Search Results (3,887)

Advances in screening, surgical techniques, perioperative care, and multimodality treatment have progressively expanded the population of long-term survivors with early-stage non-small cell lung cancer (NSCLC). However, disease-free survival does not necessarily correspond to complete functional recovery after curative-intent treatment. Many patients continue to experience persistent fatigue, dyspnea, reduced physical activity, impaired exercise tolerance, muscle loss, and deterioration in health-related quality of life despite adequate oncologic control. This narrative review discusses functional recovery as a survivorship endpoint in early-stage NSCLC, focusing on recovery trajectories, physiologic vulnerability, frailty, sarcopenia, rehabilitation, symptom burden, and emerging biologic frameworks such as allostatic load. Increasing evidence suggests that survivorship after NSCLC should not be interpreted exclusively according to recurrence or survival metrics, but also according to the ability to recover physiologic reserve, autonomy, and daily functioning after treatment. Functional recovery appears heterogeneous and influenced by multiple interacting factors, including baseline reserve, systemic inflammation, physical inactivity, behavioral adaptation, and cumulative stress burden. Rehabilitation strategies, structured symptom surveillance, and patient-reported outcomes may help identify vulnerable patients and improve long-term survivorship trajectories. Future survivorship models should probably integrate oncologic outcomes with longitudinal functional assessment to better characterize recovery patterns after treatment. Full article

Dynamin-related protein 1 (Drp1) is essential for mitochondrial dynamics in skeletal muscle, particularly in regulating fission, mitophagy, and maintaining mitochondrial function. Exercise is crucial for sustaining muscle function, promoting mitochondrial adaptations that enhance energy metabolism and oxidative capacity in skeletal muscle. In this Review, we discuss the role of Drp1 in exercise-induced mitochondrial adaptations and its potential implications for skeletal muscle health. We first address the evidence that Drp1 activity must be maintained within a narrow physiological range. Both Drp1 deficiency and overabundance provoke muscle atrophy and dysfunction, establishing a Goldilocks principle for mitochondrial fission. We then examine the multi-layered post-translational modification code that governs Drp1 activity, including canonical phosphorylation, redox-sensing modifications, and the receptor selectivity model that may specify distinct fission programs. A three-stage model of exercise-induced mitochondrial adaptation is presented, describing how Drp1 activity is temporally orchestrated from acute fragmentation through short-term remodeling to long-term network optimization, and how these morphological transitions govern substrate metabolism and determine exercise performance. The pathological consequences of Drp1 dysregulation are examined in metabolic disease, where Drp1 is chronically hyperactivated, and in aging, where Drp1 activity is deficient. Finally, we analyze the ROS-Drp1 signaling axis as the mechanistic basis for the bidirectional regulation of Drp1 by exercise. Moderate exercise-induced ROS production activates Nrf2 and AMPK signaling, which suppress excessive fission in metabolic disease while restoring insufficient fission in aging, thereby moving Drp1 activity toward the physiological Goldilocks zone in both contexts. This context-dependent, bidirectional regulation distinguishes exercise from pharmacological inhibitors and identifies the ROS-Drp1 axis as a therapeutic target for conditions at opposite ends of the Drp1 activity continuum, such as sarcopenia and type 2 diabetes. Full article

Introduction: Population aging is a growing and challenging phenomenon, primarily due to its association with functional decline and sarcopenia, which increase the risk of falls. These events have significant impacts on public health and the quality of life of older adults. Regular physical activity has shown benefits in reducing falls and their consequences, with systemic vibratory therapy (SVT) emerging as a promising strategy to mitigate these adverse outcomes. However, evidence on the actual effectiveness of this therapeutic approach remains limited, as does clarity regarding optimal body position, protocol parameters, and equipment when combined with physical activity programs. Objectives: To compare the effect of systemic vibratory therapy (SVT) associated with a physical activity program on the perception of fear of falling in older adults (M01.060.116.100). As secondary outcomes, the study will assess functional physical conditioning, electromyographic activity, muscular synergy, and center of pressure oscillation in this population. Methods: A randomized controlled clinical trial with blinded outcome assessors and blinded statistical analysis will be conducted with 192 older adults participating in the UNATI/UNISUAM program. Participants will be allocated into three groups: (A) usual physical activity; (B) usual physical activity + SVT in a semi-squat position; and (C) usual physical activity + SVT in a seated position. Assessments will include sociodemographic data, concern about falling assessed using the Falls Efficacy Scale-International (FES-I), physical performance (2 min stationary march test), surface electromyography of the tibialis anterior and medial gastrocnemius muscles, along with posturography using a force platform. Results: This study will provide information on outcomes related to fall risk, balance, physical fitness, and neuromuscular variables in older adults undergoing two distinct SVT protocols. Clinical Trials Registration: Brazilian Registry of Clinical Trials RBR-68pry5j. Registered on 8 December 2025. Full article

Low back pain (LBP) is a major global health problem and can result in a variety of movement impairments. Advances in smart technology have enabled the collection of novel streams of movement data, and machine learning (ML) methods have been increasingly used for data analysis. However, many existing technologies remain expensive and unsuitable for widespread clinical use, and ML approaches have largely focused on distinguishing people with LBP from healthy controls rather than identifying meaningful subgroups within the LBP population. Motion Tape (MT) is a recently developed wearable strain sensor that translates skin deformation from underlying movement and muscle engagement into electrical signals. In this exploratory study involving 10 participants with LBP, we demonstrate that MT data from six sensors applied on the lower back capture rich movement information capable of characterizing movement patterns among participants with LBP. We propose a feature engineering approach based on biomechanical features as well as time-series causal discovery applied to multivariate sensor time-series data to extract directed inter-segment coordination patterns. We further develop an exploratory subgroup discovery pipeline by aggregating clustering coassociation information across diverse movement tasks. Our causal coordination features show promising discriminative information across several movement types, capturing aspects of motor control not reflected in amplitude-based or embedding-based features alone, such as asymmetries and movement restrictions. Preliminary ensemble clustering analysis indicates three potential LBP subgroups distinguished by biomechanical and inter-segment coordination patterns, which may reflect varied strategies under different movement demands. We investigate the differences in clinical characteristics among these LBP subgroups. We show that time-series foundation models are not well suited for LBP subgrouping due to their uninterpretability, which is improved in our feature engineering pipeline. This framework could reveal additional subgroups with larger cohorts and may generalize to other sensor modalities. Full article

In recent years, bisphenol F (BPF) and bisphenol S (BPS) have been used in several everyday products to replace bisphenol A (BPA), since exposure to BPA has been associated with the development of several pathologies. However, recent studies have also been associating exposure to BPA substitutes with the development of various pathologies, including cardiovascular diseases, and the safety of BPA substitutes for human health has been questioned. Thus, this study aimed to investigate and compare BPA, BPF and BPS effects on arterial tone and to explore the mechanisms involved. The results suggest that BPA, BPS and BPF exert non-genomic and endothelium-independent relaxant effects on arteries and smooth muscle cells from the umbilical cord. Regarding genomic effects, the results suggest that BPA, BPF, and BPS disrupted the primary mechanisms underlying HUA relaxation by interfering with the cGMP signaling pathway and modulating the Ca²⁺ channels activity. Moreover, these results suggest that BPF alters the vasorelaxant response more than BPA and BPS. Therefore, replacing BPA with its substitutes does not appear to be beneficial for human cardiovascular health. Thus, in the future, the vascular effects of these bisphenols should be further evaluated to clarify their modes of action and future implications for maternal-fetal health. Full article

Objectives: To examine disordered eating behaviors, orthorexic tendencies, binge-eating episodes, attitudes toward exercise, perceived hormone-related symptoms and body image perception among competitive bodybuilders across different levels of competitive experience. Methods: In this cross-sectional study, 60 competitive bodybuilders (29 men, 31 women) completed an anonymous online questionnaire. The survey evaluated demographic characteristics, coaching and training management, phase-specific symptoms (such as libido, sleep, eating behaviors, and menstrual alterations), orthorexic tendencies, exercise addiction, and body-image perception. Results: Both sexes reported reduced libido, increased hunger, and sleep disturbances, along with frequent weight monitoring and common binge-eating episodes. Moreover, females frequently reported menstrual irregularities. ORTO-15 scores indicated a potential risk of orthorexia nervosa, while EAI-3 scores suggested a risk of exercise addiction in novice females and advanced males, with differences in mood regulation and guilt across sex and experience. Males showed higher perceived and ideal muscle mass, whereas females reported higher perceived body fat and a preference for leaner physiques. Conclusions: Competitive bodybuilders of both sexes exhibit post-competition binge eating, mood- and appearance-driven exercise behaviors, and pronounced body-image concerns. Screening, education on energy availability, structured post-competition support, and health-focused coaching are recommended to prevent the progression from sport-specific practices to clinical pathology. Full article

Mercury (Hg) is a major neurotoxicant and public health concern and gold mining is a significant source of Hg contamination in the Amazon. There, Indigenous peoples are vulnerable to this exposure. Individual susceptibility influences both internal mercury levels and related clinical outcomes. In this context, the GSTP1 gene stands out due to its role in detoxification of xenobiotics. The objectives were to assess the associations between: (1) Hg levels and neurotoxicity signs; (2) the GSTP1 rs1695 polymorphism and Hg levels; and (3) whether the GSTP1 rs1695 polymorphism modifies the effect of mercury on neurotoxicity signs. A cross-sectional study was conducted between April and May 2023, with 113 Paiter-Suruí Indigenous people. Sociodemographic and clinical data were collected using a validated methodology. Hair and oral mucosa cells were collected to assess Hg levels and the GSTP1 rs1695 polymorphism. Hg levels ranged from 0.1 μg/g to 6.5 μg/g (median = 1 μg/g, IQR = 1.43). Individuals with impaired memory and muscle strength had significantly higher mercury levels (β = 4.39 and β = 1.24). Carriers of the GSTP1AA genotype showed a 0.46-point reduction for each 1 μg/g increase in mean Hg levels, compared to individuals with the GSTP1GG genotype (β = −0.46). These results may support public policies by identifying priority groups for intervention based on genetic profiles. Full article

Objective: This study aimed to examine the associations of morphological variables, maximal isometric handgrip strength (MIHS), and static postural balance with self-esteem, motivational climate, school climate, and health-related quality of life (HRQoL) in early adolescents. Methods: A cross-sectional study was conducted in 235 Chilean adolescents, in whom morphological variables, MIHS, and static postural balance were assessed using center-of-pressure (CoP) parameters under eyes-open (EO) and eyes-closed (EC) conditions. Psychosocial variables, including self-esteem, motivational climate, school climate, and HRQoL, were evaluated via validated questionnaires. Multiple linear regression analyses were performed to determine associations between physical and psychosocial variables. Results: Reduced CoP sway area and lower CoP velocity under eyes-closed conditions were significantly associated with higher self-esteem (R² = 0.168; p < 0.001). Greater non-dominant MIHS and younger age were associated with more favorable perceptions of a task-involving motivational climate (R² = 0.438; p < 0.001). Higher HRQoL scores were associated with male sex and better postural balance performance. Conclusions: Better static postural balance and greater muscle strength were associated with more favorable psychosocial outcomes, particularly self-esteem and HRQoL. However, these findings should be interpreted as associative rather than causal relationships due to the cross-sectional design. Full article

Jiangshan black-bone chicken is well known for its nutritional and health-promoting benefits, and the high melanin content in its muscles gives it a distinctive black appearance. Melanin possesses strong free radical scavenging ability, which may influence the antioxidant capacity and flavor characteristics of muscle tissue. Therefore, we conducted RNA sequencing and non-targeted liquid chromatography–mass spectrometry (LC-MS)-based metabolomics sequencing on the pectoralis major muscles of Jiangshan black-bone chickens and ordinary chickens (Baier buff chickens), to investigate differences in muscle metabolic regulation between two types of chickens. We detected 88 differentially expressed genes (DEGs) and 124 differential metabolites (DMs), identified enrichment in the “Oxidative phosphorylation”, “Glutathione metabolism”, and “Melanogenesis” pathways. As a result, genes CHAC1, GSTA2, DCT, EDNRB, TYRP1, ATP5F1EP2 and metabolites “Adenosine diphosphate (ADP)”, “Phosphate (Pi)”, “Pyrophosphate (PPi)”, “Oxidized glutathione (GSSG)”, “Spermine”, contributed to differences in antioxidant capacity between the pectoralis major muscles of Jiangshan black-bone chickens and Baier buff chickens. Our results indicated that the Jiangshan black-bone chickens could generate more adenosine diphosphate (ADP), thereby enhancing glutathione metabolism and melanin synthesis, which may facilitate the removal of reactive oxygen species (ROS) in muscle tissue. Full article

Canned fish products enable long-term preservation of fish, a vital source of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Despite research on lipid composition, gaps remain in understanding the bidirectional fatty acid (FA) exchange between fish muscle and coating media during processing and storage. After a systematic literature search across five databases (PubMed, Scopus, Web of Science, Wiley Online Library, Cochrane Library), 20 studies were included examining FA profiles across fish species, filling media (vegetable oils, brine, tomato sauce), and storage durations (up to 5 years). Five studies showed that n-3 FAs migrate from fish to the filling medium, enhancing its nutritional value, while fish muscle absorbs FAs from the oil, increasingly resembling the filling medium. The use of n-6 FA-rich oils (sunflower, soybean) lowered the n-3/n-6 ratio in flesh. Conversely, aqueous media (brine) and tomato sauce maintained better ratios. EPA and DHA content generally decreased due to canning and storage, with retention varying by fish species, filling medium, and sterilization method. This review underscores significant FA exchange between fish and filling media, confirming bidirectional lipid interchange during processing. To optimize health benefits, aqueous packing media are recommended to preserve lipid profiles or to consume the covering oil to recover nutrients. Further research is needed on other factors altering FA content in canned fish such as environmental and geographical variables (including catching season), pre-canning preparation and sterilization steps (such as freezing, steaming, and frying), sterilization conditions (time, temperature, F₀ value) and lipid oxidation induced by thermal processing. Full article

The understanding of oxidative stress is being refined leading to the use of the terms “oxidative distress” and “eustress”. This reflects the dual role of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in both pathology and physiology, emphasizing the complexity of the mechanisms influencing the redox status. This review discusses how these redox mechanisms interact with key signaling pathways, specifically the mammalian/mechanistic target of rapamycin (mTOR) and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), which are crucial for mitochondrial health and muscle recovery. During exercise, the contraction of skeletal muscles increases ROS production which, through redox signaling, triggers mitochondrial biogenesis, enhances the antioxidant defenses and stimulates glucose metabolism, contributing to cardiovascular function and health. There is a large consensus about the importance of physical exercise in maintaining the redox homeostasis. However, the redox status could be disturbed after an intense and/or long physical effort, and signs such as markers of oxidative distress were identified. In that context, antioxidant strategies are warranted to prevent oxidative damage and help recovery. Given the many factors influencing the redox status of the body, including the training status, the duration and type of exercises and effort, diet, lifestyle, genetic polymorphisms, and circulating cytokines, a personalized approach is necessary. Targeted therapeutic interventions become important for preventing oxidative damage and helping recovery. In this review, we discuss the potential benefits of micro-immunotherapy (MI), as a multi-target approach utilizing signaling molecules, including cytokines at low doses (LD, typically 3–5 centesimal Hahnemannian CH dilutions) and ultra-low doses (ULD, from 6 CH upwards). We focused specifically on the investigational MI medicine 2LMIREG, and propose its application in preventing oxidative distress and restoring redox balance. Additionally, this review explores how the redox status interplays with the immune system, presenting preclinical data on 2LMIREG as a proof-of-concept for a tailored immunoregulatory strategy to enhance both immune and oxidative adaptations. Full article

Background: Stress urinary incontinence (SUI) is defined as involuntary urine loss during activities that increase intra-abdominal pressure. It is highly prevalent among women and significantly affects physical, emotional, and social well-being. Pelvic floor muscle training (PFMT) is the gold-standard conservative therapy. Second-generation radiofrequency (RF) therapy has shown promise as an alternative. It stimulates collagen synthesis and promotes tissue remodeling. This study will compare the effects of PFMT, RF, and their combination on pelvic floor function, urethral stability, and health-related quality of life (HRQoL) in women with SUI due to urethral hypermobility. Methods/Design: This will be a single-blinded, three-arm, randomized controlled trial conducted at Clínica Traña (San José, Costa Rica). Women aged ≥18 years with clinically confirmed SUI and a retrovesical (β) angle ≥ 140° during the Valsalva maneuver on functional transperineal ultrasound will be randomized (1:1:1) to PFMT (16 weeks, twice-weekly supervised sessions), RF (5 weekly sessions using Capenergy^® C500 Urogyne), or combined RF + PFMT (39 per arm; total N = 117 accounting for 30% attrition). The primary outcome is the change from baseline in pelvic floor muscle strength at 12 months post-intervention, measured by the modified Oxford scale and vaginal manometry. Secondary outcomes will include urethral stability (retrovesical β angle and bladder neck descent on ultrasound), incontinence severity (Sandvik Severity Index), and HRQoL (ICIQ-UI SF and King’s Health Questionnaire). All outcomes will be assessed at baseline, immediately post-intervention, 15 days, 3 months, 6 months, and 12 months follow-up. Assessments will be performed by blinded evaluators. Analysis will follow intention-to-treat principles using repeated-measures ANOVA or non-parametric equivalents (SPSS v.29; p < 0.05). The trial was prospectively registered on ClinicalTrials.gov (NCT07095283, registered on 24 July 2025), prior to the recruitment of the first participant. Expected outcomes: This study will provide comparative effectiveness data on whether the addition of RF to PFMT offers additional benefits over PFMT alone in the management of SUI. Full article

Background/Objectives: The Indian star tortoise (Geochelone elegans) is a protected species for which physiological and molecular health indicators remain poorly characterized. This study aimed to monitor and analyze plasma proteome profiles and biochemical parameters in captive adult Indian star tortoises and to identify potential diagnostic biomarkers. Methods: Plasma samples from nine clinically healthy adult Indian star tortoises (four males and five females) maintained in captivity were subjected to biochemical profiling and proteomic analysis. Sex-related differences in biochemical parameters were evaluated, and differentially expressed proteins were mapped to Homo sapiens Reactome pathways to identify significantly enriched biological processes. Results: Plasma biochemical profiling established baseline reference values, indicating stable hepatic and metabolic function in captive tortoises. Creatinine and urea concentrations were significantly higher in females than in males (p < 0.05), suggesting sex-related differences in protein metabolism or renal function. No significant sex-related differences were observed in hepatic enzymes (ALP, ALT, AST, and GGT), muscle-associated enzymes (CK and LDH), glucose, cholesterol, triglycerides, total proteins, albumin, or electrolyte concentrations (Na, K, Ca, Mg, Cl, P, and Fe). Proteomic analysis identified 12 differentially expressed proteins, including nine upregulated and three downregulated proteins. Functional pathway analysis revealed 90 significantly enriched Reactome pathways (FDR < 0.05). Upregulated proteins were primarily associated with cytoskeletal organization (KRT75, KRT5, and KRT17), lipid transport and remodeling (APOB), coagulation (F10), extracellular transport (TTR), immune response (WFDC3), transmembrane signaling (KCP), and gamete interaction (ZAN). Downregulated proteins (C7, SERPING1, and PZP) were linked to complement activation and acute-phase response pathways. Conclusions: Captive Indian star tortoises exhibited increased cytoskeletal remodeling and coagulation activity together with reduced complement activation. These findings provide novel insights into the plasma proteome of this species and identify candidate biomarkers that may support future health assessment, physiological monitoring, and diagnostic applications in Indian star tortoises. Full article

Background/Objectives: African Swine Fever (ASF) represents one of the most serious threats to animal health and global food security. The causative agent of ASF is the African swine fever virus (ASFV), a DNA virus belonging to the Asfarviridae family. Here, we describe ex vivo results for an original anti-ASFV vaccine approach based on the cellular immune response induced by extracellular vesicles (EVs) engineered to express four ASFV proteins. EV engineering was achieved by expressing a DNA vector encoding a biologically inactive HIV-1 Nef protein (Nef^mut), which exhibits unusually high efficiency of incorporation into EVs, even when fused to foreign proteins. Previous studies have demonstrated that intramuscular injection of Nef^mut-based vectors leads to the engineering of Evs, spontaneously released by muscle cells, and induction of antigen-specific CD8⁺ T cell immunity. Methods: We designed DNA vectors expressing the fusion products between Nef^mut and each of the four ASFV structural proteins p30, p54, pp62, and p72. Engineered EVs were molecularly characterized by Western blot and nanotrack analysis, and their potential immunogenicity was assessed by priming and cross-presentation assays. Results: We assessed that the four fusion proteins were successfully expressed in transfected mammalian cells, with the release of valuable amounts of engineered EVs. When immature swine dendritic cells were challenged with the engineered EVs and then co-cultivated with autologous peripheral blood lymphocytes in priming assays, lymphocyte subpopulations specifically reacting against each ASFV antigen were elicited, as detected by an IFN-γ ELISpot assay. In addition, we provide evidence that the Nef^mut-based fusion products incorporated into the engineered EVs can be cross-presented by professional antigen-presenting cells, leading to cross-priming of autologous lymphocytes. Conclusions: These results represent the best premise to go forward with experiments examining immunogenicity and antiviral efficiency in pigs. Full article

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. Full article