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23 pages, 2619 KB  
Article
Monitoring of First Responders Biomedical Data During Training with Innovative Virtual Reality Technologies
by Lýdie Leová, Martin Molek, Petr Volf, Marek Sokol, Jan Hejda, Zdeněk Hon, Marek Bureš and Patrik Kutilek
Big Data Cogn. Comput. 2025, 9(10), 251; https://doi.org/10.3390/bdcc9100251 - 30 Sep 2025
Abstract
Traditional training methods for first responders are often limited by time, resources, and safety constraints, which reduces their consistency and effectiveness. This study focused on two main issues: whether exposure to virtual reality training scenarios induces measurable physiological changes in heart rate and [...] Read more.
Traditional training methods for first responders are often limited by time, resources, and safety constraints, which reduces their consistency and effectiveness. This study focused on two main issues: whether exposure to virtual reality training scenarios induces measurable physiological changes in heart rate and heart rate variability, and whether these responses differ between police and firefighter contexts. The aim of this study was to explore the integration of virtual reality technologies into responder training and to evaluate how biomedical monitoring can be used to assess training effectiveness. A pilot measurement was conducted with ten participants who completed systematic crime scene investigation scenarios in both domains. Heart activity was continuously recorded using a wearable sensor and analyzed for heart rate and heart rate variability parameters, while cognitive load and task performance were also assessed. The collected data were statistically evaluated using tests of normality and paired comparisons between baseline and virtual reality phases. The results showed a significant increase in heart rate and a decrease in heart rate variability during virtual reality exposure compared to baseline, with higher cognitive load and success rates in police scenarios compared to firefighter scenarios. These findings indicate that virtual reality scenarios can elicit measurable psychophysiological responses and highlight the potential of combining immersive technologies with biomedical monitoring for the development of adaptive and effective training methods for first responders. Full article
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15 pages, 912 KB  
Article
A Structured Low-Intensity Home-Based Walking Program to Improve Physical and Mental Functioning After Hospitalization for Severe COVID-19: A Pragmatic Nonrandomized Controlled Trial
by Nicola Lamberti, Andrea Baroni, Giovanni Piva, Giulia Fregna, Nicola Schincaglia, Anna Crepaldi, Lorenzo Gamberini, Antonella Occhi, Sofia Straudi and Fabio Manfredini
J. Clin. Med. 2025, 14(19), 6938; https://doi.org/10.3390/jcm14196938 - 30 Sep 2025
Abstract
Background/Objectives: We aimed to test whether home-based low-intensity interval training (LIIT) could be equally or more effective than traditional continuous walking advice (TWA) in a population hospitalized and healed from severe COVID-19. Methods: This pragmatic nonrandomized controlled trial (NCT04615390) enrolled patients [...] Read more.
Background/Objectives: We aimed to test whether home-based low-intensity interval training (LIIT) could be equally or more effective than traditional continuous walking advice (TWA) in a population hospitalized and healed from severe COVID-19. Methods: This pragmatic nonrandomized controlled trial (NCT04615390) enrolled patients admitted to intensive care units due to COVID-19 who at discharge from the hospital were given a choice between either a home-based LIIT program or TWA. The former received a structured LIIT walking (1:1 walk:rest ratio per 10 times) to be performed at a prescribed progressively increasing speed maintained with a metronome. The latter received TWA according to the guidelines (30 min or moderate intensity activity, 5 days/week). Outcome measures, collected at baseline, at the end of the 3-month training and at the 6-month follow-up, included 6 min walking distance (primary), lower limb strength, quality of life, depression and cognitive status. Results: From a total of 85 enrolled patients, 69 of them (LIIT n = 32; TWA n = 37) completed the study. Home exercise was safely executed with an 82% adherence for the LIIT group and 64% adherence for TWA. After the 3-month program, both groups significantly improved the 6MWD (LIIT: +87 m vs. TWA +42 m; p < 0.001) with a significant difference that was also maintained at follow-up (LIIT: +138 m vs. TWA +69 m; p < 0.001). No other significant between-group differences were noted. However, patients in the LIIT group significantly improved in the majority of the outcomes, while patients of TWA improved in only the primary outcome and the physical component of quality of life. Conclusions: Compared with TWA, LIIT walking was feasible, safe and associated with more favorable multidimensional recovery in COVID-19 survivors after hospitalization for severe pneumonitis. Full article
(This article belongs to the Special Issue Rehabilitation and Treatment of Post-COVID-19 Condition)
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25 pages, 5512 KB  
Review
Histone Deacetylases in Neurodegenerative Diseases and Their Potential Role as Therapeutic Targets: Shedding Light on Astrocytes
by Pedro de Sena Murteira Pinheiro, Luan Pereira Diniz, Lucas S. Franco, Michele Siqueira and Flávia Carvalho Alcantara Gomes
Pharmaceuticals 2025, 18(10), 1471; https://doi.org/10.3390/ph18101471 - 30 Sep 2025
Abstract
Histone deacetylases (HDACs) are crucial enzymes involved in the regulation of gene expression through chromatin remodeling, impacting numerous cellular processes, including cell proliferation, differentiation, and survival. In recent years, HDACs have emerged as therapeutic targets for neurodegenerative diseases (NDDs), such as Alzheimer’s disease, [...] Read more.
Histone deacetylases (HDACs) are crucial enzymes involved in the regulation of gene expression through chromatin remodeling, impacting numerous cellular processes, including cell proliferation, differentiation, and survival. In recent years, HDACs have emerged as therapeutic targets for neurodegenerative diseases (NDDs), such as Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease, given their role in modulating neuronal plasticity, neuroinflammation, and neuronal survival. HDAC inhibitors (HDACi) are small molecules that prevent the deacetylation of histones, thereby promoting a more relaxed chromatin structure and enhancing gene expression associated with neuroprotective pathways. Preclinical and clinical studies have demonstrated that HDACi can mitigate neurodegeneration, reduce neuroinflammatory markers, and improve cognitive and motor functions, positioning them as promising therapeutic agents for NDDs. Given the complexity and multifactorial nature of NDDs, therapeutic success will likely depend on multi-target drugs as well as new cellular and molecular therapeutic targets. Emerging evidence suggests that HDACi can modulate the function of astrocytes, a glial cell type critically involved in neuroinflammation, synaptic regulation, and the progression of neurodegenerative diseases. Consequently, HDACi targeting astrocytic pathways represent a novel approach in NDDs therapy. By modulating HDAC activity specifically in astrocytes, these inhibitors may attenuate pathological inflammation and promote a neuroprotective environment, offering a complementary strategy to neuron-focused treatments. This review aims to provide an overview of HDACs and HDACi in the context of neurodegeneration, emphasizing their molecular mechanisms, therapeutic potential, and limitations. Additionally, it explores the emerging role of astrocytes as targets for HDACi, proposing that this glial cell type could enhance the efficacy of HDACs-targeted therapies in NDD management. Full article
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20 pages, 12181 KB  
Article
Neuroprotective and Neurotrophic Potential of Flammulina velutipes Extracts in Primary Hippocampal Neuronal Culture
by Sarmistha Mitra, Raju Dash, Md Abul Bashar, Kishor Mazumder and Il Soo Moon
Nutrients 2025, 17(19), 3107; https://doi.org/10.3390/nu17193107 - 30 Sep 2025
Abstract
Flammulina velutipes (enoki mushroom) is a functional edible mushroom rich in antioxidants, polysaccharides, mycosterols, fiber, and minerals. Accumulating evidence highlights its therapeutic potential across diverse pathological contexts, including boosting cognitive function. However, its role in neuromodulation has not been systematically explored. This study [...] Read more.
Flammulina velutipes (enoki mushroom) is a functional edible mushroom rich in antioxidants, polysaccharides, mycosterols, fiber, and minerals. Accumulating evidence highlights its therapeutic potential across diverse pathological contexts, including boosting cognitive function. However, its role in neuromodulation has not been systematically explored. This study examined the effects of methanolic and ethanolic extracts of F. velutipes on primary hippocampal neurons. Neurons were treated with different extract concentrations, followed by assessments of cell viability, cytoarchitecture, neuritogenesis, maturation, and neuroprotection under oxidative stress. The extracts were further characterized by GC-MS to identify bioactive metabolites, and molecular docking combined with MM-GBSA binding energy analysis was employed to predict potential modulators. Our results demonstrated that the methanolic extract significantly enhanced neurite outgrowth, improved neuronal cytoarchitecture, and promoted survival under oxidative stress, whereas the ethanolic extract produced moderate effects. Mechanistic studies indicated that these neuroprotective and neurodevelopmental benefits were mediated through activation of the NTRK receptors, as validated by both in vitro assays and molecular docking studies. Collectively, these findings suggest that F. velutipes extracts, particularly methanolic fractions, may serve as promising neuromodulatory agents for promoting neuronal development and protecting neurons from oxidative stress. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health—2nd Edition)
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17 pages, 1744 KB  
Article
Predicting Mortality in Older Adults Using Comprehensive Geriatric Assessment: A Comparative Study of Traditional Statistics and Machine Learning Approaches
by Esin Avsar Kucukkurt, Esra Tokur Sonuvar, Dilek Yapar, Yasemin Demir Avcı, Irem Tanriverdi, Andisha Behzad and Pinar Soysal
Diagnostics 2025, 15(19), 2491; https://doi.org/10.3390/diagnostics15192491 - 30 Sep 2025
Abstract
Objective: The objective was to evaluate the ability of Comprehensive Geriatric Assessment (CGA) parameters to predict all-cause mortality in older adults using both traditional statistical methods and machine learning (ML) approaches. Methods: A total of 1.974 older adults from a university hospital outpatient [...] Read more.
Objective: The objective was to evaluate the ability of Comprehensive Geriatric Assessment (CGA) parameters to predict all-cause mortality in older adults using both traditional statistical methods and machine learning (ML) approaches. Methods: A total of 1.974 older adults from a university hospital outpatient clinic were included in this study. Ninety-six CGA-related variables encompassing functional and nutritional status, frailty, mobility, cognition, mood, chronic conditions, and laboratory findings were assessed. Cox proportional hazards regression and six ML algorithms (logistic regression, support vector machine, decision tree, random forest, extreme gradient boosting, and artificial neural networks) were employed to identify mortality predictors. Model performance was evaluated using area under the curve (AUC), sensitivity, and F1-score. Results: During a median follow-up of 617 days (interquartile range [IQR]: 297–1015), 430 participants (21.7%) died. Lower Lawton instrumental activities of daily living scores, unintentional weight loss, slower gait speed, and elevated C-reactive protein levels were consistent mortality predictors across all models. The artificial neural network demonstrated the highest predictive performance (AUC = 0.970), followed by logistic regression (AUC = 0.851). SHapley Additive explanations (SHAP) analysis confirmed the relevance of these key features. Conclusions: CGA parameters provide robust prognostic information regarding mortality risk in older adults. Functional decline and inflammation markers offer greater predictive power than chronological age alone in assessing overall health and survival probability. Full article
(This article belongs to the Section Machine Learning and Artificial Intelligence in Diagnostics)
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14 pages, 695 KB  
Article
Active Breaks Enhance Complex Processing Speed, Math Performance, and Physical Activity in Primary School Children: A Randomized Controlled Trial
by Giovanni Fiorilli, Gloria Di Claudio, Domenico Di Fonza, Francesca Baralla, Giovanna Aquino, Giulia Di Martino, Carlo Della Valle, Marco Centorbi, Giuseppe Calcagno, Andrea Buonsenso and Alessandra di Cagno
J. Funct. Morphol. Kinesiol. 2025, 10(4), 376; https://doi.org/10.3390/jfmk10040376 - 29 Sep 2025
Abstract
Objectives: This study aimed to evaluate the effects of a 12-week Active Breaks (ABs) program on physical, cognitive, and academic outcomes in primary school children. Methods: Eighty primary school students (age: 7.52 ± 0.50) (BMI: 18.35 ± 3.07) were recruited and [...] Read more.
Objectives: This study aimed to evaluate the effects of a 12-week Active Breaks (ABs) program on physical, cognitive, and academic outcomes in primary school children. Methods: Eighty primary school students (age: 7.52 ± 0.50) (BMI: 18.35 ± 3.07) were recruited and randomly assigned to three experimental groups—involving creativity-based (CRE) (age: 7.97 ± 0.18 years) (BMI: 20.01 ± 3.59), fitness-based (FIT) (age: 7.93 ± 0.26 years) (BMI: 16.74 ± 1.76), and combined (COM) (age: 7.97 ± 0.18 years) (BMI: 19.38 ± 4.24) ABs—and a control group (CON) (age: 7.42 ± 0.49 years) (BMI: 18.31 ± 2.64). The intervention consisted of two daily sessions (10 min each) three times per week over a 12-week period. Numerical skills, calculation abilities, and arithmetic problem-solving performance were evaluated using the “Test for the Assessment of Calculation and Problem-Solving Skills” (AC-MT 6-11). Attention and concentration performance were assessed using the Reynolds Interference Task (RIT). Motor skill performance was assessed using the MOTORFIT tests. Results: The FIT and CRE groups showed higher improvement in physical performances (p < 0.05). Regarding cognitive outcomes, the COM group outperformed the CON group in the Total Correct Index (p = 0.032). Regarding mathematical performance, all EGs achieved higher results than the CON group (p < 0.042), with the COM group achieving the highest scores in operations, problem-solving, and total scores (p < 0.032). Conclusions: Incorporating structured physical activity through ABs during curricular hours is an effective strategy to enhance physical, cognitive, and academic performance in primary school children. A combined approach appears to be especially beneficial, supporting both physical and cognitive development simultaneously. Full article
(This article belongs to the Special Issue Sports Medicine and Public Health)
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23 pages, 2134 KB  
Review
Think Outside the Block: Rehabilitation Continuum After ACL Reconstruction with Adaptive Macro-Blocks—A Narrative Review
by Giandomenico Campardo, Roberto Ricupito, Carlotta Vercesi, Firas Mourad, Georgios Kakavas and Florian Forelli
Healthcare 2025, 13(19), 2480; https://doi.org/10.3390/healthcare13192480 - 29 Sep 2025
Abstract
Background: Conventional rehabilitation after anterior cruciate ligament reconstruction often follows a rigid, phase-based model. This structure may overlook individual differences in healing, neuromuscular control, and psychological readiness, leading to low return-to-sport rates and a high risk of reinjury. Methods: This narrative review proposes [...] Read more.
Background: Conventional rehabilitation after anterior cruciate ligament reconstruction often follows a rigid, phase-based model. This structure may overlook individual differences in healing, neuromuscular control, and psychological readiness, leading to low return-to-sport rates and a high risk of reinjury. Methods: This narrative review proposes a flexible rehabilitation framework based on overlapping progression blocks. Inspired by principles of strength and conditioning, motor learning, and cognitive training, this model emphasizes continuous, individualized development instead of fixed timelines. Results: The proposed model integrates essential components—such as joint mobility, muscle activation, motor control, and psychological factors—throughout the entire recovery process. Functional testing is redefined as a dynamic and ongoing diagnostic tool that helps clinicians identify areas needing further development, rather than acting as a simple pass/fail gateway. Progression is guided by demonstrated readiness rather than time or phase completion. Conclusions: Rehabilitation using adaptive, overlapping progression blocks offers a more holistic and responsive approach. It allows for better personalization, supports safer decision-making, and improves the transition back to sport through sustained development of physical and cognitive capacities. Full article
(This article belongs to the Special Issue Advances in Physical Therapy for Sports-Related Injuries and Pain)
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8 pages, 1509 KB  
Article
Neuroimaging Findings and Neurocognitive Features of Patients with Ochoa Syndrome (Urofacial Syndrome)—A Prospective Experimental Study
by Aykut Akinci, Murat Can Karaburun, Mehmet Fatih Ozkaya, Muhammed Arif Ibis, Tugba Babayigit, Merve Cikili Uytun, Elif Peker, Sena Unal, Seda Kaynak Sahap, Gozde Vatansever, Sertac Ustun, Tarkan Soygur and Berk Burgu
Diagnostics 2025, 15(19), 2488; https://doi.org/10.3390/diagnostics15192488 - 29 Sep 2025
Abstract
Background/Objectives: To characterize functional brain activation during smiling and to assess cognitive profiles in patients with Ochoa (Urofacial) syndrome (UFS). Materials and Methods: In a block-design fMRI paradigm, participants alternated between imitating a smiling emoji and viewing a fixation cross. Images were preprocessed [...] Read more.
Background/Objectives: To characterize functional brain activation during smiling and to assess cognitive profiles in patients with Ochoa (Urofacial) syndrome (UFS). Materials and Methods: In a block-design fMRI paradigm, participants alternated between imitating a smiling emoji and viewing a fixation cross. Images were preprocessed and analyzed in SPM12; Smile > Rest contrasts were tested with a voxelwise threshold of p < 0.001 (uncorrected). Cognitive levels were assessed using age-appropriate Wechsler scales administered by certified psychologists. Results: Six patients (mean age 20 years; 50% female) with genetically/clinically confirmed UFS were included. Smile > Rest elicited robust activation in the supplementary motor area (highest Z = 4.70), insula (largest cluster), dorsal anterior cingulate, primary motor cortex, and frontal eye fields, among others. Five patients completed cognitive testing; Full-Scale IQ ranged 50–74, consistent with mild intellectual disability to borderline intellectual functioning. Conclusions: During voluntary smiling, UFS patients exhibit activation patterns that overlap extensively with those reported in healthy cohorts. Nevertheless, cognitive performance was limited in this sample. Given the rarity of UFS and the small cohort, findings should be interpreted cautiously and validated in multicenter studies. Full article
(This article belongs to the Section Clinical Diagnosis and Prognosis)
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17 pages, 1359 KB  
Review
Spaceflight and Ground-Based Microgravity Simulation Impact on Cognition and Brain Plasticity
by Jiaqi Hao, Jun Chang and Yulin Deng
Int. J. Mol. Sci. 2025, 26(19), 9521; https://doi.org/10.3390/ijms26199521 - 29 Sep 2025
Abstract
Microgravity exposure during spaceflight has been linked to cognitive impairments, including deficits in attention, executive function, and spatial memory. Both space missions and ground-based analogs—such as head-down bed rest, dry immersion, and hindlimb unloading—consistently demonstrate that altered gravity disrupts brain structure and neural [...] Read more.
Microgravity exposure during spaceflight has been linked to cognitive impairments, including deficits in attention, executive function, and spatial memory. Both space missions and ground-based analogs—such as head-down bed rest, dry immersion, and hindlimb unloading—consistently demonstrate that altered gravity disrupts brain structure and neural plasticity. Neuroimaging data reveal significant changes in brain morphology, functional connectivity, and cerebrospinal fluid dynamics. At the cellular level, simulated microgravity impairs synaptic plasticity, alters dendritic spine architecture, and compromises neurotransmitter release. These changes are accompanied by dysregulation of neuroendocrine signaling, decreased expression of neurotrophic factors, and activation of oxidative stress and neuroinflammatory pathways. Molecular and omics-level analyses further point to mitochondrial dysfunction and disruptions in key signaling cascades governing synaptic integrity, energy metabolism, and neuronal survival. Despite these advances, discrepancies across studies—due to differences in models, durations, and endpoints—limit mechanistic clarity and translational relevance. Human data remain scarce, emphasizing the need for standardized, longitudinal, and multimodal investigations. This review provides an integrated synthesis of current evidence on the cognitive and neurobiological effects of microgravity, spanning behavioral, structural, cellular, and molecular domains. By identifying consistent patterns and unresolved questions, we highlight critical targets for future research and the development of effective neuroprotective strategies for long-duration space missions. Full article
(This article belongs to the Section Molecular Neurobiology)
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23 pages, 2269 KB  
Review
A Review of Human–Robot Collaboration Safety in Construction
by Peng Lin, Ningshuang Zeng, Qiming Li and Konrad Nübel
Systems 2025, 13(10), 856; https://doi.org/10.3390/systems13100856 - 29 Sep 2025
Abstract
Integrating human–robot collaboration (HRC) into construction sites has significantly enhanced efficiency and quality. However, it also introduces new or intensifies existing risks as it brings in new entities, relationships, and construction activities. Safety remains the top priority and a persistent concern in HRC [...] Read more.
Integrating human–robot collaboration (HRC) into construction sites has significantly enhanced efficiency and quality. However, it also introduces new or intensifies existing risks as it brings in new entities, relationships, and construction activities. Safety remains the top priority and a persistent concern in HRC systems. However, the current literature on human–robot collaboration safety (HRCS) is vast yet fragmented, and a systematic exploration of its status and research trends in the construction context is still lacking. This paper explores advances in HRCS over the past two decades through a mixed quantitative and qualitative analysis method. Initially, 287 related articles were identified by keyword-searching in Scopus, followed by bibliometric analysis using CiteSpace to uncover the knowledge structure and track emerging research trends. Subsequently, a qualitative discussion highlights achievements in HRCS across five dimensions: (1) optimization of remote intelligent machinery; (2) hazard analysis and risk assessment in HRCS; (3) digital twin for safety monitoring; (4) cognitive and psychological impacts; (5) organizational management perspective. This study quantitatively maps the scientific landscape of HRCS at a macro level and qualitatively identifies key research areas. It provides a comprehensive foundation for understanding the evolution of HRCS and exploring future research directions and applications. Full article
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32 pages, 1782 KB  
Review
Neurobiological and Behavioral Heterogeneity in Adolescents with Autism Spectrum Disorder
by Gerry Leisman, Rahela Alfasi and Robert Melillo
Brain Sci. 2025, 15(10), 1057; https://doi.org/10.3390/brainsci15101057 - 28 Sep 2025
Abstract
Background: Adolescents with autism spectrum disorder (ASD) display distinct neurodevelopmental trajectories marked by atypical neural activation and white matter maturation compared to neurotypical peers. Introduction: While improvements in face recognition and cognitive skills occur during childhood and adolescence, individuals with ASD often experience [...] Read more.
Background: Adolescents with autism spectrum disorder (ASD) display distinct neurodevelopmental trajectories marked by atypical neural activation and white matter maturation compared to neurotypical peers. Introduction: While improvements in face recognition and cognitive skills occur during childhood and adolescence, individuals with ASD often experience a plateau in these areas as they transition to adulthood, impacting daily living, executive function, social cognition, and emotional awareness. Results: Neuroimaging studies reveal altered white matter growth and connectivity in brain regions associated with social processing, which may underlie these functional challenges. Intellectual disability further compounds developmental difficulties by limiting foundational abilities and slowing progress. Discussion: The multifaceted and persistent service needs spanning legal, educational, vocational, health, and psychosocial domains highlight the necessity for coordinated, individualized, and family-centered approaches, particularly during the transition to adulthood. Advances in research integrating genetic, neurobiological, and behavioral data hold potential for refining diagnostic subgroups and personalizing interventions. Conclusion: Continued advocacy and innovation in service delivery are essential to address gaps in adult support systems and enhance long-term outcomes for individuals with ASD. Full article
(This article belongs to the Special Issue Rethinking Neurodevelopmental Disorders: Beyond One-Size-Fits-All)
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27 pages, 3178 KB  
Review
The Role of GABA Pathway Components in Pathogenesis of Neurodevelopmental Disorders
by Ekaterina V. Marilovtseva, Amal Abdurazakov, Artemiy O. Kurishev, Vera A. Mikhailova and Vera E. Golimbet
Int. J. Mol. Sci. 2025, 26(19), 9492; https://doi.org/10.3390/ijms26199492 - 28 Sep 2025
Abstract
γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), regulates neuronal excitability, synaptic plasticity, and oscillatory activity essential for cognition, emotion, and behavior. Disruptions in GABAergic signaling are increasingly recognized as key contributors to a range of neurodevelopmental disorders [...] Read more.
γ-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system (CNS), regulates neuronal excitability, synaptic plasticity, and oscillatory activity essential for cognition, emotion, and behavior. Disruptions in GABAergic signaling are increasingly recognized as key contributors to a range of neurodevelopmental disorders (NDDs), including schizophrenia (SZ), autism spectrum disorder (ASD), major depressive disorder (MDD), bipolar disorder (BD), and intellectual disability (ID). In this review, we analyze the data available from the literature concerning the components of the GABA pathway. We describe the main steps of GABA metabolism, including GABA synthesis and release, GABA receptors neurotransmission, GABA reuptake and catabolism, and evaluate their involvement in the pathogenesis of neurodevelopmental disorders. We suggest the possibility of existence of so far undescribed mechanisms which maintain the concentrations of GABA at a relatively physiological level when the function of glutamic acid decarboxylases is compromised by mutations. Searching for these mechanisms could be important for better understanding neurodevelopment and could give a clue for future searches for new therapeutic approaches for treating or alleviating the symptoms of BD and SZ. We also argue that the metabolic stage of the GABA pathway has only a minor direct effect on GABA signaling and rather causes clinical effects due to accumulation of neurotoxic byproducts. Full article
(This article belongs to the Special Issue Molecular Investigations in Neurodevelopmental Disorders)
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62 pages, 1598 KB  
Review
Small-Molecule Inhibitors of Amyloid Beta: Insights from Molecular Dynamics—Part B: Natural Compounds
by Mariyana Atanasova
Pharmaceuticals 2025, 18(10), 1457; https://doi.org/10.3390/ph18101457 - 28 Sep 2025
Abstract
Alzheimer’s disease (AD) is the most common form of dementia, characterized by progressive memory loss and cognitive decline. Its key pathological hallmarks include extracellular amyloid plaques composed of amyloid beta (Aβ) peptides and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein. Although numerous [...] Read more.
Alzheimer’s disease (AD) is the most common form of dementia, characterized by progressive memory loss and cognitive decline. Its key pathological hallmarks include extracellular amyloid plaques composed of amyloid beta (Aβ) peptides and intracellular neurofibrillary tangles formed by hyperphosphorylated tau protein. Although numerous studies have investigated the complex pathology of AD, its underlying mechanisms remain incompletely understood. The amyloid cascade hypothesis continues to be the leading model of AD pathogenesis. It suggests that Aβ aggregation is the initial trigger of neurotoxicity, setting off a cascade of pathological events including inflammation, oxidative stress, tau hyperphosphorylation, synaptic dysfunction, and, ultimately, dementia. Molecular dynamics (MD) is a powerful tool in structure-based drug design (SBDD). By simulating biomolecular motions at the atomic level, MD provides unique insights into molecular properties, functions, and inhibition mechanisms—insights often inaccessible through other experimental or computational techniques. When integrated with experimental data, MD further deepens our understanding of molecular interactions and biological processes. Natural compounds, known for their pleiotropic pharmacological activities, favorable safety profiles, and general tolerability (despite occasional side effects), are increasingly explored for their potential in both the treatment and prevention of various diseases, including AD. In this review, we summarize current findings from MD simulations of natural compounds with anti-amyloidogenic potential. This work builds upon our previous publication, which focused on endogenous compounds and repurposed drugs. The review is structured as follows: an overview of the amyloid cascade hypothesis; a discussion of Aβ oligomeric structures and their stabilizing interactions; a section on molecular dynamics, including its challenges and future directions; and a comprehensive analysis of the inhibitory mechanisms of natural compounds, categorized by their shared structural features. Full article
(This article belongs to the Section Medicinal Chemistry)
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25 pages, 765 KB  
Article
A Randomized Controlled Trial of an Enhanced Version of a Cognitive–Behavioral Video Game Intervention Aimed at Promoting Active Aging: Assessments of Perceived Health and Healthy Lifestyle Habits at Pre- and Post-Intervention
by Tania Cotardo, Patricia Otero, Eling D. de Bruin, Vanessa Blanco, Manuel Arrojo, Mario Páramo, María J. Ferraces, Ángela J. Torres and Fernando L. Vázquez
J. Clin. Med. 2025, 14(19), 6873; https://doi.org/10.3390/jcm14196873 - 28 Sep 2025
Abstract
Background/Objective: Video games offer an innovative tool for delivering active aging interventions. The objective of this study was to analyze the efficacy of an enhanced version of a cognitive–behavioral intervention to promote active aging, administered through a video game, on perceived health and [...] Read more.
Background/Objective: Video games offer an innovative tool for delivering active aging interventions. The objective of this study was to analyze the efficacy of an enhanced version of a cognitive–behavioral intervention to promote active aging, administered through a video game, on perceived health and healthy lifestyle habits. Methods: A total of 556 participants aged 45 or older (74.3% women, mean age of 60.8 [SD = 8.0]) were randomly assigned to a cognitive–behavioral intervention to promote active aging administered via an interactive, multimedia, online, and serious video game with a complementary smartphone app (CBI-V; n = 279) or to a control group receiving non-specific online information (CG; n = 277). Perceived health (General Health, Body Pain, Physical Functioning, Physical Role, Vitality, Social Functioning, Emotional Role, Mental Health, Physical and Mental Summary Indices); healthy habits, including sleep hygiene behaviors, physical activity, and eating habits; dropouts; adherence to the intervention (completed modules; total playtime; time devoted to cognitive training; number of cognitive task attempts and tasks completed between modules); and satisfaction with the intervention were assessed by independent, blind evaluators via an online platform before and after the intervention. Results: At the post-intervention, the CBI-V group obtained significantly better scores in General Health (p < 0.001), Mental Health (p = 0.015), sleep hygiene (p < 0.001), physical activity (p = 0.024), and eating habits (p = 0.001) than the CG. The effect sizes were small (d = −0.188 to 0.334). Clinically significant changes were higher in the CBI-V group than in the CG in General Health (p = 0.029), Physical Function (p = 0.028), Social Function (p = 0.011), Emotional Role (p = 0.008), Mental Health (p = 0.026), Physical Summary Index (p = 0.010), sleep hygiene (p = 0.020), and eating habits (p = 0.019). Participants reported a high level of satisfaction with the intervention, with a mean score of 25.4 (SD = 4.0) out of a maximum of 32 on the intervention satisfaction measure. Conclusions: These findings support the efficacy of a cognitive–behavioral video game intervention in enhancing perceived health and promoting healthy lifestyle habits among people aged 45 and above. Full article
(This article belongs to the Section Mental Health)
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19 pages, 472 KB  
Review
Nutrition and Physical Activity in the University Population: A Scoping Review of Combined Impacts on Psychological Well-Being, Cognitive Performance, and Quality of Life
by Paride Vasco, Salvatore Allocca, Claudia Casella, Francesco Paolo Colecchia, Maria Ruberto, Nicola Mancini, Maria Casillo, Antonietta Messina, Marcellino Monda, Giovanni Messina, Vincenzo Monda, Antonietta Monda, Fiorenzo Moscatelli and Rita Polito
J. Funct. Morphol. Kinesiol. 2025, 10(4), 374; https://doi.org/10.3390/jfmk10040374 - 27 Sep 2025
Abstract
Background: University students are particularly vulnerable to psychological distress due to the transitional nature of this life phase and increasing academic, social, and financial pressures. Accumulating evidence indicates that lifestyle behaviors—especially nutrition and physical activity—play a critical role in shaping mental health, cognitive [...] Read more.
Background: University students are particularly vulnerable to psychological distress due to the transitional nature of this life phase and increasing academic, social, and financial pressures. Accumulating evidence indicates that lifestyle behaviors—especially nutrition and physical activity—play a critical role in shaping mental health, cognitive functioning, and overall well-being in this population. Methods: The objective of this scoping review was to systematically map the literature on the combined impacts of diet and physical activity on psychological well-being among university students. Following PRISMA-ScR guidelines, an initial search of three major databases (PubMed, Sciencedirect, and Wiley) yielded 718 articles. After a multi-stage screening process, 39 articles of various designs (including cross-sectional, interventional, and review studies) focusing on non-clinical student populations were included. The studies were then thematically analyzed. Results: While most research explored isolated behaviors, a smaller set of integrated studies revealed synergistic effects, reporting enhanced outcomes in mental health and quality of life. Notably, several articles proposed practical strategies—such as app-based tools, structured wellness initiatives, and interdisciplinary educational programs—as effective means to support healthier habits. Conclusions: The evidence strongly suggests that universities should prioritize holistic, multi-component wellness strategies over siloed, single-behavior initiatives. Developing integrated programs that combine nutritional education and physical activity support represents a practical and effective approach to enhance student well-being. Full article
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