Malignancy Risk of Follicular Neoplasm (Bethesda IV) With Variable Cutoffs of Tumor Size: A Systemic Review and Meta-Analysis.

CONTEXT: The decision on diagnostic lobectomy for follicular neoplasms (FN) is challenging. OBJECTIVE: This meta-analysis investigates whether an appropriate size cutoff exists for recommending surgery for thyroid nodules diagnosed as FN by fine needle aspiration. METHODS: The Ovid-Medline, EMBASE, Cochrane, and KoreaMed databases were searched for studies reporting the malignancy rate of FN/suspicious for FN (FN/SFN) according to tumor size, using search terms "fine needle aspiration," "follicular neoplasm," "lobectomy," "surgery," and "thyroidectomy." RESULTS: Fourteen observational studies comprising 2016 FN/SFN nodules with postsurgical pathologic reports were included, and 2 studies included malignancy rates with various tumor sizes. The pooled malignancy risk of FN/SFN nodules according to size was: odds ratio (OR) 2.29 (95% CI, 1.68-3.11) with cutoff of 4 cm (9 studies), OR 2.39 (95% CI, 1.45-3.95) with cutoff of 3 cm (3 studies), and OR 1.81 (95% CI, 0.94-3.50) with cutoff of 2 cm (5 studies). However, tumors ≥2 cm also showed a higher risk (OR 2.43; 95% CI, 1.54-3.82) based on the leave-one-out meta-analysis after removal of 1 influence study. When each cutoff size was evaluated by summary receiver operating characteristic (sROC) curves, the cutoff of 4 cm showed the highest summary area under the curve (sAUC, 0.645) compared to other cutoffs (sAUC, 0.58 with 2 cm, and 0.62 with 3 cm), although there was no significant difference. CONCLUSION: Although the risk of malignancy increases with increasing tumor size, the risk remains significant at all tumor sizes and no cutoff limit can be recommended as a decision-making parameter for diagnostic surgery in Bethesda IV thyroid nodules.

NQO1 regulates cell cycle progression at the G2/M phase.

Rationale: Overexpression of NAD(P)H:quinone oxidoreductase 1 (NQO1) is associated with tumor cell proliferation and growth in several human cancer types. However, the molecular mechanisms underlying the activity of NQO1 in cell cycle progression are currently unclear. Here, we report a novel function of NQO1 in modulation of the cell cycle regulator, cyclin-dependent kinase subunit-1 (CKS1), at the G2/M phase through effects on the stability of c­Fos. Methods: The roles of the NQO1/c-Fos/CKS1 signaling pathway in cell cycle progression were analyzed in cancer cells using synchronization of the cell cycle and flow cytometry. The mechanisms underlying NQO1/c-Fos/CKS1-mediated regulation of cell cycle progression in cancer cells were studied using siRNA approaches, overexpression systems, reporter assays, co-immunoprecipitation, pull-down assays, microarray analysis, and CDK1 kinase assays. In addition, publicly available data sets and immunohistochemistry were used to investigate the correlation between NQO1 expression levels and clinicopathological features in cancer patients. Results: Our results suggest that NQO1 directly interacts with the unstructured DNA-binding domain of c-Fos, which has been implicated in cancer proliferation, differentiation, and development as well as patient survival, and inhibits its proteasome-mediated degradation, thereby inducing CKS1 expression and regulation of cell cycle progression at the G2/M phase. Notably, a NQO1 deficiency in human cancer cell lines led to suppression of c-Fos-mediated CKS1 expression and cell cycle progression. Consistent with this, high NQO1 expression was correlated with increased CKS1 and poor prognosis in cancer patients. Conclusions: Collectively, our results support a novel regulatory role of NQO1 in the mechanism of cell cycle progression at the G2/M phase in cancer through effects on c­Fos/CKS1 signaling.

Graves' disease, its treatments, and the risk of atrial fibrillation: A Korean population-based study.

Background: Atrial fibrillation (AF) is occasionally diagnosed in individuals with Graves' disease. Definite treatments, including radioactive iodine therapy (RAIT) or surgery might lower the risk of AF in the literature. However, no studies have compared the effects of anti-thyroid drugs (ATDs), RAIT, and surgery on the risk of AF. Methods: This retrospective cohort study included 94,060 newly diagnosed Graves' disease patients and 470,300 controls from the Korean National Health Insurance database. The incidence of AF was evaluated in patients and controls. Patients were categorized based on treatment method into ATD (95.6%), RAIT (3.5%), and surgery (0.9%) groups. In the ATD group, the dose and duration of ATDs were calculated for each patient. In the RAIT and surgery groups, remission was defined as levothyroxine prescription. Results: Graves' disease patients had a 2.2-fold higher risk of developing AF than controls. Regardless of demographic factors, the patient group had a consistently higher risk of AF than controls, with the highest risk of AF (HR, 5.49) in the younger patient group. The surgery group had a similar risk of AF compared with controls, whereas the ATD (HR, 2.23) and RAIT (HR, 2.00) groups had increased risks of AF, even in patients reaching hypothyroid status after RAIT. Patients with higher dose or longer treatment duration of ATDs were at greater risk of AF. Conclusion: We observed differing risks of AF according to methods of treatment for Graves' disease, and that definite treatment can be an option for subjects needing sustained medical treatment considering the risk of AF.

Tuning of Peptide Cytotoxicity with Cell Penetrating Motif Activatable by Matrix Metalloproteinase-2.

Although diverse cell penetrating motifs not only from naturally occurring proteins but also from synthetic peptides have been discovered and developed, the selectivity of cargo delivery connected to these motifs into the desired target cells is generally low. Here, we demonstrate the selective cytotoxicity tuning of an anticancer KLA peptide with a cell penetrating motif activatable by matrix metalloproteinase-2 (MMP2). The anionic masking sequence introduced at the end of the KLA peptide through an MMP2-cleavable linker is selectively cleaved by MMP2 and the cationic cell penetrating motif is activated. Upon treatment of the peptide to H1299 cells (high MMP2 level), it is selectively internalized into the cells by MMP2, which consequently induces membrane disruption and cell death. In contrast, the peptide shows negligible cytotoxicity toward A549 cancer cells with low MMP2 levels. Furthermore, the selective therapeutic efficacy of the peptide induced by MMP2 is also corroborated using in vivo study.

Graves' disease and the risk of Parkinson's disease: a Korean population-based study.

Two European cohort studies have suggested that Graves' disease is associated with the development of Parkinson's disease, although the results were limited and controversial. We evaluated whether patients with Graves' disease had an increased risk of developing Parkinson's disease according to treatment modality. We included 65 380 Graves' disease patients and 326 900 healthy controls matched according to age and sex, using the Korean National Health Insurance database. The primary outcome was the incidences of Parkinson's disease amongst Graves' disease patients and controls. Subgroup analyses of Graves' disease patients were performed according to anti-thyroid drug treatment, radioactive iodine therapy and surgery. The cumulative dose and duration values of anti-thyroid drug were calculated for each patient and categorized into highest, middle and lowest tertiles. Amongst 65 380 Graves' disease patients, 301 Parkinson's disease cases were diagnosed during 453 654 person-years of follow-up. Relative to the controls, and regardless of age, sex or comorbidities, the Graves' disease patients had a 33% higher risk of developing Parkinson's disease (hazard ratio: 1.33, 95% confidence interval: 1.17-1.51). Most Graves' disease patients (96%) had received medical therapy, and increased risks of Parkinson's disease were observed in the various subgroups for cumulative dose and treatment duration. This study revealed that Graves' disease was an independent risk factor for developing Parkinson's disease, and that the risk remained elevated regardless of demographic factors or treatment duration/dosage of the anti-thyroid drug. Clinicians should be aware that Graves' disease patients have an increased risk of developing Parkinson's disease, even though Graves' disease patients are often relatively young.

Prevalence and clinical characteristics of fulminant type 1 diabetes mellitus in Korean adults: A multi-institutional joint research.

AIMS/INTRODUCTION: We aimed to determine the hospital-based prevalence and clinical features of fulminant type 1 diabetes mellitus in Korea. MATERIALS AND METHODS: We identified all patients with diabetes who regularly visited the Endocrinology outpatient clinics at eight centers for a period >1 year between January 2012 and June 2017. We investigated their medical records retrospectively. RESULTS: During this period, 76,309 patients with diabetes had been regularly followed up. Among them, 913 (1.2%) patients had type 1 diabetes mellitus . There were 462 patients with type 1 diabetes mellitus whose data at the time of the first diagnosis could be identified (359 and 103 with non-ketosis and ketosis onset, respectively). Of these, 15 (3.2% of type 1 diabetes mellitus, 14.6% of ketosis onset diabetes) patients had fulminant type 1 diabetes mellitus. The median ages at diagnosis were 40 and 27 years in the fulminant type 1 diabetes mellitus and non-fulminant type 1 diabetes mellitus groups, respectively. The patients with fulminant type 1 diabetes mellitus had higher body mass index, lower glycated hemoglobin and fasting/peak C-peptide, and lower frequent glutamic acid decarboxylase antibody-positive rate (P =0.0010) at diagnosis. Furthermore, they had lower glycated hemoglobin at the last follow-up examination than those with non-fulminant type 1 diabetes mellitus. CONCLUSIONS: In this study, the prevalence of type 1 diabetes mellitus was 1.2% among all patients with diabetes, and that of fulminant type 1 diabetes mellitus was 3.2% among those newly diagnosed with type 1 diabetes mellitus. The glycated hemoglobin levels were lower in patients with fulminant type 1 diabetes mellitus than in those with non-fulminant type 1 diabetes mellitus at diagnosis and at the last follow-up examination.

Sex Differences of Visceral Fat Area and Visceral-to-Subcutaneous Fat Ratio for the Risk of Incident Type 2 Diabetes Mellitus.

BACKGROUND: This study aimed to determine the optimal cut-off values of visceral fat area (VFA) and visceral-to-subcutaneous fat ratio (VSR) for predicting incident type 2 diabetes mellitus (T2DM). METHODS: A total of 10,882 individuals (6,835 men; 4,047 women) free of T2DM at baseline aged between 30 and 79 years who underwent abdominal computed tomography scan between 2012 and 2013 as a part of routine health check-ups were included and followed. VFA, subcutaneous fat area, and VSR on L3 vertebral level were measured at baseline. RESULTS: During a median follow-up of 4.8 years, 730 (8.1% for men; 4.3% for women) incident cases of T2DM were identified. Receiver operating characteristic curve analysis showed that the optimal cut-off values of VFA and VSR for predicting incident T2DM were 130.03 cm2 and 1.08 in men, respectively, and 85.7 cm2 and 0.48 in women, respectively. Regardless of sex, higher VFA and VSR were significantly associated with a higher risk of incident T2DM. Compared with the lowest quartiles of VFA and VSR, the highest quartiles had adjusted odds ratios of 2.62 (95% confidence interval [CI], 1.73 to 3.97) and 1.55 (95% CI, 1.14 to 2.11) in men, respectively, and 32.49 (95% CI, 7.42 to 142.02) and 11.07 (95% CI, 3.89 to 31.50) in women, respectively. CONCLUSION: Higher VFA and VSR at baseline were independent risk factors for the development of T2DM. Sex-specific reference values for visceral fat obesity (VFA ≥130 cm2 or VSR ≥1.0 in men; VFA ≥85 cm2 or VSR ≥0.5 in women) are proposed for the prediction of incident T2DM.

Associations between obesity, weight change and decreased renal function in Korean type 2 diabetic patients: a longitudinal follow-up study.

BACKGROUND: We aimed to examine the associations between the risk of decreased renal function, obesity, and weight changes in Korean type 2 diabetic patients with normal renal function. METHODS: Type 2 diabetic patients (n = 1060) who visited the diabetic clinic at Soonchunhyang University Bucheon Hospital between 2001 and 2007 with follow up surveys completed in 2016 to 2017 were recruited into the study. Decreased renal function was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2. Weight change was calculated between baseline and each follow-up survey. Multivariate analysis was used to evaluate the longitudinal association of baseline obesity and weight changes with the risk of decreased renal function. RESULTS: This study revealed that baseline obesity was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients (odds ratio [OR] 1.40; 95% confidence intervals [CI] 1.08-2.04; p = 0.025). Follow-up (mean = 12 years) revealed that weight gain > 10% was associated with the risk of decreased renal function after adjusting for clinical variables in type 2 diabetic patients with normal renal function at baseline (OR 1.43; CI 1.11-2.00; p = 0.016). Weight loss was not associated with the risk of decreased renal function in type 2 diabetic patients with normal renal function at baseline. CONCLUSIONS: Baseline obesity was associated with the increased risk of decreased renal function in Korean type 2 diabetic patients with normal renal function. Weight gain > 10% independently predicted the risk of decreased renal function. Large prospective studies are needed to clarify causal associations between obesity, weight change, and decreased renal function in patients with type 2 diabetes.

Comparison of muscle mass and quality between metabolically healthy and unhealthy phenotypes.

OBJECTIVE: The aim of this study was to examine whether higher skeletal muscle mass is associated with a metabolically healthy phenotype and whether muscle quality affects metabolic health. METHODS: This cross-sectional analysis included 20,659 participants (7,966 women) who underwent abdominal computed tomography scans during health checkups. The total abdominal muscle area (TAMA) on the third lumbar vertebral level was demarcated. Intermuscular adipose tissue and skeletal muscle area were measured. The skeletal muscle area was divided into normal attenuation muscle area (NAMA) and low attenuation muscle area (LAMA). The NAMA/TAMA index was calculated. The metabolically unhealthy phenotype was defined as having two or more components of metabolic syndrome or the presence of hypertension or diabetes. RESULTS: TAMA and skeletal muscle area were not significantly different or even lower in metabolically healthy phenotypes compared with metabolically unhealthy phenotypes. However, metabolically healthy phenotypes had significantly higher NAMA (except in women with obesity) and NAMA/TAMA index than in the metabolically unhealthy phenotypes. In people without obesity, lower NAMA/TAMA index was independently associated with higher risk of the metabolically unhealthy phenotype in the fully adjusted model. CONCLUSIONS: The metabolically healthy phenotypes had more good-quality muscles than did the metabolically unhealthy phenotypes. These results suggest that not only muscle mass but also muscle quality (i.e., degree of myosteatosis) are associated with metabolic health.

Myostatin/Appendicular Skeletal Muscle Mass (ASM) Ratio, Not Myostatin, Is Associated with Low Handgrip Strength in Community-Dwelling Older Women.

BACKGROUND/AIMS: Elevated levels of serum myostatin have been proposed as a biomarker for sarcopenia. Recent studies have shown that elevated level of serum myostatin was associated with physical fitness and performance. This study aimed to examine the significance of myostatin in the association between muscle mass and physical performance in the elderly. METHODS: This cross-sectional study is based on the Korean Frailty and Aging Cohort study involving 1053 people aged 70 years or over. Anthropometric, physical performance, and laboratory data were collected. RESULTS: The mean age of the participants was 75.8 years, and 50.7% of them were female. Serum myostatin levels in men (3.7 ± 1.2 vs. 3.2 ± 1.1 ng/mL, p < 0.001) were higher compared with that in women. Serum myostatin level was associated with appendicular skeletal muscle mass (ASM) index and eGFR by cystatin C. Serum myostatin/ASM ratio was associated with handgrip strength in women. CONCLUSION: Higher serum myostatin levels were related with higher muscle mass and better physical performances in the elderly. Serum myostatin/ASM ratio may be a predictor for physical performance rather than myostatin.

Inter- and Intra-Molecular Organocatalysis of SN2 Fluorination by Crown Ether: Kinetics and Quantum Chemical Analysis.

We present the intra- and inter-molecular organocatalysis of SN2 fluorination using CsF by crown ether to estimate the efficacy of the promoter and to elucidate the reaction mechanism. The yields of intramolecular SN2 fluorination of the veratrole substrates are measured to be very small (<1% in 12 h) in the absence of crown ether promoters, whereas the SN2 fluorination of the substrate possessing a crown ether unit proceeds to near completion (~99%) in 12 h. We also studied the efficacy of intermolecular rate acceleration by an independent promoter 18-crown-6 for comparison. We find that the fluorinating yield of a veratrole substrate (leaving group = -OMs) in the presence of 18-crown-6 follows the almost identical kinetic course as that of intramolecular SN2 fluorination, indicating the mechanistic similarity of intra- and inter-molecular organocatalysis of the crown ether for SN2 fluorination. The calculated relative Gibbs free energies of activation for these reactions, in which the crown ether units act as Lewis base promoters for SN2 fluorination, are in excellent agreement with the experimentally measured yields of fluorination. The role of the metal salt CsF is briefly discussed in terms of whether it reacts as a contact ion pair or as a "free" nucleophile F-.

Association between alcohol consumption status and obesity-related comorbidities in men: data from the 2016 Korean community health survey.

BACKGROUND: This study was performed to investigate the association between the amount of alcohol consumption or binge drinking and obesity-related comorbidities in Korean men. METHODS: A total of 103,048 men aged 19 years or older were investigated in the 2016 Korean Community Health Survey. The participants were divided into five groups according to the standard number of alcoholic drinks consumed per week. RESULTS: Of the total participants, 20.7% were in the high alcohol consumption group, consuming more than 28 drinks per week. After adjustment for clinical factors, high alcohol consumption was significantly associated with higher odds ratios (ORs) of obesity (OR, 1.449; 95% confidence interval [CI], 1.412 to 1.591; P < 0.0001), hypertension (OR, 1.76; 95% CI, 1.636 to 1.894; P < 0.0001), and dyslipidemia (OR, 1.356; 95% CI, 1.247 to 1.474; P < 0.0001). In contrast, mild to moderate alcohol consumption was associated with a lower risk of diabetes (OR, 0.799; 95% CI, 0.726 to 0.88; P = 0.0015) and high alcohol consumption was not associated with a higher risk of diabetes (OR, 0.945; 95% CI, 0.86 to 1.039; P = 0.0662). Among drinkers, except for social drinkers, binge drinking was significantly associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia. CONCLUSIONS: High alcohol consumption was associated with higher risks of obesity, hypertension, and dyslipidemia in Korean men. In contrast, high consumption was not associated with a higher risk of diabetes. In particular, binge drinkers were associated with higher risks of obesity, hypertension, diabetes, and dyslipidemia compared to non-binge drinkers.

Anti-inflammatory and Antioxidant Effects of Selenium on Orbital Fibroblasts of Patients With Graves Ophthalmopathy.

PURPOSE: In the present study, the authors investigated the effects of selenium on inflammation, hyaluronan production, and oxidative stress in primary cultured orbital fibroblasts of patients with Graves ophthalmopathy (GO). METHODS: Orbital adipose/connective tissue specimens were obtained during the course of orbital surgery for patients with GO (n = 7) and other noninflammatory problems (n = 5). After incubation with various concentrations of sodium selenite for 48 hours, supernatants from primary cultures were collected. Hyaluronan and cytokine levels were measured using commercially available enzyme-linked immunosorbent assay kits. To determine the effect of selenium on reactive oxygen species (ROS) production stimulated by H2O2 (100 µM) for 30 minutes, the cells were pretreated with various concentrations of sodium selenite for 60 minutes. RESULTS: Interleukin (IL)-6 and tumor necrosis factor-alpha levels were significantly higher in orbital fibroblasts of patients with GO than in orbital fibroblasts of control patients. Hyaluronan production was suppressed by selenium in cultured orbital fibroblasts of patients with GO. Inflammatory cytokines such as IL-1α, IL-8, and tumor necrosis factor-alpha were suppressed by selenium in cultured orbital fibroblasts of patients with GO. IL-1ß and IL-6 were not suppressed by selenium in cultured orbital fibroblasts of patients with GO. Selenium pretreatment reduced intracellular ROS generation stimulated by H2O2 in cultured orbital fibroblasts of patients with GO. CONCLUSIONS: In conclusion, hyaluronan production, inflammatory cytokines, and intracellular ROS generation were suppressed by selenium in cultured orbital fibroblasts of patients with GO. Several inflammatory cytokines may be suppressed by selenium in cultured orbital fibroblasts of patients with GO. This study provide the basis for use of selenium in the treatment of GO.

Quality Matters as Much as Quantity of Skeletal Muscle: Clinical Implications of Myosteatosis in Cardiometabolic Health.

Although age-related changes in skeletal muscles are closely associated with decreases in muscle strength and functional decline, their associations with cardiometabolic diseases in the literature are inconsistent. Such inconsistency could be explained by the fact that muscle quality-which is closely associated with fatty infiltration of the muscle (i.e., myosteatosis)-is as important as muscle quantity in cardiometabolic health. However, muscle quality has been less explored compared with muscle mass. Moreover, the standard definition of myosteatosis and its assessment methods have not been established yet. Recently, some techniques using single axial computed tomography (CT) images have been introduced and utilized in many studies, as the mass and quality of abdominal muscles could be measured opportunistically on abdominal CT scans obtained during routine clinical care. Yet, the mechanisms by which myosteatosis affect metabolic and cardiovascular health remain largely unknown. In this review, we explore the recent advances in the assessment of myosteatosis and its changes associated with aging. We also review the recent literature on the clinical implication of myosteatosis by focusing on metabolic and cardiovascular diseases. Finally, we discuss the challenges and unanswered questions that need addressing to set myosteatosis as a therapeutic target for the prevention or treatment of cardiometabolic diseases.

Association between Sleep Quality and Painless Diabetic Peripheral Neuropathy Assessed by Current Perception Threshold in Type 2 Diabetes Mellitus.

Background: It is known that the painful sensation of diabetic peripheral neuropathy (DPN) results in sleep problems in type 2 diabetes mellitus (T2DM). However, it is not known that the painless DPN also is associated with poor sleep quality in T2DM. The purpose of the current study was to investigate the association between painless DPN and poor sleep quality in T2DM. Methods: A total of 146 patients of T2DM who do not have any painful symptoms of DPN were recruited into the study. Among the patients, painless DPN was diagnosed by using the current perception threshold test. Sleep quality was assessed using the Pittsburgh Sleep Quality Index questionnaire. Results: The percentage of painless DPN was significantly higher in the poor sleep quality group than the good sleep quality group (70.0% vs. 35.5%, P<0.001). In the subscale results, stimulus values at 2,000 Hz, hypoesthesia and hyperesthesia were more common in the poor sleep quality group than in the good sleep quality group (45.7% vs. 25.0%, P=0.009; 34.3% vs. 18.4%, P=0.029; 40.0% vs. 19.7%, P=0.007, respectively). The association of painless DPN and poor sleep quality remained significant after adjustment for significant covariates (odds ratio, 3.825; 95% confidence interval, 1.674 to 8.742; P<0.001). Conclusion: The current study showed that painless DPN was associated with poor sleep quality. Future studies are required to clarify the pathophysiologic causal relationship between painless DPN and sleep quality.

Gestational diabetes in Korea: Temporal trends in prevalence, treatment, and short-term consequences from a national health insurance claims database between 2012 and 2016.

AIMS: This population-based cross-sectional study aimed to investigate recent trends in the prevalence and treatment of gestational diabetes mellitus (GDM) in Korea. We also investigated trends in annual prevalence rate of pregnancy-induced hypertension (PIH) and cesarean section (C-section) in GDM patients. METHODS: We used data from the Health Insurance Review and Assessment-National Patient Sample (HIRA-NPS) database, 2012-2016. Non-GDM (n = 53,698) and GDM (n = 7956) patient data were analyzed for each year. RESULTS: The annual increase in the prevalence of GDM was 11.1% over 2012-2016, with a significant continuously increasing trend (p < 0.0001). Age-stratified analysis showed that the annual prevalence of GDM significantly increased in patients below 40 years of age, but was not statistically significant as an increasing trend in patients above 40 years of age. Annual PIH prevalence rate among GDM women showed decreasing trend but was not statistically significant. An annual increase in C-section rate above 5% in GDM patients was statistically significant in both unadjusted and adjusted for age and PIH models. CONCLUSIONS: The prevalence of GDM in Korean women and C-section rates in women with GDM showed a significantly increasing trend, 2012-2016. There is a need for further efforts to monitor this trend and to identify associated risk factors for GDM in Korean women.

Relationship of Sarcopenia with Microcirculation Measured by Skin Perfusion Pressure in Patients with Type 2 Diabetes.

BACKGROUND: Few studies have examined the relationship of sarcopenia with the microcirculation. The current study investigated the relationship of sarcopenia with microcirculatory function, as assessed by skin perfusion pressure (SPP), in type 2 diabetes mellitus (T2DM) patients. METHODS: In total, 102 T2DM patients who underwent SPP measurements and bioelectrical impedance analysis (BIA) were enrolled in this cross-sectional study. SPP was assessed using the laser Doppler technique. Sarcopenia was defined as low height-adjusted appendicular muscle mass (men, <7 kg/m2; women, <5.7 kg/m2) using BIA. We divided the participants into two groups based on SPP (≤50 and >50 mm Hg), and an SPP below 50 mm Hg was considered to reflect impaired microcirculation. RESULTS: Fourteen patients (13.7%) were diagnosed with impaired microcirculatory function of the lower limb based on SPP. The prevalence of sarcopenia in all subjects was 11.8%, but the percentage of patients with an SPP ≤50 mm Hg who had sarcopenia was more than triple that of patients with an SPP >50 mm Hg (28.6% vs. 9.1%, P=0.036). A significant positive correlation was found between SPP and appendicular muscle mass adjusted for height (P=0.041 for right-sided SPP). Multiple logistic regression analysis showed that patients with sarcopenia had an odds ratio of 4.1 (95% confidence interval, 1.01 to 24.9) for having an SPP ≤50 mm Hg even after adjustment for confounding factors. CONCLUSION: These results suggest that sarcopenia may be significantly associated with impaired microcirculation in patients with T2DM. Nonetheless, the small number of patients and wide CI require cautious interpretation of the results.

Stimuli-Responsive Conformational Transformation of Peptides for Tunable Cytotoxicity.

The stimuli-responsive conformational transformation of peptides possessing a constrained form triggered by specific biological microenvironment would provide an effective strategy for the development of highly specific peptide therapeutics. Here, we developed a peptide containing a cytotoxic helical KLA sequence with therapeutic specificity through the use of stimuli-responsive conformational transformation. The KLA peptide is modified to form a cyclic structure to allow for constrained helicity that confers low cytotoxicity. The modified KLA peptide is electrostatically complexed to hyaluronic acid to facilitate enhanced endocytosis into the cancer cells. After endocytosis, the peptide is released from the complex into the cellular cytoplasm by hyaluronidases on the surface of the cellular membrane. Specific intracellular stimuli then trigger the release of the strain that suppresses peptide helicity, and the inherent helical conformation of the KLA peptide is restored. Therefore, the stimuli-responsive conformational transformation of a peptide from low to high helicity selectively induces cell death by disruption of the plasma and mitochondrial membrane.

Prognostic value of acoustic structure quantification in patients with Hashimoto's thyroiditis.

OBJECTIVES: Assessment of thyroid parenchymal echogenicity on ultrasonography is a predictor of future thyroid dysfunction. Our objective was to determine the prognostic value of acoustic structure quantification (ASQ) to predict the outcome of patients with Hashimoto's thyroiditis (HT). MATERIALS AND METHODS: We prospectively evaluated 90 patients with HT using ASQ from May to December 2013. Surveillance for the development of overt hypothyroidism was conducted over a median period of 40 months (3-55). ASQ were dichotomized based on optimal cutoff values obtained from ROC curve analysis. The probability of developing overt hypothyroidism was compared between the dichotomized subgroups using Kaplan-Meier analysis and log-rank tests. Multivariate Cox regression analysis was performed to determine significant prognostic factors. RESULTS: The cumulative rate of overt hypothyroidism was 67.7%. The median interval to overt hypothyroidism was 27.9 months (95% confidence interval, 12.0-38.0 months). There was no significant difference in the risk of overt hypothyroidism using qualitative echogenicity between groups (p = 0.669) according to Kaplan-Meier analysis. However, the ASQ average (p < 0.001), standard deviation (p = 0.015), and focal disturbance ratio (p < 0.001) were significantly associated with an increased risk of overt hypothyroidism. Multivariate Cox regression analysis revealed that a higher ASQ average (hazard ratio, 1.03; p = 0.03) and higher thyroid-stimulating hormone level (hazard ratio, 1.02; p = 0.02) were independent predictors of overt hypothyroidism. CONCLUSIONS: ASQ has potential as a prognostic biomarker for predicting the risk of overt hypothyroidism in patients with HT. KEY POINTS: • ASQ provides quantitative prognostic information of thyroid parenchymal echogenicity. • ASQ parameters improved the stratification of patients who are prone to develop overt hypothyroidism in HT. • ASQ can serve as prognostic biomarker in HT.

Efficacy and Safety of Prescription Omega-3 Fatty Acids Added to Stable Statin Therapy in Korean Patients with Type 2 Diabetes and Hypertriglyceridemia: a Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to investigate the effects of omega-3 fatty acids added to statin monotherapy in Korean patients with type 2 diabetes who have persistent hypertriglyceridemia despite statin therapy. METHODS: This study was a randomized controlled trial conducted in 4 clinical sites between February 2009 and February 2011. The inclusion criteria were patients with type 2 diabetes who had received ≥6 weeks of statin therapy and had fasting triglyceride (TG) levels ≥1.7mmol/L and low-density lipoprotein (LDL) cholesterol levels <2.6 mmol/L. The study regimen consisted of 16 weeks of randomized treatment with omega-3 fatty acids (4 g/day) plus a statin (n=26) or statin only (n=30). The primary endpoint was the change from baseline to final visit in mean TG level. RESULTS: A total of 56 participants were analyzed. At week 16, the change in the TG level in the combination therapy group differed significantly from the change in the statin monotherapy group (-34.8% vs. -15.2%, p=0.0176). Treatment with omega-3 fatty acids plus a statin was also associated with a significant decrease in non-high-density lipoprotein cholesterol compared with baseline, but the difference was not significant compared with the statin monotherapy group (-8.0% vs. -2.5%, p=0.165). The changes in LDL cholesterol and HbA1c levels did not differ significantly between groups. The study medications were well tolerated, and adverse events were comparable between two groups. CONCLUSION: Adding omega-3 fatty acids to statin treatment reduced TG levels more effectively than statin monotherapy without undesirable effects in Korean type 2 diabetic patients who had hypertriglyceridemia despite well-controlled LDL cholesterol on stable statin therapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02305355.