搜索结果：Neurology India

Epilepsy remains highly underdiagnosed and undertreated in low- and middle-income countries, largely due to inadequate training, misconceptions, and stigma among Primary Healthcare Providers (PHCPs). They play a pivotal role in reducing the epilepsy treatment gap, particularly in rural and tribal regions of India. However, evidence on the long-term impact of structured epilepsy training on their knowledge, attitudes, and practices (KAP) is limited. We conducted a longitudinal pre-post intervention study for PHCPs in two rural blocks of Chhattisgarh, India. A one-day, cadre-specific epilepsy training workshop was delivered to doctors, nurses/community health officers (CHOs), and Accredited Social Health Activists (ASHAs). The training covered epilepsy recognition, basic management, seizure first aid, referral pathways, and stigma reduction. All PHCPs underwent a questionnaire-based KAP assessment administered twice - six months before the intervention and one year after. Item-level responses were compared using McNemar and Wilcoxon signed-rank tests. Domain-wise composite scores were analysed using paired Student's t-test or Wilcoxon signed-rank test, as appropriate. A total of 978 PHCPs (40 doctors, 191 nurses/CHOs, and 747 ASHAs/ASHAs Trainers) with matched and sufficiently complete pre-post responses were included in the final analysis. Significant improvements in knowledge, attitudes, and practices were observed within all participant groups at the one-year post-intervention assessment compared with baseline (p&#xa0;<&#xa0;0.0001). Among doctors and nurses/CHOs, improvements were greatest in the knowledge domain, whereas among ASHAs/ASHAs Trainers the largest improvement was observed in the attitude domain. A structured, role-specific epilepsy training intervention was associated with statistically significant improvements in knowledge, attitudes, and practices within PHCPs in a resource-limited rural setting that remained evident at the one year follow-up suggesting retention of training-related gains over time when compared to baseline. Scaling up such culturally tailored training programs may contribute meaningfully to reducing stigma and narrowing the epilepsy treatment gap in similar contexts.

Obesity rates are rising globally, placing a significant strain on individuals, society, and economies. The gut microbiota (GM) plays a pivotal role in the development of obesity. Many studies have identified differences in GM composition between obese and normal-weight people worldwide. However, there is limited data on the GM profiles of obese and control Indian individuals. Fecal samples from 20 participants (10 obese, 10 control) underwent 16&#xa0;S rRNA gene sequencing. Anthropometric analysis confirmed significant differences in weight and BMI, with no significant variance in age or height. Taxonomic profiling and diversity indices (Chao1, Shannon, Simpson) were evaluated using the NCBI database. Sequencing identified 1,359 Operational Taxonomic Units. The obese cohort exhibited an elevated Firmicutes-to-Bacteroidetes (F/B) ratio, with Firmicutes increasing to 53.78% and Bacteroidetes decreasing to 25.54%. A significant reduction in Fusobacteria was observed in the Ob group (p&#x2009;=&#x2009;0.034). Seven species were nominally enriched in obese subjects: Bifidobacterium catenulatum (p&#x2009;=&#x2009;0.031), Anaerostipes hadrus (p&#x2009;=&#x2009;0.014), Eggerthella lenta(p&#x2009;=&#x2009;0.032), Bifidobacterium bifidum (p&#x2009;=&#x2009;0.037), Clostridium butyricum(p&#x2009;=&#x2009;0.012), Phascolarctobacterium sp.(p&#x2009;=&#x2009;0.046), and Alistipes onderdonkii(p&#x2009;=&#x2009;0.033). Rarefaction curves showed higher species richness in the control group, whereas PCA plots indicated greater community similarity (lower beta diversity) in the obese group. Obesity is associated with distinct microbial dysbiosis, characterized by a significant loss of Fusobacteria and an enrichment of SCFA-producing species. These specific taxonomic shifts, rather than broad diversity indices, provide a more sensitive signature for metabolic changes associated with obesity, supporting the energy harvest hypothesis.

Progressive Supranuclear Palsy (PSP) is a rare atypical Parkinsonian disorder associated with tau pathology, with an estimated global incidence of 1-18 cases per 100,000 individuals per year. Richardson Syndrome (PSP-RS) is the most prevalent clinical subtype. Induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells of a clinically confirmed PSP-RS patient using Sendai virus-mediated reprogramming. Comprehensive characterization confirmed their self-renewal ability and the expression of markers associated with the undifferentiated pluripotent state. The resulting iPSC line serves as a valuable biological resource for investigating disease pathophysiology in derived cell types and provides a valuable platform for biomarker discovery and drug screening.

Multiple System Atrophy (MSA) is a rare, adult-onset, and rapidly progressive neurodegenerative disorder characterized by motor dysfunction and autonomic failure, with an estimated prevalence of 1.9-4.9 per 100,000 individuals per year. Clinically, MSA is broadly classified into two major phenotypes: cerebellar-dominant (MSA-C) and Parkinsonian-dominant (MSA-P). In this study, induced pluripotent stem cells (iPSCs) were generated from peripheral blood mononuclear cells of a clinically diagnosed MSA-P patient using Sendai virus-mediated reprogramming. Detailed characterization demonstrated robust self-renewal capacity and expression of key markers associated with the undifferentiated pluripotent state. This iPSC line represents a valuable biological resource for modelling disease mechanisms in patient-derived cell types and provides a promising platform for biomarker identification and therapeutic drug screening.

BackgroundThe burden of early-onset Alzheimer's disease and other dementias (EOAD) in BRICS nations (Brazil, Russia, India, China, South Africa, Egypt, Ethiopia, Iran, Saudi Arabia, the United Arab Emirates, and Indonesia) is poorly characterized.ObjectiveOur aims are to characterize national trends, identify high-burden populations, quantify sex- and risk factor-specific burdens, and inform targeted prevention and age-inclusive healthcare strategies in these key nations.MethodsUsing data from the Global Burden of Disease Study (GBD) 2023, we analyzed EOAD (ages 40-64) across BRICS countries from 1990-2023, employing decomposition, Joinpoint regression, and Bayesian Age-Period-Cohort modeling to project trends to 2035.ResultsPrevalent cases increased in all nations, led by China. Age-standardized incidence rose in China (average annual percentage change 0.461%) but declined in India and Iran. Females consistently bore a higher burden. Ambient particulate matter drove substantial disability-adjusted life years in Iran (74.43/100,000) and Saudi Arabia, while household air pollution was key in Ethiopia and India. Projections indicate divergence by 2035, with Russia's incidence rising to 56.22 and Saudi Arabia's prevalence falling to 160.10 per 100,000.ConclusionsEOAD burden in BRICS is heterogeneous, driven by aging, sex, and modifiable risks, necessitating tailored public health strategies.

Background and objectives Emerging evidence indicates a complex relationship between glycated haemoglobin (HbA1c) levels and motor symptom severity in Parkinson's disease. Both elevated (>6.1%) and low (<5.3%) HbA1c have been linked to increased disability. This study examined the association between HbA1c levels and motor symptoms in patients with Parkinson's disease from Jodhpur, India. Methods A cross-sectional observational study was conducted at the department of Neurology, Mathura Das Mathur Hospital, Jodhpur between March 2023 and February 2024. One hundred patients with Parkinson's disease patients fulfilling the UK Parkinson's Disease Society Brain Bank (UKPDSBB) criteria were enrolled. Participants underwent HbA1c testing, motor evaluation with the Unified Parkinson's Disease Rating Scale (UPDRS III) in ON and OFF states, and cognitive screening with the Montreal Cognitive Assessment (MoCA). Patients were categorised into three groups based on HbA1c: &#x2264;4.9% (Low), 5.0-5.9% (Normal-to-Prediabetic), and &#x2265;6.0% (High). Disease duration and medication history were also recorded. Results No significant group differences were found for age, sex, body mass index (BMI), or disease duration, between the three groups, based on HbA1c levels. UPDRS and MoCA scores differed significantly across HbA1c categories (P<0.001). Higher HbA1c strongly correlated with worse motor outcomes (UPDRS ON: Spearman's &#x3c1;=0.90; OFF: &#x3c1;=0.84) and poorer cognition (MoCA: &#x3c1;= -0.79). Interpretation and conclusions Elevated HbA1c levels were significantly associated with greater motor impairment and cognitive dysfunction in Parkinson's disease. These findings highlight the potential role of metabolic dysregulation in progression of Parkinson's disease and underscore the need for longitudinal studies to clarify causal links and therapeutic implications.

ObjectiveTo characterize the clinical profile, functional and developmental status, radiologic patterns, and comorbidity burden in children aged 1-14 years diagnosed with hemiplegic cerebral palsy (HCP) at a tertiary pediatric neurology center.MethodsThis cross-sectional study included 70 children with HCP. Functional assessments were done with the Gross Motor Function Classification System (GMFCS), Manual Ability Classification System (MACS), and the Quality of Upper Extremity Skills Test (QUEST). Development was evaluated using Developmental Profile-3 (DP-3), whereas caregiver-reported health-related quality of life was assessed through the Caregiver Questionnaire (CQ). Correlations among functional measures, developmental scores, and epilepsy were examined.ResultsThe mean age was 62.4&#x2009;&#xb1;&#x2009;38.3 months, with a male predominance (71.4%) and more right-sided involvement. Antenatal complications were present in 30% of pregnancies, and 41% of children required resuscitation at birth. Postnatal complications, including respiratory distress and neonatal seizures, occurred in 43%. Most children demonstrated mild to moderate motor impairment, with 73% classified as GMFCS levels I and II, and reduced hand function was common, with 88% falling within MACS levels II and III. The mean QUEST score was 68.1&#x2009;&#xb1;&#x2009;6.7, indicating mild to moderate impairment of upper-extremity quality, particularly in dissociated movements and grasp. Epilepsy occurred in 38.5%, visual impairment in 31%, and hearing loss in 7%. Poorer manual ability corresponded with higher GMFCS levels and lower developmental scores.ConclusionChildren with HCP exhibit a consistent pattern of structural brain injury, substantial comorbidity burden, and measurable functional limitations, underscoring the need for early, targeted multidisciplinary intervention.

Epilepsy is a complex neurological disorder that includes recurrent seizures and significant cognitive impairment, which substantially contribute to disease burden. This review presents an integrated mechanistic and clinical framework linking epilepsy, cognition, and addiction, emphasizing their shared and interacting neurobiological pathways. Recurrent seizure activity induces chronic neuroinflammation, oxidative stress, and mitochondrial dysfunction, leading to disrupted synaptic plasticity and neurotransmitter imbalance, particularly within glutamatergic and dopaminergic systems. These alterations underlie deficits in memory, attention, and executive function. Concurrently, dysfunction of mesocorticolimbic reward circuitry increases susceptibility to substance use disorders, including alcohol, nicotine, opioid, and cannabis dependence. Substance use further destabilizes neuronal excitability, alters antiseizure drug pharmacokinetics, and accelerates cognitive decline, establishing a bidirectional and self-reinforcing cycle. Epigenetic modifications and maladaptive neuroplasticity further sustain this interaction. Clinically, the coexistence of epilepsy, cognitive impairment, and substance use presents major challenges, including diagnostic complexity, poor treatment adherence, polypharmacy, increased hospitalization, reduced functional independence, and elevated risk of mortality, including sudden unexpected death in epilepsy. These challenges highlight the limitations of seizure-focused care and the need for comprehensive management strategies. Moreover, therapeutic approaches should integrate cognitive rehabilitation, behavioral and psychological interventions, dietary therapies, neuromodulation techniques, and rational pharmacological optimization, alongside structured addiction management and supportive lifestyle measures. Multidisciplinary care models combining neurology, psychiatry, neuropsychology, and addiction medicine are essential for improving outcomes. Additionally, future directions should prioritize biomarker-driven precision medicine, longitudinal and standardized cognitive assessment, development of dual-targeted interventions, neuroprotective and anti-inflammatory therapies, and the use of digital health technologies for monitoring and intervention. Early identification and integrated care remain critical to preventing long-term cognitive decline and addiction-related complications.

Nipah virus infection is an uncommon but highly lethal zoonotic illness that primarily presents with acute encephalitis and respiratory disease in humans. After its initial identification during the Malaysia-Singapore outbreak of 1998-1999, human outbreaks have since been reported in Bangladesh and India. Despite the relatively small number of reported cases, the Nipah virus remains a major clinical and public health concern because of its high mortality, capacity for person-to-person transmission, lack of approved antiviral treatment, and potential for amplification within healthcare settings. For clinicians, the major challenge lies in early recognition of a disease that initially presents with nonspecific febrile symptoms but may rapidly progress to severe encephalitis, acute respiratory distress syndrome, or both. Human-to-human transmission has been well documented in South Asian outbreaks, particularly in household and healthcare settings, underscoring the importance of prompt isolation and infection prevention measures. Laboratory confirmation relies primarily on reverse transcription polymerase chain reaction, with serology providing supportive evidence later in the course of illness. Management remains largely supportive, with intensive care often required in severe cases. This review provides a practical clinician-oriented overview of Nipah virus infection, focusing on epidemiology relevant to frontline practice, clinical presentation, transmission, diagnostic approach, infection control, treatment, prognosis, and outbreak response.

Multiple sclerosis lesions are dominated by clonally expanded CD8+ T cells within an IFN&#x3b3;-rich inflammatory microenvironment and neurons may be targets of these effector cells. However, the peptide antigens that CD8+ T cells recognize on neurons are largely undefined. Neurons constitutively express low levels of HLA class I, and whether inflamed human neurons are competent to present a class I ligandome, what that ligandome contains, and whether presentation has functional consequences for autoreactive CD8+ T cells remain open questions. Here we combine human iPSC-derived neural aggregates (HNAs), HLA class I immunoprecipitation coupled to LC-MS/MS immunopeptidomics, and microfluidic co-culture assays to map IFN&#x3b3;-induced HLA class I presentation by neurons and to test antigen-specific cytotoxicity. IFN&#x3b3; stimulation induced HLA class I upregulation in HNAs and enabled recovery of a canonical 8-12-mer class I ligandome enriched for 9-mers. Neuron-restricted expression of a synapsin-driven polyepitope cassette yielded presentation of defined exogenous 9-mer peptides on donor HLA class I molecules and, in the presence of IFN&#x3b3;, elicited activation of autologous antigen-specific CD8+ T cells and antigen-dependent neurite injury. Across four donors, comparative immunopeptidomics identified IFN&#x3b3;-associated neural peptide repertoires that were distinct from those of matched fibroblasts and enriched for predicted HLA-B binding peptides. &#x3b2;2-microglobulin deletion ablated peptide recovery, and neuron-restricted reconstitution enabled identification of candidate neuron-derived peptides, including recurrent neurofilament light (NEFL)-derived peptides detected across donors. Together, these findings establish a human iPSC-derived platform for studying inflammatory neuronal HLA class I antigen presentation and antigen-dependent CD8+ T cell engagement.

Parkinson's disease is a major neurodegenerative disorder, and mitochondrial dysfunction has been increasingly recognized as a key contributor to its pathogenesis. Recent studies suggest that treatment with mesenchymal stem cell-derived small extracellular vesicles offers a promising cell-free strategy for mitigating neurodegeneration. In the present study, we investigated the effects of induced pluripotent stem cell-derived mesenchymal stem cell-derived small extracellular vesicles on dopaminergic neurons in a murine Parkinson's disease model and explored the underlying mechanisms related to mitochondrial impairment. A Parkinson's disease mouse model was established using 1-methyl-4-phenyl-1,2,4,5- tetrahydropyridine-induced neurotoxicity, followed by the intranasal administration of mesenchymal stem cell-derived small extracellular vesicles and comprehensive behavioral and pathological assessments. To elucidate the mechanistic basis of any effects, we examined mitochondrial function and Homer protein homolog 3 (Homer3) expression in brain tissue. Mice with Homer3 knockdown were used to validate the role of Homer3 in the therapeutic effects of mesenchymal stem cell-derived small extracellular vesicles. Mesenchymal stem cell-derived small extracellular vesicle administration significantly reduced motor dysfunction in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine-induced Parkinson's disease mice by protecting dopaminergic neurons. Furthermore, mesenchymal stem cell-derived small extracellular vesicles increased both mitochondrial number and function through Homer3 upregulation in Parkinson's disease mice. The therapeutic benefits of mesenchymal stem cell-derived small extracellular vesicles in rescuing dopaminergic neurons were impaired by Homer3 knockdown. Collectively, these findings suggest that, at least in part, mesenchymal stem cell-derived small extracellular vesicles ameliorate dopaminergic neuron damage via the Homer3-mediated restoration of mitochondrial function in a mouse model of Parkinson's disease. Our results highlight the neuroprotective role of mesenchymal stem cell- derived small extracellular vesicles in Parkinson's disease and provide new perspectives on their therapeutic potential.

Traumatic encephalopathy syndrome (TES) is a clinical research construct used to identify individuals at risk for chronic traumatic encephalopathy (CTE) following exposure to repetitive head impacts (RHI). Adjudication of TES relies on clinical features such as progressive cognitive impairment and neurobehavioral dysregulation. Blood-based biomarkers and structural neuroimaging abnormalities have been associated with TES but are not part of the criteria. This study evaluated whether TES identification was associated with the combined contribution of cognitive performance, blood biomarkers, and structural neuroimaging measures across two well-characterized cohorts. Participants included 158 professional fighters from the Professional Athletes Brain Health Study and 149 former American football players from The DIAGNOSE CTE Research Project. Three indices were constructed representing complementary domains: a cognitive index reflecting cohort-specific cognitive features, a blood biomarker index including plasma neurofilament light chain, glial fibrillary acidic protein, total tau, tau phosphorylated at amino acid 231, and APOE-&#x3b5;4 carrier status, and an imaging index comprising volumetric MRI measures of subcortical structures, ventricles, and corpus callosum subregions. Grouped weighted quantile sum regression models were estimated within each cohort to evaluate associations between these indices and TES while adjusting for age, race, competition status, and RHI exposure. Multidomain models demonstrated improved model performance compared with single-domain models in both cohorts (PABHS: AUC&#x2009;=&#x2009;0.91, PPV&#x2009;=&#x2009;0.80; DIAGNOSE CTE: AUC&#x2009;=&#x2009;0.84, PPV&#x2009;=&#x2009;0.85). Biomarker and imaging indices contributed additional information across cohorts, although imaging contributions were more prominent in fighters whereas blood biomarker associations were stronger in football players. TES in RHI-exposed athletes was associated with a convergent clinicobiological profile observed across two independent cohorts with distinct exposure patterns. These findings support multidomain analytic frameworks for evaluating correlated biological signals in RHI-exposed populations and may inform future studies of TES and CTE.

Glucagon-like peptide-1 receptor agonists have been shown to have neuroprotective effects in metabolic diseases, but their application in neurodegenerative diseases (stroke and Parkinson's disease) has not been adequately studied. To assess the neuroprotective effects of GLP-1 receptor agonists in experimental stroke and Parkinson's disease models, in terms of mechanisms, properties of intervention, and major neurological outcomes. A systematic review was performed according to PRISMA. Four databases Cochrane CENTRAL, PubMed, Web of Science and Scopus were searched and 1643 records identified and 13 experimental animal studies were included. The SYRCLE tool was used to extract data and assess the risk of bias. 13 experimental studies published in 2013-2026 were included, which involved models of stroke and Parkinson disease. The MCAO models were the main models used in stroke studies, with a significant decrease in infarct volume, such as 15.4 % &#xb1; 1.3 % (liraglutide) and 40 % reduction with linagliptin. The score in neurological deficit was also found to improve (1.1 &#xb1; 0.14; P < 0.05) and the size of the infarct in treated groups had also reduced (36.5 % to 8.2 %; P = 0.001). The research on Parkinson disease showed that there was a notable improvement in motor functions (P < 0.001), preservation of dopaminergic neurons, and a decrease in the aggregation of &#x3b1;-synuclein. GLP-1 agonists decreased neuroinflammatory (TNF-&#x3b1;, IL-1b, IL-6), oxidative (ROS, 4-HNE), and apoptotic (increased Bcl-2, decreased Bax) markers. The treatment was between 24 h and 20 weeks, and the doses also differed among the agents. The overall quality of risk of bias assessment was moderate, with four studies having a high risk because of small sample size and inadequate reporting on the randomization and blinding. GLP-1 receptor agonists have powerful neuroprotective activity in preclinical models of stroke and Parkinson disease, which is multi-targeted. To ensure translational potential and to maximize therapeutic strategies, standardized studies and clinical trials are needed.

Residential greenness has been associated with reduced risk of inflammatory bowel disease (IBD), but its association in the context of COVID-19, a condition associated with increased IBD risk, remains unclear. We evaluated whether the protective association between greenness and IBD persisted among individuals with SARS-CoV-2 infection. We conducted a nationwide cohort study of 6,900,341 individuals with confirmed COVID-19 in South Korea, using linked data from the National Health Insurance Service, Korea Disease Control and Prevention Agency, and satellite-derived normalized difference vegetation index (NDVI) from NASA's Terra MODIS (MOD13A3, version 6.1). Individuals were categorized into low (0.2 to <0.4), moderate (0.4 to <0.6), or high (&#x2265;0.6) NDVI groups. The primary outcome was incident IBD (Crohn's disease and ulcerative colitis) &#x2265;30 days after infection, defined using ICD-10 codes. Inverse probability of treatment weighting balanced covariates, and weighted Cox models estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). Higher residential greenness was associated with lower risk of developing IBD following COVID-19 infection, with aHRs of 0.93 (95% CI, 0.90-0.97) for moderate and 0.71 (0.68-0.74) for high NDVI compared with low. Subtype analyses showed more consistent associations for ulcerative colitis (aHR 0.91 [95% CI, 0.87-0.96] for moderate; aHR 0.60 [0.57-0.63] for high NDVI). For Crohn's disease, associations were weaker and limited to individuals exposed to high NDVI (aHR, 0.90 [95% CI, 0.85-0.96]). Associations were more apparent among individuals with mild COVID-19 and were stronger among females, adults aged 40 to 59 years, and those with pre-existing comorbidities. Higher residential greenness was associated with a lower incidence of IBD after COVID-19. Maintaining access to greenness during periods of restricted mobility may help counteract infection-related inflammation.

We report a case of super-refractory convulsive status epilepticus managed in our intensive care unit. Although the outcome was ultimately fatal, we present serial continuous electroencephalography (EEG) recordings obtained throughout this short but severe illness. Using this case as a framework, we explore the nuances and complexities of interpreting continuous EEG findings and related electrographic phenomena. In particular, we highlight the indications for continuous EEG monitoring based on validated instruments and examine the relationship between specific electrographic patterns and seizures or status epilepticus, including lateralized periodic discharges, lateralized rhythmic delta activity, generalized periodic discharges, and their modifiers. We also outline the evolving stages of status epilepticus as identified on continuous EEG, along with their therapeutic and prognostic implications. Finally, we demonstrate the role of continuous EEG in guiding therapeutic decision-making during status epilepticus, with particular emphasis on defining electrographic targets for anesthetic management.

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Delirium is a common manifestation of acute brain dysfunction during critical illness, strongly associated with persistent cognitive impairment among ICU survivors. Although delirium duration and severity have been linked to adverse neurocognitive outcomes, it remains uncertain whether delirium-directed interventions implemented during ICU admission or after discharge can meaningfully modify cognitive trajectories. We conducted a systematic review of randomized clinical trials to evaluate whether delirium-directed interventions improve long-term cognitive outcomes in adult ICU survivors. This PRISMA-compliant systematic review was prospectively registered in PROSPERO (CRD420261295266). We included randomized clinical trials enrolling adults admitted to medical or surgical ICUs with acute respiratory failure requiring mechanical ventilation and/or shock. Eligible studies evaluated delirium-directed pharmacological or non-pharmacological interventions and reported validated cognitive outcomes assessed at least 3&#x202f;months after discharge. Risk of bias was evaluated using the Cochrane RoB 2 tool. Due to substantial heterogeneity, findings were synthesized narratively rather than quantitatively. Four randomized clinical trials met all inclusion criteria; one additional trial (Schweickert et al., 2009) was reviewed as contextual evidence given absence of post-discharge neuropsychological outcomes. Two trials derived from the same parent cohort (MIND-USA 2018 and its 2024 long-term follow-up), yielding three effective independent randomized comparisons. Two trials evaluated pharmacological treatment of established ICU delirium using antipsychotic agents. Two trials evaluated non-pharmacological rehabilitation-based interventions with validated post-discharge cognitive outcomes. Rehabilitation-based interventions were feasible and associated with signals of improved executive function. Antipsychotic treatment did not improve global cognition, functional status, or quality of life at 3 or 12&#x202f;months. Rehabilitation-based delirium-directed interventions demonstrate biological plausibility and preliminary signals of benefit for long-term cognitive outcomes after critical illness, whereas antipsychotic treatment of established ICU delirium does not confer sustained cognitive benefit. The evidence base comprises three distinct randomized comparisons, underscoring the need for larger, cognition-powered trials with harmonized survivorship endpoints. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261295266, CRD420261295266.

Metastatic triple-negative breast cancer (TNBC) remains highly challenging to treat despite advances in oncology. This study investigated whether non-invasive alternating, low-intensity induced electric fields (iEFs) could suppress tumor growth and metastasis while modulating anti-tumor immunity in TNBC. Orthotopic TNBC mouse models were treated with alternating (100 kHz) and low-intensity (2.7 mV/cm peak), induced electric fields (iEFs), which were delivered non-invasively via a solenoid coil system. Tumor growth and lung metastasis were assessed following treatment. Immune profiling was performed to evaluate changes in T cell states and myeloid cell populations within both primary tumors and metastatic lung tissue. iEF treatment significantly reduced primary tumor growth (n=9) and lung metastases (n=5). Within the tumor microenvironment, iEFs decreased infiltration of immunosuppressive myeloid cells (n=8). In the lung metastatic niche, iEF therapy increased CD8+ T cell abundance while reducing immunosuppressive myeloid populations (n=8). We also observed that iEFs reduced the metastatic potential of cancer cells by inhibiting epithelial-to-mesenchymal transition (n=3). Induced electric field therapy enhances anti-tumor immunity and suppresses metastatic progression in TNBC by enhancing T cell activity and remodeling immunosuppressive myeloid environments. These findings support iEFs as a promising non-invasive immunomodulatory strategy for metastatic TNBC.

Meditation offers a tractable model for probing altered states of consciousness, yet consistent physiological markers remain elusive. This study characterized within-subject autonomic and respiratory modulation across pre-meditation, during-meditation, and post-meditation states in trained Rajyoga practitioners using multiscale heart rate variability (HRV) metrics and HRV-respiration coupling. Sex-stratified analyses were presented exploratorily to summarize state-dependent effects. A single-lead electrocardiogram (ECG) was recorded from 55 Rajyoga practitioners (31 male, 24 female) during three consecutive 10-min states: pre-meditation, during meditation, and post-meditation. After artifact correction, 27 HRV indices spanning time-domain, frequency-domain, and non-linear dynamics, including multiscale entropy (MSE 1-20), were computed in Kubios HRV Scientific. State-dependent effects were tested using Friedman tests with Bonferroni-adjusted post-hoc contrasts, and cardiorespiratory coupling was assessed through correlations between respiration frequency and low-frequency (LF) and high-frequency (HF) HRV powers. Meditation was associated with robust state-dependent modulation. Time-domain indices and frequency-domain powers increased during meditation with partial post-session recovery, while selected non-linear features shifted significantly. Respiration frequency was reduced, and HRV-respiration coupling was strengthened, consistent with increased parasympathetic engagement. Exploratory sex-stratified summaries indicated potential differences in effect magnitudes that warrant confirmation in studies powered for interaction testing. These findings identify a reproducible physiological signature of the meditative state by integrating HRV magnitude, complexity, and cardiorespiratory coupling. The results support the usefulness of multiscale cardiorespiratory analysis as an operational marker of altered consciousness induced by Rajyoga meditation.