Aim:This study aims to investigate the effects of administering coenzyme Q10 (CoQ10) after both short-term and long-term sciatic nerve damage.
Methods:Six groups of adult male Wistar albino rats were used. Sciatic nerve injury was performed on the rats in the short-term injury (STI) and long-term injury (LTI) groups for 15 and 60 s. For 21 days, the rats in the CoQ10, STI + CoQ10, and LTI + CoQ10 groups were also administered CoQ10 orally at a dose of 10 mg/kg of body weight; the control (Cont) group received no treatment. The nerve samples were evaluated by electrophysiology, the sciatic functional index (SFI), stereological investigations, and light and electron microscopic methods.
Results:The number of myelinated axons was higher in the LTI group according to the Cont and the sham groups. The numbers of axons in the LTI and LTI + CoQ10 groups were higher than that in the STI and STI + CoQ10 groups. Latency and amplitude levels were significantly changed following STI and LTI treatment and CoQ10 treatment significantly improved the results following the injuries. SFI results showed highly significant differences between the Cont and STI, Cont and LTI, Cont and STI + CoQ10, STI + CoQ10 and LTI + CoQ10, and Cont and LTI + CoQ10 groups. Microscopic examinations indicated that LTI produced a significant change in the nerve structure than STI. CoQ10 ameliorated the degree of injury.
Conclusions:Treatment with CoQ10 following sciatic nerve damage was more successful in the LTI than the STI group, and it may, therefore, effectively improve peripheral nerve regeneration, especially following LTI.

Aim:This study investigates the association between ApoE genotype, plasma cholesteryl ester (CE) levels, and Alzheimer’s disease (AD) status, with a focus on CE(20:4) and CE(22:5) levels as potential indicators of lipid metabolism alterations in AD patients.
Methods:Publicly available metabolomics data (DOI: 10.3233/JAD-215448) from 94 AD patients and 62 controls aged 55 and older were re-analyzed. CE levels were examined using non-parametric tests due to the non-normal overall data distribution. Comparisons were stratified by ApoE genotypes (ε3/ε3 and ε3/ε4).
Results:Significant increases in CE(20:4) and CE(22:5) levels were observed in AD patients with the ApoE ε3/ε4 genotype compared to controls (p-values 0.0387 and 0.0348, respectively). No significant differences were found for other CEs or among ε3/ε3 carriers (except for sex). Overlap between CE levels in AD and control groups limits their potential as diagnostic biomarkers but underscores their role in lipid dysregulation in AD pathophysiology.
Conclusions:Elevated CE(20:4) and CE(22:5) levels in ε3/ε4 AD patients highlight lipid metabolism alterations associated with ApoE genotype. While not providing standalone biomarkers, these findings offer insights into AD-related lipid dysregulation and warrant further investigation in high-risk ε4/ε4 carriers and therapeutic targeting of lipid metabolism.

Neurodegenerative diseases are a complex ensemble of ailments characterized by progressive neuronal deterioration and ultimate loss, resulting in drastic impairments of memory, cognition and other brain functions. These incapacitating conditions are challenging for the public health system worldwide, with unfortunately no real cure and lack of efficient drugs capable of delaying or reversing these diseases. In this context, the endocannabinoid system and exogenous cannabinoids represent an interesting field of research due to numerous studies highlighting the neuroprotective effect of cannabinoids from different sources, i.e., endogenous, phytocannabinoids, and synthetic cannabinoids. This review highlights the multilayered effects of cannabinoids and the endocannabinoid system to block the progression of neurodegeneration and minimize the deleterious effects of insults that affect the brain. We illustrate examples showing that the main effects of cannabinoids modulate different components of the brain response to these insults at the level of three major mechanisms involved in neurodegeneration: neuroinflammation, excitotoxicity, and oxidative stress.

Aim: Growing evidence suggests that Attention Deficit Hyperactivity Disorder (ADHD) may not be a single entity with a universal remedy, but rather a group of conditions resulting from interactive bio-psycho-social factors and requiring specifically targeted interventions. ADHD research, including neurophysiology, faces inconsistent findings due to heterogeneity. This variety might indicate different physiopathogenic mechanisms. This study aimed to identify dysfunctional mechanisms behind ADHD symptoms and test if targeting these dysfunctions can improve clinical outcomes.
Methods: 230 children with ADHD diagnosis studied with hypothesis-related variables from electroencephalogram (EEG) visual inspection and quantitative z-scored power, coherence and ratios, and from event-related brain potentials (ERPs) z-sored P50, N100, N200, P300 latencies amplitudes and ratios. Parametric and non-parametric classifications were conducted on neurophysiological findings to identify clusters and design neuropsychologically-based recommended treatments (NBRTx). Treatment response evaluated through ADHD scores comparing NBRTx with guidelines recommended treatment (GBRTx). Treatment selected by agreement between each child’s physician and the parents, both parties thoroughly informed.
Results: Six clusters of neurophysiological findings were identified, each characterized by a combination of EEG/ERP abnormalities hypothetically related to distinct dysfunctional mechanisms. Cluster (C) findings, hypothetical dysfunction, and treatment recommendations: C1: Longer P300 latencies, hypodopaminergia: methylphenidate. C2: Centrotemporal spikes, hyperexcitable network: carbamazepine. C3: Bisynchronous spike-waves complexes, thalamocortical involvement: valproic. C4: Altered psychosis-related variables: risperidone. C5: Altered migraine-related variables: valproic. C6: Abnormal maturational interhemispheric rate: tailored psychotherapy. At 3 months, ADHD scores decreased with methylphenidate (MPH) only in C1. In other clusters children under NBRTx had good responses, those under GBRTx did not, and were switched to NBRTx with significant improvement at 6 months.
Conclusions: Six different neurophysiological mechanisms responding to targeted interventions were identified by neurophysiological signatures. A personalized medicine approach guided by physiopathogenic mechanisms may be necessary when facing multifactorial, heterogeneous disorders such as ADHD.

Similar to other psychiatric disorders, drug addiction is linked to changes in neuronal activity within the mesolimbic system, which consists of dopamine (DA) neurons of the ventral tegmental area projecting to the ventral part of the striatum, the nucleus accumbens (NAc). All drugs of abuse indeed artificially increase DA concentration in the NAc, which hijacks the reward system and triggers lasting behavioral alterations, including compulsive drug-seeking and drug-taking behavior despite negative consequences and a high rate of relapse after abstinence. DA chiefly signals through DA receptor (DAR) type 1 (D1R) and type 2 (D2R), which are G protein-coupled receptor (GPCR) that are positively and negatively coupled to adenyl cyclase, respectively. Multiple evidence indicates that the potent modulatory roles of DA on other neurotransmitters and neuromodulator systems implicate the direct physical interactions (i.e., heteromerization) of DAR with other receptors. DAR heteromerization, which is increased in several preclinical models of psychiatric disorders, leads to a reciprocal and fine-tuned modulation of DAR and partner receptors, therefore suggesting that targeting DAR heteromerization may contribute to the development of clinically relevant strategies. Herein, we provide an overview of current methodologies used for detecting receptor heteromers both in heterologous systems and in situ in the brain and discuss their respective advantages and limitations. We also argue that D1R and D2R have been shown to form heteromers with multiple partner receptors in heterologous systems but only few studies were able to a provide proof of their existence in the brain or establish their biological roles. This review will emphasize on studies describing the modulation and functions of DAR heteromerization in the brain in preclinical models of psychiatric disorders, with a particular focus on addiction, a field in which those heteromerization processes have been the most extensively studied.

Stroke is the third leading cause of death and disability in industrialized countries. The estimated costs of stroke to the healthcare system are $85 billion in the United States and $40 billion in the European Union. Despite the extensive research over the past decades, only therapies aimed at restoring blood flow to the affected area have been successful. However, the high risk of causing intracranial hemorrhage limits the application of this type of therapy to a small number of patients. Several studies have shown that, in addition to its well-known regulatory function in erythropoiesis, erythropoietin (EPO) is a potent neuroprotective agent against ischemic stroke. However, the use of EPO to treat stroke requires long-term protocols, high doses, and multiple administrations, which may cause thromboembolic complications due to increased hematocrit and blood viscosity, making EPO treatment unsuitable. To mitigate these adverse effects, various EPO analogues with neuroprotective properties but lacking erythropoietic activity have been investigated. This review aims to provide an overview of the protective mechanisms of EPO and its derivatives in the treatment of stroke.

Chronic upper limb pain is rather common among people in general and is characterized by a complex diagnosis due to the wide variety of factors that are involved in its development. In terms of treatment, pharmacology and manual therapy have classically been the most used options. However, based on current evidence, recommendations are more inclined to apply multimodal treatments, mainly with exercise therapy and pain education, based on the patient-centered care model. This case report details the evaluation and treatment of a 23-year-old woman with chronic upper limb pain using a multimodal physical therapy with a biobehavioral approach. The intervention lasted 12 weeks with a total of 9 sessions, in which manual therapy, therapeutic exercise, pain neuroscience education, motion representation methods, and sensory retraining were applied. The treatment resulted in a substantial improvement in the patient’s health condition. This case report indicates that a multimodal physical therapy treatment based on a biobehavioral approach may offer benefits in reducing pain symptoms and enhancing somatosensory, motor-functional, and affective-cognitive abilities in patients with chronic upper limb pain, as observed in the described case. Accordingly, this treatment can be a therapeutic option for patients with chronic upper limb pain.

The diagnosis of attention deficit hyperactivity disorder (ADHD) poses several diagnostic problems, as is widely acknowledged. The name points to two symptoms only, which are unspecific and embedded in many more neuropsychological symptoms. The additional deficits, such as problems with orientation, memory, cognition, emotion, autonomic nervous regulation, and motor dysfunctions, can be more important for patients in their daily lives than attention and hyperactivity. The general term “neurodevelopmental disorder (6A0)” in the International Classification of Diseases (ICD-11) is more appropriate and should be used instead. A further question is, when a dysfunction, such as inattention, becomes a clinical sign. As outlined in the International Classification of Functioning, Disability and Health (ICF), the context and the associated impairment decide on the clinical relevance of dysfunctions. Accordingly, the diagnosis of neurodevelopmental disorders must start with the description of context requirements, then assess capacity restrictions, and finally relate these to neuropsychological deficits. Subdimensions of neurodevelopmental disorders, as listed in ICD-11, are of no additional benefit, as they are comorbid merging syndromes.

Neurodegenerative diseases represent a significant and growing challenge to public health worldwide. Current therapeutic strategies often fall short in halting or reversing disease progression, highlighting the urgent need for novel approaches. Extracellular vesicles (EVs) have garnered attention as potential therapeutic agents due to their role in intercellular communication and their ability to transport bioactive cargo, including proteins, nucleic acids, and lipids. This review provides a comprehensive overview of the biology of EVs, their involvement in neurodegenerative diseases, and the potential for EV-based therapies. We discuss the different types of EVs, their biogenesis, and their cargo composition, emphasizing their relevance to neurological processes such as protein misfolding, neuroinflammation, and oxidative stress. Preclinical studies investigating EVs as carriers of therapeutic cargo and their ability to promote neuronal survival and regeneration are examined, with a focus on evidence from animal models of neurodegenerative disorders. We explore the use of EVs in the treatment of neurodegenerative diseases, including ongoing clinical trials, methods for EV isolation and modification, and future perspectives on personalized EV-based therapies designed to meet the unique needs of individual patients. Overall, this review highlights the potential of EVs as a promising avenue for neurodegenerative disease therapy, while also addressing key research gaps and translational hurdles that need to be overcome for their successful clinical implementation.

Neuroinflammation is a hallmark of various neurodegenerative and neuropsychiatric disorders, driven by complex interactions between neurotransmitter receptors and immune signaling pathways. Among these, heteroreceptor complexes-functional assemblies formed by the physical interaction of different G protein-coupled or ionotropic receptor subtypes within the same membrane microdomain-play a crucial role in modulating synaptic activity, neuroimmune responses, and inflammatory cascades. For example, the A2A-D2 receptor complex modulates dopaminergic signaling in the striatum and has been implicated in Parkinson’s disease pathology. These receptor-receptor interactions influence key signaling pathways involving dopamine, serotonin, glutamate, adenosine, and cannabinoid systems, thereby contributing to the pathophysiology of Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, schizophrenia, and depression. Dysregulation of heteroreceptor complexes disrupts neuronal homeostasis, exacerbates neuroinflammatory responses, and influences microglial and astrocytic activation. Understanding the molecular mechanisms governing these interactions, including allosteric modulation and biased agonism, offers novel therapeutic avenues for targeting neuroinflammation. Pharmacological strategies, such as selective allosteric modulators, biased agonists, and receptor-specific ligands, aim to restore heteroreceptor function and mitigate neuroinflammatory damage. Emerging clinical trials-such as those evaluating A2A receptor antagonists like istradefylline for Parkinson’s disease and 5-HT2A antagonists for schizophrenia-have shown promising neuroprotective and anti-inflammatory effects, although larger-scale, long-term studies are needed to confirm efficacy. This review highlights the pivotal role of heteroreceptor complexes in neuroinflammation, discusses their therapeutic potential, and underscores the need for further research into their functional dynamics to develop effective interventions for neurodegenerative and neuropsychiatric diseases.

Background:High-intensity training (HIT) increases walking speed for individuals with chronic stroke. Several recent studies have examined its application for those in the subacute phase following a stroke. This systematic review examines the application of HIT in the subacute phase following a stroke.
Methods:A systematic search for studies that compared HIT (defined as 60–84% heart rate reserve or 77–93% heart rate maximum) to lower-intensity training, conventional physical therapy, placebo, or no intervention in adults 0–6 months post stroke. Randomized or quasi-randomized controlled trials, cohort studies, and case-controlled studies published in peer-reviewed journals in English were included. The primary outcome of interest was walking speed; the secondary outcome was walking endurance. Two independent evaluators performed literature selection, data extraction, and assessed study quality using the revised Cochrane risk-of-bias tool. Reporting followed PRISMA guidelines.
Results:Of 1,642 studies initially retrieved, 10 studies with a total of 677 participants were included. All experimental groups showed an average positive change in self-selected walking speed (range: 0.20–0.56 m/s). HIT resulted in statistically significant improvements in walking speed versus comparison interventions in 4 studies. Eight studies that measured walking endurance found an average increase of 60 to 197 m following HIT.
Discussion:HIT demonstrated superior outcomes in self-selected walking speed and walking endurance for individuals in the subacute phase post stroke, both immediately following intervention and at follow-up. These findings align with the clinical practice guideline (CPG) for chronic stroke patients. Further randomized clinical trials are needed to strengthen the evidence.

Polyunsaturated fatty acids (PUFAs) are critical for human health, serving as key components of cellular membranes and regulators of various physiological functions. Since the body can endogenously synthesize only a small amount of these fatty acids from precursors, adequate dietary intake is essential. This article discusses the vital role of omega-3 fatty acids, particularly docosahexaenoic acid (DHA), in fetal brain development, with maternal omega-3 intake during pregnancy linked to improved neurodevelopment and long-term cognitive outcomes. However, variability in study findings highlights the need for further research to clarify DHA’s mechanisms of action. This article explores recent findings indicating that insufficient omega-3 levels during pregnancy disrupt key neurodevelopmental processes, particularly microglial function, potentially elevating the risk of cognitive impairments and neurodevelopmental disorders, highlighting the need for further research to confirm these effects and elucidate underlying mechanisms and long-term consequences. Ensuring adequate maternal omega-3 intake is vital for supporting healthy brain development and reducing these risks. Additionally, DHA and eicosapentaenoic acid (EPA) show promise in treating pediatric depression by modulating the gut-brain axis, reducing neuroinflammation, and restoring autonomic nervous system function-mechanisms implicated in depression. While omega-3 supplementation holds potential as an adjunctive treatment for pediatric major depressive disorder (MDD), further research is necessary to refine dosing strategies and explore underlying mechanisms, ultimately advancing neuropsychiatric care.

Aim: Aging and early Alzheimer’s disease (AD) affect pattern separation (PS) based mnemonic discrimination in humans. PS function involves the dentate gyrus (DG), a brain region producing new neurons during adulthood. Aging and AD presumably affect PS and DG function through different mechanisms, although it has never been clearly shown within the same study. Passive immunotherapy targeting β-amyloid peptides (Aβ) was used to determine the relative contribution of abnormal levels of Aβ to early PS deficits in two mouse models of aging and amyloid pathology, and potential involvement of adult neurogenesis.
Methods: Female Tg2576 mice were tested in a spatial PS task from the age of three months to determine the age of onset of PS deficits. A cohort of five-month-old female Tg2576 mice and a cohort of 20-month-old male C57BL/6J mice were treated with passive immunization for four weeks, and then tested for PS performance. ELISA assays were used to quantify Aβ levels in CA3/DG regions of these mouse models. DG recruitment during PS testing was assessed with an Egr-1 ex vivo imagery. The contribution of adult-born neurons to a potential rescue of PS performances was evaluated using bromodeoxyuridine and doublecortin co-immunostainings.
Results: Spatial PS deficits appeared first in four-month-old female Tg2576 mice, an early pre-plaque stage of Alzheimer pathology. Aβ immunotherapy restored PS performance in Tg2576 mice, but not in aged male C57BL/6J mice. PS impairments were associated with an overactivation of the DG in both models and a potentially abnormal level of immature adult-born neurons in Tg2576 mice.
Conclusions: Alleviation of PS deficits following Aβ immunotherapy in Tg2576 mice is associated with reduced DG activation and improved adult-born neurons maturation. The absence of beneficial effects in aged mice suggests that PS deficits in aging and AD may be related to different underlying mechanisms.

Aim:Our previous research (Abstract, J Vessels Circ. 2021;2) suggested an increased risk of thrombotic events, including ischemic strokes, in patients with COVID-19. This study aims to determine the mortality rate and its predictors in patients with stroke and concurrent COVID-19 infection.
Methods:A retrospective analysis was conducted on stroke patients admitted to three Iranian referral hospitals within a 3-month period during the COVID-19 pandemic (COV-pos and COV-neg groups). The mortality rate was compared to a similar period one year before the pandemic (non-COV group). The Cox proportional hazards model was used to assess the independent and interactive effects of various variables on mortality.
Results:Among 124 stroke admissions, 59 (47.6%) had confirmed COVID-19 infection. The COV-pos group had a significantly higher initial NIHSS score (P = 0.001) compared to other groups. Mortality rates were 49.2%, 24.2%, and 17.3% in the COV-pos, COV-neg, and non-COV groups, respectively (P ＜ 0.001). Posterior cerebral artery (PCA) stroke (HR = 65.099), internal carotid artery (ICA) stroke (HR = 19.102), and a history of diabetes mellitus (HR = 3.824) were identified as the most significant predictors of mortality in patients with stroke and COVID-19 infection.
Conclusions:Stroke patients with COVID-19 infection exhibited a significantly higher mortality rate compared to patients without COVID-19. The type of stroke involving the PCA or ICA and a history of diabetes emerged as the strongest predictors of mortality in the studied population.

Neurodevelopmental disorders form a considerable group in the DSM-5, the diagnostic mental disorders manual employed in numerous regions. Some disorders are identified with biomedical tests while those from unknown sources are verified with behavioural scales. They are ubiquitous in youths, significantly impacting their behaviours and lives. They begin in early development and persist mostly throughout their lifespan with chronogeneity, i.e., changes over time. They often form comorbidities, adding to the complexity by creating “new” phenotypes at the intersection. The article aims to provide clinically critical views of ADHD and the added burden of alexithymia comorbidities with profound effects on developmental language disorder (DLD) and autism. The noted problem is the DSM-5’s mental health categorical measure of disease identification of the disorders’ symptoms, but the neglect of comorbidity. The article’s guiding theory is the adoption of the dimensional approach in addressing the target disorders, and the Vygotskian social interactional and linguistic-cognitive learning theory in proposing dimensional treatments. The ADHD including alexithymia in these disorders exhibit commonalities: 1. all are dimensional conditions rather than categorical ones requiring dimensional approaches as these include the entire continuum; 2. all show accompanying developmental language and learning limitations, and 3. all have histories of literacy acquisition problems that impact their academic trajectory while sabotaging their executive functions (EFs) development and undermining the affected individuals and the clinicians’ treatment efforts. The suggested interventions target multiple ages based on the Vygotskian social-interactional learning theory acknowledging cognitive development as language and knowledge transmitted via psychosocial interactions facilitating the internalization of education that actively forges learners’ character, psychology, and behaviours. They are meant to address their conditions’ dimensionality, remediate cognitive linguistic lags, alleviate symptoms, and substitute ineffective learning and thinking habits with more functional ones. Issues to be addressed in developing a clinical plan complete the review.

MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a pivotal role in post-transcriptional gene regulation, influencing various biological processes such as cell division, proliferation, and apoptosis. Recent research has illuminated the significant involvement of miRNAs in neurological disorders, which encompass a wide range of conditions affecting both the central and peripheral nervous systems. These disorders, including neurodegenerative diseases like Alzheimer’s and Parkinson’s, as well as psychiatric conditions such as depression and schizophrenia, impose a substantial burden on global health. Dysregulated miRNAs contribute to disease pathogenesis by modulating neuronal differentiation and related signaling cascades. This review explores the biogenesis of miRNAs and their dysregulation in neurological disorders, highlighting specific miRNAs that serve as potential biomarkers and therapeutic targets. For instance, decreased levels of miR-125b-5p and miR-26b-5p in cerebrospinal fluid have been associated with Alzheimer’s disease progression. In Parkinson’s disease, distinct profiles of dysregulated miRNAs have been identified, including miR-7-5p and miR-153-3p, which target α-synuclein. Furthermore, studies have demonstrated the potential of miRNA-based therapies to modulate disease processes and improve clinical outcomes. This review critically evaluates current therapeutic strategies for miRNA delivery in neurological disorders, focusing on advanced platforms such as nanocarriers, exosomes, viral vectors, and ligand-mediated systems designed to overcome the blood-brain barrier. We also explore the future of miRNA research in the context of precision medicine, highlighting the importance of targeted delivery, safety optimization, and integration of patient-specific molecular profiles. A comprehensive understanding of miRNA-regulated networks will be essential for developing innovative diagnostics and personalized treatments for neurodegenerative and neuroinflammatory diseases.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating multisystem disorder affecting an estimated 0.4% to 2.5% of community populations. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and marked metabolic heterogeneity underscore its complex pathophysiology. The hypothalamic peptides hypocretin-1 and -2 (also known as orexin-A and orexin-B), synthesized by neurons in the lateral hypothalamus, regulate sleep-wake cycles, arousal, autonomic function, and energy homeostasis. This integrative review aimed to synthesize current evidence on hypothalamic orexinergic dysfunction in ME/CFS and assess its potential as a biomarker framework for stratification in precision medicine. The review followed Whittemore and Knafl’s five-stage methodology. Comprehensive searches were conducted across PubMed, Scopus, Web of Science, and OpenAlex up to April 2025, supplemented by manual screening of reference lists. Data extraction and synthesis were performed using constant comparison techniques to integrate quantitative outcomes with theoretical insights. Twenty-seven studies met the inclusion criteria, consistently reporting reduced orexin-A levels in individuals with ME/CFS and variable orexin-B responses indicative of biomarker potential. Neuroendocrine findings, including alterations in cortisol and adrenocorticotropic hormone levels, along with inflammatory profiles, confirmed the involvement of neuroimmune interactions. Multi-omics analyses further delineated distinct patient subtypes characterized by unique molecular signatures. Hypothalamic orexinergic dysfunction emerges as a central feature of ME/CFS, with orexin-B representing a promising candidate biomarker. The integration of orexin profiling with multi-omics data and machine learning strategies provides a viable pathway towards precision-medicine interventions for this heterogeneous condition.

Aim:Epilepsy is associated with cognitive and neuropsychiatric impairments, affecting attention, memory, executive functions, and emotional well-being. While these impairments are well-documented in general epilepsy populations, limited research focuses on economically active young adults who face unique cognitive demands in competitive academic and professional environments. The objective of this research was to evaluate the cognitive and neuropsychiatric outcomes in economically active young adults with epilepsy compared to matched controls.
Methods:An observational, analytical, case-control study was conducted at a secondary medical center in Mexico. Participants included 25 patients with well-controlled epilepsy and 25 matched controls. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Addenbrooke’s Cognitive Examination III (ACE-III). Anxiety and depression were evaluated using the Beck Anxiety Inventory and Patient Health Questionnaire-9 (PHQ-9). Statistical analysis included Student’s T-test and Chi-square for cognitive scores and Wilcoxon rank-sum tests for non-parametric data.
Results:Cognitive impairments were significantly more frequent in patients with epilepsy than in controls, particularly in attention (p = 0.041), episodic memory (p = 0.048), clock drawing (p = 0.004), and cube copying (p ＜ 0.001). Verbal (p = 0.011) and semantic fluency (p = 0.027) were also affected. No significant differences were observed in anxiety (p = 0.221) or depression (p = 0.800) between groups.
Conclusions:Economically active young adults with well-controlled epilepsy showed significant cognitive impairments, particularly in attention, memory, visuospatial, and executive functions, independent of anxiety and depression levels. This study underscores the need for comprehensive cognitive and neuropsychiatric evaluations in epilepsy treatment, regardless of seizure control. It advocates for targeted cognitive rehabilitation and a holistic approach to epilepsy care beyond seizure frequency control.

Aim: Pain and overuse syndromes are common problems among musicians. The prevalence of musculoskeletal complaints in professional musicians ranges from 62% to 93%. Excessive muscle tension, rigidity, weakness, and stiffness in various anatomical regions such as the arm, neck, and lower back are common complaints. This study investigates the prevalence and severity of musculoskeletal symptoms, such as the amount and distribution of pain in the cranio-cervical-mandibular complex, the presence of bruxism and temporomandibular noises in conservatory clarinet students.
Methods:A 36-item questionnaire regarding the presence of musculoskeletal symptoms was sent to all clarinet students at Italian conservatories.
Results:From the analysis of the responses of 100 students, the occurrence of pain was not related to experience and was higher during non-musical activities (70%) than during performance (38%) (P = 0.001). Female players reported higher levels of pain using a 0–10 numeric rating scale: 4 during performance, 5 during non-musical activities, while males scored 3 in both conditions. A slight positive correlation emerged between pain and years of study (P = 0.03). The most painful regions were those of the posterior neck (29–45%) and the masseter muscle (28–31%). Temporomandibular noises were prevalent in female students (female 43%, male 22%, P = 0.005) and were often associated with bruxism (P = 0.015).
Conclusions:Clarinet students should be informed about the symptoms they may experience, but also about the prevention of these symptoms and the techniques to improve clarinet performance.

Exercise may be one of the most potent tools for protecting the brain-but only through active participation can its benefits be realized. This perspective provides a brief overview of current research avenues and key insights into the role of physical activity and exercise in preventing and mitigating chronic and neurodegenerative diseases and promoting optimal health across the population. The perspective opens with a summary of key findings on how exercise supports brain health and cognitive well-being. It then draws on rodent model studies which shed light on the molecular mechanisms behind these benefits. The paper addresses challenges in translating this research into effective, real-world exercise programs and introduces a new framework aimed at fostering global, inclusive initiatives. This transformative approach is designed to reach individuals across all ages, backgrounds, and health statuses. A central theme throughout is the critical role of psychological factors in exercise adherence-highlighting the need to tackle these barriers if scientific advances are to translate into meaningful benefits for diverse populations.

Aim:Post-exertional malaise (PEM) has been a challenging construct to measure, particularly with self-report instruments, which have the benefits of being less expensive and less invasive than cardiopulmonary exercise tests. Existing PEM questionnaires have often been used for diagnostic purposes and less frequently as outcome measures. Few self-report PEM measures address comprehensive PEM domains, including types of triggers, duration of symptoms, delayed symptom onset, number of symptoms, frequency and severity of symptoms, as well as whether pacing or other strategies reduce or eliminate PEM. Without characterizing these features, salient aspects of PEM would be overlooked. However, efforts to assess all these domains can be time-consuming and potentially burdensome.
Methods:The current study offers investigators a brief but comprehensive instrument of critical PEM domains, called the DePaul Symptom Questionnaire (DSQ)-PEM-2, to assess PEM. Validation data were derived from a large sample of individuals with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).
Results:The DSQ-PEM-2 was developed using an existing dataset of individuals with ME, CFS, or both ME and CFS, allowing comprehensive coverage of key PEM domains.
Conclusions:The DSQ-PEM-2 can be used either for diagnostic purposes or as an outcome measure. The instrument’s time frames for symptom manifestation can be adapted to suit a variety of research or clinical contexts. Future validation studies need to include a healthy control group.

Healthcare professionals, especially those in rehabilitation, are increasingly vulnerable to occupational burnout, particularly in the post-pandemic landscape. This review synthesizes existing literature on the prevalence of burnout, possible contributing factors, resilience mechanisms, and interventions tailored to physiotherapists and related disciplines. A narrative review was carried out by combing through databases including PubMed, Scopus, and Web of Science for literature published between 2020 and 2025. The studies focused on burnout, mental health, and resilience among rehabilitation professionals were included in the review. Burnout remains prevalent, with emotional exhaustion and reduced personal growth commonly reported. Risk factors include lack of support, excessive workload, and exposure to workplace bullying. Protective mechanisms entail individual resilience behaviors, social support, and institutional strategies such as regulated supervision and workload management. Addressing burnout in rehabilitation settings requires a dual approach-strengthening individual factors and directing systemic organizational reforms. Embedding resilience education into the training core curriculum and workplace code of conduct may boost mental well-being.

Tau phosphorylated at threonine 217 (p-tau217) has moved from research novelty to clinical reality, but its greatest value lies in dynamic monitoring, not static stratification. The pace of adoption of the plasma measurement of p-tau217 now demands clear guidance on optimal use. Two complementary evidence strands inform this perspective. First, a multi-cohort evaluation of a commercial assay shows high concordance with amyloid and tau reference standards and supports a pragmatic three-zone interpretation, rule-out, indeterminate, and rule-in, that can streamline diagnostic pathways while preserving accuracy. Second, longitudinal analyses in amyloid-positive individuals reveal that the most informative property of p-tau217 is dynamic: steeper rises occur in those who decline faster, whereas baseline values substantially overlap across outcome groups. These findings show that plasma p-tau217 levels can be a complementary tool for triage, enrichment, and longitudinal monitoring, but not as a time-stable baseline stratifier for defining trial cohorts or assessing therapeutic efficacy. Stratification should instead anchor to independent, stable measures such as tau burden measured by positron emission tomography (PET), structural magnetic resonance imaging (MRI), and cognitive history, reducing misclassification and avoiding circular validation. Comparable scrutiny should be applied to other p-tau biomarkers and to composite measures, such as the p-tau217/Aβ_1–42 ratio, to rigorously define their risk-benefit profile, guide therapeutic evaluation, and maximize translational impact.

Parkinson’s disease (PD) is a devastating neurodegenerative condition characterized primarily by the degeneration of the dopaminergic neurons in the substantia nigra, causing motor dysfunction and many non-motor symptoms. Available pharmacological treatments and therapies provide symptomatic relief but do not halt the progression of PD. Gene therapy has been recognized as a valuable therapeutic frontier, providing the possibility of disease modification by targeting the underlying molecular and cellular mechanisms of PD. The parts of the methodology used for gene therapy entail the delivery of genetic material into particular regions of the brain with the aid of viral vectors to improve the synthesis of dopamine, maintain the integrity of neurons, or control pathological pathways. Recent clinical trials have shown promising efficacy and safety profiles for many gene therapy methods, consisting of those targeting enzymes in the biosynthesis of dopamine [e.g., L-amino acid decarboxylase (AADC)], synuclein alpha pathology, and neurotrophic factors [e.g., growth-derived neurotrophic factor (GDNF)]. However, in spite of these developments, there are limitations in vector delivery and prolonged expression of genes, as well as patient-specific responses. This review highlights the present landscape of gene therapy in PD, discussing the latest successes, ongoing clinical trials, and future perspectives that could shape therapeutic paradigms for PD.

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, neuroinflammation, and accumulation of amyloid-beta plaques and tau tangles. Emerging research emphasizes the gut-brain axis as a key modulator of AD pathogenesis, with gut microbiota influencing neuroimmune, neurochemical, and metabolic pathways. This review examines the therapeutic and preventive potential of probiotics, live beneficial microorganisms, in modulating the gut-brain axis to mitigate AD progression. Modifying gut microbiota presents a novel, potentially modifiable approach to influence AD pathophysiology and improve cognitive outcomes, offering insights for adjunctive clinical strategies. A systematic literature search was conducted across PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library for studies published up to July 2025. Studies were classified by design, sample size, follow-up duration, cognitive and biomarker outcomes, and risk of bias, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines to ensure transparency and reproducibility. Preclinical studies indicate that probiotics can regulate gut microbiota, reduce oxidative stress, suppress neuroinflammation, and enhance synaptic plasticity, improving cognition in animal models. Clinical trials suggest potential benefits in humans, including improved memory scores and reduced inflammatory biomarkers, though limited sample sizes, trial duration, and strain variability constrain conclusions. Overall, probiotics demonstrate promise as an adjunctive intervention in AD. Further long-term, strain-specific, and large-scale clinical studies are needed to confirm efficacy, establish causality, and optimize therapeutic strategies.

The investigations pertaining to the effectiveness of natural products in novel drug development for the prevention of a myriad of neurodegenerative diseases are offering encouraging prospects in novel drug development. This review endeavors to offer a comprehensive insight into the neuroprotective effects of baicalein (BE) and baicalin (BI), bioactive flavonoids found in Scutellaria baicalensis, primarily from the perspective of Alzheimer’s disease (AD). It systematically encompasses the scientifically pertinent investigations on BE’s prospective benefits in AD models, highlighting its mechanistic approaches and impending therapeutic applications in the amelioration of AD. The multifaceted pharmacological interventions offered by these bioactives, including antioxidant, anti-inflammatory, and immunomodulation effects, reinforce the scientific evidence supporting them as promising candidates for anti-AD agents and for preventing and managing other allied neurodegenerative disorders. These findings suggest that BE and BI, along with other nutraceuticals, may offer a valuable therapeutic strategy for improving symptoms and slowing disease progression in neurodegenerative disorders. Thus, the review intends to offer comprehensive illustrations warranting further investigation to corroborate the safety and efficacy of these bioactives in clinical settings. The researchers are progressively entrusting nature’s own compounds for the treatment of neurodegeneration. Conclusively, this manuscript could aptly serve as an insight to embark upon the remarkable pharmacological actions of these bioactives, which might be harnessed to prevent and manage AD. Nevertheless, the findings so far are promising; still, further investigations are incumbent to establish their safety and efficacy in humans, as BE and BI may offer novel modalities to circumvent this devastating disease.

Aim:Systemic inflammation is a key factor in cognitive decline and neurodegenerative diseases. Polyphenols, such as curcumin, resveratrol, and salidroside, exhibit neuroprotective effects, but their low bioavailability raises questions about their mechanism of action. The gut-brain axis, mediated by microbiome modulation, may play a critical role in their cognitive benefits. This study investigated whether polyphenols (curcumin, resveratrol, and salidroside) improve cognitive function in mice with lipopolysaccharide (LPS)-induced gut inflammation by modulating the gut microbiome and reducing neuroinflammation.
Methods:C57BL/6 mice were divided into five groups: control, LPS, and LPS + polyphenol treatments (curcumin, resveratrol, or salidroside). LPS was administered intraperitoneally to induce inflammation, while polyphenols were given orally for three weeks. Cognitive performance was assessed using the Morris water maze. Gut microbiome composition (16S rRNA sequencing), mitochondrial DNA (mtDNA) damage, and gene expression in brain regions were analyzed.
Results:LPS impaired spatial memory, but resveratrol and salidroside significantly mitigated these deficits. Polyphenols restored beneficial bacteria (e.g., Alloprevotella, Eubacterium) and suppressed pathogenic taxa (e.g., Peptostreptococcales). They also reduced pro-inflammatory markers in the cortex and hippocampus. Curcumin showed weaker effects. No significant mtDNA damage was detected.
Conclusions:Polyphenols, particularly resveratrol and salidroside, improve cognition during systemic inflammation by remodeling the gut microbiome and attenuating neuroinflammation. These findings highlight the gut-brain axis as a therapeutic target for inflammation-driven cognitive disorders.

The glymphatic system (GS) consists of a paravascular fluid-exchange network that regulates cerebrospinal and interstitial fluid dynamics, clears metabolic waste, and modulates neuroinflammation. Aquaporin-4 (AQP-4), expressed in astrocytic end-feet, is central to GS function and blood-brain barrier integrity, but in cerebral ischemia (CI), GS disruption and AQP-4 mislocalization drive cytotoxic edema, inflammation, and vascular dysfunction, worsening outcomes. This review aimed to examine the role of the GS in CI, focusing on pathophysiology and potential therapeutic targets. A PubMed-based literature review was conducted, selecting 51 studies from 115 screened that addressed GS, AQP-4, and ischemic stroke. Evidence suggests that modulating GS flow, through strategies such as enhancing arterial pulsations or regulating AQP-4, may reduce edema and neuroinflammation, although selectively targeting AQP-4 without impairing waste clearance remains a key challenge. The GS represents a promising therapeutic target in ischemic stroke, and a deeper understanding of its physiology may guide the development of neuroprotective interventions; future research should refine pharmacological strategies to optimize glymphatic function and improve recovery in CI patients.

The increasing prevalence of neurodegenerative diseases (NDs), such as Alzheimer’s, Parkinson’s, Huntington’s, multiple sclerosis, and amyotrophic lateral sclerosis, represents a serious global public health issue. Consequently, the search for compounds with neuroprotective potential has intensified. In this context, resveratrol (RSV), a stilbene polyphenol found mainly in red grapes, exhibits important pharmacological properties, such as antioxidant and anti-inflammatory, and has been widely investigated in neuroscience due to its potential in the prevention and treatment of NDs. This narrative review was conducted using the PubMed^® database, with the keywords “resveratrol”, “molecular mechanisms”, “mechanisms of action”, “neuroinflammation”, “oxidative stress”, “autophagy”, “gene regulation”, and “clinical studies”. This study discusses the molecular mechanisms of RSV on NDs, focusing on signaling pathways involved in neuroinflammation, oxidative stress, gene regulation, autophagy, and cell death. Intracellular pathways such as NF-κB, JAK/STAT, MAPK/ERK, PI3K/Akt, and Nrf2/Keap1 are associated with immune modulation mediated by RSV, leading to a decrease in oxidative stress, induction of autophagy, and inhibition of apoptosis. RSV has pharmacokinetic limitations, such as low bioavailability and stability, although RSV can cross the blood-brain barrier. Thus, researches involving nonencapsulated formulations aim to enhance their delivery to the central nervous system. Current in vitro and in vivo studies are promising, although further clinical trials are needed, as few have been conducted and available data remain preliminary. In conclusion, RSV presents multiple benefits to neurological health and shows therapeutic potential in NDs; however, additional clinical studies and translational research are essential to validate and optimize its application.

Background:This study aims to assess oral alpha lipoic acid’s (ALA’s) safety and effectiveness in managing diabetic neuropathy.
Methods:A thorough search of the literature was conducted using PubMed, Google Scholar, and Embase databases, and the study was performed as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results:Based on inclusion and exclusion criteria, nine randomized controlled trials (RCTs) comprising 1,345 subjects were selected. The results showed that ALA has shown significant reduction in glycated hemoglobin (HbA1C) [inverse variance (IV): –0.66, (–0.81 → –0.51) at 95% CI, p ＜ 0.00001, I² = 92%], neuropathy impairment score (NIS) [IV: –1.19, (–2.28 → –0.09) at 95% CI, p = 0.03, I² = 58%], along with improving the neuropathy symptoms and change (NSC) number [IV: –0.18, (–0.35 → –0.01) at 95% CI, p = 0.04, I² = 0%], NSC severity score [IV: –0.65, (–0.83 → –0.48) at 95% CI, p ＜ 0.00001, I² = 89%], total severity score (TSS) [IV: –0.43, (–0.59 → –0.27) at 95% CI, p ＜ 0.00001, I² = 98%], neurological disability score (NDS) [IV: –0.72, (–1.03 → –0.40) at 95% CI, p ＜ 0.00001, I² = 98%], vibration perception threshold (VPT) [IV: –0.35, (–0.50 → –0.19) at 95% CI, p ＜ 0.0001, I² = 96%] and global satisfaction [Mantel-Haenszel (M-H) odds ratio (OR): 3.51, (1.06 → 11.61) at 95% CI, p = 0.04, I² = 72%] when compared to the control or placebo group. However, ALA has not shown significant changes in motor nerve conduction velocity (MNCV) score [IV: 0.26, (–0.44 → 0.96) at 95% CI, p = 0.47, I² = 49%] and NIS-low limb (NIS-LL) [IV: –0.58, (–1.35 → 0.19) at 95% CI, p = 0.14, I² = 0%] when compared to the placebo group.
Discussion:Based on the available moderate to high-quality evidence, we can conclude that oral administration of ALA at doses of 600–1,800 mg may be beneficial in improving/alleviating the symptoms resulting from diabetic neuropathy.

Non-traumatic arterial dissection exhibits a propensity for the Asian population and predominantly affects the posterior circulation. Regrettably, during the initial fortnight prior to diagnosis, approximately one in thirty cervicocephalic artery dissections (CAD) are misdiagnosed. Overlooked CAD, more prevalent in the younger demographic, can result in severe complications such as ischemic stroke, subarachnoid hemorrhage, and possibly death. Comprehensive investigations are necessary to prevent overlooking such a diagnosis. Digital subtraction angiography (DSA) is universally acknowledged as the most efficacious technique for assessing luminal morphology and hemodynamics, but may miss the vessel wall characteristics, an important component for diagnosing dissection. Magnetic resonance angiography (MRA), conversely, is less invasive and can assess vessel wall properties. A high-resolution MRA with vascular wall imaging can efficiently identify conditions such as intimal flaps, double-lumen signs, intramural hematomas, mural thrombi, and pseudoaneurysms, aiding in the evaluation of suspected CAD. MRA with vascular wall imaging and DSA complement each other in the identification and characterization of cerebral artery dissections, both contributing to treatment. In cases of undefined stroke etiology, particularly among the young demographic, utilizing both tests (when one yields no significant findings) may assist in detecting overlooked instances of CAD. The prompt identification and treatment of CAD are essential, particularly for surgical intervention and to avert recurrence in predisposed patients. Identifying the etiology of a stroke or transient ischemic attack is important for providing precise therapy and preventing recurrence.

Background: Ischemic stroke is a leading cause of disability, with calcium (Ca²⁺) dysregulation contributing to neuronal injury and impaired recovery. While early clinical trials targeting calcium signaling showed limited success, growing preclinical evidence supports the potential of calcium modulation for long-term neuroprotection. This systematic review evaluates the long-term effects of calcium modulation in animal models of ischemic stroke.
Methods: A comprehensive search across PubMed, Scopus, Web of Science, and the Cochrane Library up to June 2025 identified studies investigating calcium-targeted interventions (e.g., calcium channel blockers, chelators, antioxidants) with ≥ 30 days of follow-up. Risk of bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I).
Results: Nine studies met the inclusion criteria. Interventions like L-type calcium channel blockers, magnesium sulfate, and ischemic preconditioning consistently reduced infarct volume (e.g., 22.4 ± 0.5% with preconditioning vs. 51.6 ± 2.1% with knockout) and improved neurobehavioral outcomes [e.g., epigallocatechin gallate (EGCG)-treated rats scored 2.17 ± 0.05 vs. 3.63 ± 0.06 in controls]. Molecular pathways involved included phosphoinositide 3-kinase (PI3K)/AKT, stromal interaction molecule 1 (STIM1)/ORAI1, and calcium-sensor proteins such as NCKX2.
Discussion: Calcium modulation holds strong promise for neuroprotection in ischemic stroke models. Although clinical gaps remain, these findings support the development of calcium-targeted therapies for stroke recovery, especially when combined with multimodal strategies.

Aim:Alzheimer’s disease (AD) devastates learning and memory, the defining faculties of the human species. Extracellular amyloid beta (Aβ) deposits and intracellular hyperphosphorylated tau are hallmarks of AD pathology. The exact cause of the disease remains unknown, but a lot of data support AD to be a multifactorial disease. Given the central roles of oxidative stress and neuroinflammation in AD pathogenesis, apocynin, a potent antioxidant and anti-inflammatory agent, was selected for investigation. Apocynin is an aromatic ketone, a naturally occurring methoxy-substituted catechol known to possess numerous biological activities, namely anti-oxidant, anti-inflammatory, etc. The present study assessed apocynin’s potential against an Aβ_1–42-induced sporadic AD rat model.
Methods:In the present study, Wistar rats were subjected to intrahippocampal administration of 200 µmol/L of Aβ_1–42 peptide in right hemisphere. Further were treated with apocynin 50, 150, and 300 mg/kg per orally for 28 days. The study examined the neurobehavioral aspects using the Barnes Maze test (BMT). Hippocampus was examined for the antioxidant (SOD, GSH, catalase, and LPO), inflammatory (TNF-α) parameters, RAGE, caspase-3, PGC-1α expression, and IHC analysis for Aβ load, adult hippocampal neurogenesis markers (BDNF, Ki67, DCX, NeuN), at the end of 28 days.
Results:Apocynin administration demonstrated significant improvement in cognitive functions, diminished oxidative stress and inflammatory response triggered by Aβ administration. Apocynin additionally instigated adult hippocampal neurogenesis and triggered mitochondrial biogenesis.
Conclusions: These primary results strongly advocate apocynin’s nootropic, neurotrophic and neuroprotective potential in an Aβ induced neurotoxicity in rats.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms, in which gut microbiota alterations have emerged as a potential pathogenic factor, causing disruption of the brain-gut-microbiota (BGM) axis. Recent evidence supports the role of BGM axis disruption in enhancing neuroinflammation, alpha-synuclein (α-syn) aggregation, and dopaminergic neurodegeneration. Emerging therapeutic strategies targeting dysbiosis, such as probiotics and fecal microbiota transplantation (FMT), have become a new focus of investigation for PD treatment. Proposed mechanisms include modulation of immune responses, enhancement of intestinal barrier integrity, production of neuroactive metabolites such as short-chain fatty acids, and reduction of oxidative stress. This narrative review summarizes current evidence on probiotics as a therapeutic strategy in PD. By analyzing data from randomized controlled trials and preclinical studies, we highlight the beneficial effects of probiotics in improving motor and non-motor symptoms of PD, including constipation, depression, and anxiety. Strains such as Lactobacillus plantarum PS128 and Bifidobacterium animalis Probio-M8 show particular promise. Although probiotics have demonstrated a favorable safety profile and potential as an adjunctive therapy for PD, future research should focus on standardized protocols, biomarker identification, and exploration of combined microbiota-targeted strategies.

Apparent increases in autism and other forms of neurodivergence are often interpreted as a rise in incidence. Yet demographic expansion, diagnostic broadening, and growing cultural awareness all contribute to higher prevalence estimates. At the same time, contemporary sensory and digital environments have become increasingly overstimulating, characterized by persistent noise, visual saturation, hyperconnectivity, and unpredictable social rhythms. These conditions heighten sensory and cognitive load for many individuals, making neurodivergent traits more visible and increasing the urgency of diagnosis. Drawing on cognitive ecology, sensory neuroscience, and neuroaffirmative scholarship, this perspective proposes that neurodivergence can be understood as an adaptive response to environments that exceed nervous-system thresholds. Autistic regulatory behaviors-including withdrawal, shutdown, sensory avoidance, and monotropism-driven focus-may serve as mechanisms for maintaining coherence in overstimulating contexts. Interpreting neurodivergence as an ecological signal offers new pathways for public health, accessibility design, and social policy. It reframes autistic embodiment not as internal dysfunction but as meaningful information about the livability of contemporary environments.

The oral microbiome has been increasingly implicated in the development and progression of neurological disorders. This narrative review synthesizes contemporary literature on alterations of oral microbial communities in Alzheimer’s disease, Parkinson’s disease, and migraine and evaluates their potential contribution to neuroinflammation and neurodegeneration. We first outline the core oral taxa that maintain microbial homeostasis and summarize evidence that patients with these neurological conditions exhibit dysbiosis characterized by reduced diversity and enrichment of periodontal pathogens. Proposed mechanisms include hematogenous or neural translocation of oral bacteria and their virulence factors, amplification of systemic inflammation, disruption of the blood-brain barrier, altered production of neuroactive metabolites, and bidirectional signaling along the ‘oral-gut-brain’ axis. On this mechanistic basis, microbiome-targeted strategies, particularly probiotics and fecal microbiota transplantation, have been explored as adjunctive approaches to restore microbial balance and potentially improve neurological outcomes, although available clinical data remain preliminary and heterogeneous. Current evidence is further limited by small samples, methodological variability in microbiome profiling, and a paucity of longitudinal and interventional studies, which hampers causal inference. Future research should adopt standardized sampling and multi-omic approaches and prioritize well-designed clinical trials to determine whether modulation of the oral microbiome can be translated into preventive or therapeutic strategies for neurological diseases.

Aim: Parkinson’s disease (PD) and Alzheimer’s disease (AD) represent critical neurological disorders that have emerged as significant health concerns in the 21st century. The pharmacological interventions currently employed to manage these diseases demonstrate limited efficacy and some adverse side effects. Historically, natural products have been used to develop therapeutic agents targeting neurodegenerative disorders. This study aimed to apply in silico techniques to investigate the pharmacological mechanisms of capsaicin as a possible alternative treatment or coadjutant phytotherapy for PD and AD.
Methods: We obtained target genes for capsaicin, PD, and AD from the HERB database, the Swiss Target Prediction database, the Comparative Toxicogenomics Database, and the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and matched them. Subsequently, we constructed a protein-protein interaction network and performed enrichment analysis of the common targets. Then, the interactions of capsaicin with the proteins with the highest degree were tested using molecular docking. The stability of the complexes was verified using molecular dynamics techniques.
Results: A total of 25 targets were found in common from the databases for capsaicin, AD, and PD. The enrichment analysis revealed that proteins from these targets influenced integrin activity in the IGF1-IGF1R complex, cholinesterase activity, and dopamine neurotransmitter receptor activity, all of which are coupled via protein G_i/G_o, among other cellular processes. From the protein-protein interaction network, we identified the hub proteins IL6, GSK3B, CASP, BCL2, ESR1, SIRT1, NGF, IGF1, and HMOX1. Furthermore, molecular docking studies between hub proteins and capsaicin showed strong binding affinity. Finally, molecular dynamics simulations support a stable interaction between capsaicin and SIRT1, ESR1, HMOX1, and NGF.
Conclusions: This work contributes to understanding the neuroprotective activity of capsaicin in PD and AD. However, these bioinformatic predictions require further experimental validation.

Age-related neurological disorders such as ALS (Lou Gehrig’s disease), Parkinson’s disease, and Alzheimer’s disease have few truly effective treatment options. At best, these may slow the inexorable disease progression without providing a cure. Part of the problem with therapeutic approaches may arise due to the stage at which these diseases are detected, particularly the sporadic forms. In most cases, early signs and symptoms may be insidious, thus hiding the significant damage done to the areas of the nervous system impacted prior to any firm clinical diagnosis. This situation appears to necessitate the development of earlier detection methods for “biomarkers” that might allow for much earlier phase disease state treatments that might serve to significantly slow or even halt disease progression. Currently, most biomarkers in use serve primarily as aids to disease diagnosis, at which point there are no successful treatment options. In contrast, a search for more effective early treatment options would need to identify characteristic and specific molecular signatures of disease onset and progression using methods that are simple, such as blood-based analytical assays, relatively cheap, and crucially minimally invasive.

Aim: This study examined differences in attentional control and awareness of interference among children with attention-deficit/hyperactivity disorder (ADHD), children with subthreshold ADHD (children showing some but not all symptoms required for diagnosis), and children with typical development. Specifically, we investigated how visual and auditory distractions affect behavioral performance and eye movements, to clarify the degree and nature of attentional control impairments associated with subthreshold versus clinically diagnosed ADHD.
Methods: One hundred and two children (mean age = 7.23 years, SD = 1.23; 34 per group) participated in three eye-tracking tasks involving a bouncing ball under no, visual, and auditory interference. Behavioral accuracy (number of correctly counted bounces), fixation duration on the target, gaze reorientation latency, and distractor awareness were analyzed using mixed-design analyses of variance (ANOVAs) and chi-square tests.
Results: Significant group differences were found in counting accuracy, F(2, 99) = 16.42, p = 0.00069, η²_p = 0.245, with typically developing children performing best, followed by those with subthreshold and full ADHD. Eye-tracking indices showed a similar gradient: fixation duration decreased with symptom severity, F(4, 198) = 7.65, p = 0.00094, η²_p = 0.134, while gaze reorientation latency increased, F(2, 99) = 12.18, p = 0.00093, η²_p = 0.197 (typical development ≈ 480 ms; subthreshold ≈ 621 ms; ADHD ≈ 721 ms). Awareness of distractors also varied significantly across groups, χ²(2, n = 102) = 38.12, p ＜ 0.001, Cramer’s V = 0.61, with detection rates of approximately 80% (typical development), 50% (subthreshold), and 25% (ADHD).
Conclusions: Both children with ADHD and children with subthreshold ADHD show measurable deficits in attentional control and awareness of interference, particularly under visual and auditory distraction. Children with subthreshold ADHD exhibited an intermediate profile, supporting a continuum rather than a categorical distinction in cognitive control impairments. These findings highlight the importance of early identification and interventions targeting attentional regulation and metacognitive monitoring across the ADHD spectrum.

Aim:Neurodegenerative diseases, such as Alzheimer’s, are strongly associated with amyloid-β aggregation. This study aimed to explore bioactive metabolites from endophytic bacteria as potential anti-aggregation agents with relevance to neuroprotection, focusing on isolate D11 obtained from a geothermal fern at Gedong Songo hot springs.
Methods:Isolate D11 was characterized by Gram staining and 16S rRNA sequencing. Growth curve analysis was conducted to determine metabolite production phases. Phytochemical screening, bovine serum albumin (BSA) aggregation inhibition assays, liquid chromatography mass spectroscopy (LCMS) profiling, and molecular docking against amyloid-β were employed to evaluate bioactivity and metabolite composition.
Results:D11 was identified as a Gram-negative rod with 97.94% similarity to Stutzerimonas stutzeri. Metabolite production peaked during the stationary and death phases. Phytochemical tests revealed alkaloids and tannins in aqueous fractions. BSA aggregation inhibition assays demonstrated potent inhibitory activity, with IC₅₀ values (2.40–3.29 µg/mL) significantly lower than quercetin. LCMS profiling identified diverse metabolites, dominated by flavonoid glycosides such as kaempferol-7- O-deoxyhexosyl-3- O-acetylhexoside, along with alkaloids, peptides, and diterpenoids. Molecular docking confirmed strong binding affinities of flavonoid glycosides to amyloid β (–7.6 kcal/mol), outperforming quercetin (–6.0 kcal/mol).
Conclusions:These findings suggest that isolate D11 Stutzerimonas produces bioactive metabolites with anti-aggregation activity and potential relevance to neuroprotection . However, since Stutzerimonas-derived metabolites remain poorly explored and the docking results are tentative, further in-depth characterization and in vivo validation are required to confirm their therapeutic relevance, and further validation using amyloid-β or α-synuclein models is required to confirm therapeutic implications.