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.

Purpose: This study explored current pediatric palliative care (PPC) in South Korea and suggests future directions based on the perspectives of full-time PPC workers. Methods: A mixed-methods secondary analysis was conducted using survey data from nurses and social workers involved in a government PPC project. The survey assessed services provided by hospitals, nurses, and social workers, and gathered perceptions of challenging tasks, evidence needs, the significance of PPC, and future expectations through open-ended questions. Data were analyzed using frequency and conventional content analyses. Results: Eighteen full-time workers from nine of the ten project hospitals participated. Eight hospitals provided pain and symptom management and all offered counseling and education for patients and parents. Only one provided respite care and legacy-making services. Bereavement care was offered in all hospitals primarily through individual counseling and there were also three self-help groups. Nurses have diverse roles including in practice, education, leadership, research, and consultation. Social workers address psychosocial and economic challenges, rehabilitation and social reintegration. The workers highlighted the challenges in end-of-life care and communication, stressing the need for protocols and further training.PPC was seen as meaningful by patients and families, as well as staff. Conclusion Despite significant progress in PPC in South Korea, quantitative capacity remains limited. Further qualitative improvements in policies, practices, human resource development, and healthcare training are essential. This study provides insights into current PPC practices and their limitations. The development of practical evidence to enhance employment stability warrants further investigation.

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.

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.

Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant i