Problemy sotsial'noi gigieny, zdravookhraneniia i istorii meditsinyM S Cherepianskii, A V Baranov, G O Penina
The multiple sclerosis is chronic autoimmune disease with high risk of disability. The effective management of this disease directly depends on the timely prescription and escalation of treatment with medications altering course of multiple sclerosis. The key factor in optimizing medical care is organization of specialized structures. The specialized Multiple Sclerosis Clinic was opened in the Komi Republic in the beginning of 2021. The purpose of the study is to assess dynamics of key indicators of medication therapy of multiple sclerosis during 2018-2024 and to determine impact of opening of Multiple Sclerosis Clinic on these indicators using methods of statistical analysis.
Journal of medical economicsJohn Vissing, Geoffroy Coteur, Ibrahim Turkoz, Kavita Gandhi
AIMS: Generalized myasthenia gravis (gMG) is a rare, chronic autoimmune disorder with substantial healthcare resource utilization (HRU) and high economic burden. This study evaluated HRU, costs, and predictors of high-cost events in adults with gMG, using data from VIVACITY-MG3. METHODS: Post-hoc analyses used the primary efficacy dataset from VIVACITY-MG3, a randomized, double-blind, placebo-controlled study of nipocalimab and standard-of-care (SoC) versus placebo and SoC in seropositive adults with gMG. HRU endpoints included hospital admissions (HA), emergency department visits (EDV), and hospital days. Logistic regression analysis identified clinical and demographic HA/EDV predictors. Hospital costs per patient per year (PPPY) were estimated using United States (US) cost data from published sources and from a claims database, adjusted to 2024 US dollars. RESULTS: Among 153 patients, nipocalimab numerically reduced the proportion experiencing ≥1 all-cause (9.1% vs 15.8%) and gMG-related (3.9% vs 7.9%) HA/EDV events versus placebo. The incidence rate of HA/EDV events was 51% numerically lower with nipocalimab. Mean hospital stay duration was numerically shorter with nipocalimab for all-cause (8.4 vs 14.6 days) and gMG-related admissions (11.2 vs 17.6 days). All-cause and gMG-related hospital days per 100 patient-years were statistically significantly reduced by 60% and 68% with nipocalimab, respectively. Estimated cost offsets for reduced HRU were $10,860-$13,253 PPPY. Multivariate analysis identified worsening in Myasthenia Gravis-Activities of Daily Living (MG-ADL) total score and higher baseline Quantitative Myasthenia Gravis (QMG) respiratory total score as independent predictors. Patients switching from placebo to nipocalimab in the VIVACITY-MG3 open-label extension experienced a 64% reduction in hospital days PPPY. LIMITATIONS AND CONCLUSION: Study limitations include the post-hoc nature of the analysis and the relatively short study duration. Nipocalimab added to SoC significantly reduces overall HRU and associated costs in adults with gMG, particularly by lowering rates and severity of HA/EDV events. Clinical deterioration and high baseline disease severity independently predict high-cost events.
Myasthenia gravis (MG) is a complex autoimmune neuromuscular disorder, and the role of lipid metabolism dysregulation in MG pathogenesis remains unclear. This study aimed to investigate the molecular mechanisms of lipid metabolism regulation in myasthenia gravis development by integrating single-cell and bulk transcriptomic data. This study analyzed bulk RNA sequencing data from the GSE85452 dataset (13 MG patients and 12 healthy controls) and single-cell RNA sequencing data from the GSE227835 dataset (10 MG patients and 10 healthy controls). Differential expression analysis was performed, and weighted gene co-expression network analysis (WGCNA) was conducted to identify disease-related modules. Key genes were screened through the intersection of differentially expressed genes (DEGs), WGCNA hub genes, and lipid metabolism-related genes. Functional enrichment analysis, protein‒protein interaction (PPI) network construction, immune infiltration analysis, and regulatory network analysis were performed. Single-cell analysis was used to characterize cellular heterogeneity and intercellular communication features. A nomogram prediction model was constructed and internally validated using leave-one-out cross-validation (LOOCV). Potential therapeutic compounds were identified through drug prediction and molecular docking analysis. Furthermore, key genes were validated by RT-qPCR in an independent cohort of 5 MG patients and 5 healthy controls. A total of 823 DEGs and 13 co-expression modules were identified, of which 4 modules were significantly associated with MG. Twenty-one candidate genes were screened, and 2 key genes (IRS2 and ALDH2) were ultimately determined. IRS2 was significantly downregulated while ALDH2 was significantly upregulated in MG patients. The nomogram model based on key genes demonstrated excellent predictive performance (AUC = 0.897). Immune infiltration analysis showed increased regulatory T cells (Tregs) and decreased CD4+ memory activated T cells in MG patients. Single-cell analysis identified 10 major cell types. Cell‒cell communication analysis revealed dense interactions among CD4+ T cells, B cells, and CD14+ monocytes. Drug prediction identified metformin and cyclophosphamide as potential therapeutic candidates, and molecular docking confirmed favorable binding affinities. This integrative study generated the hypothesis that lipid metabolism dysregulation, potentially mediated by IRS2 and ALDH2, may contribute to immune dysfunction in MG pathogenesis. These findings provide preliminary insights into the molecular mechanisms underlying MG development and suggest potential diagnostic biomarkers and therapeutic targets. However, these results are hypothesis-generating, and clinical translation is contingent upon rigorous mechanistic validation through functional experiments, animal models, and larger multicenter clinical cohorts.
European journal of psychotraumatologyZheng Zhang, Ying Liu, Yuan Zhao
Background: Childhood maltreatment (CM) is associated with sleep disturbance, but observational findings may be affected by confounding, shared familial liability, and reverse-direction explanations. We conducted bidirectional two-sample Mendelian randomization (MR) to examine genetic evidence linking composite CM liability with six sleep-related phenotypes.Methods: Genetic instruments for CM were obtained from a large European-ancestry multi-cohort GWAS meta-analysis. CM was defined as a composite phenotype encompassing multiple abuse and neglect subtypes and ascertainment modes. Summary statistics for chronotype, daytime sleepiness (DS), insomnia symptoms, sleep apnea (SA), daytime napping (DN), and sleep duration (SD) were derived from large European-ancestry GWASs. Inverse-variance weighted MR was the primary method, with weighted median and MR-Egger sensitivity analyses. Benjamini-Hochberg correction was applied and reported as P(BH).Results: In forward MR, genetically proxied CM was associated with higher DS (OR = 1.04, 95% CI 1.01-1.07; P(BH) = 0.030), insomnia symptoms (OR = 1.08, 95% CI 1.01-1.15; P(BH) = 0.030), and DN (β = 0.07, 95% CI 0.03-0.09; P(BH) = 0.002). Little evidence was observed for chronotype, SA, or SD. In exploratory reverse-direction MR, genetic liability to DN (β = 0.16, 95% CI 0.05-0.27; P(BH) = 0.012) and insomnia symptoms (β = 0.21, 95% CI 0.07-0.35; P(BH) = 0.012) was associated with CM liability.Conclusions: This study provides suggestive genetic evidence linking composite CM liability with selected sleep-related phenotypes, particularly self-reported DS, insomnia symptoms, and DN. Reverse-direction findings may reflect shared genetic liability, gene-environment correlation, reporting-related mechanisms, or broader familial pathways rather than temporal effects of adult sleep traits on CM. Given modest effects and uneven sensitivity support, findings should be interpreted cautiously.
Artificial cells, nanomedicine, and biotechnologyLeila Kafshdooz, Reza Safaralizadeh
OBJECTIVE: This review introduces the 'nanomaterial-microbiome-brain interface' as a conceptual framework uniting three systems: gut microbiota, nanoparticles, and neurodegeneration. MAIN FINDINGS: We synthesize evidence showing that titanium dioxide, silver, and zinc oxide nanoparticles differentially alter microbial composition. These microbial shifts intersect with established gut-brain mechanisms, including short-chain fatty acid production and immune modulation, providing plausible pathways linking nanomaterial exposure to neurological outcomes. CONCLUSION: We propose the 'nanomaterial-microbiome-brain interface' as a novel conceptual framework with twofold relevance-serving both as a potential contributor to Parkinson's disease pathogenesis through unintentional environmental exposure, and as an underexplored avenue for therapeutic intervention. Critical knowledge gaps persist. Addressing these gaps will require integrated approaches that bridge nanomaterial research, microbiome science, and neurodegeneration studies.
Annals of medicineJinglong Li, Qisen Zhu, Mohamad Nabil Mohd Noor, Chan Choong Foong
BACKGROUND: Cerebral Palsy (CP) is the main cause of motor disabilities in childhood, necessitating innovative approaches to rehabilitation and assistive technology (AT). Simultaneously, artificial intelligence (AI) is increasingly being integrated into devices to create more adaptive, personalized, and effective AT. This systematic review aimed to evaluate the effectiveness and usability of AI-powered assistive technologies designed to support daily activities and rehabilitation in children with CP. MATERIALS AND METHODS: Five databases, including Scopus, Web of Science, PubMed, Embase, and IEEE Xplore, were systematically searched, and 23 articles were included in the final analysis. Articles were identified, selected, and categorized into emerging thematic areas based on the primary function and application of the technology. RESULTS: Five key thematic topics were identified: 1) AI-driven motor rehabilitation and gait training for functional mobility; 2) intelligent assessment and monitoring systems for clinical decision support; 3) AI-supported communication, social interaction, and intention recognition tools; 4) gamified and virtual reality-based interventions to enhance engagement and usability; and 5) smart assistive systems supporting daily living and independent mobility. The findings demonstrate a strong trend toward the application of AI technologies in personalized, engaging, and data-driven interventions for children with CP. However, the field is predominantly in the proof-of-concept stage, with limitations including small sample sizes, lack of long-term clinical validation, challenges in user-centered design, and usability for children with CP. CONCLUSION: AI-powered assistive technologies hold significant potential for transforming the care of children with CP by enabling highly personalized and engaging interventions. To actualize this potential, future work must realize that practical application remains challenging owing to limited clinical validation, technological integration, and usability barriers for children with CP. Future research must prioritize user-centered design and multidisciplinary collaboration to ensure that AI and robotic advancements improve the usability and quality of life for children with CP.
Cell cycle (Georgetown, Tex.)Yunchang Yang, XiangXiang Cao, Nan Feng, Xinyao Kang, Yaofeng Wang, Yunqin Sun
Glioblastoma (GBM) is defined by extreme lethality and transcriptomic plasticity, but the signatures driving the most aggressive tumors remain incompletely defined. In this exploratory in silico study, TCGA-GBM patients were stratified using a strict 1-year overall survival threshold. We integrated differential expression analysis, WGCNA, single-cell RNA-seq, spatial transcriptomics, and virtual knockout simulations. A high-risk signature centered on CCL2 and TIMP1 was identified. Single-cell and spatial mapping linked these genes to an inflammatory, macrophage-enriched microenvironment. The signature inversely correlated with neuronal synapse mimicry scores, suggesting that extreme aggressiveness involves a macroscopic shift from differentiated neuronal states toward an undifferentiated inflammatory phenotype. Virtual perturbation modeling confirmed CCL2 and TIMP1 as highly interconnected network hubs. Despite limitations inherent to computational and retrospective cohorts, our rigorous multi-omics validation identifies the CCL2/TIMP1 axis as a driver of potential prognostic indicator. These findings generate the hypothesis that these mediators reflect a critical inflammatory, mesenchymal-like tumor microenvironment shift, warranting independent cohort validation and experimental investigation.
Gut microbesQiong Li, Baowen Fan, Yao Xiao, Zhe Zhang, Siyi Zhao, Bin Liao, Jie Zeng, Xuesong Shan, Haonan Ye, Yuqi Wen, Lieliang Zhang, Hua Guo, Feng Xiao, Hong Zhu
Diseases that cause neurological dysfunction, such as Parkinson's disease (PD), Alzheimer's disease (AD), and maple syrup urine disease (MSUD), among others, are characterized by complex and multifaceted etiologies. There is growing evidence that branched-chain amino acids (BCAAs), regulated by the gut microbiota, play a critical role in the development of the central nervous system (CNS) disorders. This review focuses on the potential role of branched-chain amino acid metabolism in regulating brain function and gut microbiota. First, we summarize the current understanding of BCAAs, encompassing their biochemical metabolism, function, and systemic metabolic mechanisms. Subsequently, we delve into the mechanisms through which the gut microbiota regulates branched-chain amino acid metabolism, along with its mechanistic insights and recent evidence of its impact on neurological disorders. Finally, we discuss future research directions and challenges regarding gut BCAAs metabolism as a potential treatment for brain and gastrointestinal dysfunction.
Human vaccines & immunotherapeuticsAshok Kumar Dutta, Rashna Dass Hazarika, K L Ravikumar, Vijay Yewale, Sanjay Niranjan, Jaydeep Choudhury, Gurpreet Singh, Suresh Panuganti, Jeetendra Gavhane, …
Invasive meningococcal disease (IMD) is a significant but under-recognized public health challenge in India, marked by rapid progression, high mortality, and severe sequelae. This consensus document, developed from literature review, outbreak analyses, and deliberations by 14 Indian experts, highlights outbreaks from 1966 (Delhi: 616 cases, case fatality ration: CFR 20.9%) to 2022-2023 (Kolkata). Serogroup A remains predominant, with emerging serogroups C, W, and Y. Systematic review evidence shows 12.1% prevalence in epidemics (CFR 12.8%) and 0.76% in endemic settings (CFR 3.0%), though true burden is underestimated due to weak surveillance. IMD shows bimodal age distribution, highest in children < 5 y (61.8%) and adolescents. MenACWY conjugate vaccines show 95.7-99.5% seroprotection across serogroups. Experts recommend vaccination at 9-12 months with booster at 10-11 y, mandatory reporting, sentinel surveillance, and clinician awareness. The roadmap stresses awareness, short-term surveillance, and long-term data generation toward National Immunization Program inclusion.
BACKGROUND: Multiple sclerosis (MS) significantly affects patients' quality of life (QoL), particularly in resource-limited settings. This multicentre study aimed to identify factors influencing QoL among MS patients in Northwest Ethiopia, where data are scarce. METHODS: A cross-sectional study was conducted from January to June 2024 among 427 MS patients (≥18 years, diagnosed using McDonald criteria) attending three referral hospitals (University of Gondar, Debre Tabor, Felege Hiwot). Stratified sampling ensured representation across disease severity. Sociodemographic, clinical, psychological and behavioural data were collected. QoL was measured using the MSQOL-54 questionnaire. Multiple regression identified predictors of QoL, expressed as β coefficients and p values. Treatment adherence was assessed only among patients receiving disease-modifying therapy (DMT) (n = 310), and this subgroup was used for adherence-related analyses. RESULTS: The mean age of participants was 43 years, and 58.3% were female. Disease severity was classified as mild in 50.4%, moderate in 34.7%, and severe in 15.0% of participants. Low physical and mental QoL were reported in 34.9% and 31.6%, respectively. Lower QoL was significantly associated with greater disease severity (β = -0.85, p = 0.001), illness duration >10 years (β = -0.35, p = 0.002), fatigue (β = -1.10, p < 0.001), anxiety (β = -1.00, p < 0.001), depression (β = -1.20, p < 0.001), cognitive impairment and treatment non-adherence (evaluated only among DMT-treated patients). Moderate-to-high physical activity (β = 0.60, p = 0.001) and strong social support (β = 0.70, p = 0.001) were associated with higher QoL. CONCLUSIONS: QoL among MS patients was strongly influenced by disease severity, treatment adherence (among patients receiving DMT), fatigue, psychological distress, cognitive function, physical activity and social support. Interventions targeting these modifiable factors may improve patient outcomes. This study provides important evidence from Ethiopia and helps address a significant knowledge gap regarding MS care in resource-limited settings.
Annals of medicineJun Yang, Xiaocui Yang, Jiajia Liu, Ke Li, Jiawei Shi, Yingzhun Liang, Shuangshuang Liang, Hanjie Liu, Hui Qiao, Xing Fan
BACKGROUND: Microvascular decompression (MVD) is the current definitive treatment for achieving a radical cure of primary hemifacial spasm (pHFS). The current study aimed to integrate blink reflex (BR) monitoring into MVD for pHFS to assess surgical efficacy and explore its predictive value for postoperative spasm when combining with lateral spread response (LSR) monitoring. METHODS: A prospective cohort study included 105 patients with pHFS undergoing MVD. Intraoperative zygomatic LSR (ZYG-LSR), mandibular LSR (MAN-LSR), and BR were monitored. Multivariate logistic regression was used to assess independent predictors of postoperative spasm at 3 months after surgery. Two predictive models (Model 1: LSR; Model 2: LSR plus BR) for postoperative spasm were compared using Receiver Operating Characteristic (ROC) curve analysis at four postoperative time points: 1 day, 1 week, 1 month, and 3 months, with the area under the curve (AUC) quantifying overall accuracy and the DeLong test for comparison. RESULTS: BR showed a higher elicitation rate (99.0%) than ZYG-LSR (97.1%) and MAN-LSR (91.4%). Persistent ZYG-LSR (odds ratio 28.99), MAN-LSR (odds ratio 12.06), and BR (odds ratio 10.38) were identified as independent predictors for postoperative spasm at 3 months after surgery (all p < 0.05). Regarding the two predictive models, their performance improved over time. At 3 months, Model 2 showed a numerically higher AUC than Model 1 (0.955 versus 0.901), while the DeLong test still did not reach statistical significance (p = 0.083). CONCLUSION: In conclusion, intraoperative BR monitoring appears to be a feasible and potentially useful adjunct to conventional LSR monitoring in MVD for pHFS, and warrants further evaluation in larger studies.
Annals of medicineXiaoxuan Hu, Chong Fu, Guorong Bi, Qiyun Tan, Yaoyu Ying, Weiming Zhao, Xuechun Cai, Nan Yin, Xin Wang, Hong Liu, Lingzhong Meng, Fu-Hai Ji, Qiang Sun, Baojian…
INTRODUCTION: Emergence agitation (EA) is a clinically significant complication during early recovery from general anesthesia. This protocol describes a randomized controlled trial designed to determine whether intraoperative low-dose remimazolam maintenance reduces the incidence of EA without prolonging emergence time in patients undergoing oral surgery. PATIENTS AND METHODS: This multicenter, randomized, controlled clinical trial will enroll 388 patients scheduled for oral surgery under general anesthesia. Patients will be randomly allocated in a 1:1 ratio to either the remimazolam group, receiving a low-dose intraoperative infusion of remimazolam, or the control group, receiving an equivalent volume of normal saline. The primary outcome is the incidence of emergence agitation; the key secondary outcome is emergence time. Emergence time will be evaluated within a non-inferiority framework, whereas the incidence of emergence agitation will be tested for superiority. Additional endpoints comprise pain scores, analgesic use, the rate of postoperative nausea and vomiting (PONV), recourse to rescue antiemetics, the occurrence of postoperative sleep disturbance (PSD), time spent in the post-anesthesia care unit (PACU), postoperative hospital length of stay, overall recovery quality, the frequency of perioperative adverse events, and patient satisfaction. DISCUSSION: This trial will investigate the efficacy and safety of intraoperative low-dose remimazolam maintenance in patients undergoing oral surgery. The findings may provide evidence supporting a practical pharmacological intervention to reduce EA and enhance postoperative recovery. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2600116544).
Annals of medicineYonghan Luo, Yuemei Feng, Yan Guo, Yanchun Wang, Xueshan Xia, Yue Feng
OBJECTIVE: This study aims to develop an interpretable machine learning model for predicting the risk of FS in children with enterovirus (EV) infections and to implement it for clinical application. METHODS: This retrospective study included 446 hospitalized children with EV infection (144 FS, 302 non‑FS). LASSO regression and BORUTA algorithm selected 15 key predictors from 53 clinical variables. Six models (logistic regression, KNN, Naive Bayes, MLP, random forest, XGBoost) were constructed and evaluated using AUC, sensitivity, specificity, F1 score, and decision curve analysis. SHAP values provided interpretability, and a Shiny web‑based calculator was developed. RESULTS: The XGBoost model demonstrated the best predictive performance: the training set AUC reached 0.972 (95% CI: 0.958-0.987), with sensitivity of 0.892 and specificity of 0.905. The internal validation set achieved an AUC of 0.842 (95% CI: 0.757-0.926). DCA confirmed its strong clinical applicability. SHAP analysis identified key features contributing to the model: fever duration, disease course, immunoglobulin M, neutrophil count, fibrinogen, CD8+ T-cell percentage, aspartate aminotransferase, CD3+ T-cell percentage, procalcitonin, presence of hand-foot herpes lesions, CD19+ B-cell percentage, erythrocyte sedimentation rate, lymphocyte count, serum ferritin level, and alanine aminotransferase. The 'Shiny' calculator facilitates personalized risk assessment. CONCLUSION: The XGBoost predictive model developed in this study demonstrated both high accuracy and clinical interpretability. The associated web-based calculator offers a new tool for risk stratification and management of FS in children with EV infections.
BACKGROUND: Sleep disorders-including sleep deprivation, obstructive sleep apnea (OSA), and circadian rhythm disruption-and metabolic diseases such as obesity and type 2 diabetes represent major, interconnected public health challenges. This review aims to synthesize current evidence on the bidirectional crosstalk between these conditions, with a focus on the mediating role of dysregulated adipokine secretion. DISCUSSION: We elaborate a mechanistic framework wherein specific sleep disturbances disrupt circadian rhythms and alter the secretory profiles of key adipokines, including leptin, adiponectin, interleukin-6 (IL-6), and angiopoietin-like protein 4 (ANGPTL4). Sleep deprivation and fragmentation promote a state of leptin dysregulation and reduce adiponectin levels, while OSA-driven intermittent hypoxia potently upregulates IL-6 and ANGPTL4. These alterations collectively contribute to insulin resistance, dyslipidemia, and chronic low-grade inflammation, thereby elevating metabolic disease risk. Conversely, obesity and diabetes exacerbate sleep disorders through pathways involving visceral adiposity, neuroendocrine dysfunction (e.g. HPA-axis activation), and diabetes-related symptoms (e.g. nocturia, neuropathic pain), forming a vicious cycle. Clinical and preclinical evidence underscores that the synchronization of sleep-circadian biology is fundamental to maintaining adipokine homeostasis and metabolic health. CONCLUSION: The evidence positions sleep and circadian health as critical, modifiable determinants of metabolic risk. Integrating sleep assessment and evidence-based interventions (e.g. CPAP for OSA, sleep extension, circadian realignment) into standard preventive and clinical frameworks for metabolic diseases is a promising strategy. Public health initiatives should elevate 'quality sleep' as a pillar of health alongside nutrition and physical activity to mitigate the intertwined epidemics of metabolic and sleep disorders.
Renal failureRuitong Liao, Xuemei Zhang, Lian Lin, Zhiyun Ning, Xiyan He, Yifan Lin, Yiqiang Zhan, Xiaoqing Ye
This study examined the associations of anxiety, insomnia, and psychological resilience with health-related quality of life (HRQoL) among maintenance dialysis patients and explored potential mediating roles. In this cross-sectional study, 207 adult patients undergoing maintenance dialysis were recruited. HRQoL was assessed using the Short Form-36 Health Survey (SF-36), generating Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Anxiety, insomnia, and psychological resilience were measured using the Generalized Anxiety Disorder-7 (GAD-7), Athens Insomnia Scale (AIS), and 25-item Connor-Davidson Resilience Scale (CD-RISC-25), respectively. Multivariable linear regression and bootstrap-based mediation analyses were conducted. Furthermore, subgroup analyses were conducted to examine the robustness of the results.Higher anxiety and insomnia scores were independently associated with lower PCS and MCS, whereas resilience was positively associated with both components. Each one-point increase in anxiety score was associated with a 1.61-point decrease in PCS and a 1.15-point decrease in MCS; corresponding decreases for insomnia were 1.01 and 0.91 points. Psychological resilience partially mediated the association between anxiety and HRQoL (23.46% for PCS; 30.37% for MCS), but no significant mediation was observed for insomnia. Subgroup analyses showed consistent associations for insomnia, while the anxiety-HRQoL relationship was modified by smoking status and diabetes. Anxiety and insomnia are independently associated with impaired HRQoL in dialysis patients. Psychological resilience partially explains the adverse impact of anxiety, but not insomnia, suggesting distinct patterns of association and potential targets for tailored psychosocial interventions.
Gut microbesDoyeon Kim, Minshu Li, Thi Ha Nguyen, Yu-Jeong Choi, Sojeong Jang, Minhyeong Kim, Young-Kwang Kim, Min-Kyoo Shin, Arvie Camille V de Guzman, Sunghyouk Park
The gut microbiome modulates host neuropathology, but the mechanisms linking specific microbial genes and metabolites to host phenotypes remain poorly defined. Here, we identify microbiome-derived vitamin B6 (VB6) and its biosynthesis gene as key regulators of host dopaminergic homeostasis. Metagenomic analysis of fecal samples from Parkinson's disease (PD) patients revealed enrichment of biosynthetic pathways for pyridoxal-5'-phosphate (PLP), the active form of VB6, and tyrosine decarboxylase genes. Using E. coli-C. elegans symbiotic models, we demonstrate that the bacterial pdxJ gene, encoding a key enzyme in de novo VB6 synthesis, is essential in regulating host dopaminergic homeostasis. Colonization with pdxJ-deficient bacteria led to reduced host VB6 and dopamine levels, reduced dopaminergic enzyme activity, and altered motor behavior, which were all rescued by VB6 supplementation. In PD-relevant C. elegans models, bacterial PLP biosynthesis modulated α-synuclein aggregation and behavioral deficits associated with human LRRK2 mutations. In mice, colonization with pdxJ-deficient bacteria reduced serum VB6 levels, decreased tyrosine hydroxylase staining in the substantia nigra, and impaired motor coordination, which were rescued by VB6 supplementation. Overall, our results define a bacterial pdxJ-PLP-dopamine axis that links gut microbial metabolism to host dopaminergic phenotypes and suggest bacterial VB6 biosynthesis as a potential modifier of PD risk and a context-dependent therapeutic target.
Gut microbesGautham Siddarth Ragunagam, Anand Anbarasu, Gothandam Kodiveri Muthukaliannan
Fusobacterium nucleatum has emerged as a pathobiont that associates oral dysbiosis with systemic diseases through coaggregation, hematogenous dissemination, and immune modulation. This review provides molecular insights through which they are involved in systemic diseases such as colorectal cancer, adverse pregnancy outcomes, cardiovascular diseases, neurodegenerative disorders, and diabetes mellitus. Key virulence factors include the adhesins of FadA, Fap2, and RadD, lipopolysaccharides, and outer membrane vesicles, which mediate epithelial invasion and endothelial permeafbility and facilitate immune suppression through TLR4-NF-κB, β-catenin/Wnt, and MAPK signaling pathways. These interactions result in impaired tissue homeostasis, propagate chronic inflammation, and promote oncogenic and metabolic modulation. Systemic pleiotropy of F. nucleatum is further substantiated by its involvement in chemoresistance, placental dysfunction, vascular inflammation, and neuronal injury, substantiating its systemic pleiotropy. Emerging therapeutic strategies, such as blocking adhesins, neutralizing outer membrane vesicles, microbiome manipulation, and using CRISPR-based clearance, provide precision techniques for mitigating diseases. Therefore, this review identifies F. nucleatum as the primary microbial mediator of oral-systemic pathology and its translational significance in the development of targeted antimicrobial and host-directed therapies.
Amyotrophic lateral sclerosis (ALS) has been linked to gastrointestinal symptoms and alterations in the gut microbiota. The enteric nervous system (ENS) coordinates intestinal function and sits at the host-microbe interface. The mechanisms by which luminal changes relay to the central nervous system (CNS), where motor neurons reside, have yet to be completely defined. In this narrative review, we first present evidence from ALS patient cohorts and preclinical models alongside mechanistic studies of infection, dysbiosis, and related neurodegenerative diseases to discuss how the microbiota and its metabolites may affect the ENS and CNS in ALS. Next, we propose a plausible mechanism of ALS pathogenesis through the gut-microbiome-brain axis. We further offer a summary of clinical trials that have studied the impacts of the microbiota on human ALS. Finally, we discuss future directions for studies of microbiota-ENS-CNS interactions in ALS. Better understanding of the dynamic interactions among the microbiota, microbial metabolites, neuroactive metabolites, and inflammation through the ENS/CNS in ALS will provide innovative insights into ALS prevention and treatment.
Global health actionNaiyuan Liang, Cheng Huang, Qiang Pan
BACKGROUND: Maternal folic acid supplementation is a cornerstone of public health for preventing neural tube defects (NTDs), yet its long-term impact on child development remains underexplored. OBJECTIVE: This study evaluates the long-term cognitive and mental health associations of maternal folic acid supplementation by utilising China's 2009 Folic Acid Supplementation Programme for rural women as a quasi-experimental framework. METHODS: We analysed 1,953 children aged 10-15 years from the 2020 China Family Panel Studies. Using provincial NTD prevalence in 2009 from the Maternal and Child Health Surveillance system as a proxy for intervention intensity, we employed difference-in-differences models to estimate associations, adjusting for demographic and parental covariates. RESULTS: Maternal folic acid supplementation was significantly associated with improved outcomes among girls: higher memory scores (β [95% CI], 0.232 [0.069, 0.394]), enhanced numerical reasoning skills (5.234, [2.188, 8.279]), lower Center for Epidemiological Studies Depression Scale score (-0.523 [-0.933, -0.113]), and reduced likelihood of depressive symptoms (-0.024 [-0.048, -0.001]). No comparable associations were observed in the boys. Although cognitive associations were observed across socioeconomic status (SES) groups among girls, the mental health associations were concentrated among girls from higher-SES families. Results were robust to adjustment for covariates. CONCLUSIONS: This study highlights sex-specific, long-term associations of maternal folic acid supplementation but reveals that socioeconomic disparities may constrain mental health gains. Thus, universal nutrition interventions alone may be insufficient to bridge health equity gaps. The findings should be interpreted within the broader nutritional ecology and alongside concurrent macro-social changes that shape child development outcomes.
Gynecological endocrinology : the official journal of the International Society of Gynecological EndocrinologyNicola Pluchino, Jonas Vibert, Mareike Roth, Ursula Gobrecht, Janna Pape, Susanna Weidlinger, Gabriele Merki-Feld
OBJECTIVE: To review recent evidence on the association between progestin exposure and meningioma risk and to propose practical recommendations for hormonal management in women requiring progestin therapy. METHODS: A narrative review of studies published between 2015 and 2025 evaluating the relationship between exogenous progestins and meningioma development, growth, or progression was performed. Evidence regarding different progestin compounds, cumulative exposure, reversibility after discontinuation, and implications for gynecologic practice was analyzed. RESULTS: Meningiomas account for more than one-third of intracranial tumors and occur two to three times more frequently in women, supporting a potential hormonal influence mediated by progesterone receptors, which are expressed in most tumors. The increasing use of MRI has led to more frequent detection of incidental meningiomas in premenopausal women using progestins for contraception or gynecologic conditions such as endometriosis and heavy menstrual bleeding. Consistent associations with increased meningioma risk were observed for high-dose or prolonged exposure to cyproterone acetate, chlormadinone acetate, nomegestrol acetate, and medroxyprogesterone acetate. Risk appeared to increase with cumulative exposure and decrease after treatment discontinuation. Evidence for other progestins, including desogestrel, dienogest, levonorgestrel, and the levonorgestrel-releasing intrauterine system, remains limited and less conclusive. CONCLUSIONS: Women's health specialists should systematically assess a history of meningioma before prescribing progestins. In patients with incidental meningioma, discontinuation of high-risk progestins should be considered, followed by MRI reassessment within 3-6 months. When hormonal treatment remains necessary, the lowest effective dose and regular neuro-oncologic monitoring are recommended. Increased awareness and individualized counseling are essential to optimize hormonal management in women at risk of meningioma.