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Background: Most recent clinical practice guidelines addressing the management of infantile hemangiomas (IHs) recommend oral propranolol, a non-selective beta-adrenergic antagonist, as first-line treatment. However, few reports have provided continuous follow-up data regarding cardiac evaluations. Methods: Sixty-four patients diagnosed with IHs and treated with oral propranolol before 2 years of age at the Department of Pediatrics, Kangbuk Samsung Hospital (Seoul, Republic of Korea), with regular examinations between 2017 and 2021, were included. Cardiac evaluations, including electrocardiography, Holter monitoring, chest X-ray, and echocardiography, were performed. Results: Sixty-four patients with IHs successfully underwent continuous follow-up cardiac evaluations. The median age at diagnosis was 2 weeks (1 day to 34.3 weeks). The median age at treatment initiation was 13.6 weeks (2.4-87.9 weeks), the mean longitudinal diameter of hemangioma at diagnosis was 2.8 ± 2.1 cm (0.3-12.0 cm), and the mean percentage of size decrease after 1 year of oral propranolol treatment was 71.8%. None of the 64 patients experienced severe adverse side effects during propranolol treatment. There was no statistically significant differences in echocardiographic function and electrocardiographic data after treatment. Conclusions: Propranolol treatment ≥6 months was effective and safe without significant cardiac toxicity in the treatment of patients with infantile hemangiomas.

Hereditary hemolytic anemia (HHA) is considered a group of rare hematological diseases in Korea, primarily because of its unique ethnic characteristics and diagnostic challenges. Recently, the prevalence of HHA has increased in Korea, reflecting the increasing number of international marriages and increased awareness of the disease. In particular, the diagnosis of red blood cell (RBC) enzymopathy experienced a resurgence, given the advances in diagnostic techniques. In 2007, the RBC Disorder Working Party of the Korean Society of Hematology developed the Korean Standard Operating Procedure for the Diagnosis of Hereditary Hemolytic Anemia, which has been continuously updated since then. The latest Korean clinical practice guidelines for diagnosing HHA recommends performing next-generation sequencing as a preliminary step before analyzing RBC membrane proteins and enzymes. Recent breakthroughs in molecular genetic testing methods, particularly next-generation sequencing, are proving critical in identifying and providing insight into cases of HHA with previously unknown diagnoses. These innovative molecular genetic testing methods have now become important tools for the management and care planning of patients with HHA. This review aims to provide a comprehensive overview of recent advances in molecular genetic testing for the diagnosis of HHA, with particular emphasis on the Korean context., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Triptorelin, a long-acting gonadotropin-releasing hormone (GnRH) agonist, is available in 1-, 3-, and 6-month formulations to treat central precocious puberty (CPP). The triptorelin pamoate 22.5-mg 6-month formulation recently approved for CPP offers greater convenience to children by reducing the injection frequency. However, worldwide research on using the 6-month formulation to treat CPP is scarce. This study aimed to determine the impact of the 6-month formulation on predicted adult height (PAH), changes in gonadotropin levels, and related variables., Methods: We included 42 patients (33 girls and nine boys) with idiopathic CPP treated with a 6-month triptorelin (6-mo TP) formulation for over 12 months. Auxological parameters, including chronological age, bone age, height (cm and standard deviation score [SDS]), weight (kg and SDS), target height (TH), and Tanner stage, were evaluated at baseline, and after 6, 12, and 18 months of treatment. Hormonal parameters, including serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol for girls or testosterone for boys, were analyzed concurrently., Results: The mean age at treatment initiation was 8.6 ± 0.83 (8.3 ± 0.62 for girls, 9.6 ± 0.68 for boys). The peak LH level following intravenous GnRH stimulation at diagnosis was 15.47 ± 9.94 IU/L. No progression of the modified Tanner stage was observed during treatment. Compared to baseline, LH, FSH, estradiol, and testosterone were significantly reduced. In particular, the basal LH levels were well suppressed to less than l.0 IU/L, and the LH/FSH ratio was less than 0.66. The bone age/chronological age ratio remained stable with a decreasing trend (1.15 at the start of treatment, 1.13 at 12 months, 1.11 at 18 months). PAH SDS increased during treatment (0.77 ± 0.79 at baseline, 0.87 ± 0.84 at the start of treatment, 1.01 ± 0.93 at six months, and 0.91 ± 0.79 at 12 months). No adverse effects were observed during treatment., Conclusion: The 6-mo TP suppressed the pituitary-gonadal axis stably and improved the PAH during treatment. Considering its convenience and effectiveness, a significant shift to long-acting formulations can be expected., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yoo, Kim, Jung, Shim, Shim, Kim, Kwak, Kim and Yang.)

Purpose: Renal tumors account for approximately 7% of all childhood cancers. These include Wilms tumor (WT), clear cell sarcoma of the kidney (CCSK), malignant rhabdoid tumor of the kidney (MRTK), renal cell carcinoma (RCC), congenital mesoblastic nephroma (CMN) and other rare tumors. We investigated the epidemiology of pediatric renal tumors in Korea., Materials and Methods: From January 2001 to December 2015, data of pediatric patients (0-18 years) newly-diagnosed with renal tumors at 26 hospitals were retrospectively analyzed., Results: Among 439 patients (male, 240), the most common tumor was WT (n=342, 77.9%), followed by RCC (n=36, 8.2%), CCSK (n=24, 5.5%), MRTK (n=16, 3.6%), CMN (n=12, 2.7%), and others (n=9, 2.1%). Median age at diagnosis was 27.1 months (range 0-225.5) and median follow-up duration was 88.5 months (range 0-211.6). Overall, 32 patients died, of whom 17, 11, 1, and 3 died of relapse, progressive disease, second malignant neoplasm, and treatment-related mortality. Five-year overall survival and event free survival were 97.2% and 84.8% in WT, 90.6% and 82.1% in RCC, 81.1% and 63.6% in CCSK, 60.3% and 56.2% in MRTK, and 100% and 91.7% in CMN, respectively (p < 0.001)., Conclusion: The pediatric renal tumor types in Korea are similar to those previously reported in other countries. WT accounted for a large proportion and survival was excellent. Non-Wilms renal tumors included a variety of tumors and showed inferior outcome, especially MRTK. Further efforts are necessary to optimize the treatment and analyze the genetic characteristics of pediatric renal tumors in Korea.

Purpose: The 'DSD Pathways' study was initiated to assess health status and patterns of care among people enrolled in large integrated healthcare systems and diagnosed with conditions comprising the broad category of disorders (differences) of sex development (DSD). The objectives of this communication are to describe methods of cohort ascertainment for two specific DSD conditions-classic congenital adrenal hyperplasia with 46,XX karyotype (46,XX CAH) and complete androgen insensitivity syndrome (CAIS)., Participants: Using electronic health records we developed an algorithm that combined diagnostic codes, clinical notes, laboratory data and pharmacy records to assign each cohort candidate a 'strength-of-evidence' score supporting the diagnosis of interest. A sample of cohort candidates underwent a review of the full medical record to determine the score cutoffs for final cohort validation., Findings to Date: Among 5404 classic 46,XX CAH cohort candidates the strength-of-evidence scores ranged between 0 and 10. Based on sample validation, the eligibility cut-off for full review was set at the strength-of-evidence score of ≥7 among children under the age of 8 years and ≥8 among older cohort candidates. The final validation of all cohort candidates who met the cut-off criteria identified 115 persons with classic 46,XX CAH. The strength-of-evidence scores among 648 CAIS cohort candidates ranged from 2 to 10. There were no confirmed CAIS cases among cohort candidates with scores <6. The in-depth medical record review for candidates with scores ≥6 identified 61 confirmed cases of CAIS., Future Plans: As the first cohort of this type, the DSD Pathways study is well-positioned to fill existing knowledge gaps related to management and outcomes in this heterogeneous population. Analyses will examine diagnostic and referral patterns, adherence to care recommendations and physical and mental health morbidities examined through comparisons of DSD and reference populations and analyses of health status across DSD categories., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Although the prevalence of hereditary hemolytic anemia (HHA) is relatively low in Korea, it has been gradually increasing in recent decades due to increment in the proportions of hemoglobinopathies from immigrants of South East Asia, raising awareness of the disease among clinicians, and advances in diagnostic technology. As such, the red blood cell (RBC) Disorder Working Party (WP), previously called HHA WP, of the Korean Society of Hematology (KSH) developed the Korean Standard Operating Procedures (SOPs) for the diagnosis of HHA in 2007. These SOPs have been continuously revised and updated following advances in diagnostic technology [e.g., flow cytometric osmotic fragility test (FOFT) and eosin-5-maleimide (EMA) binding test], current methods for membrane protein or enzyme analysis [e.g., liquid chromatography-tandem mass spectrometry (LC-MS/MS), ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), high-performance liquid chromatography (HPLC)], and molecular genetic tests using next-generation sequencing (NGS). However, the diagnosis and treatment of HHA remain challenging as they require considerable experience and understanding of the disease. Therefore, in this new Korean Clinical Practice Guidelines for the Diagnosis of HHA, on behalf of the RBC Disorder WP of KSH, updated guidelines to approach patients suspected of HHA are summarized. NGS is proposed to perform prior to membrane protein or enzyme analysis by LC-MS/MS, UPLC-MS/MS or HPLC techniques due to the availability of gene testing in more laboratories in Korea. We hope that this guideline will be helpful for clinicians in making diagnostic decisions for patients with HHA in Korea.

The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5%-10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age. High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a nonselective beta-adrenergic antagonist, is the first-line treatment for IHs at a dosage of 2-3 mg/kg/day divided into 2 daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical nonselective beta-blocker, may be used for small superficial type IHs at a dosage of 1-2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.

The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of ITGB3 was the most common, followed by c.2333A>C (p.Gln778Pro) of ITGB2B . Known variants of GT, including c.917A>C (p.His306Pro) of ITGB3 and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of ITGA2B , were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of ITGB3 and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of ITGA2B , were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel RASGRP2 variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs.

Objectives: To evaluate the prognostic value of ultrasound and MRI findings in patients with infantile hemangioma undergoing propranolol therapy., Methods: This study was based on retrospective interpretation of prospectively acquired data. Thirty-eight consecutive patients (28 females and 10 males; mean age ± standard deviation, 3.2 ± 2.2 months) who underwent propranolol treatment for infantile hemangioma were included. Pre-treatment ultrasound images were assessed in terms of echogenicity, lesion height and vascularity. Presence of prominent intratumoral fat, non-fat septa, and enhancement pattern on MRI were retrospectively evaluated. Mann-Whitney test, chi-square, and Fisher's exact tests were used to compare imaging parameters between patients with treatment success and failure., Results: All patients underwent ultrasound and 15 patients underwent MRI. A total of 24 patients showed successful treatment. Between patients with treatment success and failure, there were significant differences in increased vascularity on pre-treatment ultrasound (19/24 vs. 6/14, p = 0.025), decreased vascularity on post-treatment ultrasound (21/24 vs. 5/14, p = 0.001), and prominent intratumoral fat on MRI (1/8 vs. 5/7 p = 0.033). There were no significant differences in echogenicity, lesion height on ultrasound, non-fat septa and MR enhancement pattern., Conclusions: Increased vascularity on pre-treatment ultrasound was significantly associated with successful treatment for propranolol therapy in patients with infantile hemangioma, whereas prominent fat component on MRI was significantly associated with treatment failure., Competing Interests: The authors have declared that no competing interests exist.

Background: Anemia is associated with high morbidity and mortality in older people. However, the prevalence and characteristics of anemia in older individuals are not fully understood, and national data on these aspects in older Korean adults are lacking. This study aimed to evaluate the prevalence and characteristics of anemia in older adults using data from the Korea National Health and Nutrition Examination Survey (KNHANES), which is a nationwide cross-sectional epidemiological study conducted by the Korean Ministry of Health and Welfare., Methods: Data from a total of 62,825 participants of the 2007-2016 KNHANES were compiled and analyzed to investigate differences in participant characteristics and potential risk factors for anemia. Differences in clinical characteristics of participants were compared across subgroups using the chi-square test for categorical variables and independent t-test for continuous variables. Univariate and multivariate analyses using logistic regression were performed to identify related clinical factors., Results: The prevalence of anemia was higher in the population aged ≥65 years than in the younger population. Anemia was also more prevalent among females than among males, but this difference was not significant in people aged > 85 years. Being underweight, receiving a social allowance, living alone, and having comorbidities such as hypertension, rheumatoid arthritis, diabetes mellitus (DM), cancer, and chronic renal failure (CRF) were more common among older adults with anemia than among the population without anemia. In univariate and multivariate analyses, older age, female sex, underweight, and presence of comorbidities including rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia., Conclusions: This study revealed that age, female sex, underweight, and the presence of comorbidities such as rheumatoid arthritis, DM, cancer, and CRF were associated with an increased risk of anemia in older Korean adults. Further study on causal relationships between anemia and other variables in the older population is necessary.

Background: Oral propranolol has become first-line treatment for infantile hemangiomas (IHs). This study focused on identifying cytokines related to the biology of IH and early regression indicators of IH after propranolol treatment., Methods: For inclusion, the patients had to be aged less than 1 year and have an IH with a largest diameter ≥2 cm. Patients were scheduled to receive 1 year of propranolol treatment. Serum cytokines involved in angiogenesis, vasculogenesis, and/or chronic inflammation were analyzed at 0, 1, and/or 12 months after treatment using Multiplex Luminex assays., Results: Among the 49 evaluable patients, 33 completed the 1-year treatment: 16 showed excellent response and 12 had good response to propranolol. Significant decreases in serum MMP-2, bFGF, VEGF-α, and MCP-1 levels were observed after 1 year of treatment compared to pretreatment values. The maximal diameters of the lesions significantly correlated with pretreatment serum VEGF-α, bFGF, and MMP-9. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year., Conclusion: MMP-2, VEGF-α, bFGF, and MCP-1 may involve in the biology of IH and their downregulation may be associated with involution processes of IH. Pretreatment bFGF and VEGF could be novel biomarkers for predicting response to propranolol., Impact: We found that decreases in the concentrations of MMP-2, bFGF, VEGF, and MCP-1 were associated with regression of the hemangioma, which indicates that one of the mechanisms of propranolol in the treatment of proliferative hemangiomas may involve downregulation of those cytokines. Patients with higher bFGF and VEGF levels showed better response to propranolol at 1 year. Importantly, serum bFGF higher than 37.07 pg/mL may predict an excellent response to propranolol. Therefore, along with the patient's age and the size and visual characteristics of the lesion, bFGF levels could help determine the viability of propranolol use in the treatment of IHs. Our study represented extensive serum profiling in IH, reporting the indicators and molecules clearly related to IH regression with propranolol treatment. The authors believe that monitoring serum cytokines, including MMP-2, bFGF, VEGF, and MCP-1, in IH patients could be important, in addition to clinical follow-up, for determining when to start and end propranolol treatment.

Purpose: Climate and lifestyle changes increase an individual's susceptibility to various allergens and also the incidence of allergic diseases. We aimed to examine the changes in sensitization rate for aeroallergens over a 10-year period in Korean children., Materials and Methods: We retrospectively reviewed the medical records of 4493 children who visited the allergy clinic at a tertiary hospital in Korea for allergic rhinitis or asthma from January 2009 to December 2018. The serum specific immunoglobulin E (IgE) levels were measured to confirm the sensitization against Dermatophagoides farinae ( D. farinae ), Alternaria , weed and tree pollen mixtures, as well as cat and dog dander through ImmunoCAP test., Results: D. farinae was the most common sensitizing aeroallergen (45.9%) during the 10-year span. The sensitization rate for tree pollen mixture ( p for trend <0.001), weed pollen mixtures ( p for trend <0.001), dog dander ( p for trend=0.025), and cat dander ( p for trend=0.003) showed ascending trends during the 10-year study period. Furthermore, the sensitization rate for multiple allergens (≥2) in 2018 increased significantly compared to that in 2009 ( p for trend=0.013). Compared with children without sensitization to D. farinae , those with sensitization to D. farinae showed higher sensitization rates to other aeroallergens ( p for interaction <0.001)., Conclusion: Children's sensitization rate to cat and dog dander and weed and tree pollen mixtures significantly increased during the 10-year period in Korea. Children with sensitization to D. farinae are likely to be sensitized to other aeroallergens as well., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Background: Hereditary hemolytic anemia (HHA) is a rare disease characterized by premature red blood cell (RBC) destruction due to intrinsic RBC defects. The RBC Disorder Working Party of the Korean Society of Hematology established and updated the standard operating procedure for making an accurate diagnosis of HHA since 2007. The aim of this study was to investigate a nationwide epidemiology of Korean HHA., Methods: We collected the data of a newly diagnosed pediatric HHA cohort (2007-2016) and compared this cohort's characteristics with those of a previously surveyed pediatric HHA cohort (1997-2006) in Korea. Each participant's information was retrospectively collected by a questionnaire survey., Results: A total of 369 children with HHA from 38 hospitals distributed in 16 of 17 districts of Korea were investigated. RBC membranopathies, hemoglobinopathies, RBC enzymopathies, and unknown etiologies accounted for 263 (71.3%), 59 (16.0%), 23 (6.2%), and 24 (6.5%) of the cases, respectively. Compared to the cohort from the previous decade, the proportions of hemoglobinopathies and RBC enzymopathies significantly increased ( P < 0.001 and P = 0.008, respectively). Twenty-three of the 59 hemoglobinopathy patients had immigrant mothers, mostly from South-East Asia., Conclusion: In Korea, thalassemia traits have increased over the past 10 years, reflecting both increased awareness of this disease and increased international marriages. The enhanced recognition of RBC enzymopathies is due to advances in diagnostic technique; however, 6.5% of HHA patients still do not have a clear diagnosis. It is necessary to improve accessibility of diagnosing HHA., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

The quadrivalent meningococcal conjugate vaccine MenACWY-CRM is approved in the Republic of Korea for use in individuals from 2 months of age. This single-arm, open-label, observational, multicenter, post-marketing study (NCT01766206) assessed the safety of MenACWY-CRM vaccine administered according to local clinical practice. A total of 3939 individuals aged 2 months-55 years provided safety data post-vaccination; the analysis was conducted on the per-protocol set (3920 participants). Solicited and unsolicited adverse events (AEs) were collected over 7 days post-vaccination and medically-attended AEs (MAAEs) and serious AEs (SAEs) over 29 days post-vaccination. Among recorded solicited AEs, injection site AEs were reported by 21.38% of participants, with tenderness/pain being most frequent across age groups; systemic AEs were reported in 13.95% of participants, with irritability (in ˂6-year-olds), headache and myalgia (in ≥6 year-olds) being the most frequently reported. Most solicited AEs were mild or moderate in nature. The percentage of participants reporting unsolicited AEs varied in the study population, i.e. 12.56% in participants aged 2-23 months and 3.18% in those ≥2 years of age. Overall, less than 22% of unsolicited AEs were considered as related to vaccination. MAAEs (10.89% of participants) were mostly mild; 2.82% were considered as related to vaccination. Three (0.46%) and 5 (0.15%) SAEs (none vaccination-related) occurred in participants aged 2-23 months and 2-55 years, respectively. No deaths were reported. The safety profile for MenACWY-CRM in this post-marketing surveillance was consistent with observations from studies conducted during the vaccine's clinical development, with no new safety concerns.

Background: Although the clinical importance of the immunological benefits of breastfeeding has been emphasized for decades, their direct relationship with acute pyelonephritis (APN) is still not clear. Our goal was to determine whether breastfeeding truly provides protection against APNs, while investigating the effects of other factors such as sex, age, mode of delivery, and birth weight on APN., Methods: A total of 62 infants under 6 months of age who had both microbiologically and radiologically-confirmed APN were enrolled in the case group. Healthy infants (n = 178) who visited the hospital for scheduled vaccinations were enrolled in the control group. The following participant characteristics were compared between the case and control groups: age, sex, birth order among siblings, feeding methods, weight percentile by month, birth weight percentile by gestational age, gestational age at birth, and mode of delivery., Results: Babies exclusively fed with manufactured infant formulae before 6 months of age had significantly higher risk for APN than breastfed or mixed-fed infants (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.687-7.031; P = 0.001). Firstborn babies had lower risk for APN than 2nd- or 3rd-born babies (OR, 0.43; 95% CI, 0.210-0.919). Other factors that increased the risk for APN were low birth weight percentiles (OR, 8.33; 95% CI, 2.300-30.166) and birth via caesarean section (OR, 2.32; 95% CI, 1.097-4.887). There were more preterm births in the case group (10.9% vs. 1.7%; P = 0.002), but this did not increase the risk for APN (OR, 4.47; P = 0.063)., Conclusion: Feeding exclusively with formula before 6 months of age was related to higher risk for APN, which demonstrates that breastfeeding has a protective effect against APN. The other risk factors for APN were birth order (≥ 2nd-born), low birth weight, and birth via caesarean section., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2020 The Korean Academy of Medical Sciences.)

Background: There was no practical guideline for the management of patients with central nervous system tumor in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, has developed the guideline for glioblastoma. Subsequently, the KSNO guideline for World Health Organization (WHO) grade II cerebral glioma in adults is established., Methods: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified by searching PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL databases using specific and sensitive keywords as well as combinations of keywords regarding diffuse astrocytoma and oligodendroglioma of brain in adults., Results: Whenever radiological feature suggests lower grade glioma, the maximal safe resection if feasible is recommended globally. After molecular and histological examinations, patients with diffuse astrocytoma, isocitrate dehydrogenase ( IDH )-wildtype without molecular feature of glioblastoma should be primarily treated by standard brain radiotherapy and adjuvant temozolomide chemotherapy (Level III) while those with molecular feature of glioblastoma should be treated following the protocol for glioblastomas. In terms of patients with diffuse astrocytoma, IDH -mutant and oligodendroglioma ( IDH -mutant and 1p19q codeletion), standard brain radiotherapy and adjuvant PCV (procarbazine+lomustine+vincristine) combination chemotherapy should be considered primarily for the high-risk group while observation with regular follow up should be considered for the low-risk group., Conclusion: The KSNO's guideline recommends that WHO grade II gliomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to molecular and histological features of tumors and clinical characteristics of patients., Competing Interests: The authors have no potential conflicts of interest., (Copyright © 2019 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Background: Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS., Methods: Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform., Results: Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations., Conclusions: This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.

Background: There has been no practical guidelines for the management of patients with central nervous system (CNS) tumors in Korea for many years. Thus, the Korean Society for Neuro-Oncology (KSNO), a multidisciplinary academic society, started to prepare guidelines for CNS tumors from February 2018., Methods: The Working Group was composed of 35 multidisciplinary medical experts in Korea. References were identified through searches of PubMed, MEDLINE, EMBASE, and Cochrane CENTRAL using specific and sensitive keywords as well as combinations of keywords., Results: First, the maximal safe resection if feasible is recommended. After the diagnosis of a glioblastoma with neurosurgical intervention, patients aged ≤70 years with good performance should be treated by concurrent chemoradiotherapy with temozolomide followed by adjuvant temozolomide chemotherapy (Stupp's protocol) or standard brain radiotherapy alone. However, those with poor performance should be treated by hypofractionated brain radiotherapy (preferred)±concurrent or adjuvant temozolomide, temozolomide alone (Level III), or supportive treatment. Alternatively, patients aged >70 years with good performance should be treated by hypofractionated brain radiotherapy+concurrent and adjuvant temozolomide or Stupp's protocol or hypofractionated brain radiotherapy alone, while those with poor performance should be treated by hypofractionated brain radiotherapy alone or temozolomide chemotherapy if the patient has methylated MGMT gene promoter (Level III), or supportive treatment., Conclusion: The KSNO's guideline recommends that glioblastomas should be treated by maximal safe resection, if feasible, followed by radiotherapy and/or chemotherapy according to the individual comprehensive condition of the patient., Competing Interests: The authors have no potential conflicts of interest., (Copyright © 2019 The Korean Brain Tumor Society, The Korean Society for Neuro-Oncology, and The Korean Society for Pediatric Neuro-Oncology.)

Although chebulic acid isolated from Terminalia chebular has diverse biological effects, its effects on the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and the expression of downstream genes have not been elucidated. The purpose of this research is to investigate the hepatoprotective mechanism of chebulic acid against oxidative stress produced by tert -butyl hydroperoxide ( t -BHP) in liver cells. The treatment with chebulic acid attenuated cell death in t -BHP-induced HepG2 liver cells and increased intracellular glutathione content, upregulated the activity of heme oxygenase-1, and also increased the translocation of Nrf2 into the nucleus and Nrf2 target gene expression in a dose-dependent manner. The exposure of chebulic acid activated the phosphorylation of mitogen-activated protein kinases. The overall result is that chebulic acid has cytoprotective effect on t -BHP-induced hepatotoxicity in HepG2 cells through Nrf2-mediated antioxidant enzymes., Competing Interests: Compliance with ethical standardsThe authors declare that are no conflict of interest.

Purpose: Macrolide-resistant Mycoplasma pneumoniae pneumonia (MPP) is characterized by prolonged fever and radiological progression despite macrolide treatment. Few studies have examined serum procalcitonin (PCT) level in children with MPP. We aimed to investigate the association of acute inflammation markers including PCT with clinical parameters in children with MPP., Methods: A total of 147 children were recruited. The diagnosis of MPP relied on serial measurement of IgM antibody against mycoplasma and/or polymerase chain reaction. We evaluated the relationships between C-reactive protein (CRP), PCT, and lactate dehydrogenase (LDH) levels and white blood cell (WBC) counts, and clinical severity of the disease. We used multivariate logistic regression analysis to estimate the odds ratio for prolonged fever (>3 days after admission) and hospital stay (> 6 days), comparing quintiles 2-5 of the PCT levels with the lowest quintile., Results: The serum PCT and CRP levels were higher in children with fever and hospital stay than in those with fever lasting ≤ 3 days after admission and hospital stay ≤ 6 days. CRP level was higher in segmental/lobar pneumonia than in bronchopneumonia. The LDH level and WBC counts were higher in children with fever lasting for >3 days before compared to those with fever lasting for ≤ 3 days. The highest quintile of PCT levels was associated with a significantly higher risk of prolonged fever and/or hospital stay than the lowest quintile., Conclusion: Serum PCT and CRP levels on admission day were associated with persistent fever and longer hospitalization in children with MPP.

In this study, the effect of adipose tissue stem cells (ASCs) on the growth of acute lymphoblastic leukemia (ALL) cells was examined in an in vivo model. We established ALL cell lines expressing firefly luciferase (ALL/fLuc) by lentiviral infection that were injected intraperitoneally to NOD/SCID mice. The luciferase activities were significantly higher in mice co-injected with 10 5 ALL/fLuc cells and ASCs than in those injected with ALL/fLuc cells alone. Co-injection of 10 5 ALL/fLuc cells and ASCs in differing ratios into mice gradually increased the bioluminescence intensity in all groups, and mice co-injected with 1 or 2 × 10 6 ASCs showed higher bioluminescence intensity than those receiving lower numbers. Interestingly, in the mice injected with 10 5 or 10 7 ALL/fLuc cells alone, the formation of tumor masses was not observed for at least five weeks. Moreover, co-injection of 10 7 ALL/fLuc cells and 5 × 10 5 ASCs into mice increased the bioluminescence intensity in all groups, and showed significantly higher bioluminescence intensity compared to mice co-injected with human normal fibroblast HS68 cells. Overall, ASCs promote the growth of ALL cells in vivo, suggesting that ASCs negatively influence hematologic malignancy, which should be considered in developing cell therapy using ASCs.

Luteolin, a flavonoid nutraceutical abundant in vegetables and fruits, exhibits a wide range of bioactive properties, including antioxidant, anti-inflammatory and anti-cancer activities. Pituitary tumor-transforming gene 1 (PTTG1), an oncoprotein that regulates cell proliferation, is highly expressed in several types of cancer cells including leukemia. In this study, we aim to investigate the anti-cancer effects of luteolin on cells with differential PTTG1 expression and their underlying mechanisms in human myeloid leukemia cells. Methyl thiazolyl tetrazolium (MTT) assay data showed that luteolin (25-100 μM) significantly reduced cell viability in THP-1, HL-60 and K562 cells but did not affect normal peripheral blood mononuclear cells (PBMCs). Flow cytometric analysis and Western blot data demonstrated that luteolin induced a stronger apoptosis on undifferentiated myeloid leukemia cells with higher PTTG1 protein levels than on 12-myristate 13-acetate (PMA)- or all-trans-retinoic acid (ATRA)-differentiated cells with lower PTTG1 expression. Furthermore, PTTG1 knockdown by shRNA in leukemia cells suppressed cell proliferation, arrested cell-cycle progression and impaired the effectiveness of luteolin on cell-cycle regulation. Moreover, PTTG1-knockdown cells with luteolin exposure presented a reduction of the apoptotic proteins and maintained higher levels of the anti-apoptotic proteins such as Mcl-1, Bcl-2 and p21, which exhibited greater resistance to apoptosis. Finally, microarray analysis showed that 20 genes associated with cell proliferation, such as CXCL10 , VEGFA , TNF , TP63 and FGFR1 , were dramatically down-regulated in PTTG1-knockdown cells. Our current findings clearly demonstrate that luteolin-triggered leukemic cell apoptosis is modulated by the differential expression of the PTTG1. PTTG1 oncoprotein overexpression may modulate cell proliferation-related regulators and enhance the response of myeloid leukemia cells to luteolin. Luteolin is beneficial for the treatment of cancer cells with highly expressed PTTG1 oncoprotein., Competing Interests: The authors declare no conflict of interest.

Objective:: To know the usefulness of the oblique coronal view of the posterior cruciate ligament (PCL) in the evaluation of the graft normal anatomy and the diagnostic accuracy of combining the PCL view with orthogonal views for the evaluation of PCL graft failure or impingement after reconstruction procedures., Methods:: This retrospective study included 54 patients who underwent PCL-view MRI after PCL reconstruction surgery. Anatomic identification of graft failure and impingement was scored by two radiologists. The ability to diagnose PCL graft failure with the PCL view, orthogonal view or combined PCL/orthogonal views was evaluated by calculating the sensitivity, specificity and accuracy., Results:: The entire width discrimination scores and margin sharpness scores for the PCL view were significantly higher than those for the orthogonal view for both readers. The specificities and accuracies for the PCL view and the combined PCL/orthogonal views were higher than those for the orthogonal view alone, but these differences were not statistically significant., Conclusion:: The PCL view provided a better anatomic evaluation than the orthogonal view with regard to the entire width evaluation and margin sharpness evaluation of the PCL graft. The combined view of orthogonal and PCL views was slightly more sensitive and accurate, but not significantly so, in the diagnoses of graft failure and impingement., Advances in Knowledge:: The PCL view provided a better anatomic evaluation than the orthogonal view with regard to the entire width evaluation and margin sharpness evaluation of the PCL graft. The PCL view was slightly more sensitive and accurate, but not significantly so, in the diagnoses of graft failure and impingement.

The e-Transformation in higher education, in which Massive Open Online Courses (MOOCs) are playing a pivotal role, has had an impact on the modality in which behavior analysis is taught. In this paper, we survey the history and implications of online education including MOOCs and describe the implementation and results for the discipline's first MOOC, delivered at Southern Illinois University in spring 2015. Implications for the globalization and free access of higher education are discussed, as well as the parallel between MOOCs and Skinner's teaching machines.

Human mesenchymal stem cell (MSC) heterogeneity and problems associated with the ex vivo expansion of MSC are linked with the failure of MSC clinical trials. In this study, we compared the effect of MSCs cultured in different oxygen concentrations on GVHD in mice to elucidate whether hypoxia improves the immunosuppressive capacity of MSCs. Hypoxia increased the proliferative activity and the expression of several stemness and chemokine genes, such as KLF4, OCT4, C-MYC, CCL2, and CXCL10. Mice that received MSCs cultured in normoxia or hypoxia showed alleviated symptoms of GVHD and increased survival times. However, there was no significant difference in survival rates between mice that received MSCs cultured in normoxia and hypoxia. These data suggest that hypoxic culture is a useful method for maintaining and obtaining MSCs used for cell therapy and that the therapeutic potential of MSCs cultured in hypoxia warrants further investigation.

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease due to bronchial colonization of Aspergillus fumigatus that occurs in susceptible patients with asthma or cystic fibrosis. A 10-year-old girl was referred to the Department of Pediatric Pulmonology for persistent consolidations on chest radiography. Pulmonary consolidations were observed in the right upper and left lower lobes and were not resolved with a 4-week prescription of broad-spectrum antibiotics. The patient had a history of atopic dermatitis and allergic rhinitis but no history of asthma. She had no fever but produced thick and greenish sputum. Her breathing sounds were clear. On laboratory testing, her total blood eosinophil count was 1,412/mm(3) and total serum IgE level was 2,200 kU/L. Aspergillus was isolated in the sputum culture. The A. fumigatus-specific IgE level was 15.4 kU/L, and the Aspergillus antibody test was also positive. A chest computed tomography scan demonstrated bronchial wall thickening and consolidation without bronchiectasis. An antifungal agent was added but resulted in no improvement of pulmonary consolidations after 3 weeks. Pulmonary function test was normal. Methacholine provocation test was performed, revealing bronchial hyperreactivity (PC20=5.31 mg/mL). Although the patient had no history of asthma or bronchiectasis, ABPA-seropositivity was suspected. Oral prednisolone (1 mg/kg/day) combined with antifungal therapy was started. Pulmonary consolidations began decreasing after 1 week of treatment and completely resolved after 1 month. This is the first observed and treated case of seropositive ABPA in Korean children without previously documented asthma.

Purpose: Atopic dermatitis (AD) is a chronic inflammatory relapsing skin disorder. Vitamin D plays a pivotal role in the development of AD, and interleukin (IL) 31 is known to be related to pruritus in AD. The aim of our study was to determine whether 25-hydroxyvitamin D (25(OH)D) levels are related to IL-31 levels or to the severity of AD., Methods: We enrolled 91 children with AD and 32 control subjects without history or symptoms of allergic diseases. Blood was drawn to evaluate complete blood cell count, total eosinophil count (TEC), and total IgE, specific IgE to common allergens, 25(OH)D, and IL-31 levels. Serum 25(OH)D and IL-31 levels were measured using high-performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. The scoring atopic dermatitis (SCORAD) index was used to evaluate the severity of AD., Results: The mean 25(OH)D level was significantly lower in the AD group than in the control group; 25(OH)D decreased greatly in the moderate and severe AD groups compared with the mild AD group. Children with atopic sensitization showed significantly lower 25(OH)D levels than nonatopic children. However, serum IL-31 levels were not related to AD group, SCORAD index, or 25(OH)D levels. The SCORAD index was inversely correlated with serum 25(OH)D level and positively correlated with TECs and total IgE levels. Children with moderate and severe AD had significantly higher TECs than children with mild AD., Conclusion: Vitamin D is related to the severity of AD independently of IL-31.

Objectives: Current guidelines recommend the eosin-5'-maleimide (EMA) binding test and cryohemolysis test for screening for hereditary spherocytosis (HS), and the flow cytometric osmotic fragility (FC OF) test was recently developed to replace the classic OF test. We evaluatedthe performance of the EMA binding test, FC OF test, cryohemolysis test, and the hemoglobin (Hb)/mean corpuscular hemoglobin concentration (MCHC) ratio in the diagnosis of HS and assessed whether these tests reflect the clinical severity of HS., Methods: A total of 153 patients with anemia (33 with HS, 40 with autoimmune hemolytic anemia, 40 with anemia of chronic disease, and 40 with iron deficiency anemia [IDA]) and 140 healthy controls were enrolled, and the performance of the three tests was evaluated., Results: Both the EMA binding test (area under the curve [AUC], 0.996) and the FC OF test (AUC, 0.992) performed satisfactorily, but the cryohemolysis test (AUC, 0.723) performed significantly worse because of false positivity in patients with IDA. The Hb/MCHC ratio (P < .001) was able to reflect the clinical severity of HS., Conclusions: Our results demonstrate that both the EMA binding and FC OF tests are useful as screening tests for the diagnosis of HS, but the cryohemolysis test has limited use due to its false positivity in IDA, with the Hb/MCHC ratio the most useful parameter for assessing the clinical severity of HS., (Copyright© by the American Society for Clinical Pathology.)

Purpose: A nationwide outbreak of Mycoplasma pneumoniae pneumonia (MP) refractory to macrolide antibiotics occurred in Korea during 2011. Steroid therapy has been reported to be both efficacious and well tolerated in pediatric patients with refractory MP. We compared clinical features and laboratory characteristics between children with refractory MP requiring steroid treatment and those with macrolide-responsive MP and evaluated the risk factors associated with refractory MP., Methods: We investigated 203 children who were admitted to our institution with MP from June to November 2011. Refractory MP was defined by persistent fever over 38.3℃ with progressive pulmonary consolidation or pleural effusion despite administration of appropriate macrolide antibiotics for 5 days or longer after admission. Steroid therapy was initiated on the fifth day after admission for refractory cases., Results: There were 26 patients with refractory MP requiring steroid therapy. The mean duration of steroid therapy was 5.4 days and most of the patients were afebrile within 24 hours after initiation of steroid therapy. The prevalence of refractory MP was higher in patients with pleural effusion, lobar pneumonia affecting more than 2 lobes, higher levels of serum lactate dehydrogenase, increased oxygen requirements, and longer duration of hospitalization. Atopic sensitization and history of asthma were also associated with refractory MP after adjusting for age and gender., Conclusion: Children with refractory MP had more severe pneumonia. Atopic sensitization and history of asthma may be risk factors for refractory MP requiring steroid therapy in Korean children.

A nationwide survey was conducted to clarify the clinical features and outcomes of Korean children with Langerhans cell histiocytosis (LCH). Korea Histiocytosis Working Party analyzed the data of 603 patients who were diagnosed with LCH between 1986 and 2010 from 28 institutions in Korea. Median age at diagnosis was 65 months (range, 0 to 276 mo). Bone was the most frequently affected organ (79.6%) followed by skin (19.2%). Initially, 419 patients (69.5%) had single-system involvement (SS), 85 (14.1%) with multisystem (MS) disease without risk organ involvement (MS-RO), and 99 (16.4%) multisystem disease with risk organ involvement (MS-RO). The 5-year overall survival (OS) rates in the SS, MS-RO, and MS-RO groups were 99.8%, 98.4%, and 77.0%, respectively (P<0.001), and the 5-year reactivation rates were 17.9%, 33.5%, and 34.3%, respectively (P<0.001). The OS rate was lower in patients with RO involvement (P=0.025) and lack of response to initial treatment (P=0.001). MS involvement (P=0.036) was an independent risk factor for reactivation. Permanent consequences were documented in 99 patients (16.4%). Reactivation of disease, MS involvement, and age at diagnosis ≤ 2 years were associated with higher incidence of permanent consequences. This study emphasized that further efforts are required to improve survival of MS-RO patients and reduce reactivation in younger patients with MS involvement.

Previous studies conducted cell expansion ex vivo using low initial plating densities for optimal expansion and subsequent differentiation of mesenchymal stem cells (MSCs). However, MSC populations are heterogeneous and culture conditions can affect the characteristics of MSCs. In this study, differences in gene expression profiles of adipose tissue (AT)-derived MSCs were examined after harvesting cells cultured at different densities. AT-MSCs from three different donors were plated at a density of 200 or 5,000 cells/cm(2). After 7 days in culture, detailed gene expression profiles were investigated using a DNA chip microarray, and subsequently validated using a reverse transcription polymerase chain reaction (RT-PCR) analysis. Gene expression profiles were influenced primarily by the level of cell confluence at harvest. In MSCs harvested at ∼90% confluence, 177 genes were up-regulated and 102 genes down-regulated relative to cells harvested at ∼50% confluence (P<0.05, FC>2). Proliferation-related genes were highly expressed in MSCs harvested at low density, while genes that were highly expressed in MSCs harvested at high density (∼90% confluent) were linked to immunity and defense, cell communication, signal transduction and cell motility. Several cytokine, chemokine and growth factor genes involved in immunosuppression, migration, and reconstitution of damaged tissues were up-regulated in MSCs harvested at high density compared with MSCs harvested at low density. These results imply that cell density at harvest is a critical factor for modulating the specific gene-expression patterns of heterogeneous MSCs.

Purpose: In this study, we aimed to investigate the prevalence of year-round respiratory viral infection in children with lower respiratory tract infection (LRTI) and the relationship between respiratory viral infection and allergen sensitization in exacerbating asthma., Methods: We investigated the sources for acute LRTIs in children admitted to our hospital from May 2010 to April 2011. The 6 most common respiratory viruses were isolated from nasopharyngeal aspirate using multiplex reverse transcription-polymerase chain reaction in 309 children; respiratory syncytial virus (RSV), adenovirus (AV), parainfluenza virus (PIV), influenza virus (IFV), human metapneumovirus (hMPV), rhinovirus (RV). Atopic sensitization was defined if more than 1 serum specific Immunoglobulin E level measured using UniCAP (Pharmacia) was over 0.35 IU/mL., Results: RSV was the most common pathogen of bronchiolitis in hospitalized children through the year. RV or IFV infection was more prevalent in asthma exacerbations compared to other LRTIs. AV and hMPV were more likely to cause pneumonia. RV and IFV were associated with asthma exacerbations in children with atopic sensitization, but not in nonatopic children., Conclusion: RV and IFV are associated with hospitalization for asthma exacerbation in children with atopic sensitization.

To overcome the limitations of allogeneic hematopoietic stem cell transplantation (HSCT), we conducted a study to identify a strategy for enhancing hematopoietic stem cell (HSC) engraftment during HSCT. Co-transplantation experiments with mesenchymal stem cells (MSCs) derived from adult human tissues including bone marrow (BM), adipose tissue (AT), and umbilical cord blood (CB) were conducted. We showed that AT-MSCs and CB-MSCs enhanced the engraftment of HSCs as effectively as BM-MSCs in NOD/SCID mice, suggesting that AT-MSCs and CB-MSCs can be used as alternative stem cell sources for enhancing the engraftment and homing of HSCs. CB-MSCs derived from different donors showed different degrees of efficacy in enhancing the engraftment of HSCs. The most effective CB-MSCs showed higher proliferation rates and secreted more MCP-1, RANTES, EGF, and VEGF. Our results suggest that AT-MSCs and CB-MSCs could be alternative stem cell sources for co-transplantation in HSCT. Furthermore, in terms of MSCs' heterogeneity, characteristics of each population of MSCs are considerable factors for selecting MSCs suitable for co-transplantation with HSC.

Bone mineralization is strongly stimulated by weight-bearing exercise during growth and development. Judo, an Olympic combat sport, is a well-known form of strenuous and weight-bearing physical activity. Therefore, the primary goal of this study was to determine the effects of Judo practice on the bone health of male high school students in Korea. The secondary goal of this study was to measure and compare the bone mineral density (BMD) of the hands of Judo players and sedentary control subjects. Thirty Judo players (JDP) and 30 sedentary high school boys (CON) voluntarily participated in the present study, and all of the sedentary control subjects were individually matched to the Judo players by body weight. BMD was determined by using dual-energy X-ray absorptiometry (Hologic, Bedford, MA, USA). The lumbar spine, femur and forearm BMD in the JDP group were significantly greater by 22.7%, 24.5%, and 18.3%, respectively, than those in the CON group. In addition, a significant difference in the CON group was observed between the dominant hand (DH) radius (0.710 ± 0.074 g/cm(2)) and the non-dominant hand (NDH) radius (0.683 ± 0.072 g/cm(2)), but this was not observed in the JDP group (DH = 0.819 ± 0.055 g/cm(2); NDH = 810 ± 0.066 g/cm(2)) (P < 0.05). Therefore, the results of this study suggest that Judo practice during the growth period significantly improves bone health in high school male students. In addition, it seems that Judo practice could eliminate the effect of increased BMD in the dominant hand.

Purpose: Obesity has been suggested to be linked to asthma. However, it is not yet known whether obesity directly leads to airway hyperreactivity (AHR) or obesity-induced airway inflammation associated with asthma. We investigated obesity- related changes in adipokines, AHR, and lung inflammation in a murine model of asthma and obesity., Materials and Methods: We developed mouse models of chronic asthma via ovalbumin (OVA)-challenge and of obesity by feeding a high-fat diet, and then performed the methacholine bronchial provocation test, and real-time PCR for leptin, leptin receptor, adiponectin, adiponectin receptor (adipor1 and 2), vascular endothelial growth factor (VEGF), transforming growth factor (TGF) β, and tumor necrosis factor (TNF) α in lung tissue. We also measured cell counts in bronchoalveolar lavage fluid., Results: Both obese and lean mice chronically exposed to OVA developed eosinophilic lung inflammation and AHR to methacholine. However, obese mice without OVA challenge did not develop AHR or eosinophilic inflammation in lung tissue. In obese mice, lung mRNA expressions of leptin, leptin receptor, VEGF, TGF, and TNF were enhanced, and adipor1 and 2 expressions were decreased compared to mice in the control group. On the other hand, there were no differences between obese mice with or without OVA challenge., Conclusion: Diet-induced mild obesity may not augment AHR or eosinophilic lung inflammation in asthma.

Klebsiella pneumoniae has emerged as a leading pathogen that causes pyogenic liver abscesses (PLAs) in Korea. K. pneumoniae liver abscess (KLA) is potentially life threatening, and the diagnosis is difficult. In developed countries, PLA is rarely observed in children and is frequently associated with disorders of granulocyte function and previous abdominal infection. We observed a case of KLA in a healthy 12-year-old boy. To our knowledge, this is the first reported case of KLA in an immunocompetent child without an underlying disease in Korea. The patient was treated with percutaneous catheter drainage and antibiotics. The catheter was placed in the intrahepatic abscess for 3 weeks and parenteral antibiotics (ceftriaxone and amikacin) were administered for 4 weeks, followed by oral antibiotics (cefixime) for 2 weeks. We reported this case to raise awareness of KLA in immunocompetent children among physicians, and to review the diagnosis, risk factors, potential complications, and appropriate treatment of KLA.

It has been recognized that ginseng has anti-diabetic effects in skeletal muscle, but the mechanism has not been intensively investigated. The aim of this study was to investigate the effects of Korean red ginseng (Panax ginseng) supplementation on muscle glucose uptake in high-fat fed rats. Sixteen rats were randomly divided into two groups: a control group (CON, n = 8) and a Korean red ginseng group (KRG, n = 8). The KRG group ingested RG extract (1 g·kg(-1), 6 days/week) mixed in water for two weeks. After the two-week treatment, plasma lipid profiles, and glucose and insulin concentrations were measured. The triglyceride (TG) and glucose transporter 4 (GLUT-4) contents were measured in the skeletal muscle and liver. The rate of glucose transport was determined under a submaximal insulin concentration during muscle incubation. Plasma FFA concentrations were significantly decreased in KRG (P < 0.05). Liver and muscle triglyceride concentrations were also decreased in the KRG treatment group (P < 0.05) compared to the CON group. In addition, resting plasma insulin and glucose levels were significantly lower after Korean red ginseng treatment (P < 0.05). However, muscle glucose uptake was not affected by Korean red ginseng treatment, as evidenced by the rate of glucose transport in the epitorchealis muscle under submaximal insulin concentrations. These results suggest that while KRG supplementation could improve whole body insulin resistance and plasma lipid profiles, it is unlikely to have an effect on the insulin resistance of skeletal muscle, which is the major tissue responsible for plasma glucose handling., (Copyright © 2013 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

The purpose of this study was to determine the effects of a pre-exercise meal on the plasma human growth hormone (hGH) response and fat oxidation during walking. Subjects (n=8) were randomly provided with either 1 g/kg body weight of glucose in 200 mL water (CHO) or 200 mL water alone (CON) 30 min prior to exercise and subsequently walked on a treadmill at 50% of VO2max for 60 min. Plasma hGH concentrations were significantly higher in subjects who received CHO compared to those who received CON at 15 and 30 min. The fat oxidation rate in the CHO was significantly lower than the CON while walking for 5~15, 25~35 and 45~55 min. Plasma FFA levels were also significantly lower in the CHO compared to the CON at 30, 45 and 60 min. Plasma glucose levels in the CHO were significantly lower while plasma insulin levels were significantly higher than in the CON at 15 and 30 min. Therefore, the results of this study suggest that the elevation of plasma hGH levels due to the intake of a pre-exercise meal may not be strongly related to fat oxidation and plasma free fatty acid (FFA) levels during low-intensity exercise.

Background: The number of patients diagnosed with hereditary hemolytic anemia (HHA) has increased since the advent of novel diagnostic techniques that accurately identify this disorder. Here, we report data from a survey on the prevalence and characteristics of patients diagnosed with HHA in Korea from 2007 to 2011., Methods: Information on patients diagnosed with HHA in Korea and their clinical and laboratory results were collected using a survey questionnaire. Globin gene and red blood cell (RBC) enzyme analyses were performed. In addition, we analyzed data collected by pediatricians., Results: In total, 195 cases of HHA were identified. Etiologies identified for HHA were RBC membranopathies, hemoglobinopathies, and RBC enzymopathies, which accounted for 127 (64%), 39 (19.9%), and 26 (13.3%) cases, respectively. Of the 39 patients with hemoglobinopathies, 26 were confirmed by globin gene analysis, including 20 patients with β-thalassemia minor, 5 patients with α-thalassemia minor, and 1 patient with unstable hemoglobin disease., Conclusion: The number of patients diagnosed with hemoglobinopathies and RBC enzymopathies has increased considerably since the previous survey on HHA in Korea, dated from 1997 to 2006. This is likely the result of improved diagnostic techniques. Nevertheless, there is still a need for more sensitive diagnostic tests utilizing flow cytometry and for better standardization of test results to improve the accuracy of diagnosis of RBC membranopathies in Korea. Additionally, more accurate assays for the identification of RBC enzymopathies are warranted.

Background: Because of the heterogeneity of human mesenchymal stem cells (MSCs), methods for cell expansion in culture and the effects on gene expression are critical factors that need to be standardized for preparing MSCs. We investigated gene expression patterns of MSCs with different seeding densities and culture times., Methods: Bone marrow-derived MSCs were plated at densities from 200 cells/cm(2) to 5,000 cells/cm(2), and the gene expression patterns were evaluated over time using a reverse-transcription polymerase chain reaction assay., Results: The mRNA levels of factors that play a critical role in cell migration and tissue regeneration, such as podocalyxin-like protein (PODXL), α4-integrin, α6-integrin, and leukemia inhibitory factor (LIF), were higher in MSCs plated at 200 cells/cm(2) than in MSCs plated at 5,000 cells/cm(2). The mRNA levels of these factors gradually increased for 10 days and then decreased by day 15 in culture. MSCs seeded at 200 cells/cm(2) that were cultured for 10 days expressed high levels of Oct-4 and Nanog. Indoleamine 2,3-dioxygenase, cyclooxygenase-1, and hepatocyte growth factor expression were upregulated in the presence of the proinflammatory cytokine interferon-γ in these cells., Conclusion: We found differences in the gene expression patterns of MSCs under different culture conditions. MSCs from 10-day cultures seeded at a low density were efficiently expanded, expressed PODXL, α6-integrin, α4-integrin, and LIF, and maintained properties like stemness and immunomodulation. Therefore, ex vivo expansion of MSCs maintained for an adequate culture time after plating at low cell density can provide an effective regenerative medicinal strategy for cell therapies using MSCs.

Purpose: We investigated the mRNA levels of peroxisome proliferator-activated receptor (PPAR)-α, PPAR-γ, adipokines, and cytokines in the lung tissue of lean and obese mice with and without ovalbumin (OVA) challenge, and the effect of rosiglitazone, a PPAR-γ agonist., Methods: We developed 6 mice models: OVA-challenged lean mice with and without rosiglitazone; obese mice with and without rosiglitazone; and OVA-challenged obese mice with and without rosiglitazone. We performed real-time polymerase chain reaction for leptin, leptin receptor, adiponectin, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, PPAR-α and PPAR-γ from the lung tissue and determined the cell counts and cytokine levels in the bronchoalveolar lavage fluid., Results: Mice with OVA challenge showed airway hyperresponsiveness. The lung mRNA levels of PPARα and PPAR-γ increased significantly in obese mice with OVA challenge compared to that in other types of mice and decreased after rosiglitazone administeration. Leptin and leptin receptor expression increased in obese mice with and without OVA challenge and decreased following rosiglitazone treatment. Adiponectin mRNA level increased in lean mice with OVA challenge. Lung VEGF, TNF-α, and TGF-β mRNA levels increased in obese mice with and without OVA challenge compared to that in the control mice. However, rosiglitazone reduced only TGF-β expression in obese mice, and even augmented VEGF expression in all types of mice. Rosiglitazone treatment did not reduce airway responsiveness, but increased neutrophils and macrophages in the bronchoalveolar lavage fluid., Conclusion: PPAR-α and PPAR-γ expressions were upregulated in the lung tissue of OVA-challenged obese mice however, rosiglitazone treatment did not downregulate airway inflammation in these mice.