PEAK. Conclusions: A practical cardiovascular workload measure, such as percentage-based HR zones determined from treadmill testing, have distinct ventilatory and metabolic responses. Higher aerobic capacity is related to greater time spent working in higher HR zones. Full article
(This article belongs to the Special Issue Tactical Athlete Health and Performance, 2nd Edition)
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16 pages, 1784 KB  
Article
Analysis of Respiratory Behaviour of Thicklipped Grey Mullet (Chelon labrosus) Juveniles Under Different Rearing Conditions
by Daniel Salazar, María de los Ángeles Egea, Jorge León, Javier Parra and Felipe Aguado-Giménez
Fishes 2026, 11(3), 128; https://doi.org/10.3390/fishes11030128 - 24 Feb 2026
Viewed by 724
Abstract
Thicklipped grey mullet (Chelon labrosus) shows potential as an appealing species for aquaculture in the EU. Knowledge of its metabolic requirements is essential for species management and control of environmental conditions. We examined routine and postprandial oxygen consumption (OC) [...] Read more.
Thicklipped grey mullet (Chelon labrosus) shows potential as an appealing species for aquaculture in the EU. Knowledge of its metabolic requirements is essential for species management and control of environmental conditions. We examined routine and postprandial oxygen consumption (OC) in juveniles as a function of body weight (Bw: 2–85 mg) and temperature (T: 14–26 °C), as well as OC and ventilatory frequency (VF) under gradual hypoxia as a function of T (14–22 °C). Multiple regression analyses determined the effects of Bw and T on mean daily (OCmean), postprandial (OCSDA), routine (OCroutine), and maximum (OCmax) levels, as well as on OCmax/OCroutine ratio (MSF), postprandial OC duration (DSDA) and time to reach maximum activity (Dpeak). The effects of dissolved oxygen (DO) and T on OC and of T on initial VF (VFini), maximum VF (VFmax), critical DO threshold (%DOcrit), and VF change threshold (%VFch) were also analysed. All OC levels increased with T and Bw, except MSF, DSDA, and Dpeak, uninfluenced by Bw. Under gradual hypoxia, OC decreased with falling DO, more sharply at higher T, consistent with oxyconformer behaviour. VF remained stable until 50% DO, then rose progressively, reaching higher VFmax at higher T. Simulations using derived equations estimate C. labrosus respiratory response and water flow requirements under aquaculture conditions. Full article
(This article belongs to the Special Issue Fish Health and Welfare in Aquaculture and Research Settings)
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10 pages, 1550 KB  
Article
Evening Superiority in Ventilatory—Metabolic Responses and Endurance Capacity During Maximal Incremental Cycling in Trained Young Men
by Wenzheng Zha, Junqi Wu, Yuying Su, Chunlei Li and Limingfei Zhou
Appl. Sci. 2026, 16(4), 2112; https://doi.org/10.3390/app16042112 - 21 Feb 2026
Viewed by 364
Abstract
Background: This study investigated the diurnal variation in endurance performance and the corresponding ventilatory/metabolic responses during a maximal incremental cycling test. Methods: Thirty physically active young men (age = 23.5 ± 2.2 years; weekly exercise volume: ≥6 h·wk−1) with regular daily [...] Read more.
Background: This study investigated the diurnal variation in endurance performance and the corresponding ventilatory/metabolic responses during a maximal incremental cycling test. Methods: Thirty physically active young men (age = 23.5 ± 2.2 years; weekly exercise volume: ≥6 h·wk−1) with regular daily routines were recruited for a randomized crossover study. Each participant completed two maximal incremental cycling tests to volitional exhaustion: one in the morning (07:00–09:00) and another in the evening (17:00–19:00). The two sessions were separated by a one-week washout period. Key ventilatory and metabolic variables, including maximal voluntary ventilation (MVV) and maximal oxygen uptake (VO2max), were continuously measured, and time to exhaustion (TTE) was monitored. Paired-samples t-tests were used to compare morning versus evening outcomes. Results: Key performance and physiological variables, including MVV (p < 0.01), VO2max (p < 0.01), and TTE (p < 0.01), were significantly improved in the evening as compared to the morning. Conclusions: Both ventilatory/metabolic function and endurance performance during a maximal incremental cycling test induce a pronounced diurnal rhythm in trained young men, with superior outcomes observed in the evening. Full article
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15 pages, 855 KB  
Review
The Emergence of Fentanyl + Medetomidine Overdose: Pharmacology, Toxicology, and Need for Poly-Drug Reversal Therapeutics
by Robert B. Raffa, Eugene Vortsman, Joseph V. Pergolizzi, Krista Casazza and Morgan King
Future Pharmacol. 2026, 6(1), 11; https://doi.org/10.3390/futurepharmacol6010011 - 15 Feb 2026
Viewed by 1208
Abstract
The overdose mortality landscape has shifted from predominantly opioid exposures to a polysubstance epidemic increasingly driven by illicit fentanyl and fentanyl analogs combined with other centrally active agents. Among the co-intoxicants, veterinary α2-adrenoceptor (α2AR) agonists such as xylazine have [...] Read more.
The overdose mortality landscape has shifted from predominantly opioid exposures to a polysubstance epidemic increasingly driven by illicit fentanyl and fentanyl analogs combined with other centrally active agents. Among the co-intoxicants, veterinary α2-adrenoceptor (α2AR) agonists such as xylazine have emerged as clinically confounding adulterants. Recent reports from forensic toxicology, medical examiners, and border/interdiction agencies indicate that medetomidine, a veterinary sedative racemate with the highly selective α2AR agonist enantiomer dexmedetomidine, is increasingly being detected together with fentanyl and its analogs in seized materials and postmortem assays. Prior reviews have covered these aspects. The current review synthesizes current evidence and clinical experience relevant to fentanyl + medetomidine co-exposure-induced respiratory depression—a primary cause of death. We focus on convergent µ-opioid receptor (MOR) and α2AR signaling within key physiological substrates, including respiratory rhythm-generating networks, ascending arousal pathways, chemosensory reflex control of ventilation, and autonomic cardiovascular regulation, integrating mechanistic pharmacology, respiratory and cardiovascular toxicology, emergency-room treatment, and emerging public-health implications. Available evidence supports a model in which combined MOR and α2AR activation produces additive-to-synergistic suppression of ventilation and consciousness, attenuation of hypoxic ventilatory drive and CO2 responsiveness, with marked sympatholysis manifested as bradycardia and hypotension, all of which can persist beyond presumptive opioid reversal with a MOR antagonist. We discuss the implications for prehospital and emergency care. In sum, the increasing detection of medetomidine in the illicit fentanyl supply represents an emerging and potentially high-risk co-exposure pattern that may be only partially naloxone-responsive. Lastly, we highlight potential future pharmacologic countermeasures for polysubstance overdose, such as the BK-channel antagonist ENA-001, which may address naloxone-insensitive ventilatory suppression in opioid-dominant polysubstance overdose. Full article
(This article belongs to the Special Issue Feature Papers in Future Pharmacology 2026)
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21 pages, 769 KB  
Review
Vitamin D in Infectious Diseases: A Narrative Review Focusing on COVID-19, Long COVID, and Influenza
by Olga Adriana Caliman-Sturdza, Roxana Elena Gheorghita, Iuliana Soldanescu, Mihai Dimian and Serghei Mangul
Nutrients 2026, 18(4), 634; https://doi.org/10.3390/nu18040634 - 14 Feb 2026
Cited by 2 | Viewed by 2748
Abstract
Vitamin D is a secosteroid hormone traditionally recognized for its role in bone and mineral metabolism, but it is increasingly understood to also function as an important immunomodulator influencing susceptibility to and outcomes of infectious diseases. This narrative review summarizes current evidence on [...] Read more.
Vitamin D is a secosteroid hormone traditionally recognized for its role in bone and mineral metabolism, but it is increasingly understood to also function as an important immunomodulator influencing susceptibility to and outcomes of infectious diseases. This narrative review summarizes current evidence on the immunological, clinical, and preventive effects of vitamin D in the context of novel coronavirus disease (COVID-19), post-acute sequelae of SARS-CoV-2 infection (long COVID), and influenza. Mechanistically, vitamin D enhances innate immune defenses through the induction of antimicrobial peptides, including cathelicidin and defensins, and modulates adaptive immunity by suppressing maladaptive Th1/Th17 responses while promoting regulatory T-cell activity. Observational studies have frequently associated vitamin D deficiency with more severe COVID-19 outcomes; however, these associations may be influenced by confounding factors and reverse causality. Some meta-analyses suggest that vitamin D supplementation reduced rates of intensive care unit admission and ventilatory support, particularly among older adults and individuals with low baseline serum 25-hydroxyvitamin D concentrations. Emerging evidence also indicates that inadequate vitamin D status may be associated with an increased risk and symptom burden of long COVID, although causality has not been established. In the case of influenza, a limited number of randomized controlled trials (RCTs) and meta-analyses report a modest but statistically significant reduction in infection risk, especially with daily or weekly vitamin D supplementation in populations with low baseline vitamin D levels. Clinical guidelines consistently recommend maintaining adequate vitamin D status for general health but do not endorse high-dose vitamin D as a treatment for COVID-19 due to inconsistent trial findings. Overall, vitamin D should not be considered a standalone therapeutic agent; rather, maintaining sufficient vitamin D levels represents a low-risk, potentially beneficial strategy to support immune resilience against respiratory viral infections. Full article
(This article belongs to the Special Issue Prevalence and Risk Factors of Vitamin D Deficiency)
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13 pages, 366 KB  
Article
The Effect of Mountaineering Pole Use on Respiratory Muscle Fatigue During Hiking
by Athanasios Siatras, Dimos Prantsidis, Christos Galazoulas, Vasiliki Manou, Kosmas Christoulas and Thomas I. Metaxas
Appl. Sci. 2026, 16(3), 1593; https://doi.org/10.3390/app16031593 - 5 Feb 2026
Viewed by 680
Abstract
Hiking poles significantly benefit hikers by improving balance, reducing strain on lower limbs and spine, and redistributing workload to the upper extremities. However, exercise at moderate altitude often causes respiratory muscle fatigue (RMF), which limits performance. This study investigated the effect of mountaineering [...] Read more.
Hiking poles significantly benefit hikers by improving balance, reducing strain on lower limbs and spine, and redistributing workload to the upper extremities. However, exercise at moderate altitude often causes respiratory muscle fatigue (RMF), which limits performance. This study investigated the effect of mountaineering poles use on RMF during submaximal uphill walking, examining cardiovascular and pulmonary responses, perceived exertion (RPE) and perceived dyspnea (DYS). Seventeen hikers (36.2 ± 11.9 years) walked a 6.4 km trail (1010 m elevation) at 65–85% of their heart rate maximum (HRmax), with and without poles (wp/np). Maximum voluntary ventilation (MVV12), inspiratory capacity (IC), expiratory reserve volume (ERV), vital capacity (VC), tidal volume (VT), ventilation (VE), forced expiratory volume (FEV1), forced vital capacity (FVC), respiration rate (RR), heart rate (HR), oxygen saturation (SaO2), blood lactate accumulation (BLC), energy expenditure (EE), RPE, DYS, and performance (Time) were measured at the trail’s end (2070 m). Paired samples t-tests and Wilcoxon signed-rank tests were used for comparison. IC was higher when using poles compared to hiking without poles (Δ = 0.21 L, p = 0.011, adjusted p = 0.187). Non-significant differences were observed for MVV12, ERV, VT, VE, RR, and BLC. In conclusion, under the investigated submaximal conditions, pole use did not significantly alter the overall physiological load or respiratory muscle endurance. These findings suggest that recreational hikers can utilize poles for mechanical support, without additional ventilatory or cardiovascular strain. Full article
(This article belongs to the Section Applied Biosciences and Bioengineering)
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19 pages, 444 KB  
Article
Development of an AI-Based Clinical Decision Support System to Predict and Simulate Exercise-Driven Functional Improvement in Cardiac Rehabilitation
by Arturo Martinez-Rodrigo, Celia Álvarez-Bueno, Araceli Sanchis, Laura Núñez-Martínez, José Manuel Pastor and Susana Priego-Jiménez
Appl. Sci. 2026, 16(3), 1358; https://doi.org/10.3390/app16031358 - 29 Jan 2026
Viewed by 838
Abstract
Cardiac rehabilitation (CR) improves functional capacity and reduces cardiovascular morbidity, yet clinical response remains highly heterogeneous and difficult to stratify using conventional assessment. This study presents a machine-learning framework for the early stratification of CR patients into responders and non-responders based exclusively on [...] Read more.
Cardiac rehabilitation (CR) improves functional capacity and reduces cardiovascular morbidity, yet clinical response remains highly heterogeneous and difficult to stratify using conventional assessment. This study presents a machine-learning framework for the early stratification of CR patients into responders and non-responders based exclusively on pre-intervention baseline characteristics. A total of 122 patients undergoing an 8-week CR program were evaluated using 56 clinical, physiological and metabolic predictors. Multiple classification models were trained under a stratified 10-fold cross-validation scheme. Among them, an SVM-RBF classifier achieved the best performance and retained high discriminative capacity after dimensionality reduction. The final reduced model, based on the ten most informative features identified through convergence between Random Forest and SHAP analyses, preserved >95% of the full-feature performance. The predictors were physiologically coherent, reflecting muscular strength, ventilatory efficiency, chronotropic modulation and metabolic burden. SHAP-based explainability enabled patient-level attribution of improvement likelihood, identifying modifiable variables associated with favorable or limited training response. In parallel, we developed a web-based clinical decision-support prototype that estimates improvement probability and highlights the most influential determinants for each patient, illustrating translational applicability for precision rehabilitation planning. These findings support a transition toward personalized CR strategies guided by explainable AI and baseline phenotyping. Full article
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Article
Sleep Apnea Pathophysiology in Patients with a History of COVID-19
by Yeliz Celik, Scott A. Sands, Raichel Alex, Yüksel Peker and Susan Redline
J. Clin. Med. 2026, 15(2), 580; https://doi.org/10.3390/jcm15020580 - 11 Jan 2026
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Abstract
Background: Emerging evidence suggests that COVID-19 may influence obstructive sleep apnea (OSA) pathophysiology by affecting upper airway collapsibility, ventilatory control, and arousal responses, raising the possibility of a bidirectional relationship. This study examined whether individuals with a history of COVID-19 show altered [...] Read more.
Background: Emerging evidence suggests that COVID-19 may influence obstructive sleep apnea (OSA) pathophysiology by affecting upper airway collapsibility, ventilatory control, and arousal responses, raising the possibility of a bidirectional relationship. This study examined whether individuals with a history of COVID-19 show altered OSA-related physiological traits compared with those without prior infection. Methods: In a case–control study, 60 participants with a history of COVID-19 were compared to 60 matched controls who underwent overnight in-hospital polysomnography before the pandemic. The matching criteria included age (±5 years), gender, body mass index (BMI) (±5 kg/m2), and OSA presence. Key pathophysiological traits (collapsibility, loop gain, arousal threshold, muscle compensation) estimated from polysomnographic signals were compared, with adjustment for age, sex, BMI, and apnea–hypopnea index. Results: The participants (78% male, mean age 55 ± 12 years, BMI 29.4 ± 5.0 kg/m2) exhibited no meaningful differences in their average levels of collapsibility (Adj dif [95% CI]; Vpassive: −1 [−4, 2] %eupnea, p = 0.7), loop gain (LG1: 0.01 [−0.04, 0.06], p = 0.7), or arousal threshold levels (−1 [−7, 4] %eupnea) and showed similar levels of muscle compensation (Vcomp: 5 [−1, 11], p = 0.12). However, a greater ventilatory response to arousal (7 [1, 12] %eupnea) was associated with COVID-19 history. Conclusions: COVID-19 history is not associated with differences in key OSA pathophysiological traits, suggesting it is unlikely to explain observed differences in OSA presentation. The increased ventilatory response to arousal may have implications for treatment responses and outcomes. Full article
(This article belongs to the Section Respiratory Medicine)
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