Hemoglobin (Hb) and heme, which are typically confined within red blood cells (RBCs), are essential for intravascular transport of gases and nutrients. However, these molecules acquire secondary functions upon exposure to the extracellular environment. Hb and heme generate reactive oxygen species (ROS), which are potent pro-inflammatory agents that contribute to oxidative stress and cellular damage. These events are relevant to neurodegenerative processes, where oxidative stress, irregular deposition of protein aggregates, and chronic inflammation are key pathological features. Extracellular Hb, heme, and oxidative stress derived from hemorrhagic events or RBC lysis may contribute to increased blood–brain barrier (BBB) permeability. These events allow Hb and heme to interact with neuroimmune cells and pathological protein aggregates, further amplifying pro-inflammatory signaling and the progression of Alzheimer’s disease (AD) and Parkinson disease (PD). Chronic neuroinflammation, oxidative stress, and mitochondrial dysfunction lead to neuronal degeneration. Here, we sought to elucidate the pro-oxidative and inflammatory actions of extracellular Hb and heme, emphasizing their potential impact on AD and PD development.

Hemoglobin (Hb) and heme, which are typically confined within red blood cells (RBCs), are essential for intravascular transport of gases and nutrients. However, these molecules acquire secondary functions upon exposure to the extracellular environment. Hb and heme generate reactive oxygen species (ROS), which are potent pro-inflammatory agents that contribute to oxidative stress and cellular damage. These events are relevant to neurodegenerative processes, where oxidative stress, irregular deposition of protein aggregates, and chronic inflammation are key pathological features. Extracellular Hb, heme, and oxidative stress derived from hemorrhagic events or RBC lysis may contribute to increased blood–brain barrier (BBB) permeability. These events allow Hb and heme to interact with neuroimmune cells and pathological protein aggregates, further amplifying pro-inflammatory signaling and the progression of Alzheimer’s disease (AD) and Parkinson disease (PD). Chronic neuroinflammation, oxidative stress, and mitochondrial dysfunction lead to neuronal degeneration. Here, we sought to elucidate the pro-oxidative and inflammatory actions of extracellular Hb and heme, emphasizing their potential impact on AD and PD development.

Hemoglobin (Hb) and heme, which are typically confined within red blood cells (RBCs), are essential for intravascular transport of gases and nutrients. However, these molecules acquire secondary functions upon exposure to the extracellular environment. Hb and heme generate reactive oxygen species (ROS), which are potent pro-inflammatory agents that contribute to oxidative stress and cellular damage. These events are relevant to neurodegenerative processes, where oxidative stress, irregular deposition of protein aggregates, and chronic inflammation are key pathological features. Extracellular Hb, heme, and oxidative stress derived from hemorrhagic events or RBC lysis may contribute to increased blood–brain barrier (BBB) permeability. These events allow Hb and heme to interact with neuroimmune cells and pathological protein aggregates, further amplifying pro-inflammatory signaling and the progression of Alzheimer’s disease (AD) and Parkinson disease (PD). Chronic neuroinflammation, oxidative stress, and mitochondrial dysfunction lead to neuronal degeneration. Here, we sought to elucidate the pro-oxidative and inflammatory actions of extracellular Hb and heme, emphasizing their potential impact on AD and PD development.

OBJECTIVES: Previous research has predominantly focused on total bilirubin levels without clearly distinguishing between direct and indirect bilirubin. In this study, the differences between these forms were examined, and their potential causal relationships with ischemic stroke were investigated. METHODS: Two-sample multivariable Mendelian randomization (MVMR) analysis was employed, extracting summary data on bilirubin from the Korean Cancer Prevention Study-II (n=159,844) and the Korean Genome and Epidemiology Study (n=72,299). Data on ischemic stroke were obtained from BioBank Japan (n=201,800). Colocalization analysis was performed, focusing on the UGT1A1, SLCO1B1, and SLCO1B3 genes, which are the primary loci associated with serum bilirubin levels. RESULTS: Crude 2-sample Mendelian randomization analysis revealed a significant negative association between total bilirubin levels and ischemic stroke. However, in MVMR analyses, only indirect bilirubin demonstrated a significant negative association with ischemic stroke (odds ratio, 0.76; 95% confidence interval, 0.59 to 0.98). Colocalization analysis did not identify a shared causal variant between the 3 genetic loci related to indirect bilirubin and the risk of ischemic stroke. CONCLUSIONS Our study establishes a causal association between higher genetically determined levels of serum indirect bilirubin and reduced risk of ischemic stroke in an Asian population. Future research should include more in-depth analysis of shared genetic variants between indirect bilirubin and ischemic stroke.

OBJECTIVES: Previous research has predominantly focused on total bilirubin levels without clearly distinguishing between direct and indirect bilirubin. In this study, the differences between these forms were examined, and their potential causal relationships with ischemic stroke were investigated. METHODS: Two-sample multivariable Mendelian randomization (MVMR) analysis was employed, extracting summary data on bilirubin from the Korean Cancer Prevention Study-II (n=159,844) and the Korean Genome and Epidemiology Study (n=72,299). Data on ischemic stroke were obtained from BioBank Japan (n=201,800). Colocalization analysis was performed, focusing on the UGT1A1, SLCO1B1, and SLCO1B3 genes, which are the primary loci associated with serum bilirubin levels. RESULTS: Crude 2-sample Mendelian randomization analysis revealed a significant negative association between total bilirubin levels and ischemic stroke. However, in MVMR analyses, only indirect bilirubin demonstrated a significant negative association with ischemic stroke (odds ratio, 0.76; 95% confidence interval, 0.59 to 0.98). Colocalization analysis did not identify a shared causal variant between the 3 genetic loci related to indirect bilirubin and the risk of ischemic stroke. CONCLUSIONS Our study establishes a causal association between higher genetically determined levels of serum indirect bilirubin and reduced risk of ischemic stroke in an Asian population. Future research should include more in-depth analysis of shared genetic variants between indirect bilirubin and ischemic stroke.

OBJECTIVES: Previous research has predominantly focused on total bilirubin levels without clearly distinguishing between direct and indirect bilirubin. In this study, the differences between these forms were examined, and their potential causal relationships with ischemic stroke were investigated. METHODS: Two-sample multivariable Mendelian randomization (MVMR) analysis was employed, extracting summary data on bilirubin from the Korean Cancer Prevention Study-II (n=159,844) and the Korean Genome and Epidemiology Study (n=72,299). Data on ischemic stroke were obtained from BioBank Japan (n=201,800). Colocalization analysis was performed, focusing on the UGT1A1, SLCO1B1, and SLCO1B3 genes, which are the primary loci associated with serum bilirubin levels. RESULTS: Crude 2-sample Mendelian randomization analysis revealed a significant negative association between total bilirubin levels and ischemic stroke. However, in MVMR analyses, only indirect bilirubin demonstrated a significant negative association with ischemic stroke (odds ratio, 0.76; 95% confidence interval, 0.59 to 0.98). Colocalization analysis did not identify a shared causal variant between the 3 genetic loci related to indirect bilirubin and the risk of ischemic stroke. CONCLUSIONS Our study establishes a causal association between higher genetically determined levels of serum indirect bilirubin and reduced risk of ischemic stroke in an Asian population. Future research should include more in-depth analysis of shared genetic variants between indirect bilirubin and ischemic stroke.

OBJECTIVES: Previous research has predominantly focused on total bilirubin levels without clearly distinguishing between direct and indirect bilirubin. In this study, the differences between these forms were examined, and their potential causal relationships with ischemic stroke were investigated. METHODS: Two-sample multivariable Mendelian randomization (MVMR) analysis was employed, extracting summary data on bilirubin from the Korean Cancer Prevention Study-II (n=159,844) and the Korean Genome and Epidemiology Study (n=72,299). Data on ischemic stroke were obtained from BioBank Japan (n=201,800). Colocalization analysis was performed, focusing on the UGT1A1, SLCO1B1, and SLCO1B3 genes, which are the primary loci associated with serum bilirubin levels. RESULTS: Crude 2-sample Mendelian randomization analysis revealed a significant negative association between total bilirubin levels and ischemic stroke. However, in MVMR analyses, only indirect bilirubin demonstrated a significant negative association with ischemic stroke (odds ratio, 0.76; 95% confidence interval, 0.59 to 0.98). Colocalization analysis did not identify a shared causal variant between the 3 genetic loci related to indirect bilirubin and the risk of ischemic stroke. CONCLUSIONS Our study establishes a causal association between higher genetically determined levels of serum indirect bilirubin and reduced risk of ischemic stroke in an Asian population. Future research should include more in-depth analysis of shared genetic variants between indirect bilirubin and ischemic stroke.

We systematically reviewed the literature on the co-occurrence of squamous cell carcinoma (SCC) and Warthin’s tumor (WT), thought to be quite rare, to help reduce misdiagnosis and improve treatment planning. For this systematic review, we searched for articles in the Web of Science and PubMed databases, analyzed relevant studies for forward and backward citations, and identified only articles reporting on the “co-occurrence” of WT and SCC.Of the 237 studies identified, 12 comprising 18 patients met the inclusion criteria, to which we added one study from our institution. Most WTs were associated with SCC in the parotid gland or cervical lymph nodes. Most patients (89.5%) underwent selective or radical neck dissection due to identification of lesions separate from the primary SCC. Despite its frequent co-occurrence with other neoplasms, WT in the parotid or cervical lymph nodes tends to be misdiagnosed as a metastatic node when SCC is observed as the primary tumor. Factors to consider in diagnosis and neck management include identification of an association other than growth or development by lymphangiogenesis and whether the patient is a smoker, a strong risk factor.

Sleep deprivation or insomnia is one of the most common but neglected health conditions, with serious long-term consequences. In addition, insomnia is linked to poor work performance, impaired memory, and lack of concentration. Improving sleep quality is a crucial aspect of health care. Hypnotic agents, such as benzodiazepines, antidepressants, and antihistamines, are often used to enhance sleep quality; however, these medications often result in tolerance and dependence, resulting in withdrawal syndrome upon discontinuation. In recent years, studies have focused on natural and herbal therapies as alternative sleep aids to overcome the adverse effects of available sleep medications. Plant extracts contain phytochemicals that exert anxiolytic and sedative properties. This includes Passiflora incarnata (FSD-PI) and Lactuca sativa L. (FSD-LS) which can induce sleep. Herein, we assessed the effects of natural products, FSD-PI and FSD-LS, as well as their synergistic effects on pentobarbital sleep-induced ICR mice. We observed that natural extracts did not cause any behavioral changes capable of negative effects in mice. Furthermore, sleep duration was prolonged in pentobarbital-treated mice administered with FSD-LS (100 mg/kg). Our data suggest that FSD-LS may be a safe and effective sleep promoter.

This paper aims to introduce Korea’s total current health expenditure (CHE) and National Health Accounts of the year 2021 and their 2022 preliminary figures constructed on the basis of the System of Health Accounts 2011. As CHE includes expenditures for prevention, tracking, and treatment of coronavirus disease 2019 (COVID-19) and compensation for losses to medical institutions from 2020, the details are also introduced. Korea’s total CHE in 2021 is 193.3 trillion won, which is 9.3% of gross domestic product (GDP). The preliminary figure in 2022, 209.0 trillion won, exceeded the 200 trillion won line for the first time, and its “ratio to GDP” of 9.7% is expected to exceed the average of Organisation for Economic Co-Operation and Development member countries for the first time. Korea’s health expenditures, which were well controlled until the end of the 20th century, have increased at an alarming rate since the beginning of the 21st century, threatening the sustainability of national health insurance. The increase in health expenditure after 2020 is partly due to a temporary increase in response to COVID-19. However, when considering the structure of Korea’s health insurance price hike, where the ratchet effect of increased medical expenses works particularly strongly, it is unlikely that the accelerating growth trend that has lasted for more than 20 years will stop easily. More aggressive policies to control medical expenses are required in the national health insurance which not only constitutes the main financing sources of the Korean health system but also has the most powerful policy means in effect for changes in the health care provision.