Mario Muñoz-López

Migraine is the second leading cause of years lived with disability worldwide and disproportionately affects women, in whom the disorder tends to be more frequent, longer-lasting, and functionally more disabling than in men. This female preponderance, which emerges after menarche, is tightly linked to changes in estrogen levels, reproductive phases, and sex-specific responsiveness of the trigeminovascular and calcitonin gene-related peptide (CGRP) systems. Against this backdrop, nonpharmacological interventions that modulate the same physiological processes involved in migraine are particularly attractive. Resistance training (RT) has emerged from recent systematic reviews and network meta-analyses as one of the exercise modalities with the largest effect sizes on monthly migraine frequency, yet its mechanistic rationale in women is rarely addressed as a coherent biological argument. In this narrative review, we integrate the pathophysiology of migraine in females with the adaptations induced by structured RT across four convergent axes: autonomic regulation, neurovascular and endothelial function, systemic and neurogenic inflammation, and endogenous pain modulation. We interpret the current clinical evidence in light of these mechanisms, outline how the hormonal milieu in females may shape individual responsiveness, and propose a translational framework for prescribing RT as part of a comprehensive, sex-informed migraine management plan. We explicitly distinguish between robust findings, emerging signals and hypotheses that remain to be tested, and highlight the main methodological barriers that should be addressed before RT can be firmly embedded in clinical guidelines for women with migraine.

Background/Objectives: The 24 h movement behavior (24HMB) framework integrates moderate-to-vigorous physical activity (MVPA), recreational screen time, and sleep. Sociodemographic correlates of simultaneous guideline adherence among European adolescents remain poorly understood. We aimed to estimate 24HMB compliance with each guideline and their combination, identify sociodemographic correlates, and compare accelerometry- and questionnaire-based sleep models. Methods: Cross-sectional data from 444 Spanish adolescents aged 12–17 years in the Eating Healthy and Daily Life Activities (EHDLA) study, conducted in a single semi-rural municipality in the Region of Murcia, were analyzed. MVPA and sleep were measured by ActiGraph wGT3X-BT accelerometry (valid days ranged from 1 to 6); sleep and screen time were also self-reported. Firth’s penalized logistic regression was applied uniformly across binary outcomes to provide a consistent estimation framework, with primary inference based on uncorrected p-values and Benjamini–Hochberg false discovery rate (FDR) correction reported for transparency. Results: In the subsample with complete screen-time data (n = 403; 51.6% female; median age 14 years), compliance was 26.1% (MVPA), 20.3% (screen time), and 36.7%/40.2% (accelerometry-derived sleep period time/questionnaire self-reported time in bed); only 3.5–4.0% met all three guidelines simultaneously. Female sex was associated with lower MVPA (odds ratio, OR = 0.51) and screen time (OR = 0.44) compliance (both FDR-corroborated). Caucasian ethnicity was unexpectedly associated with lower MVPA compliance (OR = 0.29) in the primary complete-case analysis. Older age was associated with lower screen-time compliance (OR = 0.45; both FDR-corroborated). No predictor was significant for accelerometry-derived sleep period time compliance, and questionnaire self-reported time in bed associations did not survive FDR correction. Conclusions: Concurrent adherence to 24HMB guidelines is critically low and socially patterned. Female sex was an FDR-corroborated correlate of lower MVPA and screen-time compliance. The Caucasian ethnicity association with MVPA was specific to the primary complete-case analysis and attenuated under stricter wear-time criteria. Sleep compliance estimates and their sociodemographic correlates differed by assessment method. Future 24HMB surveillance should use validated, standardized, and clearly reported protocols, and cross-study comparisons should account for methodological differences in sleep assessment.

Exercise is a recurrent multidimensional perturbation that initiates biological adaptation, yet responses to comparable training programmes remain heterogeneous. This critical narrative Review introduces the Adaptive Cellular State (ACS) Model as a heuristic framework for examining how the biological context present before training may contribute to variation in the subsequent processing and consolidation of exercise-induced perturbations. ACS is defined as a pre-existing, dynamic and multidimensional biological configuration that may condition how exercise-induced perturbations are received, decoded, executed and retained across repeated adaptive cycles. The model organizes nine interacting domains—mitochondrial quality, metabolic flexibility, nutrient sensing, redox responsiveness, inflammatory tone, microbiota-derived signalling, endothelial function, proteostasis and epigenetic readiness—and proposes four emergent properties: gain, fidelity, biological noise and memory. These domains and properties are theoretical constructs rather than validated ACS measurements or clinical categories. Exercise remains the indispensable initiating stimulus, whereas nutrition may act through distinct routes: acute nutritional conditions may modify the internal perturbation generated during exercise, habitual dietary quality may influence selected components of the pre-existing biological context, and recovery nutrition may provide substrates or modify conditions relevant to remodelling. Nutrient-adequate dietary patterns emphasizing minimally processed foods and a diverse plant-food component represent plausible candidate exposures, but current evidence does not establish superiority over appropriately constructed high-quality omnivorous patterns or demonstrate greater long-term training adaptation. The ACS Model should therefore be interpreted as a prospective and falsifiable research framework whose validity depends on whether prespecified baseline ACS-related measures provide reproducible information about durable adaptation beyond conventional metabolic, fitness and training-history variables.

Background: Contemporary adults face fragmented schedules, sedentary digital work, cognitive load, logistical barriers, and unstable routines that can make conventional session-based exercise difficult to sustain. Exercise snacks, vigorous intermittent lifestyle physical activity (VILPA), movement breaks, low-volume high-intensity interval training (HIIT), workplace exercise, and digitally mediated physical activity may reflect a broader redesign of exercise for real-world lifestyles. Objective: To develop a conceptual framework for lifestyle-congruent exercise models: approaches that intentionally modify dose, timing, setting, delivery, autonomy, or routine integration to reduce lifestyle-related friction while preserving a plausible physiological or behavioral stimulus. Methods: This evidence-based narrative review purposively identified sources through targeted searches, citation tracking, and manual verification across exercise science, sedentary behavior, workplace health, behavioral medicine, and digital health. Sources were selected for conceptual relevance, model-family representation, evidence-type diversity, and contribution to framework development, and then charted by model family, population, context, exercise architecture, delivery, outcomes, and implementation features. No systematic protocol, formal risk-of-bias assessment, or certainty grading were applied. Results: Thirty-one sources informed the framework. Five design logics were identified: dose compression, temporal distribution, routine embedding, sedentary substitution, and delivery mediation. These logics show that brief or time-efficient models are not interchangeable; they differ in intentionality, context, behavioral demand, safety considerations, implementation logic, and dominant friction addressed. Conclusions: Lifestyle-congruent exercise models are complementary strategies, not replacements for structured aerobic and muscle-strengthening exercise. Their value lies in matching exercise architecture to lifestyle-related friction while supporting progression toward guideline-consistent activity. Future research should test safety, equity, scalability, and long-term maintenance across diverse populations.

Background: Biomarkers are increasingly used in sport science and sports medicine to monitor training load, recovery, metabolic stress, nutritional status, and potential clinical risk in athletes. However, their interpretation is often limited by overreliance on isolated values, population reference ranges, and simplified thresholds. This narrative review aims to provide a contextual and metabolically informed framework for interpreting routine and emerging biomarkers in athletes. Methods: A critical narrative synthesis was conducted across key physiological domains relevant to athlete monitoring, including exercise intensity, metabolic flexibility, muscle damage, protein catabolism, hydration, hematological and iron status, micronutrient and bone–muscle health, inflammation, endocrine stress, sport-specific interpretation, and emerging metabolomics. The review integrated routine laboratory markers with pathway-level metabolomic interpretation and practical decision-making principles. Results: Routine markers such as lactate, creatine kinase, urea/blood urea nitrogen (BUN), creatinine, electrolytes, ferritin, C-reactive protein, cortisol, testosterone, and vitamin D are useful only when interpreted in relation to individual baseline, sampling conditions, recent workload, nutrition, hydration, sleep, illness, sex-specific physiology, and performance. Metabolomics expands interpretation by identifying pathway-level signatures involving glycolysis, β-oxidation, amino acid turnover, purine degradation, ketone bodies, acylcarnitines, bile acids, oxylipins, kynurenine metabolites, and exercise-induced signaling molecules such as lactate, β-aminoisobutyric acid (BAIBA), and N-lactoyl-phenylalanine (Lac-Phe). However, omics-derived markers require careful standardization and validation before routine applied use. Conclusions: Biomarkers should refine, not replace, clinical reasoning and athlete monitoring. A BASE framework (Baseline, Analytical standardization, Sport-specific context, and Evidence of functional change) may support more precise and proportionate interpretation of both routine blood tests and emerging metabolomic tools in athletes.

Marine halophytes are gaining attention as a source of plant-derived bioactive compounds with potential applications across nutraceuticals, functional foods, and preventive nutrition. Among them, Salicornia europaea L. is a coastal succulent whose adaptation to hypersaline environments shapes a distinctive phytochemical profile of pharmacological interest. This narrative review integrates current evidence on the bioactive composition, mechanistic activities, and translational relevance of S. europaea and related Salicornia species. Their secondary metabolome includes flavonols, isorhamnetin glycosides, hydroxycinnamic acids, oleanane-type triterpene saponins, fermentable polysaccharides, carotenoids, and a mineral-rich ionic matrix. Reported activities span antioxidant, anti-inflammatory, vascular-protective, anti-adipogenic, glycaemic-modulating, antimicrobial, and microbiome-related effects, mediated through pathways involving NF-κB, PPAR-γ, endothelial nitric oxide signalling, and short-chain fatty acid production. Beyond its individual phytochemical components, the matrix as a whole may also support sodium-reduction strategies in food formulation, providing a complementary nutritional rationale for its incorporation as a functional ingredient. Despite a coherent body of mechanistic and preclinical findings, clinical evidence remains limited, particularly regarding long-term efficacy, dose standardisation, and bioavailability in humans. Future work should prioritise adequately powered intervention trials and standardised characterisation of marine halophyte bioactives to clarify their evidence-based role in functional food development and future precision nutrition applications.

Background: Skeletal muscle hypertrophy has traditionally been attributed to transient spikes in translational efficiency governed by the mTORC1 signaling cascade. However, contemporary molecular evidence reveals that sustained macroscopic growth is strongly associated with the physical expansion of the translational machinery itself. The activation of RNA Polymerase I and the subsequent synthesis of new ribosomes represent a critical biological correlate for long-term protein accretion. Objective: This comprehensive review critically examines ribosome biogenesis as the primary structural bottleneck shaping human skeletal muscle adaptation, differentiating acute signaling efficiency from chronic translational capacity. Synthesis: We dissect the molecular orchestration of nucleolar expansion and critically address the pervasive methodological pitfalls plaguing the current literature. Specifically, we highlight the moving denominator paradox, demonstrating how flawed bulk RNA normalization strategies systematically underestimate true ribosomal accretion in actively growing tissue. By synthesizing in vivo human evidence, we delineate how age, concurrent training, and training volume modulate this structural capacity. We further establish the high-responder phenotype as a function of successful nucleolar adaptation. Finally, we explore advanced molecular frontiers, including epigenetic chromatin remodeling, ribosomal heterogeneity as an emerging frontier, non-coding RNA regulation, and nuclear mechanotransduction via the YAP/TAZ axis. Conclusions: Acute anabolic signaling is merely permissive. Permanent hypertrophic adaptation fundamentally relies on overcoming the translational capacity bottleneck. Shifting the scientific and applied focus toward the architectural expansion of the nucleolus will fundamentally redefine practical hypertrophy programming and clinical interventions for sarcopenia.

The emergence of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual incretin-based therapies has fundamentally transformed obesity pharmacotherapy, enabling magnitudes of non-surgical weight loss that were previously unattainable. Yet, the clinical success of these treatments cannot be measured in kilograms alone. Total body weight is a composite, tissue-nonspecific endpoint that fails to distinguish between adipose reduction and losses in skeletal muscle mass, strength, and physical function—compartments of direct relevance to metabolic health, functional independence, and long-term resilience. This narrative review builds on and extends existing conceptualizations of weight loss quality by proposing a clinically oriented, multidimensional framework of high-quality weight loss. Within this framework, preferential adiposity reduction is achieved while preserving skeletal muscle mass, neuromuscular function, dietary adequacy, and cardiometabolic health. We examine the physiological and clinical consequences of lean tissue loss during pharmacological energy restriction, with specific attention to phenotypes at greatest risk (i.e., older adults, individuals with sarcopenic obesity, and those with type 2 diabetes). We then evaluate the evidence supporting precision protein nutrition, dietary fiber adequacy, and gastrointestinal tolerability management as nutritional countermeasures, followed by a mechanistic and clinical analysis of resistance training as the primary exercise strategy for preserving lean mass and function. Finally, we discuss body composition monitoring, integrated multidisciplinary care, and unresolved research gaps. The future of obesity treatment lies not in greater weight loss per se, but in achieving better weight loss—defined as metabolically favorable, functionally responsible, and clinically sustainable. Bone health is treated as a further dimension of high-quality weight loss, since pharmacologically driven energy restriction can adversely affect areal bone mineral density and microarchitecture, and adequate protein intake combined with mechanical loading is required to preserve skeletal integrity alongside lean mass.