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Background: Asthma is a heterogeneous disease, characterized by chronic airway inflammation. Asthma exacerbations (AE) are episodes characterized by a progressive increase in symptoms of shortness of breath, cough, wheezing, or chest tightness with a decrease in lung function. There have been previous studies that examined the role of eosinophil-derived neurotoxin (EDN) in asthma, but there have been no studies of the role of EDN in children experiencing AE. Objective: In this study, we aimed to examine the association of EDN with lung function and prognosis in children admitted for severe AE. Methods: We enrolled 82 children who were admitted for severe AE at two different university hospitals in South Korea between January 2018 and December 2019. Blood tests, including white blood cell count, myeloperoxidase (MPO), total eosinophil count, EDN, C-reactive protein (CRP) level, and interleukin (IL) 4, IL-5, IL-10 values, and lung function were measured on admission and at discharge in each patient. Results: We observed significant decreases in the levels of MPO, EDN, CRP, and IL-4, with significant improvement in lung function after treatment. We then classified the subjects into two groups of different clinical phenotypes: eosinophilic asthma exacerbation (EAE) group and non-EAE group. EDN levels were higher and lung functions were lower in the EAE group. Also, we found that the EDN level was a significant biomarker useful for predicting the number of days for hospital stay. Conclusion: We found that EDN can act as a biomarker that reflects lung function, and that EDN could act as a prognostic biomarker, which demonstrated the complex role of EDN in children experiencing AE.

The high morbidity rate of hepatocellular carcinoma (HCC) is mainly linked to late diagnosis. Early diagnosis of this leading cause of mortality is therefore extremely important. We designed a gene selection strategy to identify potential secretory proteins by predicting signal peptide cleavage sites in amino acid sequences derived from transcriptome data of human multistage HCC comprising chronic hepatitis, liver cirrhosis and early and overt HCCs. The gene selection process was validated by the detection of molecules in the serum of HCC patients. From the computational approaches, 10 gene elements were suggested as potent candidate secretory markers for detecting HCC patients. ELISA testing of serum showed that hyaluronan mediated motility receptor (HMMR), neurexophilin 4 (NXPH4), paired like homeodomain 1 (PITX1) and thrombospondin 4 (THBS4) are early-stage HCC diagnostic markers with superior predictive capability in a large cohort of HCC patients. In the assessment of differential diagnostic accuracy, receiver operating characteristic curve analyses showed that HMMR and THBS4 were superior to α-fetoprotein (AFP) in diagnosing HCC, as evidenced by the high area under the curve, sensitivity, specificity, accuracy and other values. In addition, comparative analysis of all four markers and AFP combinations demonstrated that HMMR-PITX1-AFP and HMMR-NXPH4-PITX1 trios were the optimal combinations for reaching 100% accuracy in HCC diagnosis. Serum proteins HMMR, NXPH4, PITX1 and THBS4 can complement measurement of AFP in diagnosing HCC and improve identification of patients with AFP-negative HCC as well as discriminate HCC from non-malignant chronic liver disease.

Mycoplasma pneumoniae is a major causative pathogen of community-acquired pneumonia in children, and the treatment of choice is macrolides. There is an increasing trend in reports of refractory clinical responses despite macrolide treatment due to the emergence of macrolide-resistant M. pneumoniae. Early discrimination of macrolide-refractory M. pneumoniae pneumonia (MrMP) from macrolide-sensitive M. pneumoniae pneumonia (MSMP) is vital; however, testing for macrolide susceptibility at the time of admission is not feasible. This study aimed to identify the characteristics of MrMP in Korean children, in comparison with those of MSMP. In this multicenter study, board-certified pediatric pulmonologists at 22 tertiary hospitals reviewed the medical records from 2010 to 2015 of 5294 children who were hospitalized with M. pneumoniae pneumonia and administered macrolides as the initial treatment. One-way analysis of variance and the Kruskal-Wallis test were used to compare differences between groups. Of 5294 patients (mean age, 5.6 years) included in this analysis, 240 (4.5%), 925 (17.5%), and 4129 (78.0%) had MrMP, macrolide-less effective M. pneumoniae pneumonia, and MSMP, respectively. Compared with the MSMP group, the MrMP group had a longer fever duration, overall (13.0 days) and after macrolide use (8.0 days). A higher proportion of MrMP patients had respiratory distress, pleural effusion, and lobar pneumonia. The mean aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, and C-reactive protein levels were the highest in the MrMP group, along with higher incidences of extrapulmonary manifestations and atelectasis (during and post infection). Pre-existing conditions were present in 17.4% (n = 725/4159) of patients, with asthma being the most common (n = 334/4811, 6.9%). This study verified that MrMP patients show more severe initial radiographic findings and clinical courses than MSMP patients. MrMP should be promptly managed by agents other than macrolides.

Obesity is the state of excessive body fat accumulation and is mainly caused by consuming more calories than are burned through physical activity. Herbal acupuncture (HA), also known as pharmacopuncture, has been increasingly used in clinics of Korean medical to alleviate obesity. This review analyzed four clinical studies and 16 animal studies on the effectiveness of HA as a treatment for obesity. Clinical evidence suggests that various kinds of HA might be beneficial for treating obesity; however, further investigations with well-designed, evidence-based, randomized clinical trials are needed. Animal studies support the idea that HA might be beneficial for the treatment of obesity and provide possible mechanisms, such as anti-inflammation, antioxidation, modulating lipid metabolism and so on, to explain the effect of HA on obesity. This review, based on the evidence collected, suggests that HA could have a beneficial effect for alleviating obesity by modulating inflammation, oxidative stress, lipid metabolism, leptin, and the insulin signal.

A 16p13.3 duplication syndrome has been recently suggested to be a novel recognizable syndrome as a reciprocal microduplication disease of Rubinstein–Taybi syndrome. The CREBBP gene is believed to be the dosage-sensitive critical gene responsible for the reciprocal duplication and deletion syndrome. Descriptions so far have been de novo. Here, we report a very rare case of a maternally inherited a −1 Mb sized duplication on 16p13.3 identified by SNP array testing. The patient showed moderate intellectual disability, normal growth, and characteristic facial features. The patient's mother also had mild intellectual disability, normal growth, camptodactyly, proximally implanted small thumbs, and distinctive facial features. The study provides additional information that furthers the understanding and delineation of 16p13.3 duplication syndrome.

Background Invasive bacterial infections in apparently immunocompetent children were retrospectively analyzed to figure causative bacterial organisms in Korea. Methods A total of 947 cases from 25 university hospitals were identified from 2006 to 2010 as a continuance of a previous 10-year period study from 1996 to 2005. Results Escherichia coli (41.3%), Streptococcus agalactiae (27.7%), and Staphylococcus aureus (27.1%) were the most common pathogens in infants < 3 months of age. S. agalactiae was the most prevalent cause of meningitis and pneumonia and E. coli was the major cause of bacteremia without localizing signs in this group. In children 3 to 59 months of age, Streptococcus pneumoniae (54.2%), S. aureus (20.5%), and Salmonella spp. (14.4%) were the most common pathogens. S. pneumoniae was the leading cause of pneumonia (86.0%), meningitis (65.0%), and bacteremia without localizing signs (49.0%) in this group. In children ≥ 5 years of age, S. aureus (62.8%) was the predominant pathogen, followed by Salmonella species (12.4%) and S. pneumoniae (11.5%). Salmonella species (43.0%) was the most common cause of bacteremia without localizing signs in this group. The relative proportion of S. aureus increased significantly over the 15-year period (1996–2010) in children ≥ 3 months of age (P < 0.001), while that of Haemophilus influenzae decreased significantly in both < 3 months of age group (P = 0.036) and ≥ 3 months of age groups (P < 0.001). Conclusion S. agalactiae, E. coli, S. pneumoniae, and S. aureus are common etiologic agents of invasive bacterial infections in Korean children., Graphical Abstract

Purpose: Croup is known to have epidemics in seasonal and biennial trends, and to be strongly associated with epidemics of para influenza virus. However, seasonal and annual epidemics of croup have not been clearly reported in Korea. This study aimed to ex amine the seasonal/annual patterns and etiologies of childhood croup in Korea during a consecutive 6-year period. Methods: Pediatric croup data were collected from 23 centers in Korea from 1 January 2010 to 31 December 2015. Electronic medi cal records, including multiplex reverse transcription polymerase chain reaction (RT-PCR) results, demographics and clinical informa tion were cross-sectionally reviewed and analyzed. Results: Overall, 2,598 childhood croup patients requiring hospitalization were identified during the study period. Among them, a total of 927 who underwent RT-PCR were included in the analysis. Males (61.5%) predominated, and most (63.0%) of them were younger than 2 years of age (median, 19 months; interquartile range, 11-31 months). Peak hospitalization occurred in 2010 and 2012 in even-numbered years, and parainfluenza virus (PIV, 39.7%) was the most common cause of childhood croup requiring hos pitalization, followed by respiratory syncytial virus (14.9%), human rhinovirus (12.5%), Mycoplasma pneumonaie (10.6%), and human coronavirus (7.3%). Conclusion: It is concluded that croup hospitalization has a biennial pattern in even-numbered years. PIV may be the most com mon cause of childhood croup; however, croup epidemics could be attributed to other viruses. (Allergy Asthma Respir Dis 2019;7:78-85)

Purpose Allergen-specific immunotherapy (AIT) is the only curative treatment for allergic diseases, but a few allergic patients receive AIT. In this multicenter cross-sectional study, we aimed to explore patient and physician perspectives on AIT through a questionnaire survey. Materials and Methods Allergic patients who received subcutaneous immunotherapy for at least 1 year were asked to answer a questionnaire developed by an expert panel of allergen and immunotherapy workgroup in Korea. Results A total of 267 patients (adults, 60.3%) with allergic rhinitis (91.4%), asthma (42.7%), or atopic dermatitis (20.2%) from referred hospitals completed the survey. Among patients and physicians, respectively, the overall rates of satisfaction with AIT for allergic rhinitis were 86.4% and 83.3% (kappa agreement=0.234, p

The aim of this study was to examine the effects of acupuncture on urinary incontinence and to discuss why these acupoints were selected. Seven databases were searched for any randomized controlled trials (RCTs) that investigated the use of acupuncture or acupressure as a treatment for urinary incontinence, and the Cochrane risk of bias tool was utilized to evaluate the risk of bias in each study. Four RCTs met all the inclusion criteria. The results from the selected RCTs failed to demonstrate any statistically significant improvements in urinary incontinence, although acupuncture or acupressure did exhibit favorable effects on overactive bladder symptoms and quality of life, in comparison with other conventional therapies. There have been limited results supporting acupuncture or acupressure as an effective treatment method for urinary incontinence; therefore, further RCTs are required to confirm the effectiveness of acupuncture or acupressure in the treatment of urinary incontinence.

Serum thyroid-stimulating hormone screening of asymptomatic individuals to diagnose subclinical hypothyroidism remains controversial. We evaluated the potential role of Sasang constitutional discrimination and ryodoraku testing as an alternative and complementary diagnostic tool for subclinical hypothyroidism. Among 1,105 potential subjects, 1,073 were included in this study. Of these, 134 subjects had subclinical hypothyroidism (SCH) and 939 were healthy (euthyroid; EU) control subjects. Blood parameters, including serum thyroid hormone levels, were measured. We classified the participants into the four Sasang constitutional types, Taeyang-type individuals, Taeeum-type individuals, Soyang-type individuals and Soeum-type individuals, and measured their ryodoraku scores (RS). The mean levels of free thyroxine (FT4), glucose, red blood cells and hematocrit in the SCH group were significantly lower compared to those in the EU group (p

Background The objective of this study was to assess the prevalence of education about sleep and sleep disorders in medical school education and to identify barriers to providing such education. Methods Surveys were sent to 409 medical schools across 12 countries (Australia, India, Indonesia, Japan, Malaysia, New Zealand, Singapore, South Korea, Thailand, United States, Canada and Viet Nam). Results Overall, the response rate was 25.9%, ranging from 0% in some countries (India) to 100% in other countries (New Zealand and Singapore). Overall, the average amount of time spent on sleep education is just under 2.5 h, with 27% responding that their medical school provides no sleep education. Three countries (Indonesia, Malaysia, and Viet Nam) provide no education, and only Australia and the United States/Canada provide more than 3 h of education. Paediatric topics were covered for a mere 17 min compared to over 2 h on adult-related topics. Conclusion These results suggest that there continues to be very limited coverage of sleep in medical school education despite an incredible increase in acknowledgement of the importance of sleep and need for recognition of sleep disorders by physicians.

The compound 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) is a synthetic, psychoactive drug chemically similar to the stimulant methamphetamine and the hallucinogen mescaline. Accumulated data has revealed potential toxic effects associated with MDMA on brain serotonin and dopamine neurons in animal models. However, the relevance of these adverse effects on prenatal exposure to this drug remains unknown. In this study, we demonstrated that prenatal (F0) exposure to MDMA caused permanent large-scale transcriptional changes in the brains of the offspring (F1), especially in the cerebral cortex, by gene expression profiling analysis. The expression analysis of the brain of F1 pups, after maternal ingestion of MDMA (20 mg/kg MDMA), revealed significant transcriptional changes in both male and female pups. Supervised analysis resulted in the identification of 804 outlier genes in males and 1784 outlier genes in females as MDMA-associated genes in the F1 generation. Most of the functional categories of genes, among the outlier genes, were intracellular signaling pathways, including the MAPK signaling pathway, Wnt signaling pathway, and neuroactive ligand-receptor interaction pathway. Although these genes were affected by MDMA exposure in utero, their association with brain dysfunction requires further investigation. The results of this study suggest that prenatal MDMA exposure may affect the developing brain.

Purpose: Obstructive sleep apnea syndrome (OSAS) in young children is frequently caused by adenoid and/or tonsillar hypertro phy. Adenoidectomy is the first operative method for childhood chronic rhinosinusitis (CRS). We investigated factors associated with recurrent rhinosinusitis in preschool aged children with OSAS to determine the association of 2 common diseases. Methods: One hundred forty-six children aged 2-5 years who were diagnosed as having OSAS after polysomnography between December 2003 and April 2016 were enrolled in this study. Children were divided into 2 groups with and without CRS. The 2 groups were compared in the severity of OSAS and allergy diseases and were evaluated for recurrent rhinosinusitis during the follow-up period, 1 year after diagnosis. Results: Among 108 patients with OSAS who were followed up, 81 patients (75%) were diagnosed with CRS. There were no signifi cant difference clinical and allergic characteristics between groups with and without CRS. However, bronchial asthma and otitis me dia was significantly more prevalent in patients with CRS than in those without (P=0.045 and P=0.000, respectively). Bronchial asthma and adenotonsillectomy was significantly associated with recurrent rhinosinusitis (P=0.005 and P=0.04, respectively) dur ing the 1-year follow-up. Conclusion: Approximately 75% of preschool children with OSAS have suffered from CRS. Bronchial asthma is associated with CRS among OSAS children. Recurrent rhinosinusitis is decreased after adenotonsillectomy, and bronchial asthma is an associated factor for recurrent rhinosinusitis after a follow-up. This close relationship childhood OSAS and recurrent rhinosinusitis/bronchial asthma needs further studies to investigate their role in the association. (Allergy Asthma Respir Dis 2018;6:168-173)

Thirty years have passed since the Korean Association of Pediatric Allergy and Respiratory Disease was founded. There have been great changes in the pattern of respiratory diseases in Korean children during the last 30 years with economic development in the country. Pneumonia remains the leading cause of childhood morbidity, despite advances in the prevention and management. The incidence and mortality of pneumonia caused by typical bacterial pathogens have been reduced. However, the predominance of Mycoplasma pneumoniae or virus-associated diseases is emerging, which suggests that novel diagnostic and therapeutic strategies are needed. Viral bronchiolitis is one of the most substantial health burdens for infants and young children worldwide. Although re spiratory syncytial virus is the most common pathogen, molecular diagnostic techniques have identified many other viruses includ ing human rhinovirus causing bronchiolitis. Bronchiectasis is a chronic respiratory condition characterized by chronic infection, air way inflammation, and progressive lung function decline. Research into the interactions between early life respiratory infections and development of bronchiectasis is imperative to halt the disease in its origin and improve adult outcomes. Acute respiratory dis tress syndrome (ARDS) is a severe, life-threatening lung disease with diffuse inflammatory lung injury leading to pulmonary edema and hypoxia. Although many modalities to treat ARDS have been studied, supportive therapies and lung protective ventilator sup port remains the mainstay. This review focuses on the current trends in research on these childhood respiratory diseases through lit erature review and aims to investigate the impact of Korean study results in this field. (Allergy Asthma Respir Dis 2018;6 Suppl 1:S66-76)

Graves' disease, the most common cause of hyperthyroidism, is an autoimmune disorder. Antithyroid drugs have been selected as the first-line treatment of Graves' disease in Korea, Japan, and European countries. However, antithyroid drugs such as methimazole (MMI) and prophylthiouracil (PTU) have limitations in clinical applications because of their side effects. In this study, we performed a clinical trial and in vitro study to investigate the clinical effects and action mechanism of Ahnjeonbaekho-tang (AJBHT), an herbal remedy for Graves' disease. In a clinical study of Graves' disease patients who had side effects from antithyroid drugs, we found that treatment by AJBHT resulted in a reduction of serum triiodothyronine (T3) and free thyroxine (FT4) levels and an increase in thyroid stimulating hormone (TSH) levels (T3: p

Sasang constitutional medicine classifies mankind into four constitutional types according to individual psychologic and physical traits. We hypothesized that differences among constitutional types might be explained by genetic variations.To evaluate the hypothesis, we determined the possible association in ischemic stroke patients (n = 134) of peroxisome proliferator-activated receptor (PPAR)-gamma with four constitutional types of Sasang medicine. The constitutional type of each patient and control subject (n = 129) was classified and genotyped for PPAR-gamma polymorphism Pro12Ala by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) methods.The distribution of the Pro/Ala genotypes in the ischemic stroke patients was not significantly different from that of healthy controls [odds ratio (OR)= 0.46; p = 0.1214]. However, very interestingly, we observed that all six Pro/Ala genotypes in ischemic patients were Taeeumin, one of four constitutional types of Sasang medicine. Statistical analysis revealed that Pro/Ala genotype in Taeeumin increases almost 15-fold the susceptibility to ischemic stroke compared to other constitutional types, Taeyangin, Soyangin or Soeumin (OR= 14.72; p = 0.0110).From the results in this study, we might suggest that Pro/Ala genotype in Taeeumin is associated with the susceptibility to ischemic stroke. To the author's best knowledge, this is the first report to study on genetic level the potential relationship between ischemic stroke and Sasang constitutional medicine, one of traditional Korean medicines (TKM). Authors hope that this study could provide a new approach for the study of ischemic stroke and merit further research.

The purpose of this study was to examine sleep patterns in a large sample of infants and toddlers (ages birth to 36 months) in Korea, and to compare sleep patterns, sleep problems, sleep ecology, and parental behaviors to global sleep data on young children in both predominately Asian (P-A) and predominately Caucasian (P-C) countries/regions. We additionally examined parent and child demographic information, parental behaviors, and aspects of the sleep ecology as predictors of sleep patterns among infants and toddlers in Korea. Parents/caregivers of 1,036 Korean infants and toddlers completed an expanded, internet-based version of the brief infant sleep questionnaire. Consistent with other studies of sleep in early childhood, sleep/wake patterns became increasingly consolidated with older child age for the Korea sample. Compared to both P-A and P-C infants and toddlers, children in Korea had the latest bedtimes, shortest total sleep and daytime sleep durations, and the least frequent rates of napping. Even though half of parents perceive their children’s sleep problematic, parental perceptions of severe child sleep problems were the lowest. Within Korea, breastfeeding and bottle-feeding at sleep resumption were associated with increased nocturnal awakenings. Evening television viewing was associated with later bedtimes, which may have implications for sleep hygiene recommendations in clinical practice. The current study provides important information about sleep/wake patterns, parental behaviors, and aspects of the sleep ecology for infants and toddlers for physicians to support healthy sleep in Korea., Graphical Abstract

To understand comprehensive molecular mechanisms by which Autotaxin (ENPP2) mediates, we identified large-scale molecular changes responsible for aberrant expression of Autotaxin (ATX) on breast cancer cells by using DNA microarrays. Transcriptional over-expression of ENPP2 gene was endogenously silenced by using RNA interference technique, and then recapitulated corresponding molecular changes in MDA435 breast cancer cells. Application of nonparametric Wilcoxon statistical analyses (P

Accumulated evidence has established that aberrant regulation of histone deacetylases (HDACs) is one of the major causes of the development of human malignancies. Among different iso-enzymes of HDAC and sirtuins grouped as the HDAC super family, little is known as to how histone deacetylase 2 (HDAC2) causes carcinogenesis in solid tumors. Here, in order to investigate the possible role of HDAC2 in gastric carcinogenesis, we analyzed the expression of HDAC2 in 71 gastric adenocarcinomas by immunohistochemistry. Moderate to strong expression of HDAC2 was found in 44 (62%) out of a total of 71 tumors. The majority of positive tumors, which were detected in the nucleus but not in normal gastric epithelium, did not express HDAC2 or showed only weak positive staining. Interestingly, we also noted that HDAC2 expression appeared to be associated with tumor aggressiveness as HDAC2 expression was observed to be statistically significant in advanced gastric cancer (P=0.0023, Chi-square test) and in positive lymph node metastasis (P=0.0713, Chi-square test). Taken together, these results suggest that HDAC2 may play an important role in the aggressiveness of gastric cancer.

Endothelial cell apoptosis has been postulated as the initial trigger of the progression of microvascular disease in patients with diabetes mellitus. To investigate the role of Scutellariae radix extract, we examined its effect on the endothelial cell proliferation using the [3H]-thymidine incorporation method. Scutellariae radix extract significantly stimulated endothelial cell proliferation in a dose-dependent manner. We focused on the protective action of Scutellariae radix extract on the endothelial cell apoptosis induced by high glucose concentrations. Determination of endothelial cell apoptosis was performed using DNA gel electrophoresis, terminal deoxynuclotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, and an ELISA kit. Exposure of vascular endothelial cell to high glucose (16.7 mM) for 72 h resulted in a significant increase in apoptosis, compared with the normal glucose concentrations (5.5 mM). Scutellariae radix extract inhibited high glucose-induced endothelial cell apoptosis. This result suggests that Scutellariae radix extract may contribute to antiapoptotic action against vascular endothelial cells, resulting in a beneficial effect in preventing diabetes-associated microvascular complications.

Background: The objective of this study was to assess the prevalence of education about sleep and sleep disorders in pediatric residency programs and to identify barriers to providing such education. Methods: Surveys were completed by directors of 152 pediatric residency programs across 10 countries (Hong Kong, India, Indonesia, Japan, Singapore, South Korea, Thailand, United States-Canada, and Vietnam). Results: Overall, the average amount of time spent on sleep education is 4.4 hours (median = 2.0 hours), with 23% responding that their pediatric residency program provides no sleep education. Almost all programs (94.8%) offer less than 10 hours of instruction. The predominant topics covered include sleep-related development, as well as normal sleep, sleep-related breathing disorders, parasomnias, and behavioral insomnia of childhood. Conclusions: These results indicate that there is still a need for more efforts to include sleep-related education in all pediatric residency programs, as well as coverage of the breadth of sleep-related topics. Such education would be consistent with the increased recognition of the importance of sleep and under-diagnosis of sleep disorders in children and adolescents.

This study was performed to measure early changes in the serotype distribution of pneumococci isolated from children with invasive disease during the 3-year period following the introduction of 10- and 13-valent pneumococcal conjugate vaccines (PCVs) in Korea. From January 2011 to December 2013 at 25 hospitals located throughout Korea, pneumococci were isolated among children who had invasive pneumococcal disease (IPD). Serotypes were determined using the Quellung reaction, and the change in serotype distribution was analyzed. Seventy-five cases of IPD were included. Eighty percent of patients were aged 3-59 months, and 32% had a comorbidity that increased the risk of pneumococcal infection. The most common serotypes were 19A (32.0%), 10A (8.0%), and 15C (6.7%). The PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, 23F, and 6A) accounted for 14.7% of the total isolates and the PCV13 minus PCV7 types (1, 3, 5, 7F and 19A) accounted for 32.0% of the total isolates. Serotype 19A was the only serotype in the PCV13 minus PCV7 group. The proportion of serotype 19A showed decreasing tendency from 37.5% in 2011 to 22.2% in 2013 (P = 0.309), while the proportion of non-PCV13 types showed increasing tendency from 45.8% in 2011 to 72.2% in 2013 (P = 0.108). Shortly after the introduction of extended-valent PCVs in Korea, serotype 19A continued to be the most common serotype causing IPD in children. Subsequently, the proportion of 19A decreased, and non-vaccine serotypes emerged as an important cause of IPD. The impact of extended-valent vaccines must be continuously monitored., Graphical Abstract

Histone deacetylase (HDAC) inhibitors are emerging as an exciting new class of potential anti-cancer agents for the treatment of solid and hematological malignancies. However, the best characterized HDAC function concerns the control of gene expression via the regulation of transcription activation or repression. To understand the genome-wide effects of HDAC inhibition on gene regulation, we performed serial gene expression analyses from 0 to 48 h after treating MDA-MB-435, a melanoma-derived highly metastatic tumor cell line, with Apicidin, a HDAC inhibitor. Combined-transcriptomic analysis of large-scale molecular changes induced by Apicidin resulted in the identification of 631 outlier genes that were continuously up- or down-regulated during the 48 h study period. When the 631 outlier genes were mapped to known biological processes, cell-cycle suppression emerged as the function most elicited by Apicidin. In addition comprehensive negative cell-cycle regulation by Apicidin was dissected using gene expression data and validated by Western blot analysis. We suggest the 631 outlier genes as a characteristic molecular signature for Apicidin, and propose concurrent transcriptional suppression of major components of cell-cycle regulatory circuit as potent anti-tumor mechanism of Apicidin. Genetic elements identified during this study also provide the possibility of novel therapeutic interventions in tumor metastasis.

Chronic urticaria (CU) is defined by the presence of urticaria that has been continuously or intermittently for a period of 6 weeks or longer. The prevalence of CU in the general population has been estimated to range from 0.5% to 5%. Correct diagnosis and proper management for CU is essential to improve the quality of care. To date, several practical guidelines have been available for practitioners. In this article, we reviewed and summarized the epidemiology, pathogenesis, diagnosis, and management based on case reports and studies of CU from Korea and the other part of world, and recently published guidelines. Although there are many controversies, this report for CU would provide a clinical guidance for healthcare professionals in Korea.

Purpose: We aimed to investigate the clinical characteristics and their relationship with the onset age of wheeze in school-age children and adolescents with asthma. Methods: Three hundred twenty-six patients, aged 6 to 19 years, diagnosed with asthma at 6 hospitals from Seoul, Gyeonggi, Daegu, and Busan were enrolled. They were categorized into 3 groups by the onset age of wheeze: group A, early onset (age

We analyzed the gene mutations and loss of heterozygosity (LOH) of the HCCS1 gene using intragenic polymorphic markers in a series of 88 primary HCCs. We found two sequence variations at exon 5 and 14 in both normal and tumor DNAs of case 50 and 51, respectively. The variation in case 50 led to a reading frameshift and a premature stop (TGA) at codon 125 and case 51 showed amino acid change at codon 448 (Val-->Ala, GTG-->GCG). Interestingly, these variations were not found in peripheral lymphocytes of 69 normal individuals and 227 cancer patients (86 HCC, 75 unselected gastric cancer, and 66 breast cancer), suggesting that these two variations are mutation, not polymorphism. In addition, we found 14 novel intragenic polymorphic sites in the HCCS1 gene. Thirty-two (47%) of sixty-eight informative cases showed allelic loss at at least one or more intragenic polymorphic sites, but there was no significant relationship between the frequency of LOH and clinicopathologic parameters. These results suggest that mutation of the HCCS1 gene might not be a main inactivation mechanism in the development of Korean HCC and that the HCCS1 gene might be involved in acceleration of the tumorigenic process in Korean HCC.

Purpose: Hereditary angioedema is a familial disease which is caused by a genetic deficiency or functional defect of the C1 inhibitor, and it features episodic swelling that can affect any part of the body. A great number of patients are estimated not to have an accu - rate diagnosis after the onset of symptoms, and close attention is required because sudden hereditary angioedema attacks can re- sult in even death. Methods: We sent an e-mail questionnaire to 975 members of the Korean Academy of Asthma, Allergy and Clinical Immunology. A total of 82 members replied. The questionnaire, including 15 questions about the diagnosis and management of hereditary angio- edema, was developed by the anaphylaxis/urticaria, angioedema workgroup of the Korean Academy of Asthma, Allergy and Clini- cal Immunology. Results: Forty-two percent of the respondents had experience with treatment of a suspected case of hereditary angioedema, and 15.9% made a confirmed diagnosis of hereditary angioedema. When the respondents suspected of cases, 91.4% of them performed tests for C3 and C4 concentrations and C1 inhibitor level. For maintenance treatment, most of the respondents used androgen, and only 22% found that C1 inhibitor concentrates can be prescribed through the Korea Orphan Drug Center in Korea. Conclusion: Allergy physicians in Korea substantially recognized the correct diagnosis and treatment of hereditary angioedema. However, there was a lack of awareness for the latest treatments, such as C1 inhibitor concentrates. Education of doctors and the public is needed. (Allergy Asthma Respir Dis 2014;2:277-284)

Gwang Cheon Jang*, Yoon-Seok Chang*, Sun Hee Choi, Woo-Jung Song, Soo-Young Lee, Hae-Sim Park; KAAACI Work Group (Hye-Ryun Kang, Yeong-Min Ye, Hyun-Jung Jin, Mi Yong Shin, Soo-Jin Lee, Hye One Kim, Jihyun Kim, Jae-Woo Jung); Headquarters of Korean Anaphylaxis Campaign (Hee-Bom Moon), Youngmin Ahn Department of Pediatrics, National Health Insurance Corporation Ilsan Hospital, Goyang; Department of Internal Medicine, Seoul National University College of Medicine, Seoul; Department of Pediatrics, Kyung Hee University School of Medicine, Seoul; Department of Pediatrics, Ajou University School of Medicine, Suwon; Department of Allergy & Clinical Immunology, Ajou University School of Medicine, Suwon; Korean Academy of Asthma, Allergy and Clinical Immunology, Anaphylaxis Work Group, Seoul; Headquarters of Korean Anaphylaxis Campaign, Seoul; Department of Pediatrics, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea

To validate the prevalence rate of symptoms of asthma produced by the phase I ISAAC (International Study of Asthma and Allergies in Childhood) study, hypertonic saline challenge test was carried out during the phase II study at a year after the phase I study. For the phase II study, six middle schools from three cities in the phase I study were selected. Finally, 499 children who responded to both studies were analyzed. All subjects were asked to complete the written questionnaire (WQ) first, followed by a video questionnaire (AVQ 3.0) during the phase I study. Of the 499 children, only 19 (3.8%) were positive to the hypertonic saline bronchial challenge test. The degree of agreement between responses to the two corresponding questions "wheezing at rest" and "nocturnal wheeze" in the AVQ 3.0 and WQ were moderate and weak with a Kappa indices of 0.45 and 0.23, respectively. The question on "severe wheeze" in the AVQ 3.0 had the highest Youden's index among the five questions related to asthma symptoms in the previous 12 months, but its specificity was low whereas its sensitivity was 1.0. There was no consistency of priority between the two questionnaires in predicting bronchial hyperreactivity in a group of Korean schoolchildren. Therefore we need to develop more appropriate WQ or AVQ to compare the prevalences of asthma to other countries.

Leigh's disease is a rare progressive neurological disorder that is characterized light microscopically by focal spongy necrosis in the brain and electron microscopically by mitochondriopathy. We report an autopsy case of Leigh's disease that showed abnormalities in the liver, kidney and skeletal muscle as well as the central nervous system. The patient was an 18-month-old girl who has carried a diagnosis of cerebral palsy ever since her birth to a 20-year-old mother. The baby was generally hypertonic and mentally retarded. She died of severe metabolic acidosis. Postmortem examination showed growth retardation, fatty liver, fatty kidney and soft brain. Brain section showed multifocal softenings in the brainstem, basal ganglia and periventricular areas. Microscopically increased capillaries with endothelial proliferation, vacuolar degeneration and mild gliosis were seen in the brain. The axons were relatively preserved. Liver and kidneys showed microvesicular fatty change. Myofiber degeneration of the skeletal muscle was also noted. Electron microscopic examination showed markedly increased mitochondria in the parenchymal cells of the brain, liver and kidney. The mitochondria showed round to ovoid ballooned appearance including electron-dense core-like structures and pseudoinclusions of glycogen granules.

The transplantation of dopaminergic neurons in the brain has been attempted in experimental animals and humans as the new treatment modality of Parkinson's disease. Before the trial of dopaminergic neuronal transplantation in human, the authors proceeded with the animal experiment of fetal dopaminergic cell transplantation in a rat Parkinson's disease model. The aims of this experiment were to confirm the availability of fetal mesencephalic cells as the donor, to compare the viability of cells according to different cell manipulation methods, and to follow up the functional recovery in the transplanted Parkinson's disease model. As a result, the authors concluded that the simple enzyme digestion method had a better cell survival rate than the multiple enzyme digestion method. Also, the transplanted mesencephalic cells could not only survive in the host animal but also promote functional recovery.

In a large number of allergic individuals, inhalant allergens are important causative and triggering agents in respiratory allergies. It is essential to survey the pollen and mold around the patient’s environment for the diagnosis and treatment of airborne allergy. Rotorod samplers were installed at well-ventilated places in seven collecting stations in Seoul, the capital of Korea, which has a population of 12 million. Airborne particles carrying allergens were collected daily from each station for 2 years (1 October 1995 to 30 September 1997). After being stained with Calberla’s fuchsin, they were identified, counted and recorded. The weather in Seoul was also recorded. Pollen was found from the middle of February through to the end of December. The peak date for pollen was 12 May (peak mean daily count: 701 grains/m 3 /day) and for mold it was 23 June (peak mean daily count: 936 spores/m 3 /day). Alder, birch, pine, oak, maple, elm, juniper, willow, and gingko trees were prevalent during the tree season, lasting from the middle of February to late July. Then sagebrush, ragweed, Japanese hop, and pigweed followed during the weed season, which lasts from the middle of July to the end of December. In skin prick test results, house dust mite was the most common positive allergen in Seoul, followed by cockroach. Among the pollens, mugwort was the most common positive, followed by ragweed mix, alder, birch, and grasses mix. Among the molds, there were high counts of Cladosporium and Alternaria during the year, excluding January. Ascospore of Lepto-spheria was highest during the monsoon season.