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Background: Myocardial infarction (MI) is a medical emergency resulting from coronary artery occlusion. Patients with acute MI often experience disturbed sleep and circadian rhythm. Most previous studies assessed the premorbid sleep and circadian rhythm of patients with MI and their correlations with cardiovascular disease. However, little is known about post-MI sleep and circadian rhythm and their impacts on prognosis. The use of actigraphy with different algorithms to evaluate sleep and circadian rhythm after acute MI has the potential for predicting outcomes and preventing future disease progression., Objective: We aimed to evaluate how sleep patterns and disrupted circadian rhythm affect the prognosis of MI, using actigraphy and heart rate variability (HRV). Nonparametric analysis of actigraphy data was performed to examine the circadian rhythm of patients., Methods: Patients with MI in the intensive care unit (ICU) were enrolled alongside age- and gender-matched healthy controls. Actigraphy was used to evaluate sleep and circadian rhythm, while HRV was monitored for 24 hours to assess autonomic nerve function. Nonparametric indicators were calculated to quantify the active-rest patterns, including interdaily stability, intradaily variability, the most active 10 consecutive hours (M10), the least active 5 consecutive hours (L5), the relative amplitude, and the actigraphic dichotomy index. Follow-ups were conducted at 3 and 6 months after discharge to evaluate prognosis, including the duration of current admission, the number and duration of readmission and ICU admission, and catheterization. Independent sample t tests and analysis of covariance were used to compare group differences. Pearson correlation tests were used to explore the correlations of the parameters of actigraphy and HRV with prognosis., Results: The study included 34 patients with MI (mean age 57.65, SD 9.03 years) and 17 age- and gender-matched controls. MI patients had significantly more wake after sleep onset, an increased number of awakenings, and a lower sleep efficiency than controls. Circadian rhythm analysis revealed significantly lower daytime activity in MI patients. Moreover, these patients had a lower relative amplitude and dichotomy index and a higher intradaily variability and midpoint of M10, suggesting less sleep and wake activity changes, more fragmentation of the rest-activity patterns, and a more delayed circadian rhythm. Furthermore, significant correlations were found between the parameters of circadian rhythm analysis, including nighttime activity, time of M10 and L5, and daytime and nighttime activity SD , and patient prognosis., Conclusions: Patients with acute MI experienced significantly worse sleep and disturbed circadian rhythm compared with healthy controls. Our actigraphy-based analysis revealed a disturbed circadian rhythm, including reduced daytime activities, greater fluctuation in hourly activities, and a weak rest-activity rhythm, which were correlated with prognosis. The evaluation of sleep and circadian rhythm in patients with acute MI can serve as a valuable indicator for prognosis and should be further studied., (©Wei-Chih Chin, Pao-Hsien Chu, Lung-Sheng Wu, Kuang-Tso Lee, Chen Lin, Chien-Te Ho, Wei-Sheng Yang, I-Hang Chung, Yu-Shu Huang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 04.02.2025.)

Background: Adiposity rebound (AR) refers to the period during growth when the body mass index reaches its lowest point before increasing again. The timing of AR is associated with the development of obesity and puberty onset. Although studies have evaluated AR timing in Korean children, none has focused on children born small for gestational age (SGA)., Methods: This study analyzed data from a multicenter observational clinical trial (LG Growth Study) to determine AR timing in children born SGA without catch-up growth (CUG) who were treated with growth hormone (GH) therapy. The study also aimed to identify factors associated with AR timing, examine the influence of AR timing on puberty onset, and assess the effectiveness of GH therapy., Results: A total of 151 children born SGA without CUG were included. Of them, 15% experienced AR between 4 and 5 years of age, 42% between 5 and 6 years, 27% between 6 and 7 years, and 16% after 7 years of age. A significant positive correlation was noted between the height standard deviation score at the start of treatment and AR timing. However, no significant correlation was observed between AR timing and puberty onset or the effectiveness of GH therapy., Conclusion: This study provides insights into AR timing in prepubertal children who meet the specific SGA criteria and its relationship with growth outcomes. The findings suggest that AR in children born SGA who do not experience CUG occurs later than in the general population, with no significant relationship between AR timing and puberty onset or growth outcomes., Trial Registration: ClinicalTrials.gov Identifier: NCT01604395., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2025 The Korean Academy of Medical Sciences.)

In response to the increasing demands for net-zero carbon emissions in Taiwan and globally, this study explores the feasibility of implementing microgrid technologies in convenience stores to reduce carbon emissions. The study utilizes the commercial simulation tool HomerPro to evaluate the performance of integrating solar and wind power into microgrid systems, aligning with Taiwan's current priorities in renewable energy development. The analysis incorporates carbon pricing scenarios, grid reliability considerations, and financial variables such as discount and inflation rates. We simulated 256 system configurations to identify the most economically viable solutions under various conditions. The results indicate that integrating solar and wind energy into microgrid systems can significantly lower energy costs and carbon emissions, especially in high carbon-price scenarios. These benefits provide strong incentives for businesses to adopt carbon-neutral strategies. These findings provide valuable insights for policymakers and businesses, highlighting the critical role of reducing green power purchase prices in improving economic feasibility. Future research explores the impacts of integrating other renewable energy sources, offering broader technical support for achieving carbon neutrality., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author.)

Background: Patients with myocardial infarction (MI) can have disturbed sleep, but little is known about the efficacy of light therapy on sleep and prognosis of patients with MI. We conducted a randomized controlled study to investigate its efficacy., Material and Methods: This preliminary study included 34 patients with MI. They were randomized into the blue light and the white light groups during their stay in intensive care unit. 17 age and gender matched healthy controls were also enrolled. Actigraphy was used to evaluate objective sleep since enrollment. Delirium scales were used to screen delirium. Lab work-up including vitamin D level was performed at the baseline and discharge. We used Mann-Whitney U test or Wilcoxon signed-rank test to compare the difference between the MI group and the healthy control group, and the group difference after receiving light therapy., Results: Patients with MI had significantly lower vitamin D level than healthy controls (p<0.001). They also had significantly poorer sleep, as indicated by actigraphy parameters including sleep onset latency (p=0.01), sleep efficiency (p=0.002), wake after sleep onset (p<0.001) and awake times (p=0.002). No significant group difference was found by actigraphy after light therapy except a non-significant higher relative amplitude of the blue light group (p=0.061). Besides, vitamin D level of the blue light group increased significantly (p1=0.047, p2=0.045)., Conclusions: Patients with MI had poorer sleep, highlighting the needs to develop interventions. Significantly increased vitamin D level and a non-significant better rest-active rhythm after light therapy suggest its potential with sleep and prognosis which warrants further investigation., Competing Interests: Declaration of Competing Interest None of the authors have any financial interests or conflicts of interest relevant to this article to disclose., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Height at 3 years of age, when catch-up growth based on birth history is completed, is considered a major prognostic factor for predicting short stature, underweight, and growth faltering. However, too few large-scale studies have followed and analyzed height, weight, and body mass index (BMI) changes in children whose stature was short at 3 years of age. This study followed and compared the growth parameters (height, weight, and BMI) of children with short stature at 3 years of age and children with nonshort stature at 3 years of age for 6 years after birth using nationwide, population-based data., Methods: We retrospectively analyzed physical measurement data from the National Health Screening Program for Infants and Children for people born in 2011-2014 in Korea and followed to 2020. The data were provided by the National Health Insurance Service's customized data service. Growth parameters were compared using chi-square tests, Student t-tests, analyses of variance, and linear regressions., Results: Among 210,902 enrolled participants, 759 (0.4%) and 210,143 (99.6%) were in the short stature at 3 years group and the nonshort stature at 3 years group, respectively. In both sexes, height, weight, and BMI for 6 years after birth were significantly higher in the nonshort stature at 3 years group than in the short stature at 3 years group (P<0.0001). The BMI rebound was observed later than the standard period in the short stature at 3 years group., Conclusion: Early intervention and close follow-up are necessary to prevent persistent short stature and growth faltering in children with short stature at 3 years of age.

The Committee of Central Precocious Puberty of Korean Pediatrics and Adolescents of the Korean Society of Pediatric Endocrinology has newly developed evidence-based 2022 clinical practice guidelines for central precocious puberty in Korean children and adolescents. These guidelines provide the grade of recommendations, which includes both the strength of recommendations and the level of evidence. In the absence of sufficient evidence, recommendations are based on expert opinion. These guidelines have been revised and supplement the previous guidelines "Clinical Guidelines for Precocious Puberty 2011," and are drawn from a comprehensive review of the latest domestic and international research and the grade of recommendation appropriate to the domestic situation. This review summarizes the newly revised guidelines into 8 key questions and 27 recommendations and consists of 4 sections: screening, diagnosis, treatment, and long-term outcome of central precocious puberty.

Schizophrenia and affective disorder are two major complex mental disorders with high heritability. Evidence shows that rare variants with significant clinical impacts contribute to the genetic liability of these two disorders. Also, rare variants associated with schizophrenia and affective disorders are highly personalized; each patient may carry different variants. We used whole genome sequencing analysis to study the genetic basis of two families with schizophrenia and major depressive disorder. We did not detect de novo, autosomal dominant, or recessive pathogenic or likely pathogenic variants associated with psychiatric disorders in these two families. Nevertheless, we identified multiple rare inherited variants with unknown significance in the probands. In family 1, with singleton schizophrenia, we detected four rare variants in genes implicated in schizophrenia, including p.Arg1627Trp of LAMA2 , p.Pro1338Ser of CSMD1 , p.Arg691Gly of TLR4 , and Arg182X of AGTR2 . The p.Arg691Gly of TLR4 was inherited from the father, while the other three were inherited from the mother. In family 2, with two affected sisters diagnosed with major depressive disorder, we detected three rare variants shared by the two sisters in three genes implicated in affective disorders, including p.Ala4551Gly of FAT1 , p.Val231Leu of HOMER3 , and p.Ile185Met of GPM6B . These three rare variants were assumed to be inherited from their parents. Prompted by these findings, we suggest that these rare inherited variants may interact with each other and lead to psychiatric conditions in these two families. Our observations support the conclusion that inherited rare variants may contribute to the heritability of psychiatric disorders.

Understanding the distribution of pathogens causing acute febrile illness (AFI) is important for clinical management of patients in resource-poor settings. We evaluated the proportion of AFI caused by specific pathogens among outpatients in Bangladesh. During May 2019-March 2020, physicians screened patients aged ≥2 years in outpatient departments of four tertiary level public hospitals. We randomly enrolled patients having measured fever (≥100.4°F) during assessment with onset within the past 14 days. Blood and urine samples were tested at icddr,b through rapid diagnostic tests, bacterial culture, and polymerase chain reaction (PCR). Acute and convalescent samples were sent to the Centers for Disease Control and Prevention (USA) for Rickettsia and Orientia (R/O) and Leptospira tests. Among 690 patients, 69 (10%) had enteric fever (Salmonella enterica serotype Typhi orSalmonella enterica serotype Paratyphi), 51 (7.4%) Escherichia coli, and 28 (4.1%) dengue detected. Of the 441 patients tested for R/O, 39 (8.8%) had rickettsioses. We found 7 (2%) Leptospira cases among the 403 AFI patients tested. Nine patients (1%) were hospitalized, and none died. The highest proportion of enteric fever (15%, 36/231) and rickettsioses (14%, 25/182) was in Rajshahi. Dhaka had the most dengue cases (68%, 19/28). R/O affected older children and young adults (IQR 8-23 years) and was detected more frequently in the 21-25 years age-group (17%, 12/70). R/O was more likely to be found in patients in Rajshahi region than in Sylhet (aOR 2.49, 95% CI 0.85-7.32) between July and December (aOR 2.01, 1.01-5.23), and who had a history of recent animal entry inside their house than not (aOR 2.0, 0.93-4.3). Gram-negative Enterobacteriaceae were the most common bacterial infections, and dengue was the most common viral infection among AFI patients in Bangladeshi hospitals, though there was geographic variability. These results can help guide empiric outpatient AFI management., Competing Interests: The authors have declared that no competing interests exist.

Pediatric narcolepsy is a chronic sleep-wakefulness disorder. Its symptoms frequently begin in childhood. This review article examined the literature for research reporting on the effects of treatment of pediatric narcolepsy, as well as proposed etiology and diagnostic tools. Symptoms of pediatric narcolepsy include excessive sleepiness and cataplexy. In addition, rapid-eye-movement-related phenomena such as sleep paralysis, sleep terror, and hypnagogic or hypnapompic hallucinations can also occur. These symptoms impaired children's function and negatively influenced their social interaction, studying, quality of life, and may further lead to emotional and behavioral problems. Therefore, early diagnosis and intervention are essential for children's development. Moreover, there are differences in clinical experiences between Asian and Western population. The treatment of pediatric narcolepsy should be comprehensive. In this article, we review pediatric narcolepsy and its treatment approach: medication, behavioral modification, and education/mental support. Pharmacological treatment including some promising newly-developed medication can decrease cataplexy and daytime sleepiness in children with narcolepsy. Other forms of management such as psychosocial interventions involve close cooperation between children, school, family, medical personnel, and can further assist their adjustment.

Murine typhus, which is caused by Rickettsia typhi, has a wide range of clinical manifestations. It has a low mortality rate but may result in meningoencephalitis and interstitial pneumonia in severe cases. Comparisons of complete genome sequences of R. typhi isolates from North Carolina, USA (Wilmington), Myanmar (B9991PP), and Thailand (TH1527) identified only 26 single nucleotide polymorphism (SNP) and 7 insertion-deletion (INDEL) sites in these highly syntenic genomes. Assays were developed to further define the distribution of these variant sites among 15 additional isolates of R. typhi with different histories from Asia, the USA, and Africa. Mismatch amplification mutation assays (MAMA) were validated for 22 SNP sites, while the 7 INDEL sites were analyzed directly on agarose gels. Six SNP types, 9 INDEL types, 11 total types were identified among these 18 isolates. Replicate DNA samples as well as comparisons of isolates with different passage and source histories gave consistent genetic typing profiles. Comparison of the SNP and INDEL markers to R. typhi's nearest neighbor Rickettsia prowazekii demonstrated that the majority of the SNPs represent intra-species variation that arose post divergence of these two species while several INDEL sites also exhibited intraspecies variability among the R. prowazekii genomes that have been completely sequenced. The assays for the presence of these SNP and INDEL sites, particularly the latter, comprise a low technology gel method for consistently distinguishing R. typhi and R. prowazekii as well as for differentiating genetic types of R. typhi., Competing Interests: The authors have declared that no competing interests exist.

Clinical and laboratory diagnosis of rickettsial diseases is challenging because of the undifferentiated symptoms (commonly fever, headache, and malaise) and low bacteremia (< 100 genomic copies [gc]/mL) during the early acute stage of illness. Early treatment with doxycycline is critical for a positive outcome, especially in Rickettsia rickettsii (Rocky Mountain spotted fever) infections where cases may be fatal within 5 to 10 days from symptom onset, emphasizing the need for more sensitive diagnostics. A real-time reverse transcriptase polymerase chain reaction (PCR) assay, RCKr, was developed and validated for Rickettsia spp. nucleic acid detection in human clinical samples. The limit of detection for RCKr was determined to be 20 gc/mL, compared with our 2013 (Kato et al.) laboratory developed test, PanR8 at 1,800 to 2,000 gc/mL. Inclusivity, exclusivity, accuracy, and precision results correlated as expected. From an evaluation of 49 banked clinical samples, RCKr detected 35 previously positive samples, as well as two specimens that were PanR8 real-time PCR negative yet clinically diagnosed as possible rickettsiosis. Ct values from RCKr clinical sample testing show a 100-fold increase relative to PanR8. Additional testing is needed to understand the clinical sensitivity of RCKr; however, this study demonstrates RCKr to have high analytical specificity and sensitivity for Rickettsia detection.

Background: Despite the importance of and social concern regarding prevention of diabetes at younger ages, limited data are available. This study sought to analyze changes in the prevalence of type 2 diabetes mellitus (T2DM) in Koreans younger than 30 years according to sex, age, and level of income., Methods: The dataset analyzed in this study was derived from health insurance claims recorded in the National Health Insurance Service (NHIS) database. Participants' level of income was categorized as low (quintile 1, <20% of insurance premium) or others (quintile 2-5)., Results: In males and females, the prevalence of T2DM per 10,000 people steadily increased from 2.57 in 2002 to 11.41 in 2016, and from 1.96 in 2002 to 8.63 in 2016. The prevalence of T2DM in girls was higher in the age group of 5 to 14 years. Even though the prevalence was higher among those older than 20 years, the increase had started earlier, in the early 2000s, in younger age group. Adolescents aged 10 to 19 years in low-income families showed a remarkable increase in prevalence of T2DM, especially in boys., Conclusion: The prevalence of T2DM in young Koreans increased more than 4.4-fold from 2002 to 2016, and the increase started in the early 2000s in younger age groups and in low-income families. This is the first study to examine the trend in prevalence of T2DM in children, adolescents, and young adults in Korea. Future studies and collaborations with social support systems to prevent T2DM at an early age group should be performed.

Background: Coronavirus disease 2019 (COVID-19) is generally asymptomatic or mild in otherwise healthy children, however, severe cases may occur. In this study, we report the clinical characteristics of children classified as critical COVID-19 in Korea to provide further insights into risk factors and management in children., Methods: This study was a retrospective case series of children < 18 years of age classified as critical COVID-19. Cases were identified by the Korea Disease Control and Prevention Agency surveillance system and medical records were reviewed. Critical COVID-19 was defined as cases with severe illness requiring noninvasive (high flow nasal cannula, continuous positive airway pressure, or bilevel positive airway pressure) or invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) or continuous renal replacement therapy (CRRT), between January 20, 2020 and October 7, 2021., Results: Among 39,146 cases diagnosed with COVID-19 in subjects < 18 years of age, eight cases (0.02%) were identified as critical COVID-19. The median age was 13 years (range 10 month-17 years) and male-to-female ratio was 1:1. Three children had underlying diseases; one child has asthma and major depressive disorder, one child had Lennox-Gastaut syndrome and one child had mental retardation and was newly diagnosed with type 2 diabetes mellitus with the diagnosis of COVID-19. Among the eight children, seven were obese (body mass index range [BMI] median 29.3, range 25.9-38.2, weight-for-length > 97% for infant) and one was overweight (BMI 21.3). All patients had fever, six patients had dyspnea or cough and other accompanied symptoms included sore throat, headache, lethargy and myalgia. Radiologic findings showed pneumonia within 1-8 days after symptom onset. Pneumonia progressed in these children for 2-6 days and was improved within 5-32 days after diagnosis. Among the eight critical cases, remdesivir was administered in six cases. Steroids were provided for all cases. Inotropics were administered in one case. Six cases were treated with noninvasive mechanical ventilator and three required mechanical ventilator. One case required ECMO due to acute respiratory distress syndrome. All cases were admitted to the intensive care unit and admission period ranged from 9-39 days. Among all critical COVID-19 cases < 18 years of age, there were no fatal cases., Conclusion: To develop appropriate policies for children in the COVID-19 pandemic, it is important to monitor and assess the clinical burden in this population., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Ehrlichiosis, caused by Gram-negative bacteria of the genus Ehrlichia, is considered an emerging infectious disease due to the increasing number of reported cases. Symptoms are non-specific and occur within 1 to 2 weeks following the bite of an infected tick. Confirmatory laboratory diagnostic methods vary in sensitivity and specimen requirements, which can lead to delayed diagnosis. PCR testing serves as an efficient approach to Ehrlichia confirmation in the acute stage of illness. Published assays have been effectively used to detect human ehrlichiosis at limit of detections ranging from 10 to 50 genomic copies (GC) of Ehrlichia DNA. With the discovery of new species capable of human infection, we wanted to develop assays that are sensitive and encompass a wide range of Ehrlichia. Here we developed and validated two sensitive and specific real-time PCR assays (PanE1 and PanE2) for the detection of Ehrlichia species, as well as two real-time PCR assays (ECh2 and ECh4) for the detection of Ehrlichia chaffeensis, specifically. The limit of detection was determined to be 10 GC per reaction with 100% confidence, and as little as 1 GC with lower efficiencies. Accuracy was assessed at 100% correlation. Specificity from exclusivity testing demonstrated that neither the Ehrlichia species assays (n = 60), nor the E. chaffeensis specific assays (n = 64) had cross reactivity with near neighbors or environmental bacteria. A positive predictive value of 100% and a negative predictive value of ≥93% was determined by evaluating banked clinical specimens from 62 patients with the assays. These real-time PCR assays are effective tools to detect human Ehrlichia species during the acute stage of illness. Early detection of Ehrlichia infection by these real-time PCR assays can facilitate diagnosis and treatment., (Copyright © 2021. Published by Elsevier B.V.)

Background: Children experience seasonal variations in growth whereby height increases most in spring and least in autumn, and weight increases least in spring and most in autumn. We hypothesized that activity restriction caused by efforts to contain the spread of coronavirus disease 2019 (COVID-19) would result in increased body mass index (BMI) in children, differing from conventional seasonal growth variations., Methods: We included 169 children who visited endocrine clinics of three hospitals in Korea at regular intervals under the same conditions for two years. Visit dates were D1 (January, 2019), D2 (July, 2019), D3 (January, 2020) before the COVID-19 outbreak, and D4 (July, 2020) during the pandemic. Differences in the z-score for height (HT), weight (WT), and BMI among time points and between spring seasons (i.e., S1-S3) were compared., Results: There were significant differences in BMIz among time points, which decreased from D1-D2 and increased from D2-D3 and D3-D4. WTz significantly increased from D2-D3 and D3-D4. BMIz values of S1 (spring 2019) and S3 (spring 2020) were -0.05 and 0.16, respectively, showing significant differences. WTz values between S1 and S3 were significantly different (-0.02 vs. 0.13)., Conclusions: In 2019, there were conventional seasonal variations in BMIz, which declined in spring and increased in autumn, while in 2020, BMIz increased even in spring. The COVID-19 pandemic may have affected seasonal variations in the growth of children attending endocrine clinics.

Portions of northern Mexico are experiencing a re-emergence of Rocky Mountain spotted fever (RMSF), a tickborne disease caused by Rickettsia rickettsii, a member of the spotted fever group of rickettsiae (SFGR). Infection with R. rickettsii can result in serious and life-threatening illness in people and dogs. Canine seroprevalence has been used as a sentinel for human RMSF in previous studies. This study aims to quantify SFGR seroprevalence in canines in three northern Mexican states and identify risk factors associated with seropositivity. A total of 1,136 serum samples and 942 ticks were obtained from dogs participating in government sterilization campaigns and from animal control facilities in 14 Mexican cities in three states. SFGR antibodies were detected using indirect immunofluorescence antibody assays at titre values ≥1/64. Six per cent (69 dogs) showed antibodies to SFGR, with the highest seroprevalence reported in Baja California (12%), Coahuila (4%) and Sonora (4%). Dogs from Baja California had three times higher odds of having SFGR antibodies compared to dogs from Sonora (OR = 3.38, 95% CI, 1.81-6.37). Roughly one quarter (25%) of surveyed dogs were parasitized by ticks (Rhipicephalus sanguineus sensu lato) at the time of sample collection. A portion of collected ticks were tested for rickettsial DNA using polymerase chain reaction. Positive samples were then sequenced, showing evidence of SFGR including R. massiliae, R. parkeri and R. rickettsii. Dogs that spent the majority of time on the street, such as free-roaming or community-owned dogs, showed a greater risk of tick infestation, seropositivity, bearing seropositive ticks, and may play a pivotal role in the spread of SFGR among communities. Estimating the seroprevalence of SFGR in the canine population can help public health campaigns target high-risk communities for interventions to reduce human RMSF cases., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Bacillus subtilis strain natto VK161 was selected for its high production of vitamin K 2 Its genome was sequenced and annotated in the Department of Energy-Joint Genome Institute (DOE-JGI) annotation pipeline. It resulted in a chromosome of 4,073,396 bp, which is composed of 4,332 protein-coding genes, 23 rRNA genes, and 77 tRNA genes., (Copyright © 2019 Parks et al.)

The vaginal bacterial strain AB70, belonging to the species Lactobacillus crispatus , was isolated from a vaginal swab from a healthy pregnant Korean woman. Here, we report the 2.37-Mb complete genome sequence of this strain., (Copyright © 2019 Chang et al.)

Purpose: It is well known that obesity is related to vitamin D deficiency (VDD). We investigated the response to vitamin D replacement in normal-weight and overweight children., Methods: This was a prospective study including 62 Korean children with VDD. VDD was defined as a serum 25-hydroxycholecalciferol (25(OH)D) concentration &lt;20 ng/mL. Overweight was defined as a body mass index (BMI)≥the 85th percentile (n=21), and normal weight as a BMI between the 5th and 84th percentiles (n=41). All participants received vitamin D3 supplementation (2,000 IU/day) for 8 weeks. The serum levels of 25(OH)D, PTH and biochemical parameters were measured before and after treatment., Results: The mean age was 10.0±1.4 years in normal-weight children and 10.0±2.1 years in overweight children (P=0.93). After 8 weeks of treatment, 61.9% of normal-weight children and 47.6% of overweight children achieved vitamin D sufficiency (P =0.30). The mean serum 25(OH)D levels after vitamin D replacement were 33.8±7.6 ng/mL and 30.3±6.6 ng/mL in normal-weight and overweight children, respectively (P =0.10). The mean calcium/creatinine ratios after treatment were 0.09±0.07 and 0.08±0.06 in the normal-weight and overweight groups, respectively, and no hypercalciuria was found. In multiple regression analysis, the response to vitamin D replacement was influenced by the BMI (β=-1.0, P=0.03) and sex (β=-4.0, P=0.04)., Conclusion: Eight weeks of vitamin D replacement (2,000 IU/day) is sufficient to overcome vitamin D deficiency in normal-weight and overweight children without any complications.

Purpose: The standard method used to diagnose central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test (GnRHST). However, this test is inconvenient for children because it is time-consuming and requires multiple samples. This study aimed to determine the reliability of morning unstimulated luteinizing hormone (mLH) level when screening for CPP, with an emphasis on the influence of diurnal variation., Methods: This study included 160 girls with signs of early puberty (SMR 2) under 8 years of age. They were classified as CPP or non-CPP based on their standard GnRHST. The auxological, biochemical, and hormonal characteristics of subjects were retrospectively evaluated. The prognostic value of single morning unstimulated gonadotropin level was examined for use in CPP screening., Results: Of 160 patients, 121 (75.6%) presented with CPP, and 39 (24.4%) were determined to be prepubertal. The mLH/mFSH (morning unstimulated follicular stimulating hormone) ratio showed significant differences between the 2 groups (P&lt;0.001). The mLH was correlated with GnRHST variables (r=0.532, P&lt;0.001). The mLH cutoff point when screening for CPP was 0.22 IU/L, which had sensitivity and specificity of 69.4% and 82.1%, respectively. In regression analysis, bone age (BA) (odds ratio [OR], 1.018; 95% confidence interval [CI], 0.967-1.071; P=0.506) and body mass index (BMI) (OR, 0.874; 95% CI, 0.583-1.310; P=0.515) were not significant predictors. The mLH≥0.22 IU/L group (OR, 9.596; 95% CI, 3.853-23.900; P&lt;0.001) was highly suggestive of CPP., Conclusion: In this study, single morning unstimulated luteinizing hormone had clinical efficacy for CPP screening, but BA advanced over chronological age and BMI was not useful for CPP screening.

One branch of the radial nerve to the medial head of the triceps brachii muscle (MHN) has been described as accompanying or joining the ulnar nerve. Mostly two MHN branches have been reported, with some reports of one; however, the topographical anatomy is not well documented. We dissected 52 upper limbs from adult cadavers and found one, two, and three MHN branches in 9.6%, 80.8%, and 9.6% of cases, respectively. The MHN accompanying the ulnar nerve was always the superior MHN. The relationship between the ulnar nerve and the MHN was classified into four types according to whether the MHN was enveloped along with the ulnar nerve in the connective tissue sheath and whether it was in contact with the ulnar nerve. It contacted the ulnar nerve in 75.0% of cases and accompanied it over a mean distance of 73.6 mm (range 36-116 mm). In all cases in which the connective tissue sheath enveloped the branch of the MHN and the ulnar nerve, removing the sheath confirmed that the MHN branch originated from the radial nerve. The detailed findings and anatomical measurements of the MHN in this study will help in identifying its branches during surgical procedures. Clin. Anat. 00:1-16, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Thyroid hormone (T3) and its receptor (TR) are involved in cancer progression. While deregulation of long non-coding RNA (lncRNA) expression has been detected in many tumor types, the mechanisms underlying specific involvement of lncRNAs in tumorigenicity remain unclear. Experiments from the current study revealed negative regulation of BC200 expression by T3/TR. BC200 was highly expressed in hepatocellular carcinoma (HCC) and effective as an independent prognostic marker. BC200 promoted cell growth and tumor sphere formation, which was mediated via regulation of cell cycle-related genes and stemness markers. Moreover, BC200 protected cyclin E2 mRNA from degradation. Cell growth ability was repressed by T3, but partially enhanced upon BC200 overexpression. Mechanistically, BC200 directly interacted with cyclin E2 and promoted CDK2-cyclin E2 complex formation. Upregulation of cell cycle-related genes in hepatoma samples was positively correlated with BC200 expression. Our collective findings support the utility of a potential therapeutic strategy involving targeting of BC200 for the treatment of HCC.

In the present study, the screening of Mirabegron (MBR) co-amorphous was performed to produce water-soluble and thermodynamically stable MBR co-amorphous with the purpose of overcoming the water solubility problem of MBR. MBR is Biopharmaceutics Classification System (BCS) class II drug used for the treatment of an overreactive bladder. The co-amorphous screening was carried out by means of the vacuum evaporation crystallization technique in methanol solvent using three water-soluble carboxylic acids, characterized by a pKa difference greater than 3 with MBR such as fumaric acid (FA), l-pyroglutamic acid (PG), and citric acid (CA). Powder X-ray diffraction (PXRD) results suggested that all solid materials produced at MBR-FA (1 equivalent (eq.)/1 equivalent (eq.)), MBR-PG (1 eq./1 eq.), and MBR-CA (1 eq./1 eq.) conditions were amorphous state solid materials. Furthermore, by means of solution-state nuclear magnetic resonance (NMR) (¹H, 13 C, and 2D) and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, we could assess that MBR and carboxylic acid molecules were linked via ionic interactions to produce MBR co-amorphous. Besides, solid-state cross polarization (CP)/magic angle spinning (MAS) 13 C-NMR analysis was conducted for additional assessment of MBR co-amorphous. Afterwards, dissolution tests of MBR co-amorphouses, MBR crystalline solid, and MBR amorphous were carried out for 12 h to evaluate and to compare their solubilities, dissolution rates, and phase transformation phenomenon. Here, the results suggested that MBR co-amorphouses displayed more than 57-fold higher aqueous solubility compared to MBR crystalline solid, and PXRD monitoring result suggested that MBR co-amorphouses were able to maintain their amorphous state for more than 12 h. The same results revealed that MBR amorphous exhibited increased solubility of approximatively 6.7-fold higher compared to MBR crystalline solid. However, the PXRD monitoring result suggested that MBR amorphous undergo rapid phase transformation to crystalline form in just 35 min and that within an hour all MBR amorphous are completely converted to crystalline solid. Accordingly, the increase in MBR co-amorphous' solubility was attributed to the presence of ionic interactions in MBR co-amorphous molecules. Moreover, from the differential scanning calorimetry (DSC) monitoring results, we predicted that the high glass transition temperature ( T g ) of MBR co-amorphous compared to MBR amorphous was the main factor influencing the phase stability of MBR co-amorphous.

Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma. Currently, only a few gene rearrangements have been linked to ALK-negative ALCL progression. However, the specific molecular mechanisms underlying the growth of ALK-negative ALCL tumors remain unclear. Here, we investigated aberrantly expressed, long non-coding RNAs (lncRNAs) in ALK-negative ALCL and assessed their potential biological function. MIR503HG ( miR-503 host gene) was highly expressed in ALK-negative cell lines and was significantly upregulated in tumors in mice formed from ALK-negative ALCL cell lines. Depletion of MIR503HG suppressed tumor cell proliferation in vivo and in vitro; conversely, its overexpression enhanced tumor cell growth. MIR503HG -induced proliferation was mediated by the induction of microRNA-503 ( miR - 503 ) and suppression of Smurf2, resulting in stabilization of the tumor growth factor-β receptor (TGFBR) and enhanced tumor cell growth. Collectively, these findings support a potential role for MIR503HG in cancer cell proliferation through the miR-503 /Smurf2/TGFBR axis and indicate that MIR503HG is a potential marker in ALK-negative ALCL., Competing Interests: The authors declare no conflict of interest.

Cancer cells display altered glucose metabolism characterized by a preference for aerobic glycolysis. The aerobic glycolytic phenotype of hepatocellular carcinoma (HCC) is often correlated with tumor progression and poorer clinical outcomes. However, the issue of whether glycolytic metabolism influences metastasis in HCC remains unclear. In the current study, we showed that knockdown of taurine up-regulated gene 1 (TUG1) induces marked inhibition of cell migration, invasion, and glycolysis through suppression of microRNA (miR)-455-3p. MiR-455-3p, which is transcriptionally repressed by p21, directly targets the 3' untranslated region of adenosine monophosphate-activated protein kinase subunit beta 2 (AMPKβ2). The TUG1/miR-455-3p/AMPKβ2 axis regulates cell growth, metastasis, and glycolysis through regulation of hexokinase 2 (HK2). TUG1 is clearly associated with HK2 overexpression and unfavorable prognosis in HCC patients., Conclusion: Our data collectively highlight that novel regulatory associations among TUG1, miR-455-3p, AMPKβ2, and HK2 are an important determinant of glycolytic metabolism and metastasis in HCC cells and support the potential utility of targeting TUG1/HK2 as a therapeutic strategy for HCC. (Hepatology 2018;67:188-203)., (© 2017 by the American Association for the Study of Liver Diseases.)

Thyroid hormone, 3,3',5-triiodo-l-thyronine (T 3 ), mediates several physiological processes, including embryonic development, cellular differentiation and cell proliferation, via binding to its nuclear thyroid receptors (TR). Previous microarray and Chromatin immunoprecipitation (ChIP)-on-ChIP analyses have revealed that interferon-stimulated gene 20 kDa (ISG20), an exoribonuclease involved in the antiviral function of interferon, is up-regulated by T 3 in HepG2-TR cells. However, the underlying mechanisms of ISG20 action in tumor progression remain unknown to date. Here, we verified induction of ISG20 mRNA and protein expression by T 3 in HepG2-TR cells. Based on the ChIP-on-ChIP database, potential thyroid hormone responsive element of the ISG20 promoter region was predicted, and the result confirmed with the ChIP assay. Functional assays showed that forced expression of ISG20 leads to significant promotion of metastasis and angiogenesis, both in vitro and in vivo. Furthermore, the angiogenic-related protein, interleukin-8 (IL-8), was up-regulated through a T 3 -mediated increase in ISG20, as determined using a human angiogenesis array kit. Induction of IL-8 signaling activated the p-JAK2/p-STAT3 pathway, in turn, leading to promotion of tumor metastasis and angiogenesis. Furthermore, ISG20 overexpression in hepatocellular carcinoma (HCC) specimens was positively correlated with clinical parameters, including vascular invasion, α-fetoprotein and tumor size. Higher ISG20 expression was significantly correlated with poorer recurrence-free survival in HCC patients. Our results collectively indicate higher TR-dependent expression of ISG20 in a subset of HCC, supporting an oncogenic role in HCC progression., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

African tick bite fever is the most commonly encountered travel-associated rickettsiosis, occurring in as many as 5% of travelers returning from rural subequatorial Africa. This case report illustrates that rifampin represents an effective alternative to doxycycline for treatment of African tick bite fever in some selective situations., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose: Pubertal gonadotropin secretion shows circadian pattern and the luteinizing hormone (LH) levels tend to rise in later stages of puberty in girls. We studied the usefulness of basal LH in the evaluation of central precocious puberty with emphasis on the influence of sampling time., Methods: Medical records of 334 girls that underwent gonadotropin-releasing hormone stimulation test (GnRHST) were reviewed. Auxological and laboratory data were compared between those with early morning (EM, before 10 AM) and late morning/afternoon (LM/A, after 10 AM) basal samples., Results: Among those in sexual maturity rating (SMR) 2, EM samples showed higher basal LH (P=0.004) compare to LM/A samples, whereas those in SMR 3 showed no difference in LH levels between EM and LM/A samples. Among girls with pubertal response, EM group showed higher basal LH (P=0.031) and follicular stimulating hormone (P=0.008) than LM/A group. The EM basal LH was more closely related with the peak stimulated LH than the LM/A basal LH did (rs=0.871 vs. rs=0.524). The optimal basal LH cutoffs to predict a pubertal response to GnRHST were 0.11 IU/L with a sensitivity of 66.7% and a specificity of 78.7% in EM group, and 0.07 IU/L with a sensitivity of 60.0% and a specificity of 78.9% in LM/A group, respectively., Conclusions: In girls with early stages of puberty, EM basal LH is a more sensitive screening tool than the LM/A basal LH. Diurnal variation should be considered in evaluating children with precocious puberty.

Glioma is the most common and aggressive type of brain tumor. While long non-coding RNAs (lncRNAs) are clearly more abundant in human brain than protein-coding genes, the specific roles of lncRNAs and mechanisms underlying their dysregulation in glioma remain unclear. Here, we focused on lncRNAs that are differentially expressed in brain tumor and their potential biological functions. LOC441204, a novel non-coding RNA gene displaying high expression in clinical specimens of brain tumor and significant upregulation in glioma cell lines in microarray analyses, was selected for further study. Notably, knockdown of LOC441204 suppressed tumor cell proliferation in two glioma cell lines. Moreover, LOC441204-induced tumor cell growth was mediated the stabilization of β-catenin pathway. Briefly, LOC441204 bound to β-catenin preventing its degradation, resulting in downstream p21 repression and cdk4 activation to enhance glioma cell proliferation. Collectively, our findings indicate a pro-oncogenic role of LOC441204 in tumor cell growth through activation of the β-catenin/p21/cdk4 cascade to act as a potential diagnostic marker or therapeutic target in brain tumor.

Anaplastic large-cell lymphoma (ALCL) is a rare type of highly malignant, non-Hodgkin lymphoma (NHL). Currently, only studies on the chimeric oncogene NPM-ALK have reported a link to ALCL progression. However, the specific molecular mechanisms underlying the invasion of ALCL are still unclear. Here, we sought to investigate differentially expressed, long non-coding RNAs (lncRNAs) in ALCL and their potential biological function. Our microarray analyses revealed that LINC01013, a novel non-coding RNA gene, was highly expressed in clinical specimens of ALCL and was significantly upregulated in invasive ALCL cell lines. Knockdown of LINC01013 suppressed tumor cell invasion; conversely, its overexpression enhanced tumor cell invasion. LINC01013-induced invasion was mediated by activation of the epithelial-to-mesenchymal transition (EMT)-associated proteins, snail and fibronectin. Specifically, LINC01013 induced snail, resulting in activation of fibronectin and enhanced ALCL cell invasion. Collectively, these findings support a potential role for LINC01013 in cancer cell invasion through the snail-fibronectin activation cascade and suggest that LINC01013 could potentially be utilized as a metastasis marker in ALCL.

Most patients diagnosed with takotsubo cardiomyopathies are expected to almost completely recover, and their prognosis is excellent. However, complications can occur in the acute phase. We present a case of a woman with takotsubo cardiomyopathy with right ventricular involvement who developed a rupture of the right ventricular free wall following ventricular septal rupture, as a consequence of an acute increase in right ventricular afterload by left-to-right shunt. Our case report illustrates that takotsubo cardiomyopathy can be life threatening in the acute phase. Ventricular septal rupture in biventricular takotsubo cardiomyopathy may be a harbinger of cardiac tamponade by right ventricular rupture., Competing Interests: The authors have no financial conflicts of interest.

Introduction: The aim of this study was to clarify the morphological characteristics of the intermuscular aponeurosis between the flexor carpi ulnaris (FCU) and flexor digitorum superficialis (FDS; IMAS), and that between the FCU and flexor digitorum profundus (FDP; IMAP), and their topographic relationships with the ulnar nerve., Materials and Methods: Fifty limbs of 38 adult cadavers were studied., Results: The IMAS extended along the deep surface of the FCU adjoining the FDS, having the appearance of a ladder, giving off "steps" that decreased in width from superficial to deep around the middle of the forearm. Its proximal part divided into two bands connected by a thin membrane, and was attached to the medial epicondyle and the tubercle (the most medial prominent part of the coronoid process of the ulna), respectively. The IMAP extended deep between the FCU and FDP from the antebrachial fascia, and its distal end was located on the posterior border of the FCU. The IMAP became broader toward its proximal part, and its proximal end was attached anterior and posterior to the tubercle and the olecranon, respectively. The ulnar nerve passed posterior to the medial epicondyle and then medial to the tubercle, and was crossed by the deep border of the IMAS at 58.3 ± 14.1 mm below the medial epicondyle., Conclusion: The deep border of the IMAS and aberrant tendinous structure passing across the ulnar nerve, or the parts of the IMAS and IMAP passing posterior to the ulnar nerve are potential causes of ulnar nerve compression.

The purpose of this study was to document the presence of a sublingual gland (SLG) herniating inferiorly through the mylohyoid muscle into the submandibular area. A total of 100 half-heads of 50 adult Korean cadavers were enrolled in this study. The floor of the mouth was dissected from the neck, and mylohyoid muscle patency and position of the sublingual gland were evaluated. Demographic factors of the donor and characteristics of the herniation were evaluated. Herniation was found in 29 (58.0 %) of the 50 cadavers or 42 of the 100 half-heads. Herniation was more frequently observed in females than in males (p = 0.009). However, no laterality was observed. Classifying the location of SLG herniation from the midpoint of the mandible to the hyoid bone into 3 regions, 32 (63 %) of herniations were found in the anterior one-third. No ranula formation was observed. The size and weight of normal glands tended to be larger than those of herniated glands, but no statistical significance was observed. An SLG hernia is a very common condition and is more frequently observed in females. As such, SLG herniation should be considered when a submental neck mass is evaluated.

The aim of this study was to clarify the morphological patterns and proportions of the components of the nasal septum. Anatomical examinations were performed on 70 nasal septums of embalmed Korean adult cadavers. The septal deviation was checked before cutting the nasal cavity midsagittally with the aid of a laryngoscope. The shape of each component of the nasal septum was identified, and photographs were taken from a midline sagittal view. A line was drawn on each photograph between the septal components, and then the area of each septal component was measured using software. The mean area proportions of the septal cartilage (SC), the perpendicular plate of the ethmoid bone (PPE), the vomer, and the nasal crest of the maxilla relative to the total area of the nasal septum were 25.6%, 43.0%, 25.8%, and 5.6%, respectively. The morphology of the nasal septum was classified into 3 main patterns according to the proportion of each septal component. The proportions of the SC, the PPE, the vomer, and the nasal crest of the maxilla were similar to the mean values of the present study in 45.7%. The proportions of the SC, the PPE, and the vomer were similar to each other (with a difference of <15%) in 24.3%. The proportion of the PPE exceeded 50% of the total area of the nasal septum in 22.9%. The results reported herein provide detailed anatomical knowledge that can be used as a valuable reference for rhinoplasty procedures.

Purpose: To describe the relationship between the waist-to-height ratio (WHtR) and cardiometabolic risk factors (CMRFs) and to evaluate the validity of WHtR in identifying adolescents with metabolic syndrome., Materials and Methods: We analyzed data from a pooled population of 4068 adolescents aged 10-19 years from the Korean National Health and Nutrition Examination Surveys conducted between 1998 and 2008. Overweight individuals were defined by body mass index (BMI) ≥85th percentile. Those with at least 2 CMRFs among hypertension, hyperglycemia, hypertriglyceridemia, and decreased high-density lipoprotein cholesterol (HDL-C) were classified as having multiple CMRFs., Results: WHtR was significantly related to systolic blood pressure, HDL-C, and triglycerides in both non-overweight and overweight adolescents (all p<0.01). Among overweight adolescents, the area under the curve (AUC) for WHtR in identifying multiple CMRFs was significantly greater than that for BMI (p=0.014). Metabolic syndrome was more common in overweight adolescents with a WHtR of ≥0.5 than in those with a WHtR of <0.5 (p<0.001). In non-overweight adolescents, the prevalences of multiple CMRFs (p=0.001) and metabolic syndrome (p<0.001) were higher in those with a WHtR of ≥0.5 than in those with a WHtR of <0.5. Among those without central obesity, the prevalence of multiple CMRFs was higher in those with a WHtR of ≥0.5 than in those with a WHtR of <0.5 (p=0.021)., Conclusion: WHtR is a simple and valid index for identifying adolescents with increased cardiometabolic risk and is related to CMRFs even in non-overweight adolescents. In adolescents already screened via BMI and waist circumference (WC), WHtR seems to be of additional help in discriminating those at higher cardiometabolic risk.

Triiodothyronine (T3) and its receptor (TR) modulate several physiological processes, including cell development, proliferation, differentiation and metabolism. The regulatory mechanism of T3/TR involves binding to the thyroid hormone response element (TRE) within the target gene promoter. However, the number of target genes directly regulated by TRα1 and the specific pathways of TR-regulated target genes remain largely unknown. Here, we expressed TRα1 in a HepG2 cell line and used chromatin immunoprecipitation coupled with microarray to determine the genes that are directly regulated by TRα1 and also involved in cell metabolism and proliferation. Our analysis identified E74-like factor 2 (ELF2), a transcription factor associated with tumor growth, as a direct target downregulated by T3/TR. Overexpression of ELF2 enhanced tumor cell proliferation, and conversely, its knockdown suppressed tumor growth. Additionally, ELF2 restored the proliferative ability of hepatoma cells inhibited by T3/TR. Our findings collectively support a potential role of T3/TR in tumor growth inhibition through regulation of ELF2., Competing Interests: The authors declare no conflicts of interest.

Cervical carcinoma is the third-most common cause of cancer-related deaths in women worldwide. However, the molecular mechanisms underlying the metastasis of cervical cancer are still unclear. Oligonucleotide microarrays coupled with bioinformatics analysis show that cytoskeletal remodeling and epithelial-to- mesenchymal transition (EMT) are significant pathways in clinical specimens of cervical cancer. In accord with clinical observations demonstrating ectopic expression of lipocalin 2 (LCN2), an oncogenic protein associated with EMT, in malignant tumors, was significantly upregulated in cervical cancer and correlated with lymph node metastasis. Overexpression of LCN2 enhanced tumor cell migration and invasion both in vitro and in vivo. Conversely, knockdown or neutralization of LCN2 reduced tumor cell migration and invasion. LCN2-induced migration was stimulated by activation of the EMT-associated proteins, Snail, Twist, N-cadherin, fibronectin, and MMP-9. Our findings collectively support a potential role of LCN2 in cancer cell invasion through the EMT pathway and suggest that LCN2 could be effectively utilized as a lymph node metastasis marker in cervical cancer.

The aim of this study was to revisit the morphological characteristics of the subcostal muscle and to obtain its morphometric data. One hundred and two sides of the thorax from 51 adult cadavers were used. The total number of subcostal muscles in the 102 specimens was 559. The subcostal muscle commonly comprised an aponeurosis at its superior and inferior attachments. This muscle had a thin band-like shape in 64.2% cases, while in the other 35.8% either its superior or inferior attachment was wider. It was classified into the following four types on the basis of its inferior attachment: in Types I and II it extended to two (79.3%) and three (12.0%) lower ribs, respectively; in Type III it joined adjacent muscles such as the psoas major (2.2%) or quadratus lumborum (0.7%); and in Type IV it was attached to the transverse process (0.4%) or body (3.9%) of the 12th thoracic vertebra and the body of the 1st lumbar vertebra (1.4%). The subcostal muscle was found at the deepest layer of the intercostal space, and mainly presented in the upper and lower parts of the thorax. Its width and height were 18.2 ± 10.9 mm (mean ± SD) and 56.0 ± 13.3 mm, respectively. The distances from the midsagittal line to the superior and inferior attachments of the subcostal muscle were 77.1 ± 13.0 mm and 48.9 ± 13.5 mm, respectively. The results of this study will help to advance current understanding of the subcostal muscle., (© 2015 Wiley Periodicals, Inc.)

In this paper, we propose a new metallic cylindrical antenna at terahertz frequencies using the concept of low-frequency spoof surface plasmon polaritons (SPPs). The antenna is developed by introducing an open hollow ring (OHR) in each unit cell of the conventional periodic subwavelength corrugated metallic wire (PSCMW). The new structure is referred to as the PSCMW-OHR. The dispersion properties of PSCMWs and PSCMW-OHRs, the near-field and far-field distributions, as well as the radiation efficiencies are numerically evaluated and compared. By analyzing the numerical results, we find that there are extra new propagation modes that exist in the annular groove of the PSCMW-OHR, aside from the normal transmission modes in the PSCMW. Moreover, the dispersion line of the new SPP mode exhibits a negative slope. Surprisingly and interestingly, after passing through the light line, the propagation gets into the radiation zone, where it becomes a leaky mode with a complex-valued propagation constant. We have found that the far-field radiation of propagation in the leaky mode can lead to frequency scanning effects with a scanning angle of 22°, and the radiation efficiency can be increased to 90%, provided that the total number of the periodic unit cells is large enough.

Scant information is available about the molecular basis of multiple HLA class I antigen-processing machinery defects in malignant cells, although this information contributes to our understanding of the molecular immunoescape mechanisms utilized by tumor cells and may suggest strategies to counteract them. In the present study we reveal a combination of IFN-γ-irreversible structural and epigenetic defects in HLA class I antigen-processing machinery in a recurrent melanoma metastasis after immunotherapy. These defects include loss of tapasin and one HLA haplotype as well as selective silencing of HLA-A3 gene responsiveness to IFN-γ. Tapasin loss is caused by a germ-line frameshift mutation in exon 3 (TAPBP(684delA)) along with a somatic loss of the other gene copy. Selective silencing of HLA-A3 gene and its IFN-γ responsiveness is associated with promoter CpG methylation nearby site-α and TATA box, reversible after DNA methyltransferase 1 depletion. This treatment combined with tapasin reconstitution and IFN-γ stimulation restored the highest level of HLA class I expression and its ability to elicit cytotoxic T cell responses. These results represent a novel tumor immune evasion mechanism through impairing multiple components at various levels in the HLA class I antigen presentation pathway. These findings may suggest a rational design of combinatorial cancer immunotherapy harnessing DNA demethylation and IFN-γ response., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

The thyroid hormone, 3,3',5-triiodo-L-thyronine (T3), regulates cell growth, development and differentiation via interactions with thyroid hormone receptors (TR), but the mechanisms underlying T3-mediated modulation of cancer progression are currently unclear. Lipocalin 2 (LCN2), a tumor-associated protein, is overexpressed in a variety of cancer types. Oligonucleotide microarray, coupled with proteomic analysis, has revealed that LCN2 is positively regulated by T3/TR. However, the physiological role and pathway of T3-mediated regulation of LCN2 in hepatocellular carcinogenesis remain to be characterized. Upregulation of LCN2 after T3 stimulation was observed in a time- and dose-dependent manner. Additionally, TRE on the LCN2 promoter was identified at positions -1444/-1427. Overexpression of LCN2 enhanced tumor cell migration and invasion, and conversely, its knockdown suppressed migration and invasion, both in vitro and in vivo. LCN2-induced migration occurred through activation of the Met/FAK cascade. LCN2 was overexpressed in clinical hepatocellular carcinoma (HCC) patients, compared with normal subjects, and positively correlated with TRα levels. Both TRα and LCN2 showed similar expression patterns in relation to survival rate, tumor grade, tumor stage and vascular invasion. Our findings collectively support a potential role of T3/TR in cancer progression through regulation of LCN2 via the Met/FAK cascade. LCN2 may thus be effectively utilized as a novel marker and therapeutic target in HCC.

Background & Aims: Thyroid hormone (T3) and its receptor (TR) are involved in cell growth and cancer progression. Although deregulation of microRNA (miRNA) expression has been detected in many tumor types, the mechanisms underlying functional impairment and specific involvement of miRNAs in tumor metastasis remain unclear. In the current study, we aimed to elucidate the involvement of deregulated miRNA-130b (miR-130b) and its target genes mediated by T3/TR in cancer progression., Methods: Quantitative reverse transcription-PCR, luciferase and chromatin immunoprecipitation assays were performed to identify the miR-130b transcript and the mechanisms implicated in its regulation. The effects of miR-130b on hepatocellular carcinoma (HCC) invasion were further examined in vitro and in vivo. Clinical correlations among miR-130b, TRs and interferon regulatory factor 1 (IRF1) were examined in HCC samples using Spearman correlation analysis., Results: Our experiments disclosed negative regulation of miR-130b expression by T3/TR. Overexpression of miR-130b led to marked inhibition of cell migration and invasion, which was mediated via suppression of IRF1. Cell migration ability was promoted by T3, but partially suppressed upon miR-130b overexpression. Furthermore, miR-130b suppressed expression of epithelial-mesenchymal transition (EMT)-related genes, matrix metalloproteinase-9, phosphorylated mammalian target of rapamycin (mTOR), p-ERK1/2, p-AKT and p-signal transducer and activator of transcription (STAT)-3. Notably, miR-130b was downregulated in hepatoma samples and its expression patterns were inversely correlated with those of TRα1 and IRF1., Conclusions: Our data collectively highlight a novel pathway interlinking T3/TR, miR-130b, IRF1, the EMT-related genes, p-mTOR, p-STAT3 and the p-AKT cascade, which regulates the motility and invasion of hepatoma cells., (Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

It was recently reported that the internal branch of the accessory nerve not only comprises the cranial root but also various combinations of the cranial root, spinal root, and the vagal component of the vagus nerve. The aim of this study was to demonstrate the anatomical distribution of each component of the internal branch of the human accessory nerve. Ten half-heads and necks of adult cadavers were used. The internal branch of the accessory nerve had three courses: the pharyngeal branch, the descending branch to the thorax, and the recurrent laryngeal nerve. The pharyngeal branch of the internal branch originated mainly from the vagus nerve, rather than from the cranial root of the accessory nerve. All of the components of the internal branch descended to the thorax along the vagus nerve. The recurrent laryngeal nerve comprised the internal branch and the vagus nerve in all specimens, and it was separated into bundles originating from the internal branch and vagus nerve. Both bundles gave off branches to the trachea and esophagus. The laryngeal distribution of the internal branch and vagus nerve was confirmed in the posterior cricoarytenoid, lateral cricoarytenoid, and thyroarytenoid muscles. These three laryngeal muscles were innervated by the cranial root and/or vagus nerve, but the distribution pattern was different in each specimen. Although the vagus nerve and cranial root are morphologically distinct nerves in the cranial cavity, they can be regarded functionally as the same nerve based on their distribution in the laryngeal muscles.

The aim of this study was to elucidate the definition of the borders and surface of the thyroid lobe in the anatomical position, and to compare the morphology of Zuckerkandl's tubercle (ZT) in the fresh and fixed states. One hundred thyroid lobes from 50 fresh Korean cadavers were used. The lateral border of the thyroid lobe could be defined as the most lateral margin of its anterior aspect when in the anatomical position. The posteromedial border was the margin that projected toward the trachea or tracheoesophageal groove. The lateral and posteromedial borders, and the posterior surface between these borders, could be identified in most of the fixed cadavers. The posterolateral border could only be identified in the thyroid lobe if there was compression by the internal carotid artery in cross-sectioned specimens and CT images. The ZT was identifiable in 85% of both fresh and fixed specimens. It was identified mainly at the posteromedial border of the thyroid lobe when in the anatomical position, and extended to the tracheoesophageal groove or esophagus. In the fresh state, the ZT projected as a rounded cone with a usually semicircular base, but its shape was very variable in the fixed state. In the present study, the ZT was found at the posteromedial border or posterior surface of the thyroid lobe in both the fresh and fixed states, contrary to most previous reports. The location of the ZT should be established in the anatomical position to avoid confusion., (© 2015 Wiley Periodicals, Inc.)

Despite numerous investigations on metastasis, the determinants of metastatic processes remain unclear. We aimed to identify the metastasis-associated genes in hepatocellular carcinoma (HCC). Potent metastatic SK-hep-1 (SK) cells, designated 'SKM', were generated using Transwell assay followed by selection in a mouse model. Genes expressed differentially in SKM and SK cells were identified via microarray analyses. A small form of Neural precursor cell-expressed developmentally downregulated 4 (sNEDD4) was identified to be overexpressed in SKM cells, which was confirmed as a novel transcript using liquid chromatography-mass spectrometry. In clinical specimens, sNEDD4 was significantly overexpressed in tumors and serves as a poor prognostic factor for male patients with HCC (P = 0.035). Upon subcutaneous introduction of sNEDD4-overexpressing SK cells into flanks of nude mice, tumors grew faster than those of the control group. Furthermore, sNEDD4-mediated promotion of tumor metastasis was demonstrated in the orthotopic mouse model. Overexpression of sNEDD4 increased the invasive ability of SK cells through upregulation of matrix metalloproteinase 9 and inhibited serum deprivation-induced apoptosis via upregulation of myeloid cell leukemia 1. In conclusion, sNEDD4 is a novel metastasis-associated gene, which prevents apoptosis under nutrient restriction conditions. The present findings clearly support the prognostic potential of sNEDD4 for HCC.

Purpose: The fibularis quartus muscle (FQ) is an accessory fibular muscle that can be found in humans, reportedly in up to 22%. The aim of this study was to classify morphological patterns of the FQ and its anatomical variations., Methods: Eighty lower limbs of 40 formalin-fixed adult Korean cadavers were used in this study., Results: The FQ was present in 13 of 80 specimens (16.3%). In two specimens, each specimen had two FQs with different origins and insertion sites. Thus, 15 cases of FQ were found in 13 specimens. The FQ originated from the fibularis brevis muscle (FB) in 12 cases (15%). In these cases, the FQ arose either as a muscle or as a tendon. The muscle fibers of the FQ merged into a tendon (8 of 12 cases) that inserted variously into (1) the tendon of the FB (three cases, 3.8%), (2) the lateral surface of calcaneus (two cases, 2.5%), (3) the inferior peroneal retinaculum (two cases, 2.5%), or (4) the dorsal surface of the base of fifth metatarsal bone (one case, 1.3%). The FQ arose as a tendon from the FB in 4 of 12 cases. In three of the four cases, the FQ inserted into the lateral surface of calcaneus. The FQ arose from structures other than the FB (three cases, 3.8%)., Conclusion: The present study has demonstrated a new classification for the FQ and its anatomical variations, and provided detailed data for its accurate identification of a muscle and relevant surgical procedures.

Background: The aim of this study was to elucidate the morphological charac-teristics of the muscle bundles of the flexor digitorum superficialis (FDS) attached to the intermuscular aponeurosis (IMA) and any related structure that could potentially compress the ulnar nerve., Materials and Methods: Fifty embalmed limbs of 34 adult cadavers were studied., Results: The FDS arose as multiple separate bundles from the IMA of the lateral surface of the flexor carpi ulnaris in 76% of specimens. Below their origin, these separate bundles became attached continuously as a single mass to form the muscle belly. There were 1, 2, 3, 4 and 5 arising FDS muscle bundles in 28%, 30%, 4%, 10% and 4% of specimens, respectively. The muscle bundles were attached either only superficially (24% of cases) or across the entire width (20% of cases) of the IMA. In 32% of the specimens, bundles arose from the IMA in a combined fashion, being attached to the IMA superficially, deep and across the entire structure. The muscle bundles that arose from the deep part or entire width of the IMA were in contact with the ulnar nerve in 52% of specimens. In 11 (22%) specimens, the deep borders of the lowest muscle bundles close to the ulnar nerve were composed of tendinous fibres that divided from the IMA of the lateral surface of the flexor carpi ulnaris. The distance from the medial epicondyle to the lowest point of the FDS arising from the IMA was 62.0 ± 19.7 mm., Conclusions: The thick tendinous deep border of the lowest muscle bundle of the FDS where it attaches to the IMA is a potential cause of ulnar nerve compression.

Rocky Mountain spotted fever, a tick-borne disease caused by Rickettsia rickettsii, is challenging to diagnose and rapidly fatal if not treated. We describe a decedent who was co-infected with group A β-hemolytic streptococcus and R. rickettsii. Fatal cases of Rocky Mountain spotted fever may be underreported because they present as difficult to diagnose co-infections., (© The American Society of Tropical Medicine and Hygiene.)

There has been the controversy surrounding the cranial root (CR) of the accessory nerve. This study was performed to clarify the morphological characteristics of the CR in the cranial cavity. Fifty sides of 25 adult cadaver heads were used. The accessory nerve was easily distinguished from the vagus nerve by the dura mater in the jugular foramen in 80% of 50 specimens. The trunk of the accessory nerve from the spinal cord penetrated the dura mater at various distances before entering the jugular foramen. In 20% of the specimens there was no dural boundary. In these cases, the uppermost cranial rootlet of the accessory nerve could be identified by removing the dura mater around the jugular foramen where it joined to the trunk of the accessory nerve at the superior vagal ganglion. The cranial rootlet was formed by union of two to four short filaments emerging from the medulla oblongata (66%) and emerged single, without filament (34%), and usually joined the trunk of the accessory nerve directly before the jugular foramen. The mean number of rootlets of the CR was 4.9 (range 2-9) above the cervicomedullary junction. The CR of the accessory nerve was composed of two to nine rootlets, which were formed by the union of two to four short filaments and joined the spinal root of the accessory nerve. The CR is morphologically distinct from the vagus nerve, confirming its existence., (© 2014 Wiley Periodicals, Inc.)