Alzheimer’s disease (AD) is increasingly recognized as a disorder with significant vascular involvement, with microvascular damage and thromboinflammation often preceding classical amyloid pathology by several years. Elevated levels of prothrombin and thrombin, along with aberrant platelet activation, have been reported in individuals with AD. We hypothesized that platelet hyperactivity in AD results from an exaggerated response to thrombin in the presence of elevated amyloid beta 1-40 (Aβ₁₋₄₀), a peptide that accumulates during the early stages of AD. Platelet activation in response to Aβ₁₋₄₀ and thrombin was assessed using aggregation assays with an aggregometer, adhesion measurements by confocal microscopy, and spreading via both confocal microscopy and scanning electron microscopy. Reactive oxygen species (ROS) production and integrin α IIbβ 3 activation were quantified by flow cytometry. The roles of NADPH oxidase (NOX), ROS, and integrin signaling were examined using selective inhibitors. Aβ₁₋₄₀ significantly enhanced thrombin-induced platelet adhesion, aggregation, and spreading via NOX-derived ROS and integrin α IIbβ 3 activation. Aβ₁₋₄₀ also promoted platelet binding to fibrinogen and cerebrovascular endothelial cells, accompanied by distinct morphological changes. Inhibition of NOX or integrin α IIbβ 3 significantly reduced these effects. These findings identify a novel Aβ₁₋₄₀–NOX–ROS–integrin α IIbβ 3 axis that drives platelet hyperactivation and cerebrovascular interactions in AD.Targeting this pathway with antithrombotic or antioxidative strategies may offer therapeutic potential in mitigating AD-associated vascular pathology.

Sleep deprivation (SD) disrupts homeostatic regulation and increases vulnerability to stress and mood disorders. This study investigated the duration-dependent effects of SD and elucidated the distinct roles of adenosine A1 receptors (A1R) and A2A receptors (A2AR) in behavioral and molecular alterations induced by 24, 48, and 72 h of SD in mice. SD for 48 h and 72 h, but not 24 h, significantly increased immobility time in the tail suspension test (TST) and forced swim test (FST), accompanied by elevated plasma corticosterone (CORT) levels, indicating a duration-dependent stress response. Hippocampal A1R mRNA expression was significantly reduced, whereas A2AR mRNA expression was markedly increased at 48 h and 72 h of SD. Pharmacological blockade of either A1R (DPCPX) or A2AR (SCH 58261) significantly attenuated SD-induced depression-like behaviors and CORT elevation, whereas activation of A1R with the agonist CPA exacerbated depression-like behavior at 24 h and 48 h of SD. These findings suggest that A2AR upregulation may represent a pathological response to prolonged SD, whereas A1R downregulation may reflect compensatory adaptation to sustained receptor activation. Taken together, our results demonstrate that A1R and A2AR play distinct roles in SD-induced depression-like behaviors.

Sleep–wake regulation is controlled by circadian and homeostatic processes, with adenosine acting as a key molecular mediator of homeostatic sleep pressure. Extracellular adenosine accumulates during wakefulness as a result of neuronal energy metabolism, particularly in the basal forebrain, and declines during recovery sleep, thereby reflecting the physiological need for sleep.The sleep-promoting effects of adenosine are mediated primarily by two G protein–coupled receptor subtypes, the adenosine A1 receptor and the adenosine A2A receptor. The adenosine A1 receptor, coupled to inhibitory Gi/o proteins and widely expressed in the cortex, hippocampus, thalamus, and basal forebrain, suppresses wake-promoting neuronal activity and facilitates slow-wave activity during non-rapid eye movement sleep. In contrast, the adenosine A2A receptor, coupled to stimulatory Golf proteins and enriched in the striatum and nucleus accumbens, promotes sleep by activating neurons in the preoptic hypothalamus and engaging the indirect basal ganglia pathway. Despite these well-established roles, the contributions of dysregulation of the adenosine A1 receptor and the adenosine A2A receptor to specific sleep disorders remain incompletely understood. This review examines how signaling of the adenosine A1 receptor and the adenosine A2A receptor is altered in insomnia, obstructive sleep apnea, narcolepsy, and restless legs syndrome, and evaluates the therapeutic potential of receptor-selective strategies for adenosine receptor–targeted treatment.

Purpose: North Korean refugee women face multiple vulnerabilities during pregnancy and early childrearing due to fragmented support and limited familiarity with Korea’s health and welfare systems. Existing research has examined isolated barriers. This study used a service design approach to explore their maternal–infant care experiences and identify structural discontinuities across the care pathway. Methods: Data were collected from North Korean refugee mothers and service providers from April to August 2024. A service design approach using user journey mapping, thematic analysis, and service blueprinting was employed to examine user actions, emotional trajectories, frontline interactions, and backstage and interagency processes. Results: Five structural issues were identified: fragmented information, cross-institutional access barriers, cultural and emotional isolation, discontinuity in interagency linkage, and provider resource constraints. These issues accumulated along the pathway, increasing emotional burden, delaying timely care, and reinforcing avoidance behaviors. Misalignment between user needs and multi-agency processes was also evident. Conclusion Maternal and infant care challenges among North Korean refugee women stem from structural fragmentation rather than individual factors. Based on these findings, the NK Mom Care Navigator—a pathway-based, culturally responsive service design model—is proposed to strengthen continuity of care and enhance equitable maternal–infant support for vulnerable refugee families.

Early neurologic deterioration (END) is common and occurs within a few hours to days after an ischemic stroke. Traditionally, END has been treated as a collective entity, including the occurrence of new deficits (recurrence) and the aggravation of pre-existing neurologic deficits (progression). END arises from distinct mechanisms that require different therapeutic approaches. We reviewed clinical and experimental studies addressing the epidemiology, mechanisms, and treatment of END, focusing on differentiating END due to recurrence from END due to progression and on interventions including antiplatelet therapy, direct thrombin inhibition, and induced hypertension. Early recurrence is closely associated with thrombus growth and new ischemic events, particularly in atherothrombotic disease. Early recurrence is also common in patients with cancer-associated stroke. Thrombin and platelet activation play central roles under both conditions. In contrast, progression is mainly driven by infarct growth, that is, the evolution from incomplete infarction to complete infarction due to impaired perfusion, especially in lesions involving the subcortical fiber tracts. Therapeutic implications differ accordingly. Recurrence may respond to potent antithrombotic strategies, including combined antiplatelet and direct thrombin inhibition, whereas progression may benefit from induced hypertension. However, recurrence and progression often occur simultaneously, making clinical differentiation challenging. END should be conceptualized as a spectrum of clinical presentations arising from distinct mechanisms. Recognizing recurrence and progression as separate processes is essential for mechanism-oriented treatments. Future trials should adopt this framework to develop individualized strategies and improve outcomes in patients with acute stroke.

Background: and Purpose Although gastrointestinal (GI) surgery can affect drug efficacy, its impact on oral anticoagulants (OACs) remains unclear. This study investigated the impact of GI surgery on the comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation (AF). Methods: Using a nationwide South Korean claims database, AF patients prescribed OACs between 2015 and 2021 were analyzed. The primary outcome was ischemic stroke, and secondary outcomes were major bleeding, all-cause death, and composite outcome (ischemic stroke, major bleeding, all-cause death). Outcomes were compared by OAC type (DOAC vs. warfarin) and GI surgery status using inverse probability of treatment weighting and a Fine–Gray subdistribution hazard model with time-varying covariates. Results: Among 388,214 AF patients (mean age, 71.9 yr; 42.7% male), 6,907 (1.8%) underwent GI surgery. The effect of GI surgery differed between warfarin and DOACs for ischemic stroke (Pint= 0.018), with increased risk for warfarin (adjusted HR [aHR]: 2.32; 95% confidence interval [CI] 1.17–4.62), but not for DOACs (aHR: 0.97 [95% CI 0.77–1.22]) after surgery. Effects of surgery on major bleeding, all-cause death, and composite outcome did not differ. In post–GI surgery setting, DOACs demonstrated lower ischemic stroke risk (aHR: 0.35 [95% CI 0.17–0.72]) and comparable risks for other outcomes. Exploratory analyses by surgery location suggested a more favorable profile of DOACs after upper GI surgery. Conclusions In AF patients, GI surgery significantly increased ischemic stroke risk among warfarin users, but not among DOAC users. DOACs showed generally favorable profiles after GI surgery and may remain a reasonable anticoagulant, with potentially more favorable profile after upper GI surgery.

Purpose: This study aimed to differentiate well-differentiated liposarcoma (WDLPS) from lipoma using the magnetic resonance imaging (MRI) findings and improve the preoperative diagnostic accuracy between the two tumors. Although lipoma is a benign tumor that does not necessarily require surgical intervention, WDLPS exhibits local aggressiveness and typically necessitates surgical excision, making its differentiation clinically significant. Materials and Methods: Among 363 patients diagnosed with lipoma or WDLPS at the authors’ institution between January 2013 and April 2022, 45 patients with lipoma and 15 with WDLPS were selected using propensity score matching based on age and sex. The following six MRI features were analyzed: tumor size, shape, septal thickness, tumor depth, fat content ratio, and the presence of nodular non-fatty tissue components. The sensitivity and specificity of each feature were evaluated. Results: Among the MRI features, the fat content ratio (specificity 95%) and the presence of nodular non-fatty tissue components (specificity 98%) were useful for excluding WDLPS, but their sensitivities were relatively low (46% and 27%). The sensitivities of other features, such as tumor size, shape, septal thickness, and depth, ranged from 47% to 67%, suggesting that MRI alone has limitations in reliably distinguishing the two tumors. In addition, fat content ratios below 75% and the presence of nodular non-fatty tissue components were significantly more common in WDLPS than in lipoma. Conclusion The MRI findings can serve as a useful tool for excluding WDLPS when differentiating it from lipoma. Nevertheless, MRI alone has limitations in achieving a definitive diagnosis because of the low sensitivity of individual features. Therefore, additional approaches such as radiomics analysis, artificial intelligence algorithms, and multicenter studies, are needed to improve the diagnostic accuracy and establish personalized treatment strategies.

Background: Current guidelines recommend factor IIa- or Xa-specific inhibitors over warfarin analogs for preventing thromboembolic stroke in patients with atrial fibrillation (AF).However, their plasma concentrations in Korean patients are not well understood. Methods: We conducted a single-center laboratory study to determine the distribution ranges of peak and trough concentrations of three factor Xa inhibitors (apixaban, edoxaban, and rivaroxaban) prescribed for preventing strokes in patients with AF. Patients receiving one of these drugs and undergoing blood specimen collection for laboratory tests were screened. Blood specimens were obtained from patients who had adhered to the prescribed drug regimen consistently for at least 1 week. Drug plasma concentrations were measured using heparin liquid-reagent technology-based anti-Xa chromogenic assays. Results: We selected 459 patients who were taking standard or on-label-reduced doses of apixaban (N = 252), edoxaban (N = 182), or rivaroxaban (N = 25). The 5th–95th percentile ranges of the peak concentrations were 84–414 ng/mL (apixaban), 72–424 ng/mL (edoxaban), and 97–517 ng/mL (rivaroxaban). The respective 5th–95th percentile ranges of the trough concentrations were 44–237 ng/mL, 23–93 ng/mL, and 13–219 ng/mL. Approximately 19.6% (apixaban), 33.3% (edoxaban), and 64.0% (rivaroxaban) of patients in each group had peak concentrations out of the predicted distribution ranges based on pharmacokinetic data. Approximately 7.3%, 52.8%, and 8.3% of patients had trough concentrations out of the predicted distribution ranges. Conclusions A considerable proportion of Korean patients with AF taking factor Xa inhibitors may require population-specific reference ranges to guide therapeutic monitoring.

Purpose: Early childhood dietary behaviors vary according to environmental and regional context, and evidence in rural preschool populations remains limited. Considering their persistence into adulthood and their association with health outcomes, understanding the dietary patterns among rural preschool children is important. This study examined the nutritional quotient scores and dietary behaviors according to the weight status among preschool-aged children in rural Korea. Methods: This cross-sectional study analyzed the secondary data from 233 preschool children aged 3–6 years, living in Changnyeong-gun, South Korea. The dietary behaviors were assessed using the Nutrition Quotient for Preschoolers (NQ-P), which comprises balance, moderation, and environmental domains. The anthropometric and body composition measurements were obtained using bioelectrical impedance analysis, and the weight status was defined using the age- and sex-specific body mass index percentiles. Results: The mean total NQ-P scores were comparable between non-obese children and obese children (56.0 and 56.3, respectively), with no significant differences observed in the total or domain-specific scores. The most common NQ-P grade was low among the non-obese children and medium-to-low among children with obesity, with no significant between-group differences in grade distribution. On the other hand, underweight and normal-weight children exhibited lower fruit and legume intake and were more likely to move around during meals. Conclusion The fruit and legume intake patterns and mealtime behaviors differed according to the weight status. These findings highlight the importance of nutrition and health promotion strategies tailored to the weight status and rural environment of preschool children.Nevertheless, further prospective studies will be needed to clarify the longitudinal relationships between regional factors, dietary behaviors, and growth patterns in early childhood.