Classic and backdoor pathways of androgen biosynthesis in human sexual development

Both genes and hormones regulate human sexual development. Although ovarian hormones are not essential for female external genitalia development, male sexual development requires the action of testicular testosterone and dihydrotestosterone (DHT). DHT is the most active endogenous androgen formed by the conversion of testosterone in genital skin. This synthesis route from cholesterol to DHT is called the conventional classic pathway. Recent investigations have reported an alternative ("backdoor") route for DHT formation that bypasses fetal testicular testosterone. This alternative route plays a crucial role in human hyperandrogenic disorders like congenital adrenal hyperplasia caused by P450c21 deficiency, polycystic ovary syndrome, and P450 oxidoreductase deficiency. In addition, mutations in AKR1C2 and AKR1C4, genes encoding 3α-reductases, have been implicated in disorders of sexual development, indicating that both the classic and backdoor routes are required for normal human male sexual development. More recently, androsterone was found to be the primary androgen of the human backdoor route. Androsterone and steroidal substrates specific to the backdoor route are predominantly found in the placenta, liver, and adrenal glands rather than in the testes. These findings are essential to understanding human sexual development.

Efficacy and adverse events related to the initial dose of methimazole in children and adolescents with Graves’ disease

Purpose@#The first-line antithyroid drug for children and adolescents with Graves’ disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment. @*Methods@#We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: 0.7 mg/kg/day (group C; n=28). @*Results@#The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively). @*Conclusion@#The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.

Efficacy and adverse events related to the initial dose of methimazole in children and adolescents with Graves’ disease

Purpose@#The first-line antithyroid drug for children and adolescents with Graves’ disease (GD) is methimazole (MMI). This study evaluated the relationship between the initial MMI dose and the clinical course of GD after treatment. @*Methods@#We studied the efficacy of the initial MMI dose and the relationship between the initial MMI dose and adverse events (AEs). We retrospectively enrolled 22 males and 77 females and divided those subjects into 3 groups according to the initial dose of MMI: 0.7 mg/kg/day (group C; n=28). @*Results@#The mean time to the normalization of free thyroxine (fT4) levels upon initial treatment was 5.64, 8.61, and 7.98 weeks in groups A, B, and C, respectively (P=0.116). The incidence of liver dysfunction, neutropenia, and skin rash was 12.5%, 20.5%, and 42.9% in groups A, B, and C, respectively (P=0.018). Neutropenia, as a severe AE, was absent in group A, but its prevalence was 7.7% in group B and 21.4% in group C (P=0.015). When comparing only groups B and C, the incidences of liver dysfunction and neutropenia were higher in group C (P=0.04 and P=0.021, respectively). @*Conclusion@#The mean time to the normalization of fT4 levels did not differ among the 3 groups, but the incidence of AEs was higher in the groups that received high MMI doses. High doses of MMI (>0.7 mg/kg/day) should be reconsidered as an initial treatment for children and adolescents with GD.

Clinical Features of Severely Constipated Children: Comparison of Infrequent Bowel Movement and Fecal Soiling Groups / 대한소아소화기영양학회지

Biphenotypic acute leukemia or acute leukemia of ambiguous lineage in childhood: clinical characteristics and outcome

BACKGROUND: Acute leukemia (AL), not clearly assigned to myeloid, B-lymphoid, or T-lymphoid lineage, is classified as either biphenotypic acute leukemia (BAL) based on the European Group for Immunological Classification of Leukemias (EGIL) or acute leukemia of ambiguous lineage (ALAL) encompassing acute undifferentiated leukemia (AUL) and mixed-phenotype acute leukemia (MPAL) based on the World Health Organization (WHO) criteria. METHODS: Medical records of children newly diagnosed with BAL or ALAL, based on the EGIL or the 2008/2016 WHO criteria, respectively, admitted at Chonnam National University Hospital in 2001–2017 were retrospectively reviewed. RESULTS: Twelve (3.2%) of 377 AL patients satisfied the BAL or ALAL definitions based on the EGIL or the WHO criteria, respectively. Among 12 patients including 11 with BAL and another with undefined case based on the EGIL criteria, 7 (1.9%) had ALAL based on more stringent 2016 WHO criteria (AUL, 2; MPAL, 5). One patient had MPAL with t(9;22)(q34;q11.2), BCR-ABL+, and two had MLL gene abnormality. ALL-directed regimen was associated with better complete remission rate compared with AML-directed regimen (100.0% vs. 16.7%; P=0.015). The 5-year overall survival (OS) and event-free survival (EFS) were 51.1±15.8% and 51.9±15.7%, respectively. AUL was associated with poor OS and EFS compared with MPAL (0.0% vs. 75.0±21.7%; P=0.008). CONCLUSION: Due to the rarity of the cases, future multicenter, prospective studies incorporating large number of cases are urgently warranted to identify the clinical, biologic, and molecular markers for the prediction of prognosis and determine the best tailored therapy for each patient.

CLN6 Mutation in a Patient with Progressive Myoclonus Epilepsy / 대한소아신경학회지

Neuronal ceroid lipofuscinoses (NCLs) are inherited neurodegenerative disorders, which are caused by the accumulation of lipopigment in lysosomes. Variant forms of late infantile NCLs (vLINCLs) characterized by a later onset of seizures and visual impairment (3–8 years) than in the classic form (2–4 years) are caused by mutations of the gene encoding ceroid lipofuscinosis neuronal protein 6 (CLN6). In a girl with progressive myoclonus epilepsy, we found heterozygous variants of CLN6 (NM_017882.2; NP_060352.1): c.296A>G (p.Lys99Arg) and c.307C>T (p.Arg103Trp). They were identified with whole-exome sequencing and verified with Sanger sequencing. At 7 years and 9 months, our patient had developed multiple types of seizures, prominent myoclonus with photosensitivity, regression in motor and language skills, pyramidal and extrapyramidal signs, and brain atrophy in brain images, all of which were progressive and were compatible with vLINCLs. However, this first Korean report shows no visual impairment, which resembles the previously reported Japanese case.

Relationship of dental anxiety with oral health behavior and dental caries experience in adolescents / 대한구강보건학회지

OBJECTIVES: The purpose of this study was to examine the relationship of dental anxiety with oral health behavior and dental caries experience among adolescents. METHODS: The subjects were 469 teenagers (238 middle school students and 231 high school students) in 15 different schools located in 7 regions of Bucheon in Gyeonggi Province, Daejeon, and others. A survey and interviews were conducted to evaluate subjects' oral health behavior and dental anxiety. Dental anxiety was additionally assessed by Corah's Dental Anxiety Scale. The caries experience of subjects was examined. RESULTS: There were no regional differences in dental anxiety. Girls felt more dental anxiety than boys did. Adolescents who did not receive treatment even when they needed it felt more dental anxiety than those who did receive treatment. There were also statistically significant differences in dental anxiety according to the type of treatment received. Adolescents who received extraction treatment or underwent oral surgery experienced more dental anxiety than those who received orthodontic or aesthetic treatment. Those who had a toothache or who experienced gingival bleeding felt more dental anxiety than those who did not have those conditions. Subjects with poor perceived oral health also had more dental anxiety. The number of decayed teeth and filled teeth was significantly correlated with dental anxiety. CONCLUSIONS: In adolescents, dental anxiety is related to their oral health behavior, the type of conditions they present with, the treatment received, and dental caries experience. Therefore, the kind of systematic programs that could relieve adolescents of dental anxiety should be prepared.

Readmission risk factors for children admitted to pediatric intensive care unit with respiratory tract disease

PURPOSE: Children admitted to pediatric intensive care unit (PICU) with respiratory tract disease, often have a tendency to be readmitted to PICU with disease progression. We studied the risk factors for readmission to PICU, with respiratory disease progression. METHODS: Among 286 children admitted to Seoul St. Mary's Hospital PICU from April 2009 to March 2012, 129 children admitted with respiratory tract disease were enrolled. We grouped the children readmitted to PICU with respiratory tract disease progression within 2 weeks (readmission group), and the others (control group). We compared basic and respiratory tract disease characteristics at initial PICU admission between them, by retrospective chart review. RESULTS: Among 129 children, 8 were included in the readmission group, and 121 in the control group. Mortality and underlying disease incidence were higher in the readmission group (P=0.003 and P=0.033, respectively). The readmission group showed higher parenchymal lung disease incidence, and lower initial saturation by pulse oxymeter (SpO2)/fraction of inspiratory oxygen (FiO2), despite underlying disease influence (P=0.035 and P=0.041, respectively). Logistic regression on the underlying disease and respiratory variables showed no single factor with a significantly independent influence on readmission, but parenchymal lung disease had more independent influence. CONCLUSION: For PICU readmission with respiratory tract disease progression, parenchymal lung disease and lower initial SpO2/FiO2 can be a risk factor despite underlying disease influence. Underlying disease and each respiratory characteristic were not significantly independent risk factors, suggesting a correlation of factors. But, parenchymal lung disease can be a more independent risk factor.

Utilization of dental care among mothers and children from multicultural families / 대한구강보건학회지

OBJECTIVES: The purpose of this study was to identify the status of dental care utilization among mothers and children from multicultural families and analyzing the related factors. METHODS: The subjects in this study were 131 mothers from multicultural families and 175 mothers from Korean (control) families who were selected by convenience sampling from the city of Nonsan. The dental care utilization among mothers and children from multicultural families and mothers and children from Korean families were compared. A questionnaire survey was conducted using the self-administration method for mothers from Korean families and by a face-to-face interviewing method for mothers from multicultural families. RESULTS: The proportion of subjects who visited the dentist's office in the past year was not different between the two groups of mothers. However, this proportion was lower in children from multicultural families than those from Korean families. The factors that influenced the visit to dental clinics were age and spouse's age among multicultural mothers and age, spouse's age, personal perceptions about oral health, and oral health concerns among Korean mothers. The factors that influenced dental clinic visits were mother's career, household income, education level of the mother, children's age, mother's dental clinic visits, mother's perception of children's oral health among multicultural children and father's age, marriage duration of parents, children's age, mother's dental clinical visit, and the mother's concerns about children's oral health among Korean children. CONCLUSIONS: Multicultural children visit the dental clinic a lot less than Korean children. Social economic factors such as household income, education level affect the use of dental clinic services by multicultural families.

NCAM140 and pCREB Expression after Tianeptine Treatment of SH-SY5Y Cells

OBJECTIVE: Antidepressants Modulate Neuronal Plasticity. Tianeptine, An Atypical Antidepressant, Might Be Involved In The Restoration Of Neuronal Plasticity; It Primarily Enhances The Synaptic Reuptake Of Serotonin. Ncam140 Is Involved In Neuronal Development Processes, Synaptogenesis And Synaptic Plasticity. We Investigated The Effect Of Tianeptine On The Expression Of Ncam140 And Its Downstream Signaling Molecule In The Human Neuroblastoma Cell Line Sh-sy5y. METHODS: NCAM protein expression was measured in human neuroblastoma SH-SY5Y cells that were cultivated in serum-free media and treated with 0, 10, or 20 microM tianeptine for 6, 24, or 72 hours. NCAM140 expression in the tianeptine treatment group was confirmed by Western blot, and quantified through measurement of band intensity by absorbance. CREB and pCREB expression was identified after treatment with 20 microM tianeptine for 6, 24, and 72 hours by Western blot. RESULTS: Compared to cells treated for 6 hours, cells treated with 0 or 10 microM tianeptine for 72 hours showed a significant increase in NCAM140 expression and cells treated with 20 microM tianeptine showed a significant increase after 24 and 72 hours. The pCREB level in cells treated with 20 microM tianeptine increased in time-dependent manner. CONCLUSION: Our findings indicated that the tianeptine antidepressant effect may occur by induction of NCAM140 expression and CREB phosphorylation.

Relationship between restricted activity due to oral diseases and oral health behaviors among adolescents / 대한구강보건학회지

OBJECTIVES: The purpose of this study was to investigate the relationship between restricted activity due to oral diseases and oral health behaviors among adolescents. METHODS: A cross-sectional study design was used. The subjects were 238 middle school students and 231 high school students; a total of 469 students from 15 different schools located in 7 regions of Bucheon in Gyeonggi Province, Daejeon, and others. The adolescents who participated in the survey were chosen by convenience sampling. The association between restricted activities due to oral diseases and oral health behaviors was analyzed using multiple logistic regression analysis. RESULTS: The annual experience rate of oral diseases stood at 1.4 percent, while the number of days absent and early departures from school was 0.15 days per student. The rate of middle school students who were disturbed by oral disease with respect to sleep, eating, speaking, and/or schoolwork was 33.1 percent. In high school students, it was 40.6 percent. Dental pain and gingival bleeding were identified as major factors to the restriction of activities, and being disturbed while eating was related to cariogenic beverages. CONCLUSIONS: It would be of great social interest to support and promote oral health programs among adolescents. Therefore, a national survey of the status of activity restrictions due to oral diseases in adolescents should be implemented in order to make specific future plans.

Factors related to busyness of practicing dentists / 대한구강보건학회지

OBJECTIVES: This study investigated the busyness of dentists and analyzed factors related to busyness in these professionals. METHODS: The subjects were 243 practicing dentists. Surveys were carried out via mail. Busyness was measured by using the Mumma scale. The data were analyzed using the Kruskal-Wallis test. RESULTS: The dentists' busyness index was 1.91. Of the participants, 40% of practicing dentists wanted more patients, 30.8% did not overwork but did not want more patients, and 27.1% overworked and did not want more patients. The busyness index was significantly related to the number of dental hygienists and dentists. However, it did not differ with respect to the number of assistant nurses. CONCLUSIONS: The busyness index should be considered when developing relevant human resource plans.

The Use of Radionuclide Salivagram and Videofluoroscopic Swallow Study in the Evaluation of Aspiration Pneumonia in Children / 대한소아소화기영양학회지

PURPOSE: To compare the abilities of radionuclide salivagrams (RS) and videofluoroscopic swallow studies (VFSS) to diagnose aspiration in children with aspiration pneumonia. METHODS: The records of children who were referred to the Asan Medical Center between April, 2006 and April, 2012 and who underwent both VFSS and RS to evaluate their recurrent aspiration pneumonia were reviewed (n=67). The aspiration positivity rates of the two tests were determined. The agreement between the tests was assessed by using the kappa statistic. RESULTS: VFSS was more frequently positive (n=26, 39%) than RS (n=23, 34%) (p=0.68). In the 11 children who repeat two test, Repeated examination increased positive rate in each tests (n=11), repeated RS (54%, p=1) is more frequent positive than repeated VFSS (46%, p=0.37). If a cumulative positive test had been defined as at least one positive result, the positive rate of two test was 56% (p<0.05). There was a fair agreement between RS and VFSS (kappa=0.26). CONCLUSION: The RS and VFSS positivity rates in children with aspiration pneumonia were similar but there was fair agreement between the two tests. This result suggests that these investigations to demonstrate aspiration are not interchangeable but complementary.

Fatal Cases of 2009 Pandemic Influenza A (H1N1) in Korea

The aim of this study was to describe the features of deaths associated with the 2009 pandemic influenza A (H1N1) by 26 November 2009 in Korea. We collected standardized case reports on 115 confirmed deaths through a nationwide enhanced influenza surveillance system. The median age was 61 yr (interquartile range [IQR], 0.2-97 yr) and 58 (50.4%) were females. The case fatality rate was estimated as 16 per 100,000 cases. The age-related mortality rate had a J-shaped curve. Eighty-three patients (72.2%) had at least 1 underlying medical disease. Bacterial co-infections were detected in the blood or sputum specimens from 34 patients. Of the 63 patients who were hospitalized in the intensive care unit (ICU), the median time from symptom onset to hospital admission was 2 days (IQR, 0-22 days), and the median time from hospitalization to ICU admission was 1 day (IQR, 0-17 days). Neuraminidase inhibitors were administered to 100 patients (87.0%), 36% of whom began treatment within 2 days. In conclusion, fatal cases from the 2009 influenza A (H1N1) infection in Korea are mainly aged individuals with underlying disease, and associated with pneumonia, bacterial co-infections, and multi-organ failure.

Fatal Cases of 2009 Pandemic Influenza A (H1N1) in Korea

The aim of this study was to describe the features of deaths associated with the 2009 pandemic influenza A (H1N1) by 26 November 2009 in Korea. We collected standardized case reports on 115 confirmed deaths through a nationwide enhanced influenza surveillance system. The median age was 61 yr (interquartile range [IQR], 0.2-97 yr) and 58 (50.4%) were females. The case fatality rate was estimated as 16 per 100,000 cases. The age-related mortality rate had a J-shaped curve. Eighty-three patients (72.2%) had at least 1 underlying medical disease. Bacterial co-infections were detected in the blood or sputum specimens from 34 patients. Of the 63 patients who were hospitalized in the intensive care unit (ICU), the median time from symptom onset to hospital admission was 2 days (IQR, 0-22 days), and the median time from hospitalization to ICU admission was 1 day (IQR, 0-17 days). Neuraminidase inhibitors were administered to 100 patients (87.0%), 36% of whom began treatment within 2 days. In conclusion, fatal cases from the 2009 influenza A (H1N1) infection in Korea are mainly aged individuals with underlying disease, and associated with pneumonia, bacterial co-infections, and multi-organ failure.

Comparing Quantitative EEG and Low Resolution Electromagnetic Tomography Imaging between Deficit Syndrome and Non-Deficit Syndrome of Schizophrenia / 수면정신생리

OBJECTIVES: Deficit schizophrenia (DS) constitutes a disease separate from non-deficit schizophrenia (NDS). The aim of the current study was to compare the quantitative EEG and low resolution electromagnetic tomography (LORETA) imaging between DS and NDS. METHODS: This study was performed by 32 channels EEG for 42 schizophrenia patients who we categorized into DS and NDS using proxy instrument deficit syndrome (PDS). We performed the absolute power spectral analyses for delta, theta, alpha, low beta and high beta activities. We compared power spectrum between two groups using Independent t-test. Partial correlation test was performed with clinical parameters. Standardized LORETA (sLORETA) was used for comparison of cortical activity, and statistical nonparametric mapping (SnPM) was applied for the statistical analysis. RESULTS: DS showed significantly increased delta and theta absolute power in fontal and parietal region compared with NDS (p<0.05). Power spectrum showed significant correlation with 'anergia' and 'hostility/suspiciousness' subscale of brief psychiatric rating scale (BPRS)(p<0.05). sLORETA found out the source region (anterior cingulate cortex/limbic part) that delta activity was significantly increased in DS (p=0.042). CONCLUSIONS: DS showed different cortical activity compared with NDS. Our results may suggest QEEG and LORETA could be the marker in differentiating between DS and NDS.

One-year Outcome of Monocular Implant of Aspheric Multifocal IOL

PURPOSE: To evaluate near and far visual acuity, subjective visual symptoms, and patient satisfaction with a monocular implant of aspheric multifocal IOL (AMO Tecnis ZM900(R)). METHODS: Thirty eyes of 30 patients received phacoemulsifications and monocular implantation of Tecnis ZM900 IOL. The main outcome measures at postoperative 1 week, 1 month, 3 months, and 1 year were uncorrected and corrected near and distant visual acuity, refractory errors, contrast sensitivity, subjective visual symptoms (glare and halo), spectacle independency, and satisfaction. RESULTS: At a 3 month postoperative visit, the mean uncorrected near and distant visual acuities were 0.29+/-0.17 (logMAR) and 0.16+/-0.12 (logMAR),respectively. At 1 year, the mean uncorrected near and distant visual acuities were 0.25+/-0.17 (logMAR) and 0.11+/-0.08 (logMAR). Glare and halo decreased, and contrast sensitivity increased upon 1-year follow-up after monocular implantation of ZM900. Most patients (87%) were satisfied with their visual outcome. CONCLUSIONS: Monocular implantation of multifocal IOL Tecnis ZM900 shows stable surgical outcomes with a high satisfaction rate and enables a high rate of spectacle independency. Postoperative glare and halo, youth, and residual refractive error could be risk factors for dissatisfaction with monocular implantation of multifocal IOL Tecnis ZM900. Proper patient selection can lead to satisfying outcomes.

Epidemiology of Campylobacter jejuni Outbreak in a Middle School in Incheon, Korea

On July 6, 2009, an outbreak of gastroenteritis occurred among middle school students in Incheon. An investigation to identify the source and describe the extent of the outbreak was conducted. A retrospective cohort study among students, teachers, and food handlers exposed to canteen food in the middle school was performed. Using self-administered questionnaires, information was collected concerning on symptoms, days that canteen food was consumed, and food items consumed. Stool samples were collected from 66 patients and 11 food handlers. The catering kitchen was inspected and food samples were taken. Of the 791 people who ate canteen food, 92 cases became ill, representing an attack rate of 11.6%. Thirty-one (40.3%) of the 77 stool specimens were positive for Campylobacter jejuni. Interviews with kitchen staff indicated the likelihood that undercooked chicken was provided. This is the first recognized major C. jejuni outbreak associated with contaminated chicken documented in Korea.

Ocular Sarcoidosis in a Korean Population

The aim of current study was to evaluate the incidence and characteristics of ocular sarcoidosis in a Korean population. We conducted a retrospective study of 104 consecutive patients with biopsy-proven sarcoidosis seen at Asan Medical Center in Seoul, Korea, from 1993 to 2007. Medical records, photographs, and fluorescein angiograms were reviewed. Of 104 patients, 22 (21%) had intraocular involvement with female predominance (86%, M:F=3:19). Of the 39 eyes with ocular involvement, 16 (41%) eyes had isolated anterior uveitis, 12 (31%) eyes had intermediate uveitis, 6 eyes (15%) had panuveitis with retinal vasculitis, and 5 (13%) eyes had panuveitis with punched multifocal choroiditis. Mean duration of ophthalmologic follow-up was 62 months. All ocular inflammation was well managed with topical steroid and/or systemic steroid with relatively good final visual outcomes. Ocular complications such as cataract (12 eyes, 30%), glaucoma (6 eyes, 15%), vitreous opacity (1 eye, 3%), cystoid macular edema (3 eyes, 7%), neovascularization (2 eye, 5%), and epiretinal membrane (4 eye, 10%) were related to ocular sarcoidosis. In Korea, where sarcoidosis is very rare, our study indicates relatively low ocular and predominantly non posterior segment involvement with relatively good visual prognosis.

Ocular Sarcoidosis in a Korean Population

The aim of current study was to evaluate the incidence and characteristics of ocular sarcoidosis in a Korean population. We conducted a retrospective study of 104 consecutive patients with biopsy-proven sarcoidosis seen at Asan Medical Center in Seoul, Korea, from 1993 to 2007. Medical records, photographs, and fluorescein angiograms were reviewed. Of 104 patients, 22 (21%) had intraocular involvement with female predominance (86%, M:F=3:19). Of the 39 eyes with ocular involvement, 16 (41%) eyes had isolated anterior uveitis, 12 (31%) eyes had intermediate uveitis, 6 eyes (15%) had panuveitis with retinal vasculitis, and 5 (13%) eyes had panuveitis with punched multifocal choroiditis. Mean duration of ophthalmologic follow-up was 62 months. All ocular inflammation was well managed with topical steroid and/or systemic steroid with relatively good final visual outcomes. Ocular complications such as cataract (12 eyes, 30%), glaucoma (6 eyes, 15%), vitreous opacity (1 eye, 3%), cystoid macular edema (3 eyes, 7%), neovascularization (2 eye, 5%), and epiretinal membrane (4 eye, 10%) were related to ocular sarcoidosis. In Korea, where sarcoidosis is very rare, our study indicates relatively low ocular and predominantly non posterior segment involvement with relatively good visual prognosis.