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: 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/OBJECTIVES: Recently, herbal medicines have gained attention for the treatment of benign prostatic hyperplasia (BPH), a common disease in elderly men. In this study, we aimed to determine the effect of ethanol extract of Asparagi radix (EAR), which is traditionally used to treat various diseases, on BPH development using a testosteroneinduced BPH model.MATERIALS/METHODS: Testosterone propionate (TP)-treated Sprague–Dawley rats were used to establish a BPH model in vivo. EAR was orally administered along with TP, and finasteride was used as a positive control. All rats were sacrificed at the end of the experiment, and pathological changes in the prostate tissue and levels of key biomarkers associated with BPH pathogenesis were assessed. RESULTS: Oral administration of EAR significantly inhibited TP-induced BPH by reducing the prostate weight, lumen size, and epithelial thickness in a concentration-dependent manner. EAR also significantly abrogated the expression of 5α-reductase type 2 (SRD5A2), proliferating cell nuclear antigen, and prostate-specific antigen (PSA) induced by TP.Additionally, serum levels of testosterone, dihydrotestosterone, and PSA were elevated in the TP-induced group but decreased in the EAR-treated group. EAR also decreased the expression levels of the androgen receptor (AR) and its coactivators in TP-induced BPH model rats. CONCLUSION Our findings revealed that EAR protected against BPH by inhibiting 5α-reductase activity and AR signaling pathway, suggesting its potential for BPH treatment.

Good’s syndrome is a rare cause of combined B- and T-cell immunodeficiency in adults with a history of thymectomy. The patients with Good’s syndrome are susceptible to encapsulated bacterial infections and opportunistic viral/fungal infections. We report a 63-year-old female patient who was diagnosed with cerebral toxoplasmosis in the middle of monthly immunoglobulin treatment for Good’s syndrome. She was referred owing to progressive dizziness for one week without any neurologic deficits. Although routine laboratory tests and toxoplasma serology exams were within the normal range, brain image studies suggested cerebral toxoplasmosis, which was confirmed by pathology of brain lesions. She was treated with pyrimethamine and sulfadiazine as well as with systemic corticosteroids, and improved without sequelae. Later, her medication was switched to trimethoprim/sulfamethoxazole as a second-line treatment due to sulfadiazine-related neuropathy.

Background: and Purpose Patients with cluster headache (CH) exhibit impaired health-related quality of life (HRQoL). However, there have been few studies related to the HRQoL of patients with CH from Asian backgrounds. This study aimed to determine the impact of CH on HRQoL and to identify the factors affecting HRQoL in patients with CH during cluster periods. Methods: This prospective study enrolled patients with CH from 17 headache clinics in South Korea between September 2016 and February 2021. The study aimed to determine HRQoL in patients with CH using the EuroQol 5 Dimensions (EQ-5D) index and the time trade-off (TTO) method. Age- and sex-matched headache-free participants were recruited as a control group. Results: The study included 423 patients with CH who experienced a cluster period at the time. EQ-5D scores were lower in patients with CH (0.88±0.43, mean±standard deviation) than in the controls (0.99±0.33, p<0.001). The TTO method indicated that 58 (13.6%) patients with CH exhibited moderate-to-severe HRQoL deterioration. The HRQoL states in patients with CH were associated with current smoking patterns, headache severity, frequency, and duration, and scores on the Generalized Anxiety Disorder 7-item scale (GAD-7), Patient Health Questionnaire 9-item scale (PHQ-9), 6-item Headache Impact Test, and 12-item Allodynia Symptom Checklist. Multivariable logistic regression analyses demonstrated that the HRQoL states in patients with CH were negatively correlated with the daily frequency of headaches, cluster period duration, and GAD-7 and PHQ-9 scores. Conclusions Patients with CH experienced a worse quality of life during cluster periods compared with the headache-free controls, but the degree of HRQoL deterioration varied among them. The daily frequency of headaches, cluster period duration, anxiety, and depression were factors associated with HRQoL deterioration severity in patients with CH.