No abstract available.
Erythropoietin* ; Humans ; Plasma*

Background/Aims: N-acetylcysteine (NAC) affects signaling pathways involved in apoptosis, angiogenesis, cell growth and arrest, redox-regulated gene expression, and the inflammatory response. However, it is not known how the signal mechanism for tight junctional protein claudin (CLDN) 18 is regulated in asthma patients. Methods: To investigate the effects of NAC on CLDN18 expression in a mouse model of asthma, and to assess plasma levels of CLDN18 in asthma patients. A murine model of asthma induced by ovalbumin (OVA) was established using wild-type BALB/c female mice, and the levels of CLDNs, phosphorylated-pyruvate dehydrogenase kinase 1 (p-PDK1), and protein kinase B (Akt) pathway proteins following NAC treatment were examined by Western blotting and immunohistochemistry. In addition, the plasma levels of CLDN18 were evaluated in asthmatic patients and control subjects. Results: NAC diminished OVA-induced airway hyper-responsiveness and inflammation.Levels of CLDN18 protein were higher in lung tissue from OVA mice than tissue from control mice, and were increased by treatment with NAC or dexamethasone. Treatment with NAC or dexamethasone decreased the OVA-induced increase in interleukin-1α protein levels. Although treatment with NAC increased OVA-induced p-PDK1 protein levels, it decreased phosphorylated Akt (pAkt)/Akt levels. Soluble CLDN18 levels were lower in patients with asthma than in controls and were correlated with the percentage of neutrophils, forced expiratory volume in 1 second (FEV1)/forced vital capacity % (FVC%) and FEV1%. Conclusions CLDN18 plays a role in the pathogenesis of asthma and NAC diminishes airway inflammation and responsiveness by modulating CLDN18 expression.

This study aimed to assess the prevalence and distribution pattern of dental anomalies in the permanent teeth of patients with non-syndromic cleft lip with or without cleft palate. Additionally, it aimed to compare differences in dental anomalies between cleft and non-cleft areas, considering gender and cleft phenotype. Panoramic radiographs of 164 patients diagnosed with non-syndromic orofacial clefts were retrospectively analyzed by a single examiner to confirm dental anomalies. The dental anomalies investigated included tooth agenesis, supernumerary teeth, microdontia, rotation, ectopic eruption, and enamel hypoplasia. Cleft phenotypes were categorized into 7 types based on medical and dental records. A significantly higher prevalence of supernumerary teeth was observed in males than females within non-cleft areas (p = 0.017), with no significant differences in other dental anomalies. In non-cleft area, patients with cleft palate exhibited a high prevalence of tooth agenesis (p < 0.0001) and microdontia (p = 0.012) compared to other cleft phenotypes. Maxillary incisor rotation was closely associated with adjacent tooth agenesis in unilateral cleft lip and palate cases (p = 0.034). This study suggests that the additional subphenotype based on dental anomalies in patients with orofacial cleft may serve as applicable clinical markers.

The National Evidence-based Healthcare Collaborating Agency (NECA), an institution for health technology assessment in Korea, has used public solicitation of research topics since its establishment in 2009. This creates a necessity for examining whether a given research topic was selected to be considered when prioritizing healthcare technology assessment and distributing healthcare resources. This study aimed to investigate the relationship between the research topics suggested to NECA and the disease burden in Korea. To find the correlation between disease burden and 1,112 suggested topics and 91 performed topics that were classified by Human Research Classification System a linear auxiliary trend line and scatter plot were constructed using disability-adjusted life years (DALYs), and Pearson's correlation coefficients were calculated. The results suggested that cancer was most common, followed by cardiovascular diseases, among suggested research topics and research topics performed by NECA, as well as in terms of the ratio of performed to suggested topics. The correlation between research topic and disease burden index indicated a strong correlation with DALYs and years of life lost (YLLs). However, years lived with disability and research topic had no relationship. Suggested topics showed a greater correlation with YLLs than DALYs, whereas performed topics showed a greater correlation with DALYs than YLLs, showing that despite the fact that the diseases with a high burden from morbidity were appropriately considered with respect to selecting research topics, a statistically significant difference was not found. As the first Korean study to assess the correlation between research topics and disease burden, our results will be used as base data for prioritizing the allocation of healthcare resources in the future.
Adenosine-5'-(N-ethylcarboxamide) ; Biomedical Technology* ; Cardiovascular Diseases ; Classification ; Cost of Illness ; Delivery of Health Care ; Evidence-Based Practice ; Humans ; Korea ; Technology Assessment, Biomedical*

Aspirin has been used for decades for the primary and secondary prevention of cardiovascular disease (CVD). The effect of aspirin in secondary prevention is well-known but is still debatable for primary prevention. Despite the controversy, aspirin is believed to have a beneficial effect in primary prevention and has been widely used. However, whether the doubts concerning the wide use of aspirin are correct has resulted in the publication of data from several large clinical trials recently. There are several clinical guidelines from various international organizations on the use of aspirin for the primary prevention of CVD, and they offer some conflicting recommendations. A reduction in the overall incidence of CVD with the development of modern prevention therapies has weakened the impact of aspirin in primary prevention. Large randomized clinical trials have found decreased or no difference in CVD events but a significant increase in the risk of bleeding. Taking aspirin for the primary prevention of CVD is no longer recommended, especially for patients who have a low to moderate risk. An assessment of the balance between the benefits and risks of aspirin use should be considered.
Aspirin ; Cardiovascular Diseases ; Hemorrhage ; Humans ; Incidence ; Primary Prevention ; Publications ; Risk Assessment ; Secondary Prevention

Dual oxidase maturation factor 2 (DUOXA2) is necessary for the enzymatic activity of dual oxidase 2 (DUOX2) to generate hydrogen peroxide production during thyroid hormone synthesis. We describe two Korean children, who were initially suspected to have transient congenital hypothyroidism (CH), but later confirmed to have permanent CH caused by DUOXA2 mutation. Treatment with levothyroxine was discontinued after confirming thyroid-stimulating hormone (TSH) level to be below 10 μU/mL and normal thyroid scan at the first or second trial-off therapy. However, after therapy cessation, TSH elevated to more than 10 μU/mL, and goiter developed in case 2. As a result, levothyroxine was resumed. Next-generation sequencing showed compound heterozygous mutations of DUOXA2 at Y138X and Y246X in case 1 and homozygous mutations of DUOXA2 at Y246X in case 2. In this report, a longer follow-up is recommended even after treatment termination in transient CH, and genetic studies might help assess the permanence of hypothyroidism in cases of mildly elevated TSH after trial-off therapy.

Dyshormonogenesis is caused by genetic defects in thyroid hormone synthesis. The most common form is thyroid peroxidase (TPO) deficiency. Clinically variable degree of hypothyroidism and thyroid gland enlargement depend on the severity of the defect. We report 22-year-old female with congenital hypothyroidism (CH) caused by TPO deficiency. Since goitrous CH was diagnosed at 8-year-old, L-thyroxine has been supplemented. Her goiter size was fluctuated according to the compliance on the medication. After 3.5 years of medication, ultrasonography found solid nodule, which was interpreted as nodular hyperplasia pathologically. The nodule size did not change during recent 10 years except peripheral calcification. Genetic analysis using NGS for CH revealed compound heterozygous variants of c.2757del;p.(Met921Trpfs*53) and c.1580G＞T;p.(Trp527Leu) in TPO gene. The first variant inherited from asymptomatic mother is pathogenic frame-shift mutation associated with stop codon, and the second one inherited from her asymptomatic father is predicted as deleterious in bioinformatics software program. From this case, we have observed that nodular change and calcification developed from diffuse enlarged goiter in dyshormonogenetic patient. Early molecular diagnosis of dyshormonogenesis and TSH suppression is important for not developing thyroid nodules in case of childhood euthyroid goiter without thyroid autoantibodies.

OBJECTIVES: This study investigated the correlation between bone mineral density (BMD)/trabecular bone score (TBS) and body mass index (BMI), height and weight in Korean adults. METHODS: We enrolled 2555 female participants in their 20s–80s and 1631 male participants in their 20s–70s. Participants with history of previous vertebral surgeries or current vertebral diseases were excluded. Female and male participants were divided into osteoporosis group (n = 136 and n = 31, respectively), osteopenia group (n = 822 and n = 460, respectively), and normal group (n = 1596 and n = 1140, respectively) based on their BMD T-score. Dual-energy X-ray absorptiometry image analysis and linear regression analysis were conducted on each participant in each group to determine the P-value and the correlation between BMD T-score/TBS T-score and BMI, weight, and height. RESULTS: We found a significant correlation between BMI and TBS in both male and female participants. In the male participants, the correlation coefficient increased progressively from the normal group to the osteoporosis group. In the female group, we observed a significant positive correlation between height and TBS, and in the male group a significant negative correlation between weight and TBS was observed. CONCLUSIONS: BMI and weight are closely correlated to body fat content. BMD was positively correlated to BMI and weight, while TBS was negatively correlated to BMI and weight. Therefore, although BMI causes an increase in BMD, it appears to be negatively affecting bone quality.
Absorptiometry, Photon ; Adipose Tissue ; Adult ; Body Mass Index* ; Bone Density ; Bone Diseases, Metabolic ; Female ; Humans ; Korea ; Linear Models ; Male ; Miners* ; Osteoporosis

BACKGROUND: It is difficult for surgeons to reconstruct soft tissue defects of the great toe. This report aims to evaluate the utility and efficacy of innervated distally based first dorsal metatarsal artery (FDMA) flap with a wide pedicle for reconstruction of soft tissue defects of the great toe. METHODS: This is a retrospective report. Between January 2015 and December 2017, six cases of skin defect of the great toe were reconstructed with an innervated distally based FDMA flap with a wide pedicle. One case was excluded in this report because of chronic pain on the metatarsophalangeal joint due to osteoarthritis before the injury. A total of five cases were evaluated for flap survival and sensory recovery. The sensory recovery was investigated by two-point discrimination and Semmes-Weinstein monofilament tests. The average age of the selected patients was 40 years (range, 36 to 56 years), and the average size of the defect in the toe was 8.3 cm2 (range, 4 to 13.8 cm2). The average follow-up period was 29.4 months (range, 18 to 38 months). RESULTS: All patients survived without any complications. The average two-point discrimination test value was 8.0 ± 0.89 mm (range, 7 to 9 mm), and the average value obtained from the Semmes-Weinstein monofilament test was 4.53 ± 0.33 (range, 4.17 to 4.93). The average residual pain score evaluated with a visual analog scale was 1 (range, 0 to 2). Two patients complained of stiffness in the great toe below 30° of total range of motion during the early stages after surgery, but this stiffness gradually improved after rehabilitation. The average range of motion of three patients with a remaining metatarsophalangeal joint after surgery was 80° (range, 70° to 90°). All five cases could walk regularly without any unique footwear at the final follow-up. CONCLUSIONS: The innervated distally based FDMA flap with a wide pedicle could be a good alternative method for repair of soft tissue defects of the great toe.
Arteries ; Chronic Pain ; Discrimination (Psychology) ; Follow-Up Studies ; Humans ; Metatarsal Bones ; Metatarsophalangeal Joint ; Methods ; Osteoarthritis ; Perforator Flap ; Range of Motion, Articular ; Rehabilitation ; Retrospective Studies ; Skin ; Surgeons ; Toes ; Visual Analog Scale

Luminespib (AUY922), a heat shock proteins 90 inhibitor, has anti-neoplastic and antitumor effects. However, it is not clear whether AUY922 affects events in vascular diseases. We investigated the effects of AUY922 on the platelet-derived growth factor (PDGF)-BB-stimulated proliferation and migration of vascular smooth muscle cells (VSMC). VSMC viability was detected using the XTT (2,3-bis-(2-methoxy- 4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide) reagent. To detect the attenuating effects of AUY922 on PDGF-BB-induced VSMCs migration in vitro, we performed the Boyden chamber and scratch wound healing assays. To identify AUY922- mediated changes in the signaling pathway, the phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) 1/2 was analyzed by immunoblotting. The inhibitory effects of AUY922 on migration and proliferation ex vivo were tested using an aortic ring assay. AUY922 was not cytotoxic at concentrations up to 5 nM. PDGF-BB-induced VSMC proliferation, migration, and sprout outgrowth were significantly decreased by AUY922 in a dose-dependent manner. AUY922 significantly reduced the PDGF-BB-stimulated phosphorylation of Akt and ERK1/2. Furthermore, PD98059 (a selective ERK1/2 inhibitor) and LY294002 (a selective Akt inhibitor) decreased VSMC migration and proliferation by inhibiting phosphorylation of Akt and ERK1/2. Greater attenuation of PDGF-BB-induced cell viability and migration was observed upon treatment with PD98059 or LY294002 in combination with AUY922. AUY922 showed anti-proliferation and anti-migration effects towards PDGF-BBinduced VSMCs by regulating the phosphorylation of ERK1/2 and Akt. Thus, AUY922 is a candidate for the treatment of atherosclerosis and restenosis.