Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine that selectively targets cancer cells and induces apoptosis. However, many cancers, including bladder cancer, develop resistance to TRAIL, limiting the efficacy of TRAIL-based therapies. This study investigated whether betulinic acid (BA), a pentacyclic triterpenoid with anticancer and chemosensitizing properties, increases TRAIL-mediated apoptosis in TRAIL-resistant human bladder cancer cells. Combination treatment with BA and TRAIL significantly increased cytotoxicity and apoptosis compared to either treatment alone. This combination treatment also increased reactive oxygen species (ROS) production, increased Bax expression and Bid cleavage (tBid formation), and downregulated Bcl-2 levels. These effects were accompanied by caspase activation via extrinsic and intrinsic pathways, leading to cytochrome c release via mitochondrial membrane destabilization, thereby contributing to increased apoptosis. Furthermore, the combination treatment inhibited phosphoinositide 3-kinase (PI3K) and Akt phosphorylation; this effect was amplified by a PI3K inhibitor but abrogated by ROS inhibition. Collectively, our results suggest that BA sensitizes bladder cancer cells to TRAILinduced apoptosis via ROS-dependent activation of the apoptotic pathway and inhibition of PI3K/Akt signaling. Therefore, the BA and TRAIL combination exhibits potential to overcome TRAIL resistance in human bladder cancer.

Background: and Purpose The pain lateralization in cluster headache (CH) may be related to the asymmetry in the functions of the brain hemispheres. The right-sided dominance of pain in CH has been found inconsistently across studies, and so we aimed to characterize this and identify the factors influencing pain lateralization during current and previous bouts. Methods: This study enrolled 227 patients from the Korean Cluster Headache Registry between October 2018 and December 2020. We evaluated the side of pain during current and previous bouts, demographic features, and clinical characteristics, including handedness. Multivariable logistic regression analyses were performed to identify factors associated with the side of pain. Results: The 227 patients with CH included 131 (57.7%) with right-sided pain and 86 (37.9%) with left-sided pain during the current bout (p<0.001). The 189 patients with previous bouts of CH included 86.8% who consistently reported the same side of pain throughout multiple bouts (side-locked pain), with a higher prevalence of pain on the right than the left side (55.0% vs. 31.7%, p<0.001). Multivariable analyses revealed that higher age at diagnosis (odds ratio [OR]=1.045, p=0.031) and shorter CH attacks (OR=0.992, p=0.017) were associated with left-side-locked pain. However, handedness was not associated with the lateralization of leftside-locked pain. Conclusions This study has confirmed the predominance of right-sided pain throughout multiple CH bouts. We found that higher age at diagnosis and shorter CH attacks were associated with left-side-locked pain, suggesting that certain clinical factors are associated with the pain laterality. However, the underlying mechanisms linking these factors to lateralized pain remain unclear and therefore require further investigation.

Background: and Purpose The pain lateralization in cluster headache (CH) may be related to the asymmetry in the functions of the brain hemispheres. The right-sided dominance of pain in CH has been found inconsistently across studies, and so we aimed to characterize this and identify the factors influencing pain lateralization during current and previous bouts. Methods: This study enrolled 227 patients from the Korean Cluster Headache Registry between October 2018 and December 2020. We evaluated the side of pain during current and previous bouts, demographic features, and clinical characteristics, including handedness. Multivariable logistic regression analyses were performed to identify factors associated with the side of pain. Results: The 227 patients with CH included 131 (57.7%) with right-sided pain and 86 (37.9%) with left-sided pain during the current bout (p<0.001). The 189 patients with previous bouts of CH included 86.8% who consistently reported the same side of pain throughout multiple bouts (side-locked pain), with a higher prevalence of pain on the right than the left side (55.0% vs. 31.7%, p<0.001). Multivariable analyses revealed that higher age at diagnosis (odds ratio [OR]=1.045, p=0.031) and shorter CH attacks (OR=0.992, p=0.017) were associated with left-side-locked pain. However, handedness was not associated with the lateralization of leftside-locked pain. Conclusions This study has confirmed the predominance of right-sided pain throughout multiple CH bouts. We found that higher age at diagnosis and shorter CH attacks were associated with left-side-locked pain, suggesting that certain clinical factors are associated with the pain laterality. However, the underlying mechanisms linking these factors to lateralized pain remain unclear and therefore require further investigation.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Background: and Purpose The pain lateralization in cluster headache (CH) may be related to the asymmetry in the functions of the brain hemispheres. The right-sided dominance of pain in CH has been found inconsistently across studies, and so we aimed to characterize this and identify the factors influencing pain lateralization during current and previous bouts. Methods: This study enrolled 227 patients from the Korean Cluster Headache Registry between October 2018 and December 2020. We evaluated the side of pain during current and previous bouts, demographic features, and clinical characteristics, including handedness. Multivariable logistic regression analyses were performed to identify factors associated with the side of pain. Results: The 227 patients with CH included 131 (57.7%) with right-sided pain and 86 (37.9%) with left-sided pain during the current bout (p<0.001). The 189 patients with previous bouts of CH included 86.8% who consistently reported the same side of pain throughout multiple bouts (side-locked pain), with a higher prevalence of pain on the right than the left side (55.0% vs. 31.7%, p<0.001). Multivariable analyses revealed that higher age at diagnosis (odds ratio [OR]=1.045, p=0.031) and shorter CH attacks (OR=0.992, p=0.017) were associated with left-side-locked pain. However, handedness was not associated with the lateralization of leftside-locked pain. Conclusions This study has confirmed the predominance of right-sided pain throughout multiple CH bouts. We found that higher age at diagnosis and shorter CH attacks were associated with left-side-locked pain, suggesting that certain clinical factors are associated with the pain laterality. However, the underlying mechanisms linking these factors to lateralized pain remain unclear and therefore require further investigation.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Background: With growing elderly populations, management of patients with acute stroke is increasingly important. In South Korea, the Acute Stroke Quality Assessment Program (ASQAP) has contributed to improving the quality of stroke care and practice behavior in healthcare institutions. While the mortality of hemorrhagic stroke remains high, there are only a few assessment indices associated with hemorrhagic stroke. Considering the need to develop assessment indices to improve the actual quality of care in the field of acute stroke treatment, this study aims to investigate the current status of human resources and practices related to the treatment of patients with acute stroke through a nationwide survey. Methods: For the healthcare institutions included in the Ninth ASQAP of the Health Insurance Review and Assessment Service (HIRA), data from January 2022 to December 2022 were collected through a survey on the current status and practice of healthcare providers related to the treatment of patients with acute stroke. The questionnaire consisted of 19 items, including six items on healthcare providers involved in stroke care and 10 items on the care of patients with acute stroke. Results: In the treatment of patients with hemorrhagic stroke among patients with acute stroke, neurosurgeons were the most common providers. The contribution of neurosurgeons in the treatment of ischemic stroke has also been found to be equivalent to that of neurologists. However, a number of institutions were found to be devoid of healthcare providers who perform definitive treatments, such as intra-arterial thrombectomy for patients with ischemic stroke or cerebral aneurysm clipping for subarachnoid hemorrhage. The intensity of the workload of healthcare providers involved in the care of patients with acute stroke, especially those involved in definitive treatment, was also found to be quite high. Conclusion Currently, there are almost no assessment indices specific to hemorrhagic stroke in the ASQAP for acute stroke. Furthermore, it does not reflect the reality of the healthcare providers and practices that provide definitive treatment for acute stroke. The findings of this study suggest the need for the development of appropriate assessment indices that reflect the realities of acute stroke care.

Methyl anthranilate (MA) is a botanical fragrance used in food flavoring with unexplored potential in anti-pigment cosmetics. MA dose-dependently reduced melanin content without affecting cell viability, inhibited dendrite elongation and melanosome transfer in the co-culture system of human melanoma cells (MNT-1) and human keratinocyte cell line (HaCaT), and downregulated melanogenic genes, including tyrosinase, tyrosinase-related protein 1 and 2 (TRP-1, TRP-2). Additionally, MA decreased cyclic adenosine monophosphate (cAMP) production and exhibited a significant anti-pigmentary effect in Melanoderm™. These results suggest that MA is a promising anti-pigmentary agent for replacing or complementing existing anti-pigmentary cosmetics.

Objectives: . Due to the rarity of olfactory neuroblastoma (ONB), there is ongoing debate about optimal treatment strategies, especially for early-stage or locally advanced cases. Therefore, our study aimed to explore experiences from multiple centers to identify factors that influence the oncological outcomes of ONB. Methods: . We retrospectively analyzed 195 ONB patients treated at nine tertiary hospitals in South Korea between December 1992 and December 2019. Kaplan-Meier survival analysis was used to evaluate oncological outcomes, and a Cox proportional hazards regression model was employed to analyze prognostic factors for survival outcomes. Furthermore, we conducted 1:1 nearest-neighbor matching to investigate differences in clinical outcomes according to the use of neoadjuvant chemotherapy. Results: . In our cohort, the 5-year overall survival (OS) rate was 78.6%, and the 5-year disease-free survival (DFS) rate was 62.4%. The Cox proportional hazards model revealed that the modified Kadish (mKadish) stage and Dulguerov T status were significantly associated with DFS, while the mKadish stage and Hyams grade were identified as prognostic factors for OS. The subgroup analyses indicated a trend toward improved 5-year DFS with dural resection in mKadish A and B cases, even though the result was statistically insignificant. Induction chemotherapy did not provide a survival benefit in this study after matching for the mKadish stage and nodal status. Conclusion . Clinical staging and pathologic grading are important prognostic factors in ONB. Dural resection in mKadish A and B did not show a significant survival benefit. Similarly, induction chemotherapy also did not show a survival benefit, even after stage matching.