The glymphatic system is a glia-dependent network surrounding blood vessels that facilitates the exchange of cerebrospinal fluid (CSF) and interstitial fluid, playing a crucial role in clearing neuro-metabolites from the brain. This system’s efficiency in transporting waste significantly increases during non-rapid eye movement non-REM sleep. Recent findings suggests that malfunctioning of the glymphatic system might be linked to neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and schizophrenia (SCZ), all of which often correlate with disturbed sleep patterns. Furthermore, various environmental toxicants have been shown to affect neurodevelopment negatively. Exposure to these toxicants early in life disrupts the sleep/Blood-Brain Barrier (BBB)/Aquaporin-4 connections, impairs the glymphatic system’s ability to clear substances like amyloid-beta (Aβ), tau proteins, and inflammatory mediators, ultimately skewing neurodevelopment toward an increased risk of disorders. In summary, this narrative review consolidates existing evidence. It highlights key priorities for examining the relationship between the exposome, the glymphatic system, and neurodevelopmental pathways, aiming to pave the way for future research and therapeutic interventions.

Autism is a neurodevelopmental disorder characterized by persistent challenges in social interactions and repetitive behaviors. This study aimed to investigate the prevalence of autism and autism spectrum disorder(ASD) in normal and abnormal groups, such as premature infants or seizure patients, using an umbrella review and meta-analysis. This study was conducted in accordance with the PRISMA guidelines. Scientific sources included PubMed, Scopus, Web of Science, and Google Scholar, and searches were conducted without time limits until the end of September 2024. Meta-analysis was performed using a random-effects model and heterogeneity using an I<sup>2</sup> index. Of the 799 articles identified, 30 were included in the meta-analysis. The prevalence of autism was 15.8 per 10,000 (CI = 10.5-21.0, P < 0.001) in normal samples and 600 per 10,000 (CI = 412-793, P = 0.77) in abnormal samples. The overall prevalence of autism was 18.1 per 10,000 (CI = 10.9-25.4, P < 0.001). The prevalence of ASD in normal samples was 48.9 per 10,000 (CI = 31.6-66.1, P < 0.001) and in abnormal samples 900 per 10,000 (CI = 680-1121, P < 0.001). The overall prevalence of ASD was estimated to be 153 per 10,000 (CI = 125-180, P < 0.001). Given the prevalence of ASD and its link to environmental and genetic factors, increased public awareness and better diagnostic tools are needed. In addition, timely and accurate screening is recommended to prevent delays in diagnosis and treatment.

Comprehending the nature of nerve communication is fundamental to our understanding of the functioning of nervous systems in general. The ionic mechanisms underlying action potentials in the squid giant axon were first described by Hodgkin and Huxley in 1952, and their findings have formed our orthodox view of how the physiological action potential functions. However, substantial evidence has now accumulated to show that the action potential is accompanied by a synchronized coupled soliton pressure pulse in the cell membrane, the action potential pulse (APPulse), which we have recently shown to have an essential function in computation. Computational models of the action potential usually describe it as a binary event. Still, we have shown that it must be a quantum ternary event known as the computational action potential, whose temporal fixed point is the threshold of the soliton, rather than the plastic action potential peak used in other models to facilitate meaningful computation. Here we argue that for computation to occur in neurons, it must do so at the location of convergences of neurons by frequency modulated quantum interference. The timing of frequency changes indicates that the threshold must activate in less than 10-6 s, much faster than that of synapses. APPulse in a brain neural network collide according to the latencies of the neurons and the distinct frequency patterns. Here, we review the interactions between the soliton and the ionic mechanisms known to be associated with the action potential. Elsewhere, we have demonstrated this type of frequency computation for the retina, in detail, and also provided an extensive analysis for computation for other brain neural networks. However, while the physiological action potential is important for neural connectivity, it is irrelevant to computational processes as the soliton part of the APPulse always facilitates this for computational timing and effectiveness.

Central post-stroke pain (CPSP) is a frequently underrecognized complication that contributes to long-term disability among stroke survivors. This study aimed to determine the frequency of CPSP and to describe its clinical characteristics and associated factors among stroke patients treated at Arifin Achmad General Hospital. A cross-sectional design was employed and included adult stroke patients with diagnoses confirmed by neuroimaging. CPSP was diagnosed based on the clinical criteria proposed by Klit et al., and neuropathic pain was assessed using the Indonesian version of the Douleur Neuropathique 4 questionnaire. Pain intensity was evaluated using the Numeric Rating Scale. Among 270 patients, 44 were identified with CPSP. Age and lesion site were significantly associated with CPSP. The median onset of pain was three months after stroke, with most patients reporting continuous, moderate pain affecting the face, trunk, and limbs. Burning pain and paresthesias were the most frequently reported, and hypoesthesia to pinprick was the most common sensory finding. Greater clinical awareness and systematic assessment are essential to improve recognition and management of CPSP in stroke survivors.

The inbred Krushinsky-Molodkina (KM) rat strain, characterized by latent genetic epilepsy, reduced social motivation, and a high propensity for freezing, is a promising model for translational research of social deficits in autism spectrum disorder (ASD). In clinical practice, social deficits often lead to social withdrawal and can be accompanied by aggression. It was unknown if KM rats exhibit such aggression during inescapable social encounters. We assessed intraspecific aggression in KM and control rats using the resident-intruder test, and autonomic nervous system responses were evaluated via heart rate variability analysis in a small separate cohort using a modified social-challenge paradigm that prevented direct physical contact. In the resident-intruder test, KM rats displayed significantly less aggression toward unfamiliar intruders than controls, exhibiting fewer attacks, fights, and competitive wins. Electrocardiographic analysis during the social preference test further revealed that the social challenge triggered parasympathetic, rather than sympathetic, nervous system activation in KM rats. Together, these findings indicate that social load in KM rats evokes a stress response, marked by a hypolocomotion and an atypical autonomic reaction. Conversely, control rats, which displayed a typical fight response to unfamiliar intruders, exhibited marked sympathetic activation during the sociability test. These findings suggest the KM strain may help model specific aspects of ASD-relevant social behavior alongside autonomic dysregulation.

The "Sama Code" is a protocol implemented in Iranian pre-hospital emergency services to manage time and treat patients with suspected stroke symptoms based on the FAST criteria. This study aims to analyze the workflow of patients with stroke symptoms transferred under the Sama Code. All patients with neurological symptoms who were brought to Imam Reza Hospital by pre-hospital emergency services after activating the Sama Code during the years 2021 and 2022 were included in the study. Data were collected from pre-hospital emergency records and registries, including patient age and gender, time of emergency contact, code activation, arrival of personnel at the patient’s side, clinical findings recorded in pre-hospital files, time to emergency department arrival, CT scan (Computed tomography scan), thrombolytic therapy initiation, reasons for treatment cancellation, and patient outcomes. A total of 880 patients were included in the study, with a mean age of 69.24 years (CI 95%: 68.30-70.17). The median age was 71 years, with most patients aged 61-80 years. Among the patients, 505 (57.4%) were male, and 375 (42.6%) were female. The number of patients transferred by pre-hospital emergency services under the Sama Code was roughly equal over the two years studied. The median time from emergency notification to mission start was 1 minute, while the median time from care plan initiation to patient arrival was 10 minutes. The median time from the patient’s side to transfer was 18 minutes, and from transfer initiation to hospital arrival was 10 minutes. The median time from hospital arrival to CT scan was 17 minutes. Of 880 patients, 750 were admitted to the hospital, and 13 Sama Codes were canceled during triage due to other diagnoses. Of the remaining 737 patients, only 20 received thrombolytic treatment, with a median time from CT scan to treatment of 20 minutes. According to this study’s findings, a small percentage of patients receive thrombolytic treatment; however, patient transfers in accordance with the Sama Code guidelines are well implemented, ensuring rapid CT scanning and timely decision-making.

Using a two-stage qualitative design (Stage 1: expert interviews; Stage 2: biographical interviews with people with MS), existing governmental and organizational support measures for maintaining the work capacity of individuals with multiple sclerosis (MS) were analyzed, and proposals for improvement were developed. Additional state support measures were proposed, including relaxing the criteria for state assistance, creating a centralized contact point for MS-specific inquiries, and enhancing collaboration between labour market services, healthcare providers (including occupational physicians/occupational health services), and employers. The study emphasized the need for higher investment in rehabilitation and training for specialized MS healthcare professionals. Regarding workplace support measures, respondents highlighted the importance of information and training to companies that employ individuals with MS, initiatives to combat work-related fatigue, structured return-to-work planning (e.g., reintegration agreements), and the necessity for workplace adjustments. Participants also described cross-cutting needs that are not fully covered by “classic” workplace measures, including stigma reduction, support for mental health, and guidance around disclosure of diagnosis. The proposed optimizations and enhancements, when combined with existing offerings, could reduce disease-specific absences and support the maintenance of work capacity among individuals with MS.

Difficult-to-treat depression (DTD) with inflammatory features (e.g., hs-CRP ≥3 mg/L and/or elevated IL-6) may represent a clinically and biologically distinct presentation characterized by chronicity, functional impairment, prominent cognitive-motivational symptoms, and suboptimal response to conventional treatments. Classical anti-inflammatory strategies (e.g., COX-2 inhibitors or cytokine-targeting biologics) have shown signals of efficacy in selected biomarker-enriched subgroups; however, overall evidence remains heterogeneous, with modest effect sizes and substantial limitations for real-world implementation. This Commentary advances a complementary perspective, proposing that in many patients “inflamed DTD” reflects not only increased pro-inflammatory drive but also impaired physiological resolution mechanisms across immune, autonomic, circadian, and metabolic systems. Within this “resolution failure” framework, we discuss emerging therapeutic targets and multimodal strategies and their integration into endotype-guided immunopsychiatric care. We further address limitations of the current evidence base, outline biomarker-enriched trial designs with patient-centred outcomes (functioning, quality of life, cognition), and highlight real-world barriers, including access to biomarkers, reimbursement, and equity of care. Overall, this perspective argues for moving beyond single-pathway anti-inflammatory approaches towards pragmatic, mechanistically informed interventions for inflamed DTD.

Personalized psychopharmacotherapy remains a critical yet underdeveloped frontier in psychiatry, as traditional approaches often fail to address substantial interindividual variability in drug efficacy and tolerability. While demographic, clinical, and genetic factors have improved treatment precision, they do not fully account for observed heterogeneity. Recent advances highlight the promise of personality traits, particularly as operationalized by Cloninger’s Seven-Factor Model, as novel biomarkers for treatment optimization. This model distinguishes between temperament—biologically-based, heritable predispositions—and character, which is shaped by environmental, developmental, and cultural factors. Mapping these dimensions to neurochemical pathways offers a framework for tailoring pharmacological interventions to individual neurobiological profiles, potentially enhancing symptom control, tolerability, and adherence. Integrating personality assessment with pharmacogenomics, neuroimaging, and computational phenotyping may enable more holistic patient stratification, fostering the development of precision psychiatry. However, significant methodological, practical, and ethical challenges persist, including inconsistent findings, concerns regarding validity and generalizability, and the risk of stigmatization or misuse of sensitive data. Future research should prioritize large-scale, diverse, and longitudinal studies that leverage advances in artificial intelligence and integrative biomarker platforms. Interdisciplinary collaboration and rigorous ethical oversight are essential to translate the theoretical promise of personality-informed psychopharmacotherapy into effective, equitable, and patient-centered clinical practice. Ultimately, incorporating personality biomarkers may redefine the landscape of individualized psychiatric care and advance the goals of precision psychiatry.

The study explores the crucial biological function of nitrogen in cyclic and acyclic structures with resonance potential, including tetrazoles, pyrroles, piperidines, and carbamates, within the realm of chemical neuroscience. It highlights the importance of these compounds for their biological properties and their ability to cross the blood-brain barrier (BBB) to reach the central nervous system (CNS). The study emphasizes the necessity for neurochemical drugs, like morphine, to effectively cross the BBB, as modifications to their nitrogen structure can significantly impact their pharmacological effects. Additionally, the research explores the biochemical mechanisms of opioid and opioid-like analgesics, focusing on the impact of nitrogen heteroatoms and resonance on the stability of drug structures. The results highlight the importance of nitrogen-containing compounds in drug development, especially in pain management and other central nervous system applications. This document provides a thorough overview of the synthesis, characterization, and uses of different nitrogen heterocycles in medicinal chemistry.