Background/Aims: Sorafenib is the standard of care in the management of advanced hepatocellular carcinoma (HCC). The purpose of this study was to investigate the characteristics, treatment patterns and outcomes of sorafenib among HCC patients in South Korea. Methods: This population-based retrospective, single-arm, observational study used the Korean National Health Insurance database to identify patients with HCC who received sorafenib between July 1, 2008, and December 31, 2014. A total of 9,923 patients were recruited in this study. Results: Among 9,923 patients, 6,669 patients (68.2%) received loco-regional therapy prior to sorafenib, and 1,565 patients (15.8%) received combination therapy with concomitant sorafenib;2,591 patients (26.1%) received rescue therapy after sorafenib, and transarterial chemoembolization was the most common modality applied in 1,498 patients (15.1%). A total of 3,591 patients underwent rescue therapy after sorafenib, and the median overall survival was 14.5 months compared to 4.6 months in 7,332 patients who received supportive care after sorafenib. The mean duration of sorafenib administration in all patients was 105.7 days; 7,023 patients (70.8%) received an initial dose of 600 to 800 mg. The longest survival was shown in patients who received the recommended dose of 800 mg, subsequently reduced to 400 mg (15.0 months). The second longest survival was demonstrated in patients with a starting dose of 800 mg, followed by a dose reduction to 400–600 mg (9.6 months). Conclusions Real-life data show that the efficacy of sorafenib seems similar to that observed in clinical trials, suggesting that appropriate subsequent therapy after sorafenib might prolong patient survival.

The survival rate of children admitted in the neonatal intensive care unit (NICU) after birth is on the increase; hence, proper evaluation and care of their neurodevelopment has become an important issue. Neurodevelopmental assessments of individual domains regarding motor, language, cognition, and sensory perception are crucial in planning prompt interventions for neonates requiring immediate support and rehabilitation treatment. These assessments are essential for identifying areas of weakness and designing targeted interventions to improve future functional outcomes and the quality of lives for both the infants and their families. However, initial stratification of risk to select those who are in danger of neurodevelopmental disorders is also important in terms of cost-effectiveness. Efficient and robust functional evaluations to recognize early signs of developmental disorders will help NICU graduates receive interventions and enhance functional capabilities if needed. Several age-dependent, domain-specific neurodevelopmental assessment tools are available; therefore, this review summarizes the characteristics of these tools and aims to develop multidimensional, standardized, and regular follow-up plans for NICU graduates in Korea.

Purpose: A case of a huge ethmoid sinus and orbital cyst causing ocular deviation initially diagnosed as a mucocele-like cyst and after orbitotomy eventually discovered to be a naso-orbital encephalocele is described.Case summary: A 5-year-old male with no previous medical history presented with a palpable mass in the medial canthus area with left exodeviation of the left eye. His best-corrected visual acuity was 20/25 in the right eye and 6/12 in the left eye with limitation of motion of -4 at adduction in the left eye. Brain magnetic resonance imaging scans revealed a 3.0 × 2.5 × 2.5 cm-sized cystic mass suspected as a mucocele or nasolacrimal duct cyst invading the orbital space. The cyst was removed using a Lynch and caruncle incision, and intracystic fluid was aspirated. During the excision, a small defect of the skull base was detected with cerebrospinal fluid (CSF) leakage and leaking point of dura was sealed. His pathologic result was disorganized glial and fibrous tissue, consistent with encephalocele. Three days later, CSF leakage recurred. On postoperative day 8, duroplasty was performed. A one month later, his best-corrected visual acuity was 6/12 in the left eye with orthotropic eye position. Limitation of motion was improved to -1 at adduction with enophthalmos. No other complications were detected. Conclusions Congenital naso-orbital encephalocele invading the orbit is rare. However, a cystic mass in the sinuses involving the orbit should be considered, rendering thorough physical and radiologic examinations including computed tomography scans necessary to look for bone defects.

BACKGROUND: Concerns have arisen about the classification of extra-thyroidal extension (ETE) and lateral cervical lymph node metastasis (N1b) in the 8th edition of the tumor-node-metastasis staging system (TNM-8). This study evaluated the prognostic validity of a modified-TNM staging system, focusing on ETE and N1b, in differentiated thyroid carcinoma (DTC) patients. METHODS: This multicenter retrospective cohort study included 4,878 DTC patients from five tertiary hospitals. In the modified-TNM, T3b in TNM-8 was down-staged to T2, and stage II was subdivided into stages IIA and IIB. Older patients with N1b were reclassified as stage IIB. RESULTS: The modified-TNM resulted in staging migration in 540 patients (11%) classified as stage II according to the TNM-8, with 75 (14%), 381 (71%), and 84 patients (16%) classified as stages I, IIA, and IIB, respectively. The 10-year disease-specific survival (DSS) rates in patients classified as stages I, II, III, and IV by TNM-8 were 99.8%, 95.9%, 81.0%, and 41.6%, respectively. The DSS rates of patients classified as stages I, IIA, IIB, III, and IV according to the modified-TNM were 99.8%, 96.4%, 93.3%, 81.0%, and 41.6%, respectively. DSS curves between stages on TNM-8 (P<0.001) and modified-TNM (P<0.001) differed significantly, but the modified-TNM discriminated better than TNM-8. The proportions of variation explained values of TNM-8 and modified-TNM were 6.3% and 6.5%, respectively. CONCLUSION Modification of the TNM staging system focusing on ETE and N1b could improve the prediction of DSS in patients with DTC. Further researches are needed to validate the prognostic accuracy of this modified-TNM staging system.

Background: The study aimed to compare the prognostic value of the 4th edition of World Health Organization classification (WHO-2017) with the previous WHO classification (WHO-2004) for follicular thyroid carcinoma (FTC). Methods: This multicenter retrospective cohort study included 318 patients with FTC from five tertiary centers who underwent thyroid surgery between 1996 and 2009. We evaluated the prognosis of patients with minimally invasive (MI), encapsulated angioinvasive (EA), and widely invasive (WI) FTC according to WHO-2017. Further, we evaluated the proportion of variation explained (PVE) and Harrell’s C-index to compare the predictability of disease-free survival (DFS) and disease-specific survival (DSS). Results: In total, 227, 58, and 33 patients had MI-, EA-, and WI-FTC, respectively. During a median follow-up of 10.6 years, 46 (14.5%) patients had disease recurrence and 20 (6.3%) patients died from FTC. The 10-year DFS rates of patients with MI-, EA-, and WI-FTC were 91.1%, 78.2%, and 54.9%, respectively (P<0.001, PVE=7.1%, C-index=0.649). The corresponding 10-year DSS rates were 95.9%, 93.5%, and 73.5%, respectively (P<0.001, PVE=2.6%, C-index=0.624). The PVE and C-index values were higher using WHO-2017 than using WHO-2004 for the prediction of DFS, but not for DSS. In multivariate analysis, older age (P=0.02), gross extrathyroidal extension (ETE) (P=0.003), and distant metastasis (P<0.001) were independent risk factors for DSS. Conclusion WHO-2017 improves the predictability of DFS, but not DSS, in patients with FTC. Distant metastasis, gross ETE and older age (≥55 years) were independent risk factors for DSS.

Sleep is an essential physiological process, especially for proper brain function through the formation of new pathways and processing information and cognition. Therefore, when sleep is insufficient, this can result in pathophysiologic conditions. Sleep deficiency is a risk factor for various conditions, including dementia, diabetes, and obesity. Recent studies have shown that there are differences in the prevalence of sleep disorders between genders. Insomnia, the most common type of sleep disorder, has been reported to have a higher incidence in females than in males. However, sex/gender differences in other sleep disorder sub-types are not thoroughly understood. Currently, increasing evidence suggests that gender issues should be considered important when prescribing medicine. Therefore, an investigation of the gender-dependent differences in sleep disorders is required. In this review, we first describe sex/gender differences not only in the prevalence of sleep disorders by category but in the efficacy of sleep medications. In addition, we summarize sex/gender differences in the impact of sleep disorders on incident dementia. This may help understand gender-dependent pathogenesis of sleep disorders and develop therapeutic strategies in men and women.

OBJECTIVES: The purpose of this study was to develop a systematic and standardized「The Survey on School Foodservice Program」that can identify the current status of school meals on the nationwide level. METHODS: This study was carried out in six steps of the analysis of report/investigation data related to school foodservice in metropolitan and provincial offices of education, analysis of preceding research related to the actual status of school foodservice, field verification of the actual condition of the school foodservice site, development of a draft of「The Survey on School Foodservice Program」, pilot study of a draft of 「The Survey on School Foodservice Program」, and suggestions of a final model of「The Survey on School Foodservice Program」from August to December, 2017. Statistical analysis was performed for frequency analysis and descriptive analysis using the SPSS program ver. 23. RESULTS: A draft of「The Survey on School Foodservice Program」was developed by analyzing the current status of report/research data on school meals in metropolitan and provincial offices of education, analyzing the preceding research on school meals, and identifying the actual conditions at school foodservice sites. To verify the validity of the school foodservice survey questionnaire, 1,031 schools were sampled from a total of 10,251 schools and the pilot test of ‘2017 School Foodservice Survey’ was conducted. The final model of「The Survey on School Foodservice Program」consisted of 12 survey sections, 29 survey categories, and 433 survey items, and the survey cycle was set for one year and three years for each survey item. CONCLUSIONS: Based on the objective statistical data through「The Survey on School Foodservice Program」, it is possible to develop the school foodservice policy, which will help establish the reliability of the school meals.
Education ; Humans ; Meals ; Pilot Projects

OBJECTIVES: The purpose of this study was to develop a systematic and standardized「The Survey on School Foodservice Program」that can identify the current status of school meals on the nationwide level. METHODS: This study was carried out in six steps of the analysis of report/investigation data related to school foodservice in metropolitan and provincial offices of education, analysis of preceding research related to the actual status of school foodservice, field verification of the actual condition of the school foodservice site, development of a draft of「The Survey on School Foodservice Program」, pilot study of a draft of 「The Survey on School Foodservice Program」, and suggestions of a final model of「The Survey on School Foodservice Program」from August to December, 2017. Statistical analysis was performed for frequency analysis and descriptive analysis using the SPSS program ver. 23. RESULTS: A draft of「The Survey on School Foodservice Program」was developed by analyzing the current status of report/research data on school meals in metropolitan and provincial offices of education, analyzing the preceding research on school meals, and identifying the actual conditions at school foodservice sites. To verify the validity of the school foodservice survey questionnaire, 1,031 schools were sampled from a total of 10,251 schools and the pilot test of ‘2017 School Foodservice Survey’ was conducted. The final model of「The Survey on School Foodservice Program」consisted of 12 survey sections, 29 survey categories, and 433 survey items, and the survey cycle was set for one year and three years for each survey item. CONCLUSIONS: Based on the objective statistical data through「The Survey on School Foodservice Program」, it is possible to develop the school foodservice policy, which will help establish the reliability of the school meals.
Education ; Humans ; Meals ; Pilot Projects

Rapid eye movement (REM) sleep has an essential role in the process of learning and memory in the hippocampus. It has been reported that linalool, a major component of Lavandula angustifolia, has antioxidant, anti-inflammatory, and neuroprotective effects, along with other effects. However, the effect of linalool on the cognitive impairment and behavioral alterations that are induced by REM-sleep deprivation has not yet been elucidated. Several studies have reported that REM-sleep deprivation-induced memory deficits provide a well-known model of behavioral alterations. In the present study, we examined whether linalool elicited an anti-stress effect, reversing the behavioral alterations observed following REM-sleep deprivation in mice. Furthermore, we investigated the underlying mechanism of the effect of linalool. Spatial memory and learning memory were assessed through Y maze and passive avoidance tests, respectively, and the forced swimming test was used to evaluate anti-stress activity. The mechanisms through which linalool improves memory loss and behavioral alterations in sleep-deprived mice appeared to be through an increase in the serotonin levels. Linalool significantly ameliorated the spatial and learning memory deficits, and stress activity observed in sleep-deprived animals. Moreover, linalool led to serotonin release, and cortisol level reduction. Our findings suggest that linalool has beneficial effects on the memory loss and behavioral alterations induced by REM-sleep deprivation through the regulation of serotonin levels.
Animals ; Cognition Disorders ; Hippocampus ; Hydrocortisone ; Lavandula ; Learning ; Memory Disorders* ; Memory* ; Mice ; Neuroprotective Agents ; Physical Exertion ; Serotonin ; Sleep, REM ; Spatial Memory

The Na⁺/H⁺ exchanger-1 (NHE-1) is a ubiquitously expressed pH-regulatory membrane protein that functions in the brain, heart, and other organs. It is increased by intracellular acidosis through the interaction of intracellular H⁺ with an allosteric modifier site in the transport domain. In the previous study, we reported that glutamate-induced NHE-1 phosphorylation mediated by activation of protein kinase C-β (PKC-β) in cultured neuron cells via extracellular signal-regulated kinases (ERK)/p90 ribosomal s6 kinases (p90RSK) pathway results in NHE-1 activation. However, whether glutamate stimulates NHE-1 activity solely by the allosteric mechanism remains elusive. Cultured primary cortical neuronal cells were subjected to intracellular acidosis by exposure to 100 μM glutamate or 20 mM NH₄Cl. After the desired duration of intracellular acidosis, the phosphorylation and activation of PKC-β, ERK1/2 and p90RSK were determined by Western blotting. We investigated whether the duration of intracellular acidosis is controlled by glutamate exposure time. The NHE-1 activation increased while intracellular acidosis sustained for >3 min. To determine if sustained intracellular acidosis induced NHE-1 phosphorylation, we examined phosphorylation of NHE-1 induced by intracellular acidosis by transient exposure to NH₄Cl. Sustained intracellular acidosis led to activation and phosphorylation of NHE-1. In addition, sustained intracellular acidosis also activated the PKC-β, ERK1/2, and p90RSK in neuronal cells. We conclude that glutamate stimulates NHE-1 activity through sustained intracellular acidosis, which mediates NHE-1 phosphorylation regulated by PKC-β/ERK1/2/p90RSK pathway in neuronal cells.
Acidosis* ; Blotting, Western ; Brain ; Extracellular Signal-Regulated MAP Kinases ; Glutamic Acid* ; Heart ; Membrane Proteins ; Neurons ; Phosphorylation ; Phosphotransferases ; Protein Kinases