塞梅维什大学

Abstract Background The Enhanced Games (TEG) initiative—an event that permits the off-label use of FDA-approved drugs for performance enhancement under medical supervision—represents a revolutionary yet highly controversial disruption in modern sport. Although the excessive use of certain performance-enhancing drug (PED) classes is associated with clear health risks, current evidence on PED-related cardiovascular (CV) risk is primarily derived from retrospective reports, small cohorts, or illicit use, leaving major gaps in mechanistic understanding and dose–response relationships in performance enhancement, well-being, and rehabilitation purposes. Main This review synthesizes existing data on the ergogenic mechanisms and CV toxicity of key PED classes relevant to TEG athletes, including anabolic–androgenic steroids (AAS), growth hormone and IGF-1, erythropoiesis-stimulating agents (ESAs), stimulants, β₂-agonists, diuretics, metabolic modulators, and emerging incretin-based weight management therapies. Across these agents, ergogenic effects are inconsistently demonstrated, whereas CV harm is not rare, and may be cumulative and irreversible. AAS and ESAs exhibit the strongest ergogenic signals but are also associated with myocardial remodeling, arrhythmia, and thrombotic events. Other agents provide limited or unclear performance benefits yet may disrupt autonomic balance, metabolism, or myocardial integrity. With the emergence of availability through compounding pharmacies and a rapid increase in PED use among the general population, there is an urgent need for high-quality, prospective data to inform about health risks. Since the recreational and well-being use of PEDs is on the rise among the general population, PEDs’ dose-dependent detrimental effects must be carefully evaluated. By applying rigorous pre-participation screening and long-term follow-up, TEG may provide high-quality, longitudinal data not previously available with PEDs. Conclusion TEG’s potential to provide valuable scientific insights should not be interpreted as a proof-of-concept for safe, extreme-level performance enhancement, but rather as a high-risk observational setting that demands exceptional ethical scrutiny, transparency, and long-term accountability. While ethical and regulatory debates dominate public discourse, TEG also presents a research opportunity to systematically evaluate the CV effects of PED use under controlled conditions. A dedicated, risk-adapted pre-participation screening and longitudinal monitoring framework will be essential for characterizing PED-associated CV effects and informing harm-reduction strategies.

Aging is accompanied by a progressive decline in skeletal muscle mass and function, culminating in sarcopenia, a major contributor to frailty, disability, and mortality in older adults. While skeletal muscle aging has traditionally been attributed to cell-autonomous and local tissue mechanisms, increasing evidence suggests that systemic, cell non-autonomous processes play a central role in coordinating aging across organs. The brain, particularly the hypothalamus, has emerged as a key regulator of organismal aging, yet its contribution to skeletal muscle aging remains poorly defined. Here, we tested the hypothesis that senescence confined to the brain is sufficient to induce aging-like molecular remodeling in skeletal muscle via systemic mechanisms. To model brain senescence, young mice were subjected to fractionated whole-brain irradiation (WBI), a well-established approach that induces widespread cellular senescence and neuroinflammation in the brain while sparing peripheral tissues. Two months after WBI, transcriptomic profiling of quadriceps muscle was performed and compared with that of naturally aged mice. WBI-induced robust gene expression changes in skeletal muscle that closely mirrored those observed during chronological aging. Pathway-level analyses revealed marked downregulation of mitochondrial organization, respiratory chain assembly, and metabolic processes, alongside enrichment of remodeling- and stress-associated pathways. Upstream regulator analysis identified FOXO1, FOXO3, KLF15, and STAT3, which are key drivers of muscle catabolism and atrophy, as central mediators of the observed transcriptional program. Semantic similarity analysis further demonstrated a high concordance between WBI-induced and aging-associated biological processes. Collectively, these findings demonstrate that brain senescence is sufficient to drive sarcopenia-like transcriptomic remodeling in skeletal muscle, implicating central nervous system aging as an upstream regulator of peripheral muscle decline. This brain-muscle aging axis may contribute to frailty in individuals with accelerated brain aging and in cancer survivors exposed to cranial irradiation, highlighting brain senescence as a potential therapeutic target to mitigate systemic aging and skeletal muscle dysfunction.

Aging profoundly alters the neuromotor and cognitive systems that support gait control, leading to increased variability and instability that predict functional decline and dementia risk. In this pilot study, conducted to inform the design of the Semmelweis Study gait assessment pipeline, we examined how aging and cognitive load influence the magnitude and temporal organization of gait fluctuations. The Semmelweis Study is a large, prospective workplace cohort at Semmelweis University designed to identify the determinants of unhealthy aging and the mechanisms that preserve functional resilience across the life course. One hundred three adults aged 23–87 years completed single- and dual-task walking trials on a 20-foot pressure-sensitive walkway. Gait variability was quantified using the median absolute deviation (MAD) and coefficient of variation (CoV) of key spatiotemporal parameters, while permutation entropy (PE) captured the complexity of stride-to-stride dynamics. Aging was associated with progressive increases in both the variability (MAD, CoV) and changes in orderliness (PE) of gait fluctuations, particularly under dual-task conditions, suggesting a dual contribution of neuromotor degradation and compensatory recruitment of higher-order control processes. The amplification of these effects during cognitive load highlights the vulnerability of cognitive–motor integration with advancing age. By integrating robust, relative, and nonlinear variability metrics within a unified analytical framework, this study provides a multidimensional characterization of gait control and establishes sensitive indicators for detecting early functional decline. Within the translational framework of the Semmelweis Study, these quantitative gait measures—together with vascular, metabolic, and cognitive assessments—are expected to serve as informative components of a comprehensive biomarker system aimed at identifying early determinants of unhealthy brain aging and guiding preventive strategies to promote healthy longevity.

Long COVID affects a substantial proportion of individuals recovering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, yet its underlying pathophysiology remains poorly understood. Although autoimmunity is increasingly implicated in disease pathogenesis, routine diagnostics frequently fail to detect relevant immune dysregulation. To address this gap, we analyzed sera from Long COVID patients (n = 114) and pre-pandemic controls (n = 36) using tissue-based Western blotting targeting cardiac, pulmonary, and vascular antigens, alongside standard ANA HEp-2 testing. Longitudinal samples were additionally evaluated to assess autoantibody dynamics. Autoantibodies were detected in the majority of patients (83

Abstract Background Although 22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes, a substantial proportion of patients with clinically suspected 22q11.2DS (clin22q11.2) remain without a definitive diagnosis. While CNVs other than the typical 22q11.2 deletion have been identified in patients with clin22q11.2 (defined here as phenocopies of 22q11.2DS, or phen22q11.2), SNVs associated with phen22q11.2 are less well defined. Results We aimed to investigate genetic variants associated with phen22q11.2 to achieve definitive diagnoses and improve clinical management in the clin22q11.2 cohort, while also comparing the phenotypic features of 22q11.2DS and phen22q11.2 to guide optimal diagnostic approaches. We assessed 336 consecutive pediatric patients from three centers presenting with clin22q11.2 according to Tobias criteria. Diagnostic testing included fluorescence in situ hybridization or multiplex ligation-dependent probe amplification in all patients. In subsets of patients, additional investigations were performed as clinically indicated, including but not limited to karyotyping, chromosomal microarray analysis, and/or exome sequencing (ES) with CNV detection. To identify phenotypic differences, Fisher’s exact test and Chi-squared test were performed. Genetic abnormalities were identified in 127 patients, including 88 patients diagnosed with 22q11.2DS. Phen22q11.2 was identified in 39 patients, including de novo variants in 12 patients. Several SNVs were detected, including variants in recurrently affected genes, such as CHD7 (n = 4), TBX1 (n = 2), JAG1 (n = 2), as well as variants in genes implicated in rare and ultra-rare diseases. We also described several rare and previously unreported clinical features associated with variants linked to phen22q11.2. No statistically significant phenotypic differences were observed between patients with phen22q11.2 and those with 22q11.2DS. Conclusions Phen22q11.2 is genetically and phenotypically heterogeneous. The results support the use of ES with CNV analysis as a first-tier, high-throughput diagnostic approach in clin22q11.2, as comprehensive genomic testing is essential for improving diagnostic accuracy and optimizing both genetic counseling and clinical management in this population.