PURPOSE: The Hedgehog (Hh) signaling pathway is important in embryonic development including cell differentiation and proliferation. Recently, activation of this pathway has been implicated in several forms of solid cancers. We investigated sonic hedgehog (Shh) protein expression and its relation to differentiation and clinicopathologic characteristics in thyroid cancer cell lines and tissues. METHODS: FTC-236, FTC-238, and XTC-1. We made tissue microarray slides using 80 thyroid surgical specimen: 40 benign and 40 malignant lesions. Immunohistochemical staining was performed using anti-Shh antibody. mRNA expression of NIS, thyroglobulin, and CD97 were evaluated by RT-PCR. Cyclopamine was used as a Shh signal inhibitor. RESULTS: Shh expression was more prominent in TPC-1, FTC-133, and XTC-1 cell lines than the others. Cyclopamine downregulated CD97 and upregulated thyroglobulin mRNA expression, but did not induce mRNA expression of NIS. Thyroid tissues showed varied expression of Shh in both benign and malignant diseases. Shh expression was detected in 38 of 50 (76%) normal, in 18 of 25 (72%) non-neoplastic benign, in nine of 15 (60%) benign tumors, and in 31 of 40 (77%) malignant tumors. Shh over-expression was significantly less frequent in papillary thyroid carcinomas than in normal or benign thyroid tissues. In addition, Shh protein expression did not relate to clinicopathologic characteristics in papillary thyroid carcinomas. CONCLUSION: Thyroid tissues and cell lines vary in expression of Shh. Cyclopamine can induce redifferentiation in thyroid cancer cell lines. Shh protein expression, however, is unrelated to clinicopathologic characteristics in papillary thyroid carcinomas.
Cell Differentiation ; Cell Line ; Embryonic Development ; Female ; Hedgehog Proteins* ; Hedgehogs ; Pregnancy ; RNA, Messenger ; Thyroglobulin ; Thyroid Gland* ; Thyroid Neoplasms

Streptomycin is currently utilized to treat advanced tuberculosis in Korea. However, the usefulness of intravascular streptomycin is not fully understood. In this study, streptomycin was administered intravenously in 30 patients. Intravenous administration of streptomycin may be a useful route of administration without undesirable toxicities.
Administration, Intravenous ; Humans ; Korea ; Mycobacterium tuberculosis ; Streptomycin ; Tuberculosis

BACKGROUND AND OBJECTIVES: Nationwide social inequalities of oral anticoagulation (OAC) usage after the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) have not been well identified in patients with atrial fibrillation (AF). This study assessed overall rate and social inequalities of OAC usage after the introduction of NOAC in Korea.METHODS: Between January 2002 and December 2016, we identified 888,540 patients with AF in the Korea National Health Insurance system database. The change of OAC rate in different medical systems after the introduction of NOAC were evaluated.RESULTS: In all population, overall OAC use increased from 13.2% to 23.4% (p for trend <0.001), and NOAC use increased from 0% to 14.6% (p for trend <0.001). Compared with pre-reimbursement (0.48%), the annual increase of OAC use was significantly higher after partial (1.16%, p<0.001), and full reimbursement of OAC (3.72%, p<0.001). Full reimbursement of NOAC (adjusted odds ratio, 2.10; 95% confidence interval, 2.04–2.15) was independently associated with higher OAC use. However, the difference of overall OAC usage between tertiary referral hospitals and nursing or public health centers increased from 17.9% in 2010 to 36.8% in 2016. Moreover, usage rate of NOAC was significantly different among different medical systems from 37.2% at the tertiary referral hospital and 5.5% at nursing or public health centers.CONCLUSIONS: Introduction of NOACs in routine practice for stroke prevention in AF was associated with improved rates of overall OAC use. However, significant practice-level variations in OAC and NOAC use remain producing social inequalities of OAC despite full reimbursement.
Anticoagulants ; Atrial Fibrillation ; Humans ; Insurance ; Korea ; National Health Programs ; Nursing ; Odds Ratio ; Public Health ; Socioeconomic Factors ; Stroke ; Tertiary Care Centers

BACKGROUND AND OBJECTIVES: Nationwide social inequalities of oral anticoagulation (OAC) usage after the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) have not been well identified in patients with atrial fibrillation (AF). This study assessed overall rate and social inequalities of OAC usage after the introduction of NOAC in Korea. METHODS: Between January 2002 and December 2016, we identified 888,540 patients with AF in the Korea National Health Insurance system database. The change of OAC rate in different medical systems after the introduction of NOAC were evaluated. RESULTS: In all population, overall OAC use increased from 13.2% to 23.4% (p for trend <0.001), and NOAC use increased from 0% to 14.6% (p for trend <0.001). Compared with pre-reimbursement (0.48%), the annual increase of OAC use was significantly higher after partial (1.16%, p<0.001), and full reimbursement of OAC (3.72%, p<0.001). Full reimbursement of NOAC (adjusted odds ratio, 2.10; 95% confidence interval, 2.04–2.15) was independently associated with higher OAC use. However, the difference of overall OAC usage between tertiary referral hospitals and nursing or public health centers increased from 17.9% in 2010 to 36.8% in 2016. Moreover, usage rate of NOAC was significantly different among different medical systems from 37.2% at the tertiary referral hospital and 5.5% at nursing or public health centers. CONCLUSIONS Introduction of NOACs in routine practice for stroke prevention in AF was associated with improved rates of overall OAC use. However, significant practice-level variations in OAC and NOAC use remain producing social inequalities of OAC despite full reimbursement.

The gut microbiota has an important role in the gut barrier, inflammation and metabolic functions. Studies have identified a close association between the intestinal barrier and metabolic diseases, including obesity and type 2 diabetes (T2D). Recently, Akkermansia muciniphila has been reported as a beneficial bacterium that reduces gut barrier disruption and insulin resistance. Here we evaluated the role of A. muciniphila-derived extracellular vesicles (AmEVs) in the regulation of gut permeability. We found that there are more AmEVs in the fecal samples of healthy controls compared with those of patients with T2D. In addition, AmEV administration enhanced tight junction function, reduced body weight gain and improved glucose tolerance in high-fat diet (HFD)-induced diabetic mice. To test the direct effect of AmEVs on human epithelial cells, cultured Caco-2 cells were treated with these vesicles. AmEVs decreased the gut permeability of lipopolysaccharide-treated Caco-2 cells, whereas Escherichia coli-derived EVs had no significant effect. Interestingly, the expression of occludin was increased by AmEV treatment. Overall, these results imply that AmEVs may act as a functional moiety for controlling gut permeability and that the regulation of intestinal barrier integrity can improve metabolic functions in HFD-fed mice.

OBJECTIVE: Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. METHODS: We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN). RESULTS: Four subtypes of NBIA including PKAN (n = 30), PLA2G6-related neurodegeneration (n = 2), beta-propeller protein-associated neurodegeneration (n = 1), and aceruloplasminemia (n = 1) have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG). Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. CONCLUSIONS: We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.
Adult ; Age of Onset ; Alleles ; Basal Ganglia ; Brain ; Dystonia ; Freezing ; Gait ; Gene Frequency ; Genetic Association Studies ; Humans ; Iron ; Korea ; Movement Disorders ; Neurodegenerative Diseases ; Pantothenate Kinase-Associated Neurodegeneration* ; Parkinsonian Disorders ; Phenotype ; Population Characteristics* ; Referral and Consultation ; Weather