Background: Despite various strategies designed for preventing pain from propofol injection, it is still common and distressing to the patients. The purpose of the present study was to investigate the adequate effect-site concentration (Ce) of remifentanil to prevent pain due to propofol injection. Methods: A total of 160 adults scheduled for elective surgery were randomly assigned to one of four groups receiving normal saline (group S) or remifentanil at a Ce of 2 (group R2), 3 (group R3), or 4 (group R4), administered via target-controlled infusion, followed by the injection of 2 mg/kg of propofol (delivered with 1% lipid propofol). The severity and incidence of injection pain were assessed on a four-point scale. Results: The incidence of propofol injection pain was significantly lower in group R2, R3, or R4 than in group S (30%, 5%, or 2.5% vs. 70%, respectively). Moreover, the intensity of the pain was lesser in group R2, R3, or R4 than in group S. However, the incidence or severity of injection was not different between groups R3 and R4. Conclusions During the induction of balanced anesthesia using propofol injection, pretreatment with remifentanil at a target Ce of 3 ng/ml effectively reduced propofol injection pain in adults.

TFAP2C (transcription factor-activating enhancer-binding protein 2C) expression has been positively correlated with poor prognosis in patients with certain types of cancer, but the mechanisms underlying TFAP2C-mediated tumorigenesis in non-small-cell lung cancer (NSCLC) are still unknown. We previously performed a microarray analysis to identify TFAP2C regulation genes, and TGFBR1 (transforming growth factor-β receptor type 1) was found to be upregulated by TFAP2C. We observed that TFAP2C or TGFBR1 overexpression led to oncogenic properties, such as cell viability, proliferation and cell cycle progression. TGFBR1 upregulation induced by TFAP2C also promoted cell motility and migration, leading to malignant development. We also found that PAK1 (p21 protein (Cdc42/Rac)-activated kinase 1) signaling was involved in TFAP2C/TGFBR1-induced tumorigenesis. These results were confirmed by an in vivo xenograft model and patient tissue samples. This study shows that TFAP2C promoted tumor progression by upregulation of TGFBR1 and consequent activation of PAK1 signaling.
Carcinogenesis* ; Cell Cycle ; Cell Movement ; Cell Survival ; Heterografts ; Humans ; Lung Neoplasms ; Lung* ; Microarray Analysis ; Phosphotransferases ; Prognosis ; Up-Regulation*

Atrial fibrillation (AF) is the most common form of arrhythmia in the elderly population and increases stroke risk by a factor of 4- to 5-fold. There is increasing evidence to suggest that incident AF may contribute to the development of dementia, independent of overt stroke. In particular, relatively younger patients with AF are more prone to dementia development than older patients with AF. Evidence is accumulating regarding the possible treatment strategies for preventing dementia in patients with AF. Oral anticoagulation may be effective for reducing the risk of dementia, even in patients with low stroke risks. Among oral anticoagulants, the use of non-vitamin K antagonists have been associated with a considerably decreased risk of dementia than warfarin. Moreover, successful catheter ablation for AF has also been associated with decreased dementia risk compared to medical therapy, suggesting that restoration of sinus rhythm, and not the ablation procedure itself, as the important mechanism in the prevention of AF-associated dementia. Among midlife patients with AF, there appeared to be a U-shaped association of blood pressure (BP) and a linear association of hypertension with dementia risk.A BP of 120 to 129/80 to 84 mmHg has been identified as the optimal range. Finally, integrated management of AF was associated with a reduced risk of dementia in AF patients.

Atrial fibrillation (AF) is the most common form of arrhythmia in the elderly population and increases stroke risk by a factor of 4- to 5-fold. There is increasing evidence to suggest that incident AF may contribute to the development of dementia, independent of overt stroke. In particular, relatively younger patients with AF are more prone to dementia development than older patients with AF. Evidence is accumulating regarding the possible treatment strategies for preventing dementia in patients with AF. Oral anticoagulation may be effective for reducing the risk of dementia, even in patients with low stroke risks. Among oral anticoagulants, the use of non-vitamin K antagonists have been associated with a considerably decreased risk of dementia than warfarin. Moreover, successful catheter ablation for AF has also been associated with decreased dementia risk compared to medical therapy, suggesting that restoration of sinus rhythm, and not the ablation procedure itself, as the important mechanism in the prevention of AF-associated dementia. Among midlife patients with AF, there appeared to be a U-shaped association of blood pressure (BP) and a linear association of hypertension with dementia risk.A BP of 120 to 129/80 to 84 mmHg has been identified as the optimal range. Finally, integrated management of AF was associated with a reduced risk of dementia in AF patients.

For almost 20 years, data regarding the effect of rhythm control therapy for atrial fibrillation (AF) on cardiovascular prognosis in comparison with rate control therapy has not been conclusive. The safety of rhythm control and anticoagulation therapy has generally improved. Recently, it was revealed that a rhythm-control strategy reduced the risk of adverse cardiovascular events than usual rate control in patients with recent AF (diagnosed within 1 year). Within 1 year after the AF diagnosis, early initiation of rhythm control led to more favorable cardiovascular outcomes than rate control. Early rhythm control reduced the risks of stroke and heart failure-related admission than rate control. Moreover, rhythm control was associated with lower dementia risk than rate control. Finally, early rhythm control treatment was also effective in patients with asymptomatic AF but less effective in older adults. Therefore, in patients with AF, rhythm control should be considered at earlier stages, regardless of symptom.

Objective: To identify the prevalence and characteristics of neuropathic pain (NP) in patients with spinal cord injury (SCI) and to investigate associations between NP and demographic or disease-related variables. Methods: We retrospectively reviewed medical records of patients with SCI whose pain was classified according to the International Spinal Cord Injury Pain classifications at a single hospital. Multiple statistical analyses were employed. Patients aged <19 years, and patients with other neurological disorders and congenital conditions were excluded. Results: Of 366 patients, 253 patients (69.1%) with SCI had NP. Patients who were married or had traumatic injury or depressive mood had a higher prevalence rate. When other variables were controlled, marital status and depressive mood were found to be predictors of NP. There was no association between the prevalence of NP and other demographic or clinical variables. The mean Numeric Rating Scale (NRS) of NP was 4.52, and patients mainly described pain as tingling, squeezing, and painful cold. Females and those with below-level NP reported more intense pain. An NRS cut-off value of 4.5 was determined as the most appropriate value to discriminate between patients taking pain medication and those who did not. Conclusion In total, 69.1% of patients with SCI complained of NP, indicating that NP was a major complication. Treatment planning for patients with SCI and NP should consider that marital status, mood, sex, and pain subtype may affect NP, which should be actively managed in patients with an NRS ≥4.5.

An interaction between ribosomal protein S3 (rpS3) and nuclear factor kappa B or macrophage migration inhibitory factor in non-small-cell lung cancer is responsible for radioresistance. However, the role of rpS3 in glioblastoma (GBM) has not been investigated to date. Here we found that in irradiated GBM cells, rpS3 translocated into the nucleus and was subsequently ubiquitinated by ring finger protein 138 (RNF138). Ubiquitin-dependent degradation of rpS3 consequently led to radioresistance in GBM cells. To elucidate the apoptotic role of rpS3, we analyzed the interactome of rpS3 in ΔRNF138 GBM cells. Nuclear rpS3 interacted with DNA damage inducible transcript 3 (DDIT3), leading to DDIT3-induced apoptosis in irradiated ΔRNF138 GBM cells. These results were confirmed using in vivo orthotopic xenograft models and GBM patient tissues. This study aims to clarify the role of RNF138 in GBM cells and demonstrate that rpS3 may be a promising substrate of RNF138 for the induction of GBM radioresistance, indicating RNF138 as a potential target for GBM therapy.
Apoptosis ; DNA Damage ; Fingers ; Glioblastoma ; Heterografts ; Humans ; Lung Neoplasms ; Macrophages ; NF-kappa B ; Ribosomal Proteins ; Ubiquitin ; Ubiquitination

As a new humanized monoclonal antibody against the interleukin-6 receptor, tocilizumab is currently used for the treatment of rheumatoid arthritis (RA) patients. Tocilizumab was reported to provoke drug-related liver toxicity, although there have been no reports on significant liver toxicity from tocilizumab in Korean patients with RA to date. Here, we describe the first case of tocilizumab-related liver toxicity in a patient with complicated RA, accompanied with macrophage activation syndrome, who had received tacrolimus and prednisolone and in whom both conventional disease modifying anti-rheumatic drugs, including methotrexate, leflunomide and sulfasalazine or tumor necrotizing factor-alpha blockades, were contraindicated due to drug eruption and a history of lung cancer.
Antirheumatic Agents ; Arthritis, Rheumatoid* ; Drug Eruptions ; Humans ; Interleukin-6 ; Liver ; Lung Neoplasms ; Macrophage Activation Syndrome* ; Macrophage Activation* ; Macrophages* ; Methotrexate ; Prednisolone ; Sulfasalazine ; Tacrolimus ; Tranexamic Acid*