Different Molecular Phenotypes of Progression in BRAF- and RAS-Like Papillary Thyroid Carcinoma

Background@#Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RASlike (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. @*Methods@#We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. @*Results@#Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection- invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. @*Conclusion@#The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.

Postprandial Free Fatty Acids at Mid-Pregnancy Increase the Risk of Large-for-Gestational-Age Newborns in Women with Gestational Diabetes Mellitus

Background@#To investigate the association between free fatty acid (FFA) level at mid-pregnancy and large-for-gestational-age (LGA) newborns in women with gestational diabetes mellitus (GDM). @*Methods@#We enrolled 710 pregnant women diagnosed with GDM from February 2009 to October 2016. GDM was diagnosed by a ‘two-step’ approach with Carpenter and Coustan criteria. We measured plasma lipid profiles including fasting and 2-hour postprandial FFA (2h-FFA) levels at mid-pregnancy. LGA was defined if birthweights of newborns were above the 90th percentile for their gestational age. @*Results@#Mean age of pregnant women in this study was 33.1 years. Mean pre-pregnancy body mass index (BMI) was 22.4 kg/m2. The prevalence of LGA was 8.3% (n=59). Levels of 2h-FFA were higher in women who delivered LGA newborns than in those who delivered non-LGA newborns (416.7 μEq/L vs. 352.5 μEq/L, P=0.006). However, fasting FFA was not significantly different between the two groups. The prevalence of delivering LGA newborns was increased with increasing tertile of 2h-FFA (T1, 4.3%; T2, 9.8%; T3, 10.7%; P for trend <0.05). After adjustment for maternal age, pre-pregnancy BMI, and fasting plasma glucose, the highest tertile of 2h-FFA was 2.38 times (95% confidence interval, 1.11 to 5.13) more likely to have LGA newborns than the lowest tertile. However, there was no significant difference between groups according to fasting FFA tertiles. @*Conclusion@#In women with GDM, a high 2h-FFA level (but not fasting FFA) at mid-pregnancy is associated with an increasing risk of delivering LGA newborns.

Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell

BackgroundUmbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.MethodsInsulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.ResultsGlucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.ConclusionUC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell

BackgroundUmbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell.MethodsInsulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell.ResultsGlucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSC-CM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance.ConclusionUC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Vitamin D Deficiency at Mid-Pregnancy Is Associated with a Higher Risk of Postpartum Glucose Intolerance in Women with Gestational Diabetes Mellitus

BACKGROUND: To evaluate the association between serum 25-hydroxyvitamin D (25(OH)D) at mid-pregnancy and postpartum glucose intolerance in women with gestational diabetes mellitus (GDM).METHODS: We enrolled 348 pregnant women diagnosed with GDM from August 2012 to October 2016. We measured serum 25(OH)D levels at mid-pregnancy and carried out a 75-g oral glucose tolerance test at 6 to 12 weeks after delivery. Vitamin D deficiency was defined as serum 25(OH)D <20 ng/mL.RESULTS: The prevalence of vitamin D deficiency was 76.7% (n=267). Women with vitamin D deficiency had a higher prevalence of postpartum glucose intolerance than did those without vitamin D deficiency (48.7% vs. 32.1%, P=0.011). Serum 25(OH)D level was negatively correlated with hemoglobin A1c at antepartum and postpartum period (antepartum: r=−0.186, P=0.001; postpartum: r=−0.129, P=0.047). Homeostasis model assessment of β-cell function was positively correlated with serum 25(OH)D level only postpartum (r=0.138, P=0.035). The risk of postpartum glucose intolerance was 2.00 times (95% confidence interval, 1.13 to 3.55) higher in women with vitamin D deficiency than in those without vitamin D deficiency (P=0.018).CONCLUSION: In women with GDM, vitamin D deficiency at mid-pregnancy is associated with an elevated risk of postpartum glucose intolerance.

Umbilical Cord-Mesenchymal Stem Cell-Conditioned Medium Improves Insulin Resistance in C2C12 Cell

Background@#Umbilical cord-mesenchymal stem cell-conditioned medium (UC-MSC-CM) has emerged as a promising cell-free therapy. The aim of this study was to explore the therapeutic effects of UC-MSC-CM on insulin resistance in C2C12 cell. @*Methods@#Insulin resistance was induced by palmitate. Effects of UC-MSC-CM on insulin resistance were evaluated using glucose uptake, glucose transporter type 4 (GLUT4) translocation, the insulin-signaling pathway, and mitochondrial contents and functions in C2C12 cell. @*Results@#Glucose uptake was improved by UC-MSC-CM. UC-MSC-CM treatment increased only in membranous GLUT4 expression, not in cytosolic GLUT4 expression. It restored the insulin-signaling pathway in insulin receptor substrate 1 and protein kinase B. Mitochondrial contents evaluated by mitochondrial transcription factor A, mitochondrial DNA copy number, and peroxisome proliferator-activated receptor gamma coactivator 1-alpha were increased by UC-MSC-CM. In addition, UC-MSC-CM significantly decreased mitochondrial reactive oxygen species and increased fatty acid oxidation and mitochondrial membrane potential. There was no improvement in adenosine triphosphate (ATP) contents, but ATP synthesis was improved by UC-MSCCM. Cytokine and active factor analysis of UC-MSC-CM showed that it contained many regulators inhibiting insulin resistance. @*Conclusion@#UC-MSC-CM improves insulin resistance with multiple mechanisms in C2C12 cell.

Higher Prevalence and Progression Rate of Chronic Kidney Disease in Elderly Patients with Type 2 Diabetes Mellitus

BACKGROUND: To evaluate the prevalence of chronic kidney disease (CKD) and progression rate to CKD in elderly patients with type 2 diabetes mellitus (T2DM). METHODS: We investigated the medical records of 190 elderly patients (65 years or older) with T2DM from 2005 to 2011 in 6-month increments. Mean follow-up duration was 64.5 months. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m² and/or the presence of albuminuria. RESULTS: The mean age was 70.4 years and mean diabetes duration was 10.6 years. Among all the participants, 113 patients (59.5%) had CKD. The eGFR was significantly decreased between baseline (65.7±15.0 mL/min/1.73 m²) and the end of follow-up (52.7±17.5 mL/min/1.73 m², P < 0.001). At the end of follow-up, the prevalence of eGFR < 60 mL/min/1.73 m² had increased by 61.6% (at baseline, 44.2%). Furthermore, in patients with eGFR ≥60 mL/min/1.73 m², the progression rate to more than CKD stage 3 was 39.6% at the end of follow-up; 30.2% of elderly diabetic patients had progressed to albuminuria from normoalbuminuria. Kaplan-Meier analysis showed that the time interval to worsening nephropathy was significantly shorter in elderly patients with diabetes duration ≥10 years than in those with diabetes duration < 5 years (P=0.018). CONCLUSION: CKD was commonly observed in older patients with T2DM, and the progression rate to CKD is also high. Consequently, it is important to identify and manage CKD as early as possible in elderly patients with T2DM, especially in those with diabetes duration ≥10 years.

Efficacy and Safety of Sustained-Release Recombinant Human Growth Hormone in Korean Adults with Growth Hormone Deficiency

PURPOSE: The administration of recombinant human growth hormone in adults with growth hormone deficiency has been known to improve metabolic impairment and quality of life. Patients, however, have to tolerate daily injections of growth hormone. The efficacy, safety, and compliance of weekly administered sustained-release recombinant human growth hormone (SR-rhGH, Declage(TM)) supplement in patients with growth hormone deficiency were evaluated. MATERIALS AND METHODS: This trial is 12-week prospective, single-arm, open-label trial. Men and women aged > or =20 years with diagnosed growth hormone deficiency (caused by pituitary tumor, trauma and other pituitary diseases) were eligible for this study. Each subject was given 2 mg (6 IU) of SR-rhGH once a week, subcutaneously for 12 weeks. Efficacy and safety at baseline and within 30 days after the 12th injection were assessed and compared. Score of Assessment of Growth Hormone Deficiency in Adults (AGHDA score) for quality of life and serum IGF-1 level. RESULTS: The IGF-1 level of 108.67+/-74.03 ng/mL was increased to 129.01+/-68.37 ng/mL (p=0.0111) and the AGHDA QoL score was decreased from 9.80+/-6.51 to 7.55+/-5.76 (p<0.0001) at week 12 compared with those at baseline. Adverse events included pain, swelling, erythema, and warmth sensation at the administration site, but many adverse events gradually disappeared during the investigation. CONCLUSION: Weekly administered SR-rhGH for 12 weeks effectively increased IGF-1 level and improved the quality of life in patients with GH deficiency without serious adverse events.

Low Serum Testosterone Concentrations in Hospitalized Men with Poorly Controlled Type 2 Diabetes

Our aim was to examine whether serum testosterone concentrations are in fact low in hospitalized men with poorly controlled type 2 diabetes compared with healthy men. In this study, 79 men aged 40 years or older (41 healthy men and 38 men with type 2 diabetes) were included. Total testosterone and sex hormone-binding globulin levels were measured. The average duration of diagnosed diabetes was 10.8 years and the mean glycated hemoglobin value was 10.8%. Total testosterone concentrations were lower in men with type 2 diabetes than in healthy men, after adjusting for age and body mass index (3.83+/-0.32 ng/mL vs. 5.63+/-0.31 ng/mL, P<0.001). In conclusion, this study shows that serum testosterone concentrations are lower in hospitalized men with poorly controlled type 2 diabetes than in healthy men. Therefore, men with poorly controlled type 2 diabetes should undergo further assessment for hypogonadism.

Use of ultrasound Doppler to determine tooth vitality in a discolored tooth after traumatic injury: its prospects and limitations

When a tooth shows discoloration and does not respond to the cold test or electric pulp test (EPT) after a traumatic injury, its diagnosis can be even more difficult due to the lack of proper diagnostic methods to evaluate its vitality. In these case reports, we hope to demonstrate that ultrasound Doppler might be successfully used to evaluate the vitality of the tooth after trauma, and help reduce unnecessary endodontic treatments. In all three of the present cases, the teeth were discolored after traumatic injuries and showed negative responses to the cold test and EPT. However, they showed distinctive vital reactions in the ultrasound Doppler test during the whole observation period. In the first case, the tooth color returned to normal, and the tooth showed a positive response to the cold test and EPT at 10 wk after the injury. In the second case, the tooth color had returned to its normal shade at 10 wk after the traumatic injury but remained insensitive to the cold test and EPT. In the third case, the discoloration was successfully treated with vital tooth bleaching.

Is stopping of anticoagulant therapy really required in a minor dental surgery?: How about in an endodontic microsurgery?

Nowadays, oral anticoagulants are commonly prescribed to numerous patients for preventing cardiovascular accident such as thromboembolism. An important side effect of anticoagulant is anti-hemostasis. In a major surgery, the oral anticoagulant therapy (OAT) regimen must be changed before the surgery for proper post-operative bleeding control. However, in a minor dental surgery and endodontic surgery, the necessity for changing or discontinuing the OAT is open to debate. In this study, risks of the consequences were weighed and analyzed. In patients who stop the OAT, the occurrence of thromboembolic complication is rare but the result is fatal. In patients who continuing the OAT, post-operative bleeding can be controlled well with the local hemostatic measures. In the endodontic surgery, there are almost no studies about this issue. The intra-operative bleeding control is particularly important in the endodontic surgery because of its delicate and sensitive procedures such as inspection of resected root surface using dental microscope and retrograde filling. Further studies are necessary about this issue in the viewpoint of endodontic surgery.

Management of Type 2 Diabetes Mellitus in Older Adults

In the near future, the majority of patients with diabetes will be adults aged 65 or older. Unlike young adults with diabetes, elderly diabetic people may be affected by a variety of comorbid conditions such as depression, cognitive impairment, muscle weakness (sarcopenia), falls and fractures, and physical frailty. These geriatric syndromes should be considered in the establishment of treatment goals in older adults with diabetes. Although there are several guidelines for the management of diabetes, only a few are specifically designed for the elderly with diabetes. In this review, we present specific conditions of elderly diabetes which should be taken into account in the management of diabetes in older adults. We also present advantages and disadvantages of various glucose-lowering agents that should be considered when choosing a proper regimen for older adults with diabetes.

Serum TSH Level in Healthy Koreans and the Association of TSH with Serum Lipid Concentration and Metabolic Syndrome

BACKGROUND/AIMS: The proper treatment of subclinical hypothyroidism and the normal range of serum thyroid stimulating hormone (TSH) concentration are intensely debated. However, few reports have investigated TSH concentrations in Asian ethnic groups. Therefore, the present study was designed to define the TSH reference range in a Korean population and to investigate the metabolic significance of TSH concentration. METHODS: We enrolled patients who underwent medical examination at the CHA Bundang Medical Center. Anthropometric data were evaluated, and serum TSH, free T4, and lipid profiles were assayed. RESULTS: A total of 7,270 subjects were included. Mean TSH concentration of the study population was 1.82 +/- 0.95 mU/L, and we observed a sex-related difference in TSH concentration (male, 1.67 +/- 0.87 mU/L; female, 2.02 +/- 1.01 mU/L; p < 0.01). When the 2.5 and 97.5 percentiles were calculated, 95% TSH reference limits were 0.52-4.29 mU/L. TSH concentration was higher in elderly subjects, during winter, in postmenopausal women, and in obese males. Moreover, TSH showed significantly positive correlations with serum total cholesterol, triglyceride, and low density lipoprotein cholesterol regardless of sex, age, season, obesity, or menopausal status (all p < 0.01). Finally, TSH concentration was positively related to the prevalence of metabolic syndrome. CONCLUSIONS: We demonstrated the association between TSH concentration within the normal reference range and serum lipid levels. TSH concentration varies according to sex, age, season, and body mass index (only in males). Moreover, high normal TSH levels were significantly associated with an increased prevalence of metabolic syndrome, which may be of importance when evaluating subjects with high normal TSH concentration.

The Clinical Characteristics of the Newly Diagnosed Early Onset (< 40 Years Old) Diabetes in Outpatients' Clinic / 당뇨병

BACKGROUND: The prevalence of type 2 diabetes in young adults and adolescents has increased in the last decade according to the increasing obese population. The aim of this study was to examine the clinical characteristics of patients diagnosed with diabetes mellitus before the age of 40 years as compared with patients diagnosed at older ages. METHODS: This was a cross-sectional, retrospective study using data from 350 diabetic patients who were diagnosed with diabetes in an outpatient setting between January 2005 and December 2007. Patients were diagnosed according to the criteria set forth by the American Diabetes Association. We examined the clinical characteristics and laboratory data of the patients through review of medical records and compared the early-onset diabetic patients ( or = 40 years old). RESULTS: The frequency of early-onset diabetes and usual-onset diabetes were 31.1% (n=109) and 68.9% (n=241), respectively. The early-onset diabetic patients more often had a positive family history of diabetes; higher HbA1c, fasting glucose, and postprandial glucose levels; experienced typical symptoms more frequently; had microalbuminuria more frequently; and required insulin therapy as initial treatment more frequently as compared to usual-onset diabetic patients, and these differences were significant. Conversely, hypertension was significantly more common in the usual-onset diabetic patients. CONCLUSION: It could be concluded that we should control early onset diabetes more strictly to prevent its complication because early onset diabetic patients represented more severe hyperglycemia and had more prevalent microalbuminuria.

Thyroid disease in women / 대한내과학회지

No abstract available.

Thyroid disease in women / 대한내과학회지

No abstract available.

Effect of Valsartan on Blood Pressure and Urinary Albumin Excretion in Hypertensive Type 2 Diabetic Patients: An Open-Label, Multicenter Study / 당뇨병

BACKGROUND: Activation of renin-angiotensin system (RAS) has been an important mechanism of microvascular and macrovascular complications in diabetic patients. It has been reported that RAS blockades reduce the development and progression of diabetic nephropathy. The aim of this study was to evaluate whether valsartan, an angiotensin II receptor blocker (ARB), reduced blood pressure and urinary albumin excretion rate (UAER) in hypertensive type 2 diabetic patients. METHOD: Three hundred forty-seven hypertensive type 2 diabetic patients who had not taken angiotensin converting enzyme inhibitors or ARB for 6 months prior to this study were enrolled. We measured blood pressure and UAER before and after 24 weeks of valsartan treatment. RESULT: Baseline mean systolic and diastolic blood pressure was 143 +/- 15 and 87 +/- 11 mmHg, respectively and the median albumin excretion rate was 27 ug/mg. Reduction in systolic and diastolic blood pressure was 16 mmHg/10 mmHg and the median UAER was 19.3 ug/mg after 24 weeks (P < 0.01, respectively). When we divided the subjects into three groups according to the UAER (normoalbuminuria, microalbuminuria and macroalbuminuria), significant changes were reported in the microalbuminuria and the macroalbuminuria groups. Thirty-eight (42%) patients with microalbuminuria improved to normoalbuminuria and twelve (41%) patients with macroalbuminuria improved to microalbuminuria. We found an association between the improvement of blood pressure and UAER (R = 0.165, P = 0.015). CONCLUSION: We concluded that valsartan reduces urinary albumin excretion and blood pressure in hypertensive type 2 diabetic patients.

Plasma total homocysteine and macrovascular complications are associated with food and nutrient intake in patients with Type II diabetes mellitus

The present study was conducted to document the association between plasma homocysteine levels and the presence of macrovascular angiopathy with food and nutrient intake patterns among patients with Type II diabetes mellitus in Korea. Plasma total homocysteine concentration was analyzed by HPLC-fluorescence detector method in 127 patients with non-insulin dependent diabetes mellitus. Logistic regression analyses were performed respectively to study the association of plasma homocysteine levels with clinical and dietary characteristics and macroangiopathy (MA). The average plasma homocysteine level of patients with MA was 14.2 micromol/l, which was significantly higher than that of patients without MA (11.4 micromol/l). The proportions of patients with MA showed a significant difference, being 32.3% in hyperhomocysteinemic (>14.0 micromol/l) patients and 13.5% in others with homocysteine levels lower than 14.0 micromol/l. Odds ratios for macroangiopathy by tertile increase of plasma homocysteine concentration were 1.633 (Q2) and 4.831 (Q3), when adjusted for age, sex, and cigarette smoking. Patients with MA consumed reduced amounts of vitamin B1, B2, and folate. The results indicate that the plasma homocysteine levels are significantly increased in NIDDM patients who have macroangiopathy. Dietary management such as increased fruits and vegetables and decreased potatoes and starches might be beneficial for the prevention of macroangiopathy in diabetic patients.

A Case of Non-islet Cell Tumor Hypoglycemia / 대한내분비학회지

Mesenchymal tumors including hemangiopericytomas, hepatocellular tumors, adrenal carcinomas, and a variety of other large tumors have been reported to produce excessive amounts of insulin-like growth factor (IGF) type II precursor, which binds weakly to insulin receptors and strongly to IGF-I receptors, leading to insulin like actions. In addition to increased IGF-II production, IGF-II bioavailability is increased due to complex alterations in circulating binding proteins. The authors of this article diagnosed non-islet cell tumor hypoglycemia from an 81-year-old male patient suffering from repetitive fasting hypoglycemia while he has not received any treatment for pulmonary hemangiopericytoma diagnosed in the past. Moreover, this topic is getting reported as the authors have experienced a significant improvement of catamnesis by a treatment with glucocorticoid.

The Role of Polymorphism of Adiponectin Gene in the Atherosclerosis / 대한내분비학회지

No abstract available.