Arterial ischaemic stroke (AIS) in adolescents and young adults differs from older populations due to its variety of risk factors and aetiologies. This study compares the risk factor profiles and age- and sex-related differences between adolescents and very young adults.

Pooled data from three multicentre cohort studies in Europe (Germany, France, The Netherlands) were analysed. First-ever symptomatic AIS cases in adolescents (10-18 years) and very young adults (18-30 years) were classified using both a paediatric AIS classification (multiple risk factor category system) and the modified Trial of ORG 10172 in Acute Stroke Treatment criteria for adults.

The cohort includes 142 adolescents (median age 15) and 131 very young adults (median age 25). Using the adult AIS classification, cryptogenic stroke was most common (43% in adolescents, 32% in young adults). Thirty-two percent had other determined aetiologies. The paediatric classification showed similar results regarding identified causes; 29% resulted in cryptogenic stroke, respectively. Sex distribution differed by age: male predominance in adolescents (61%) and female predominance in young adults (57%).

Adolescence and young adulthood may represent a shared age group with similar causes and risk profiles for AIS. The high rate of cryptogenic stroke suggests potential limitations in current classification systems for AIS aetiology at these ages.

This cohort highlights the need for an age-adapted risk factor system that accounts for the transitional nature and the complexity of stroke in this age group.

Evidence indicates that the Endothelial Activation and Stress Index (EASIX) is a predictor of mortality in endothelium-related conditions; however, its association with mortality risk in atrial fibrillation (AF) remains uncertain. Accordingly, this study examines the relationship between EASIX and mortality risk among patients with AF.

This retrospective analysis utilized data from the Medical Information Marketplace in Intensive Care IV (MIMIC-IV) database, which includes critically ill patients diagnosed with AF. To examine the association between EASIX scores and mortality, Kaplan-Meier survival analysis, Cox proportional hazards models, and restricted cubic spline regression were applied to evaluate the relationship between EASIX and all-cause mortality. Subgroup analyses were conducted to explore potential interactions with key patient characteristics, and sensitivity analyses were performed to further confirm the robustness of the results.

A total of 3,193 patients were included in the analysis. KM survival analysis showed that elevated EASIX levels were associated with a higher risk of both in-hospital and ICU mortality. After adjusting for potential confounders, increased EASIX levels remained significantly associated with in-hospital mortality [HR, 1.09 (95% CI 1.03, 1.15), P = 0.0002] and ICU mortality [HR, 1.10 (95% CI 1.04, 1.17), P = 0.0002]. Stratified analyses revealed a significant interaction between sepsis, respiratory failure, and EASIX in relation to both in-hospital and ICU mortality. To evaluate the robustness of the findings, a sensitivity analysis was performed. After additionally adjusting for metoprolol and heparin as covariates, patients in the highest EASIX group continued to demonstrate the greatest mortality risk: the HR for in-hospital death was 2.08 (95% CI: 1.51-2.85), and the HR for ICU death was 1.83 (95% CI: 1.21-2.65).

Elevated EASIX levels correlate with higher mortality rates, underscoring its potential as an accessible tool for identifying high-risk patients and informing clinical decisions. However, further studies are needed to explore the underlying mechanisms and validate its applicability across diverse patient populations.

We aim to evaluate the diagnostic significance of caudothalamic groove (CTG) echogenicity on cranial ultrasonography (CUS) by examining its correlation with magnetic resonance imaging (MRI) findings, including susceptibility-weighted imaging (SWI). This retrospective study screened 131 neonatal intensive care unit neonatal intensive care unit infants with diagnostic-quality CUS and MRI (including SWI) performed between January 2019 and April 2022. Among these, 34 had CTG echogenicity on CUS; 18 of the 34 had no corresponding CTG hemorrhage on SWI and formed the analytic cohort. The final cohort included 18 infants (10 males, 8 females; mean gestational age 32.7 wk, range 25.3 to 39.3 wk). Five (27.8%) were term, 13 (72.2%) were preterm. Initial CUS demonstrating CTG echogenicity was performed at a mean of 15.7 postnatal days; echogenicity was bilateral in 9 (50%) and unilateral in 9 (50%), with teardrop-like morphology in 10 (55.6%). MRI with SWI was performed at a mean of 29 postnatal days (range 2 to 90 d). No hemorrhagic changes were observed in the CTG region on SWI. Three patients (16.7%) had normal MRI findings, 15 (83.3%) showed nonhemorrhagic abnormalities, including edema, thin corpus callosum, subependymal cysts, ventricular dilatation, or cortical malformations. This study demonstrates a discordance between CUS and SWI-MRI findings in infants with CTG echogenicity. The presence of term infants and bilateral involvement suggests that CTG echogenicity may be a nonspecific imaging finding that can reflect a variable pathophysiological process. Therefore, confirmatory MRI with SWI may be valuable for accurate diagnosis and clinical decision-making in both preterm and term neonates with isolated CTG echogenicity.

Candida auris is an emerging fungal pathogen notable for its intrinsically high resistance to fluconazole, the most prescribed antifungal drug. However, the genetic regulators underlying fluconazole susceptibility in C. auris remain unclear. Here we performed a pooled screen of piggyBac (PB) transposition mutants and identified significant enrichment of mitochondrial genes whose inactivation reduces fluconazole susceptibility. A genome-wide genetic interaction analysis of a mitochondrial gene deletion mutant, pet309Δ, suggests that the vacuolar calcium pump homologue CDT1 (Calcium and Drug Transporter 1) is responsible for its reduced fluconazole susceptibility. Fluconazole induces significant upregulation of CDT1 through the calcineurin signalling pathway. Cdt1, beyond its canonical calcium-pumping function, has evolved another function in mediating fluconazole efflux through its fluconazole-induced, calcineurin- and ATP hydrolysis-dependent plasma membrane localization. In addition, Cdt1 accelerates the evolution of fluconazole resistance or tolerance, and its transcript levels are substantially elevated across resistant clinical isolates. Our findings reveal a neofunctionalized role for Cdt1 in mediating fluconazole efflux in C. auris.

Subarachnoid hemorrhage (SAH) is a devastating stroke subtype with high mortality and morbidity, causing severe brain injury through neuroinflammation and oxidative stress. Alisol A, a bioactive compound derived from Alisma orientale, has demonstrated anti-inflammatory, antioxidant, and metabolic-regulating properties. However, the potential role of alisol A in SAH has not yet been explored. This study was conducted to investigate the therapeutic role of alisol A in brain injury induced by SAH, with a particular focus on its underlying metabolic mechanisms. Our results showed that alisol A mitigated neuroinflammation and oxidative stress and alleviated brain injury and neurological deficits in SAH mice. This neuroprotective effect was associated with modulation of mitochondrial metabolism, notably a reduction in succinate accumulation, an important metabolite associated with inflammation and oxidative damage. Supplementation with succinate partially counteracted the observed anti-inflammatory and antioxidant effects of alisol A. Crucially, we identified sirtuin 3 (SIRT3) as an important mediator of these processes. The beneficial effects of alisol A on mitochondrial metabolism, as well as its anti-inflammatory and antioxidant actions, were dependent on SIRT3 upregulation. Overall, our study demonstrated that alisol A could protect against SAH-induced brain injury by upregulating SIRT3 expression, which reprogrammed mitochondrial metabolism and prevented succinate accumulation, thereby reducing neuroinflammation and oxidative stress. These findings deepen our understanding of the metabolic regulatory role of alisol A and highlight its therapeutic potential for SAH and other neurological disorders characterized by neuroinflammation and oxidative stress.

For cardiovascular diseases, diabetes, and asthma, the positive effects of dog ownership are shown. Cancer is a leading cause of death, but the influence of dogs on cancer incidence and survival is not well examined. As modifiable lifestyle factors gain importance in cancer survivorship research, the potential protective role of dog ownership warrants systematic investigation. We retrospectively analyzed clinical data from a federated global health research network, focusing on patients diagnosed with cancer (International Classification of Diseases (ICD-10): C00-D49). From these, we generated two cohorts with contact with dogs (cohort 1) and one without (cohort 2). After propensity score matching for age and sex, a total of about 55,000 patients were included. Analysis of the matched cohort demonstrated that dog ownership was significantly associated with reduced 5-year all-cause mortality in cancer patients compared to non-owners (RR = 0.44). Survival analysis revealed a significantly higher 5-year cumulative survival rate among dog-owning patients versus non-owners, with a hazard ratio (HR) of 0.36. Contact with dogs is associated with a 64% relative risk reduction in cancer mortality, potentially mediated by increased physical activity, psychosocial support, and microbiome modulation. While retrospective design precludes causal inference, this first large-scale matched cohort study provides compelling epidemiological evidence warranting prospective validation.

Experimental autoimmune encephalomyelitis (EAE) is a pivotal animal model for multiple sclerosis (MS) research. This study provides a comprehensive bibliometric analysis of 9,435 EAE-related publications from the Web of Science Core Collection (2000-2024) to map the research landscape, identify trends, and highlight emerging frontiers. The analysis reveals a shift from initial rapid growth to a stabilized output, with the USA, Germany, and China as the leading contributors. Immunology and Neurosciences form the core disciplines, with increasing integration of cell biology, microbiology, and pharmacology. Co-citation and keyword analyses demonstrate a clear evolution in research focus: while early studies centered on T-cell biology and classic neuroinflammation, recent investigations emphasize the gut-brain-immune axis, microglial/astrocyte reactivity, immunometabolism, and novel therapeutic strategies like microbiota-targeted interventions and nanomedicine. The Th17/Treg axis remains a central immunoregulatory hub. This analysis delineates the intellectual structure of the field, underscoring its progression from foundational immune mechanisms to complex, system-level understandings of neuroimmune crosstalk, and identifies promising directions for future MS therapeutic development.Experimental autoimmune encephalomyelitis (EAE) is a pivotal animal model for multiple sclerosis (MS) research. This study provides a comprehensive bibliometric analysis of 9,435 EAE-related publications from the Web of Science Core Collection (2000-2024) to map the research landscape, identify trends, and highlight emerging frontiers. The analysis reveals a shift from initial rapid growth to a stabilized output, with the USA, Germany, and China as the leading contributors. Immunology and Neurosciences form the core disciplines, with increasing integration of cell biology, microbiology, and pharmacology. Co-citation and keyword analyses demonstrate a clear evolution in research focus: while early studies centered on T-cell biology and classic neuroinflammation, recent investigations emphasize the gut-brain-immune axis, microglial/astrocyte reactivity, immunometabolism, and novel therapeutic strategies like microbiota-targeted interventions and nanomedicine. The Th17/Treg axis remains a central immunoregulatory hub. This analysis delineates the intellectual structure of the field, underscoring its progression from foundational immune mechanisms to complex, system-level understandings of neuroimmune crosstalk, and identifies promising directions for future MS therapeutic development.

Autoimmune diseases are characterized by systemic inflammation that can affect multiple tissues. In idiopathic inflammatory myopathies (IIM), skeletal muscle is primarily involved; however, subclinical cardiac dysfunction may also occur. While left ventricular ejection fraction (EF) is commonly used to assess cardiac function, global longitudinal strain (GLS) has proven more sensitive in detecting early myocardial impairment. This study aimed to evaluate left ventricular GLS (LV GLS) in patients with IIM and no known cardiovascular disease, assessing both the prevalence of reduced GLS values and their associations with clinical and laboratory parameters. We enrolled 37 outpatients from the Department of Internal Medicine at the University Hospital of Verona, who underwent comprehensive clinical and echocardiographic assessment. The mean GLS value observed (- 17.9% ± 2.2%) was below the normal reference range (- 18.2% to - 21.2%) defined by the echocardiographic system. When compared with 37 healthy controls, IIM patients showed significantly impaired GLS despite preserved EF in both groups (- 17.88 ± 2.23% vs. - 19.88 ± 1.72%, p < 0.001). This difference remained significant after adjusting for age and sex (β = +2.25%, p < 0.001). In linear regression models, GLS was independently associated with arthritis (β = 2.165, p = 0.007), lymphocyte count (β = 0.001, p = 0.025), CK levels (β = 0.000, p = 0.024), and age (β = 0.032, p = 0.020). Patients with arthritis showed significantly worse GLS values compared to those without arthritis, despite similar EF. In multivariate analysis, arthritis remained independently associated with impaired GLS and lower CK levels. Overall, our findings suggest that patients with IIM exhibit a global reduction in left ventricular longitudinal function, detectable by GLS, even in the absence of overt cardiac disease. This impairment appears particularly evident in patients presenting with arthritis and is independent of age-related effects. Longitudinal studies are warranted to investigate the progression of GLS alterations and their potential role in guiding therapeutic strategies.

The development and function of B lymphocytes require the precise integration of signaling, transcriptional networks, and metabolic programs. While interferon (IFN)-inducible proteins can bridge innate and adaptive immunity, their roles in B cells remain poorly defined. Here, we identified RNF213, a giant IFN-inducible RING finger E3 ligase, as a key orchestrator of B-cell biology. Mice lacking Rnf213 exhibited defective splenic B-cell development, impaired B-cell receptor (BCR) signaling, and compromised metabolic activity. Mechanistically, RNF213 targeted the transcription factor SPIB for proteasomal degradation via K11-linked ubiquitylation. In Rnf213‑deficient B cells, stabilized SPIB transcriptionally upregulated Pik3c3, thereby increasing phosphatidylinositol 3-phosphate (PI3P) production. Excess PI3P recruited PTEN to early endosomes, where PTEN hydrolyzed phosphatidylinositol-3,4,5-trisphosphate (PIP3) and attenuated AKT-mTOR signaling. Strikingly, both genetic deletion of Spib and pharmacological inhibition of PIK3C3 restored AKT-mTOR activation, metabolic fitness, and B-cell development in Rnf213-null mice. Furthermore, Rnf213 deficiency impaired both T-independent and T-dependent antibody responses, highlighting its critical role in humoral immunity. Overall, our work reveals a novel ubiquitin-dependent circuit that links interferon signaling to the transcriptional and metabolic control of B-cell homeostasis. This study also establishes RNF213 as a crucial bridge between innate immune sensing and the dynamic regulation of lymphocyte development.

Myocardial ischemia-reperfusion injury (MIRI) causes severe clinical complications in patients. Although gemfibrozil (GEM) has been extensively studied in metabolic diseases, its effects on MIRI remain unknown. In this study, we investigated the pharmacological effects and molecular mechanisms of GEM in alleviating MIRI through adenosine 5'-monophosphate-activated protein kinase (AMPK) modulation. The results showed that pre-administration of GEM (100 mg/kg) provided significant protection against MIRI in mice, as indicated by reduced infarct size, lower cardiac injury markers such as hydrogen peroxide (H₂O₂), lactate dehydrogenase (LDH), and creatine kinase (CK), and improved cardiac function. This cardioprotective effect of GEM was associated with enhanced myocardial antioxidant capacity, as shown by decreased dihydroethidium (DHE) fluorescence density and reduced nitric oxide (NO) and malondialdehyde (MDA) levels in ischemic cardiac tissue. GEM pretreatment also prevented the I/R-induced increase in TUNEL-positive cells and expression of caspase-3, caspase-9, and Bax, as well as the I/R-induced decrease in Bcl-2 expression in ischemic cardiac tissue, indicating an anti-apoptotic effect of GEM in MIRI. In addition, GEM pretreatment prevented the I/R-induced increase in mRNA expression levels of tumour necrosis factor-α (Tnf-α), interleukin-β (Il-1β), and Il-6 in ischemic cardiac tissue. Further analysis showed that GEM administration prevented the I/R-induced decrease in phospho-AMPK levels in ischemic cardiac tissue, and pharmacological inhibition of AMPK with dorsomorphin (DSMF) abolished all cardioprotective effects of GEM. Taken together, these results suggest that GEM mitigates MIRI-induced cardiac injury by inhibiting apoptosis and oxidative stress via modulation of AMPK, supporting its potential for reducing MIRI-related cardiac damage.