搜索结果：International review of neurobiology

The regulation of Nuclear Factor-Erythroid 2 Like 2 (NRF2) signaling has been shown to be a promising strategy to modulate the progression of the neurodegeneration associated to Parkinson's Disease (PD). Aim of this review is to update the knowledge of Nrf2 as neuroprotective agent of PD. Activation of Nrf2, a transcription factor that regulates the expression of antioxidant and cytoprotective genes, has emerged as a promising therapeutic strategy for PD. Nrf2 is a master regulator of the cellular antioxidant response and is responsible for activating the expression of genes that encode antioxidant enzymes such as superoxidedismutase, catalase, and glutathione peroxidase. Pharmacological agents such as sulforaphane, curcumin, and resveratrol have been shown to activate Nrf2 and upregulate the expression of antioxidant genes in preclinical PD models. Clinical trials are currently underway to evaluate the efficacy of these pharmacological agents in patients with PD. While the neuroprotective role of Nrf2 in PD holds great promise for the development of novel therapies, there are several challenges and limitations that need to be addressed in order to harness the full potential of this pathway in the clinic. Overcoming these obstacles will require interdisciplinary collaborations, innovative research approaches, and a greater understanding of the complex pathophysiology of PD. By addressing these challenges, we can move closer to developing effective neuroprotective therapies that can slow or stop the progression of PD and improve the quality of life for patients with this devastating disease.

The 2023 iteration of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimated prevalence, incidence, and health burden for 375 diseases and injuries, including 12 mental disorders. We assess past, current, and emerging trends in the prevalence and burden of mental disorders across sexes and age groups, for 21 regions, 204 countries and territories, and by Socio-demographic Index (SDI) quintile, from 1990 to 2023. Mental disorders included in GBD 2023 were anxiety disorders, major depressive disorder, dysthymia, bipolar disorder, schizophrenia, autism spectrum disorders, conduct disorder, attention-deficit hyperactivity disorder, anorexia nervosa, bulimia nervosa, idiopathic developmental intellectual disability, and a residual category of other mental disorders. A literature review identified epidemiological data for each disorder. These were analysed via a Bayesian meta-regression to estimate prevalence by disorder, sex, age, location, and year. Disorder-specific prevalence was multiplied by disability weights representing the severity of health loss associated with each disorder to estimate years lived with disability (YLDs). Deaths due to anorexia nervosa were assessed with a Cause of Death Ensemble modelling strategy to estimate deaths by sex, age, location, and year, and then multiplied by the standard life expectancy at age of death to estimate years of life lost (YLLs). YLDs equalled disability-adjusted life-years (DALYs) for all mental disorders except anorexia nervosa (the only mental disorder considered as an underlying cause of death in GBD), for which DALYs represented the sum of YLDs and YLLs. We presented prevalence, deaths, YLDs, YLLs, and DALYs as counts, age-specific rates per 100 000 population, and age-standardised rates per 100 000 population. We estimated 1·17 billion (95% uncertainty interval 1·06-1·31) prevalent cases of mental disorders globally in 2023, equivalent to an age-standardised prevalence rate of 14 210·7 cases (12 849·5-15 940·1) per 100 000 population. These estimates represented a 95·5% (75·0-121·2) increase in prevalent cases and 24·2% (11·4-41·4) increase in age-standardised prevalence rate between 1990 and 2023. All mental disorders showed increases in prevalent cases between 1990 and 2023, while notable increases were seen in age-standardised prevalence rates for anxiety disorders, major depressive disorder, dysthymia, anorexia nervosa, bulimia nervosa, schizophrenia, and conduct disorder. There were an estimated 171 million (127-228) DALYs due to mental disorders globally across sex and age in 2023, equivalent to an age-standardised DALY rate of 2070·5 DALYs (1519·1-2750·5) per 100 000 population. Mental disorders contributed to 6·1% (4·8-7·6) of all-cause DALYs in 2023, making them the fifth leading cause of global DALYs (up from 12th in 1990). DALYs were almost entirely composed of YLDs. Mental disorders were the leading cause of YLDs in 2023 (up from second in 1990), explaining 17·3% (14·8-20·6) of all-cause global YLDs. Leading causes of mental disorder DALYs were anxiety disorders (ranked 11th among the 304 diseases and injuries at Level 4 of the GBD cause hierarchy), major depressive disorder (15th), and schizophrenia (41st). Globally in 2023, mental disorder age-standardised DALY rates were higher among females (2239·6 [1643·7-3014·1] per 100 000) than among males (1900·2 [1399·8-2510·8] per 100 000), and peaked in the 15-19 years age group (2617·3 [1850·6-3696·8] per 100 000). All locations showed increased mental disorder DALY rates in 2023 compared with 1990, ranging across countries and territories from 1302·4 (952·7-1683·7) per 100 000 in Viet Nam to 3555·8 (2661·9-4715·0) per 100 000 in the Netherlands. Across SDI quintiles, DALY rates ranged from 1853·0 (1352·1-2469·3) per 100 000 for middle SDI to 2184·1 (1606·1-2890·3) per 100 000 for high SDI. A significant health burden was imposed by mental disorders in all countries and territories in 2023, irrespective of the health resources available. In some instances, this burden has increased over time and is unevenly distributed across populations. Stronger surveillance systems, particularly in low-income and middle-income countries, are required. Additionally, we need more coordinated and inclusive policies to reduce the burden through early treatment and prevention, tailored to sex and age differences across locations. Responding to the mental health needs of our global population, especially those most vulnerable, is an obligation, not a choice. Gates Foundation, Queensland Health, and University of Queensland.

Postpartum psychosis (PP) is an acute and severe psychiatric illness with onset within weeks after delivery and a high risk of suicide and infanticide. Most women with PP experience severe mood symptoms, including mania, mixed episodes, or depression with psychotic features. Impaired cognition, irritability, and agitation are also common. The specific timing of PP strongly suggests a biological basis, because the postpartum time period is characterized by profound endocrine, immune, neuroanatomical, and physiological changes in the brain. Genetic studies show a unique risk architecture, partly shared with bipolar disorder. PP stands out as one of the most distinct clinical phenotypes in psychiatry due to its characteristic rapid onset, severity, phenomenology, treatment response, and prognosis. Despite this, as of August 2025, PP does not have a distinct diagnostic classification in the DSM. This expert consensus panel, in close collaboration with patient organizations and key interested partners, recommends classifying PP as a distinct category within DSM-5 and ICD-11. We recommend classification within the bipolar disorders chapter of the DSM because 1) most women with PP have prominent affective symptoms; 2) treatment response to lithium and electroconvulsive therapy is excellent; 3) in half of the cases, first-onset PP is also the first onset of bipolar disorder; 4) pregnant women with bipolar disorder are at very high risk of PP; and 5) the genetic risk architecture for PP is distinct but overlapping with bipolar disorder. This consensus statement summarizes scientific evidence that PP is a distinct mental illness within the bipolar spectrum; correct classification will improve detection and treatment.

To test the agreement and usability of a novel quality appraisal tool: A MeaSurement Tool to Assess systematic Reviews of Prognostic Factor studies (AMSTAR-PF). Observational study. 14 appraisers of varied experience levels and backgrounds, including undergraduate, master's and PhD students, postgraduate researchers, research fellows and clinicians. Eight systematic reviews were rated by all reviewers using AMSTAR-PF. Planned measures included intrapair and inter-pair agreement using Cohen's and Fleiss' kappa, time of use and time to reach consensus. Interrater agreement was an added measure, and Gwet's agreement coefficient was calculated and presented due to its greater stability across agreement levels. The percentage of intrapair agreements identical or one category apart was also presented. Interrater agreement averaged 0.59 (range 0.21-0.90), inter-pair agreement 0.61 (range 0.24-0.91) and intrapair agreement 0.75 (range 0.45-0.95) across the domains, with agreement for the overall rating 0.46 (95% CI 0.30 to 0.62) for interrater agreement, 0.46 (95% CI 0.17 to 0.74) for inter-pair agreement and 0.68 (range of averages 0.22-1.00) for intrapair agreement. The majority (60.7%) of intrapair ratings were identical, with 94.6% of final ratings either identical or only one category different for the overall appraisal. The time taken to appraise a study with AMSTAR-PF improved with use and averaged around 34 min after the first two appraisals. Despite some variance in agreement for different domains and between different appraisers, the testing results suggest that AMSTAR-PF has clear utility for appraising the quality of systematic reviews of prognostic factor studies.

Lower respiratory infections (LRIs) remain the world's leading infectious cause of death. This analysis from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides global, regional, and national estimates of LRI incidence, mortality, and disability-adjusted life-years (DALYs), with attribution to 26 pathogens, including 11 newly modelled pathogens, across 204 countries and territories from 1990 to 2023. With new data and revised modelling techniques, these estimates serve as an update and expansion to GBD 2021. Through these estimates, we also aimed to assess progress towards the 2025 Global Action Plan for the Prevention and Control of Pneumonia and Diarrhoea (GAPPD) target for pneumonia mortality in children younger than 5 years. Mortality from LRIs, defined as physician-diagnosed pneumonia or bronchiolitis, was estimated using the Cause of Death Ensemble model with data from vital registration, verbal autopsy, surveillance, and minimally invasive tissue sampling. The Bayesian meta-regression tool DisMod-MR 2.1 was used to model overall morbidity due to LRIs. DALYs were calculated as the sum of years of life lost (YLLs) and years lived with disability (YLDs) for all locations, years, age groups, and sexes. We modelled pathogen-specific case-fatality ratios (CFRs) for each age group and location using splined binomial regression to create internally consistent estimates of incidence and mortality proportions attributable to viral, fungal, parasitic, and bacterial pathogens. Progress was assessed towards the GAPPD target of less than three deaths from pneumonia per 1000 livebirths, which is roughly equivalent to a mortality rate of less than 60 deaths per 100 000 children younger than 5 years. In 2023, LRIs were responsible for 2·50 million (95% uncertainty interval [UI] 2·24-2·81) deaths and 98·7 million (87·7-112) DALYs, with children younger than 5 years and adults aged 70 years and older carrying the highest burden. LRI mortality in children younger than 5 years fell by 33·4% (10·4-47·4) since 2010, with a global mortality rate of 94·8 (75·6-116·4) per 100 000 person-years in 2023. Among adults aged 70 years and older, the burden remained substantial with only marginal declines since 2010. A mortality rate of less than 60 deaths per 100 000 for children younger than 5 years was met by 129 of the 204 modelled countries in 2023. At a super-regional level, sub-Saharan Africa had an aggregate mortality rate in children younger than 5 years (hereafter referred to as under-5 mortality rate) furthest from the GAPPD target. Streptococcus pneumoniae continued to account for the largest number of LRI deaths globally (634 000 [95% UI 565 000-721 000] deaths or 25·3% [24·5-26·1] of all LRI deaths), followed by Staphylococcus aureus (271 000 [243 000-298 000] deaths or 10·9% [10·3-11·3]), and Klebsiella pneumoniae (228 000 [204 000-261 000] deaths or 9·1% [8·8-9·5]). Among pathogens newly modelled in this study, non-tuberculous mycobacteria (responsible for 177 000 [95% UI 155 000-201 000] deaths) and Aspergillus spp (responsible for 67 800 [59 900-75 900] deaths) emerged as important contributors. Altogether, the 11 newly modelled pathogens accounted for approximately 22% of LRI deaths. This comprehensive analysis underscores both the gains achieved through vaccination and the challenges that remain in controlling the LRI burden globally. Furthermore, it demonstrates persistent disparities in disease burden, with the highest mortality rates concentrated in countries in sub-Saharan Africa. Globally, as well as in these high-burden locations, the under-5 LRI mortality rate remains well above the GAPPD target. Progress towards this target requires equitable access to vaccines and preventive therapies-including newer interventions such as respiratory syncytial virus monoclonal antibodies-and health systems capable of early diagnosis and treatment. Expanding surveillance of emerging pathogens, strengthening adult immunisation programmes, and combating vaccine hesitancy are also crucial. As the global population ages, the dual challenge of sustaining gains in child survival while addressing the rising vulnerability in older adults will shape future pneumonia control strategies. Gates Foundation.

Spinal cord injury (SCI) disrupts crucial neural pathways and causes severe neurological deficits that impact the quality of life. Although preliminary research has shown some promise of Spinal Cord Stimulation (SCS) in promoting axonal regeneration and remyelination, a clear understanding of the pertinent literature remains lacking. This scoping review consolidates evidence on the effects of SCS in promoting axonal growth and myelin development, preserving spared tissue integrity, and facilitating functional recovery following SCI. Pre-clinical studies from 1946 to 2024 that involved the application of SCS in experimental SCI models, and compared outcomes with no-stimulation controls were included. Data extraction focused on injury characteristics, stimulation protocols, markers of axonal regeneration, remyelination, and functional recovery. Twenty-one studies met the inclusion criteria. Twelve reported elevated pro-regenerative markers and reduced inhibitory/apoptotic factors in SCS-treated cohorts. Ten demonstrated enhanced axonal preservation, increased axonal length, or a greater number of axons. Nine showed increased myelin content, myelin thickness, and oligodendrocyte differentiation. Twenty studies assessed locomotor outcomes through behavioral and electrophysiological tests, consistently demonstrating SCS-mediated functional recovery. Overall, SCS led to improved remyelination, axonal regeneration, and locomotor/electrophysiological function in rodent SCI models. Although the published literature supports the therapeutic potential of SCS for functional recovery, future research should refine stimulation parameters, delivery methods and timing of intervention. Specific issues of translational importance that were found lacking include autonomic recovery (2 of 21 reported), standardized outcomes, reporting common elements, and combination therapies.

Alzheimer's disease (AD) is one of the widespread neurodegenerative disorders, marked by the accumulation of amyloid-β plaques, neurofibrillary tangles of hyperphosphorylated Tau protein, and the gradual loss of neurons. While genetic and environmental factors have been associated with its onset, metabolic dysfunction has also been identified as one of the initial and most significant contributors its pathogenesis. The mitochondria are at the centre of this problem; their compromised function affects some crucial aspects of the neuronal health. Neurons have high energy demands so they are quite sensitive to the changes in the supply of the fuel. During AD pathogenesis, the loss of glucose transporters and the downregulation of key glycolytic enzymes deprives neurons of essential energy reserve. This metabolic dysregulation is further exacerbated by dysregulated lipid metabolism, pathological lipid droplet accumulation and ApoE4-driven failures in lipid trafficking which collectively leads to the oxidative stress, neuroinflammation, and Aβ aggregation. This situation is further aggravated by amino acid imbalances specifically within the glutamate-glutamine cycle. To counter this, ketone bodies have emerged as an alternative fuel source, capable of partially bypassing the impaired glucose oxidation while also demonstrating neuroprotective properties. Moreover, systemic metabolic disorders including type 2 diabetes mellitus, insulin resistance, obesity, and metabolic syndrome significantly amplify these deficits, functioning as major risk factors for AD onset and progression. Even the gut-brain axis plays a role in adding to the complexity. Taken together, these metabolic health changes not only reshape our understanding of AD but also open potential prospects for early detection through metabolic biomarkers and for novel therapeutic strategies targeting mitochondrial bioenergetics, glucose restoration, and ketogenic interventions.

Alzheimer Disease (AD) is a progressive neurodegenerative condition because of its cognitive impairment, synaptic impairment and loss of neurons. Mitochondrial dysfunction has become one of the key factors of disease development and progression and one of the several pathological characteristics of AD. The mitochondrial cascade hypothesis suggests that amyloid-β and tau pathology depend on age-related mitochondrial impairment, which is an earlier and faster process and provokes neurodegeneration. Mitochondria play critical roles in metabolism of neuronal energy, maintenance of calcium and regulation of reactive oxygen species (ROS); their dysfunction leads to bioenergetic impairment, oxidative stress, and synaptic failure. Marine ecosystems constitute an unexampled source of bioactive therapeutic-related compounds of structural diversity. Marine-derived compounds (MDCs) such as polysaccharides, oligosaccharides, polyphenols, lipids, alkaloids and peptides have antioxidant, anti-inflammatory, and neuroprotective effects. Recent reports indicate that MDCs can salvage mitochondrial performance by increasing biogenesis, restoring dynamics (fusion fission balance), modulating metabolism and improving mitochondrial quality control. The compounds also control metabolism of the brain affecting the use of glucose, lipid metabolism, and synthesis of neurotransmitters. This chapter clearly discusses the insights of marine-derived compounds as a mitochondrial rescue in AD. We stress their chemical heterogeneity, biologic activity and mode of action including the regulation of signaling pathways, e.g. AMPK, PI3K/Akt, MAPK, and SIRT1. We also talk about their effects on synaptic plasticity, neuronal survival and cognitive function. Lastly, we have also find the research gaps, research challenges, and perspectives and highlight the necessity of translational research, better bioavailability, and sustainable harvesting plans. Marine-derived compounds as a group are one of the brightest prospects in AD therapeutics by providing innovative methods to restore the state of mitochondria and control the metabolism in the brain.

Placebo effects refer to changes in outcomes driven by learning and expectations, and they can shape responses to both pharmacologic and non-pharmacologic interventions. This chapter examines the neurobiology of placebo and nocebo effects, with an emphasis on findings from human research. Drawing primarily from controlled laboratory studies, we highlight neuroimaging and transcriptomic mechanisms that shed light on the formation of placebo and nocebo responses. In particular, this chapter highlights how expectations and contextual cues can enhance or diminish the efficacy of both pharmacologic and non-pharmacologic interventions. A focus is placed on the role of open-label, cost perception, branding, and treatment modality in modulating placebo effects. The neurochemical basis of placebo analgesia is also examined, with a central role identified for endogenous opioids, and additional contributions from the endocannabinoid and dopaminergic systems. Neuroimaging studies reveal brain networks and structural markers that predict placebo responsiveness. Genetic and transcriptomic insights add a molecular layer to this understanding as well as RNA expression profiles, helping to identify placebo responders. Finally, the chapter emphasizes the clinical relevance of nocebo effects, detailing how negative expectations and communication can worsen outcomes. We also discuss the clinical relevance of these mechanisms, particularly in rheumatology, where both functional and structural brain changes have been observed. It advocates for improved communication strategies, personalized consent, and ethical integration of placebo science to optimize pain care and clinical trial designs. Future research should focus on translating individual variability in placebo and nocebo effects into strategies for advancing personalized and precision medicine.

Single-site retrospective cohort study based on medical records review from 2016-2020. Specialised rehabilitative care is required to integrate traumatic spinal cord injury (TSCI) survivors into the community. The World Health Organisation's (WHO) Rehabilitation 2030 initiative calls to strengthen rehabilitation services, and therefore, information regarding the injury profiles and length of rehabilitation stay (LORS) may assist in planning rehabilitation. The study aimed to examine the profile of individuals with TSCI, who were admitted to a rehabilitation centre, and to describe the factors associated with the LORS. Western Cape Rehabilitation centre, South Africa. The International Spinal Cord Injury Core Data Setversion 2.0 was used to extract data. One-way ANOVA and t-tests compared group means. A multiple linear regression analysis was done to account for possible intercorrelations between predictors. The population consisted predominantly of males (89.8%) in the 31--40-year-old category. Assault was the leading cause of injury (70.4%). The thoracic spine was most affected (52.4%), with complete injuries (AIS A, according to the International Standards for Neurological Classification of Spinal Cord Injury (INCSCI)) most common (42.8%). Cervical injuries were associated with significantly longer rehabilitation stays compared to thoracic or lumbar injuries. The high prevalence of assault-related etiology underscores the need for preventative strategies to reduce the incidence of TSCI among young males. The characteristics of this unique population and the factors associated with LORS have important implications for healthcare planning, particularly in optimising staff and bed resources, to enhance access to specialised care.

Chronic kidney disease (CKD) is common and ranks among the leading causes of mortality and morbidity. This analysis aimed to present global CKD estimates using the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 to inform evidence-based policies for CKD identification and treatment. This analysis focused on adults aged 20 years and older over the period 1990 to 2023, from 204 countries and territories. Data sources used were published literature, vital registration systems, kidney failure treatment registries, and household surveys. Estimates of CKD burden, including deaths, incidence, prevalence, and disability-adjusted life-years (DALYs), were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool. A comparative risk assessment approach estimated the proportion of cardiovascular deaths attributable to impaired kidney function and estimated risk factors for CKD. Globally, in 2023, 788 million (95% uncertainty interval 743-843) people aged 20 years and older were estimated to have CKD, up from 378 million (354-407) in 1990. The global age-standardised prevalence of CKD in adults was 14·2% (13·4-15·2), a relative rise of 3·5% (2·7-4·1) from 1990. The region with the highest age-standardised prevalence was north Africa and the Middle East (18·0%; 16·9-19·4). Most people had stage 1-3 CKD, with a combined prevalence of 13·9% (13·1-15·0). In 2023, CKD was the ninth leading cause of death globally, accounting for 1·48 million (1·30-1·65) deaths, and the 12th leading cause of DALYs, with an age-standardised DALY rate of 769·2 (691·8-857·4) per 100 000. Impaired kidney function as a risk factor accounted for 11·5% (8·4-14·5) of cardiovascular deaths. High fasting plasma glucose, body-mass index, and systolic blood pressure were all leading risk factors for CKD DALYs. CKD is a major global health issue, with rising prevalence and increasing importance as a cause of death and as a risk factor for cardiovascular death. A better understating of aetiology, appropriate screening, and implementation programmes are needed to translate advances in CKD treatment into improved patient outcomes. Gates Foundation, Wellcome, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

Tau is a microtubule-associated protein that plays a central role in neuronal stability and axonal transport. However, under pathological conditions, it undergoes structural and functional changes that lead to Alzheimer's disease (AD) and related tauopathies. Recent evidence highlights liquid-liquid phase separation (LLPS) as a critical mechanism underlying tau aggregation and the subsequent formation of neurofibrillary tangles (NFTs). This chapter explores the properties of tau, including its intrinsically disordered nature, isoforms, and post-translational modifications (PTMs), that predispose it to LLPS. We discuss the thermodynamic and molecular principles of LLPS, with emphasis on the interplay between multivalent interactions, crowding effects, RNA binding, and cofactors that modulate the formation of tau condensates. Special attention is given to the transition from dynamic, reversible tau droplets to irreversible fibrillar assemblies. The chapter further examines how truncation and PTM cross-talk alter the phase behavior and aggregation propensity of tau. Cellular implications of tau LLPS, including its role in stress granules, synaptic dysfunction, and seeding of NFTs, are also analyzed. Finally, we highlight the regulatory roles of chaperones, metal ions, and interacting proteins and underscore the therapeutic potential of targeting tau phase separation. Together, this synthesis positions the LLPS of tau as a pivotal event in AD pathogenesis and a promising target for therapeutic intervention.

Spinal cord injury (SCI) at or above the thoracic sixth spinal cord level disrupts descending sympathetic and parasympathetic control, leading to severe autonomic dysfunctions including cardiovascular and pelvic organ function. These complications adversely affect the quality of life and are associated with increased morbidity and mortality after SCI. Transcutaneous spinal cord stimulation (tSCS) may offer therapeutic benefits for these functions. The safety of tSCS in subacute SCI, however, remains unknown. Therefore, this study aims to evaluate the feasibility of tSCS for autonomic recovery in individuals with subacute SCI within six months since injury. We designed a two-phase clinical protocol consisting of a pilot randomized controlled trial conducted during inpatient rehabilitation (Project A), followed by a post-discharge outpatient phase with a single-arm quasi-experimental design (Project B). In Project A, 26 adults with cervical or upper thoracic (≥T6) American Spinal Injury Association Impairment Scale (AIS) A-C SCI are planned to be enrolled and randomly assigned to receive tSCS or sham stimulation for five sessions (up to 90 minutes each) in parallel with standard care. Following discharge from inpatient rehabilitation, eligible participants will be offered continuation in Project B. New eligible participants who have not participated in Project A will also be recruited into Project B. They will receive 18 tSCS sessions over six weeks in the laboratory setting. Primary outcomes focus on feasibility, including recruitment, retention, and stimulation-related adverse events. Clinical outcomes will be collected at baseline, after each intervention, and at six months and one-year post-injury. Feasibility results will be summarized descriptively, and exploratory analyses of autonomic outcomes, including cardiovascular and pelvic organ function, will provide preliminary estimates of autonomic responses. The study has been approved by the University of Washington Institutional Review Board. Written informed consent will be obtained from all participants. Results will be submitted to peer-reviewed journals and shared with the scientific/clinical communities and individuals with lived experience of SCI. ClinicalTrials.gov NCT06540859.

Neutral hypnosis offers a valuable state for researchers interested in the nature of consciousness. By minimizing external influences and suggestions, it allows for the investigation of the intrinsic qualities of hypnotic consciousness and its relationship to normal waking states. Studies have shown that neutral hypnosis can result in a significant shift in self-perception. Self-consciousness in neutral hypnosis is often characterized by distortions in the sense of self, fluctuations in self-awareness, and alterations in the experience of agency and body ownership. However, despite these clear effects, the field has largely overlooked the importance of these self-alterations, leading to a notable gap in the literature. In this chapter, we aim to address this gap by examining the existing research on self-consciousness in neutral hypnosis, emphasizing the need for more focused and well-structured studies utilizing the neurophenomenological methodology. Specifically, we propose to apply the neurophysiological three-dimensional model of complex experiential Selfhood, which conceptualizes the self as composed of three dynamically interacting aspects - first-person agency, embodiment, and narrative-reflection - each associated with three distinct sub-networks of the brain's self-referential network. These sub-networks are assessed through EEG operational synchrony analysis, providing a functional measure of their integration. Additionally, we outline several promising avenues for future research, accompanied by testable predictions regarding neurophenomenological alterations in Selfhood as a function of the depth of neutral hypnosis.

Neuronal aging is a key but often overlooked part of Alzheimer's disease. It links age-related loss of cellular energy to long-lasting problems in neuronal function. Even though neurons don't usually divide, ongoing stressors like oxidative damage, mitochondrial dysfunction, and problems with protein handling can make them appear old. This is seen as lasting DNA damage, calcium imbalance, and the release of substances that cause inflammation. These changes are closely tied to loss of balance in cell energy and redox function. Mitochondria, which make most neurons' energy, are both a main source and a target for reactive oxygen species (ROS). Long-term redox imbalance damages energy production, lowers NAD+, and disrupts SIRT1 regulation. Eventually, this leads to energy failure and loss of synaptic function. In AD, excessive ROS production and redox imbalances interact with amyloid-β toxicity, tau hyperphosphorylation, and metal ion disturbances. This convergence increases mitochondrial damage and fragmentation. When mitophagy is impaired, dysfunctional mitochondria are not removed, leading to ROS accumulation that further damages cellular structures and reinforces oxidative stress. This forms a self-perpetuating cycle that accelerates neuronal aging and neurodegeneration. Notably, research shows that energy failure and redox imbalance often precede the formation of amyloid plaques and tangles, suggesting that these mechanisms may initiate disease onset. This chapter reviews core mechanisms underlying redox signaling and neuronal senescence. It details how altered mitochondrial function disrupts neuronal energy homeostasis and triggers a cascade of molecular events that underlie Alzheimer's disease. The proposed framework connects redox failure, cellular senescence, and neurodegeneration as interdependent drivers of disease progression.

Schizophrenia is a complex, chronic psychiatric disorder with significant global impact, characterized by persistent positive, negative, and cognitive symptoms that are not fully addressed by current treatments. This review aims to synthesize established theories and advancing mechanistic concepts and also critically compare the latest international treatment guidelines. Recent evidence expands beyond the traditional dopamine hypothesis to include glutamatergic, serotonergic, and cholinergic dysfunctions, as well as emerging mechanisms such as neuroinflammation, oxidative stress, iron dysregulation, and gut-brain interactions. A review of major international guidelines (APA, NICE, CINP, WFSBP, and others) confirms consensus on the use of second-generation antipsychotics as first-line therapy and the early introduction of clozapine for treatment-resistant cases. All guidelines emphasize the essential role of integrated psychosocial interventions, including cognitive behavioral therapy for psychosis, family psychoeducation, and supported employment. Differences remain regarding the prioritization of precision medicine, pharmacogenomics, and digital health innovations. Prognosis varies widely but improves with early intervention, sustained treatment adherence, and comprehensive physical health monitoring. Overall, schizophrenia care is evolving toward a precision-based, recovery-oriented model that integrates biological, psychological, and social strategies to improve long-term outcomes and quality of life.

Understanding the neural and cognitive mechanisms underlying hypnosis has been a central focus of investigation over recent decades. Dominant approaches have often aimed to identify a single, distinct neural signature capable of accounting for the emergence of hypnotic phenomena. However, despite robust behavioural evidence supporting the concept of hypnotic responding, findings from neuroimaging and electrophysiological studies have been highly heterogeneous, limiting the establishment of a consistent neurophysiological framework. This chapter provides an up-to-date overview of the neural dynamics associated with hypnotic responses and explores the primary sources of variability in brain-based markers of hypnosis. We propose a componential approach, suggesting that the hypnotic process comprises multiple distinct yet interacting mechanisms. Specifically, we describe how different aspects of hypnotic phenomena correspond to specific neural patterns: large-scale network connectivity changes induced by hypnotic induction, localized modulations driven by suggestion, and individual susceptibility amplifying these neural responses. We further argue that additional variability may stem from individual differences beyond susceptibility, contributing to the lack of convergence across studies. The chapter concludes by advocating for a multi-componential framework as a promising direction for future research that better captures the complexity of the cognitive and neural architecture underlying hypnotic responding.

The last four decades have led to a clarification of the clinical deficits exhibited by cerebellar patients and a set of reliable and valid clinical ataxia rating scales are now available for both the assessment and follow-up of cerebellar ataxias. Cerebellar syndrome is now divided into three principal categories: the cerebellar motor syndrome (CMS), the vestibulo-cerebellar syndrome (VCS), and the cerebellar cognitive affective syndrome/ Schmahmann syndrome (CCAS/SS). CMS corresponds to motor impairments, including dysmetria, kinetic tremor, asynergia, dysdiadochokinesia, and dyschronometria. VCS includes oculomotor disturbances, such as saccadic dysmetria, jerky pursuit, downbeat nystagmus, and gaze-evoked nystagmus. CCAS/SS includes a spectrum of cognitive and affective deficits targeting executive functions, spatial cognition, language processing, and emotional regulation. The International Cooperative Ataxia Rating Scale (ICARS) was developed as an objective quantitative measure of cerebellar ataxias and assesses CMS and VCS, while the more streamlined Scale for the Assessment and Rating of Ataxia (SARA) was introduced specifically for the evaluation of motor deficits corresponding to the CMS. The Brief Ataxia Rating Scale (BARS) has also been proposed as a concise yet effective alternative, demonstrating enhanced efficiency and significant correlations with established cerebellar syndrome subtypes CMS/VCS. Furthermore, the Scale for Oculomotor Disorders in Ataxia (SODA) assesses the VCS, and the CCAS/Schmahmann Scale (CCAS-SS) and the Cerebellar Neuropsychiatric Rating Scale (CNRS and CNRS-2) assess the cognitive and emotional impairments in the CCAS/SS. Together with the Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia) that covers all of these domains, the recognition of the three types of cerebellar syndrome and the application of validated clinician-administered and patient-completed rating scales represent a key step forward in the practice of ataxiology and training of students.

The global spread of microplastics has become a serious public health concern. Once thought to be inert, microplastics are now recognized as biologically active agents capable of accumulating in the body and causing toxic effects across organ systems. This review summarizes current evidence on their oxidative and inflammatory effects in the central nervous system (CNS) and the eye. Studies show that microplastics can cross biological barriers such as the blood-brain barrier (BBB) and blood-retinal barrier (BRB), where they are taken up by cells, impair mitochondria, and trigger inflammation. Microplastics have been found in cerebrospinal fluid, brain tissue, and ocular structures, raising concern about their link to neurodegenerative and retinal diseases, including Alzheimer's, Parkinson's, macular degeneration, and other disorders. Mechanistic data indicate activation of NF-κB and TGF-β1 pathways, promotion of protein aggregation, and disruption of neural signaling. In the eye, microplastics have been linked to oxidative stress, corneal thinning, and photoreceptor damage. However, human studies are limited due to challenges in detecting tiny particles and lack of microplastic-free controls. Research is further hindered by inconsistent definitions, particle diversity, and non-physiological exposure models. We highlight the need for standardized methods, multi-omics tools, and long-term studies to better understand exposure impacts. Given the rise in neurological and ocular diseases, clarifying the role of microplastics is essential for effective public health strategies.