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Purpose: Monocyte chemoattractant protein-1 (MCP-1) is a member of the CC chemokine family, and the MCP-1 2518 A/G gene polymorphism is reported to be correlated with chronic inflammatory diseases, including insulin resistance and metabolic syndrome. However, few studies have investigated the association between MCP-1 gene polymorphisms and obesity in patients with type 2 diabetes mellitus (T2DM). We conducted a retrospective case-control study and evaluated the association between the MCP-1 2518 A/G polymorphism and obesity in Korean patients with T2DM. Patients and Methods: This single-center, retrospective, case-control study enrolled 526 Korean patients with T2DM. Obesity was defined using the body mass index (BMI) with a cutoff level of 25 kg/m2. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze MCP-1 2518 A/G polymorphism; the genotypes was presented as GG, AG, or AA. We compared the MCP-1 2518 A/G polymorphism with the prevalence of diabetic complications, as well as clinical and biochemical characteristics. Results: The obese group had a higher number of females and higher C-peptide, insulin, triglycerides, aspartate transaminase (AST), and alanine transaminase (ALT) levels. The obese group also had a higher prevalence of cardiovascular disease than the non-obese group. The obese group had a higher frequency of the MCP-1 2518 AA genotype and the A allele than the non-obese group. The results of multiple logistic regression analysis showed that the non-G allele of MCP-1 was significantly associated with obesity (odds ratio (OR), 1.888; P=0.016). Conclusion: This study demonstrates that the MCP-1 2518 A/G polymorphism is associated with obesity in Korean patients with T2DM. Further studies involving various ethnic groups are required to validate our results. [ABSTRACT FROM AUTHOR]

This paper investigates a dynamic liability-driven investment policy for defined-benefit (DB) plans by incorporating the loss aversion of a sponsor, who is assumed to be more sensitive to underfunding than overfunding. Through the lens of prospect theory, we first set up a loss-aversion utility function for a sponsor whose utility depends on the funding ratio in each period, obtained from stochastic processes of pension assets and liabilities. We then construct a multi-horizon dynamic control optimization problem to find the optimal investment strategy that maximizes the expected utility of the plan sponsor. A genetic algorithm is employed to provide a numerical solution for our nonlinear dynamic optimization problem. Our results suggest that the overall paths of the optimal equity allocation decline as the age of a plan participant reaches retirement. We also find that the equity portion of the portfolio increases when a sponsor is less loss-averse or the contribution rate is lower. [ABSTRACT FROM AUTHOR]

BackgroundSymptoms and signs of thyrotoxicosis are nonspecific and assessing its clinical status is difficult with conventional physical examinations and history taking. Increased heart rate (HR) is one of the easiest signs to quantify this, and current wearable devices can monitor HR. ObjectiveWe assessed the association between thyroid function and resting HR measured by a wearable activity tracker (WD-rHR) and evaluated the clinical feasibility of using this method in patients with thyrotoxicosis. MethodsThirty patients with thyrotoxicosis and 10 controls were included in the study. Participants were instructed to use the wearable activity tracker during the study period so that activity and HR data could be collected. The primary study outcomes were verification of changes in WD-rHR during thyrotoxicosis treatment and associations between WD-rHR and thyroid function. Linear and logistic model generalized estimating equation analyses were performed and the results were compared to conventionally obtained resting HR during clinic visits (on-site resting HR) and the Hyperthyroidism Symptom Scale. ResultsWD-rHR was higher in thyrotoxic patients than in the control groups and decreased in association with improvement of thyrotoxicosis. A one standard deviation–increase of WD-rHR of about 11 beats per minute (bpm) was associated with the increase of serum free T4 levels (beta=.492, 95% CI 0.367-0.616, P

This study analyzes the determinants of Korean households' intention to take out a trust-type home pension (Korean reverse mortgage) or switch from a collateral-type home pension to a trust-type home pension. Using a proportional odds logit model, we analyzed 2018 survey data on home pension demand. Trust-type home pension enrollment is most significantly influenced by homeowners' relationship with children after enrollment, followed by homeowners' need for retirement-related financial education. The presence (or absence) of a homeowner's spouse most significantly influenced conversion intention, affirming that for homeowners with a spouse, their priority in pension selection was securing their spouse's future entitlement. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) is the most common endocrine carcinoma and has frequent recurrence instances. Although PTC recurrence has been predicted using predictors established using various features and techniques, its early detection is still challenging. To address this issue, it is aimed to develop a deep‐learning model that utilizes not only the initial medical records but also the thyroid function tests (TFTs) performed periodically post‐surgery. Herein, a novel multimodal prediction model, called the hybrid architecture for multimodal analysis (HAMA), that can analyze numeric and time‐series data simultaneously, is proposed. For quantitative evaluation, fourfold cross validation is conducted on data of 1613 PTC patients including 63 locoregional recurrence patients, and the HAMA is achieved the following performance: sensitivity (0.9688); specificity (0.9781); F1‐score (0.7943); and area under the receiver‐operating characteristic curve, AUROC (0.9863). Furthermore, a real‐time prediction simulation is conducted at 6‐month intervals by reconstructing the data of each patient into real‐time data. It is demonstrated in the real‐time simulation results that the HAMA predicts PTC recurrence at least 1.5 years in advance by recalculating the recurrence probability using the additional follow‐up data. To the best of the knowledge, the HAMA is the first deep‐learning model to reflect continuous change in the physical condition of a patient post‐surgery. [ABSTRACT FROM AUTHOR]

We assume a hypothetical defined benefit (DB) pension plan that reflects the characteristics of the occupational pension in South Korea and propose a surplus optimization strategy using a regime‐switching model. Using conditional surplus at risk, we construct an optimized portfolio that limits extreme tail risks. Furthermore, we identify the surplus risk and return conditional on global macroeconomic status using a hidden Markov model. The main results are that (i) the DB pension portfolio should move from principal‐protected products to diverse capital market products, and (ii) the DB pension portfolio using the regime‐switching model outperforms an unconditional static portfolio. [ABSTRACT FROM AUTHOR]

Background: Vitamin D receptor (VDR) polymorphisms are associated with osteoporosis, diabetes, immunological diseases, and cancers. However, the association of obesity with VDR polymorphisms has shown inconsistent results, and perhaps it depends upon the characteristics of a population. Therefore, we evaluated the association between BsmI (rs1544410) and ApaI (rs7975232) polymorphisms of VDR and obesity in Korean patients with type 2 diabetes mellitus (T2DM). Methods: A total of 506 patients with T2DM participated in the study. Polymerase chain reaction-restriction fragment length polymorphism was used to analyze BsmI and ApaI polymorphisms; the genotypes were presented as BB, Bb, or bb for BsmI and AA, Aa, or aa for ApaI. Obesity was defined using the body mass index (BMI) with a cutoff level of 25 kg/m2. Results: The prevalence of obesity was higher in patients with the bb genotype than in those with BB or Bb genotypes (48.4% vs 33.9%, P = 0.031). The mean BMI was 25.2 ± 3.5 kg/m2 in patients with bb genotype and 24.1 ± 3.1 kg/m2 in patients with BB or Bb genotypes. Patients with Aa or aa genotypes showed a higher prevalence of obesity than patients with AA genotype (47.6% vs 26.1%, P = 0.043). Glycemic control parameters and lipid profiles did not show significant differences with either polymorphism. Conclusion: To our knowledge, this is the first study to assess the association between VDR polymorphisms and obesity in Korean patients with T2DM. Further studies in larger populations and multiethnic cohorts are needed to validate our findings. [ABSTRACT FROM AUTHOR]

Aims: To conduct a prospective randomized study to evaluate cilostazol, a phosphodiesterase 3 inhibitor, and compare it with aspirin for the prevention of the progression of atherosclerosis in patients with type 2 diabetes (T2D). Materials and methods: Fifty patients with T2D and carotid atherosclerotic plaques were randomly assigned to either a 200 mg/d cilostazol (CTZ) group or a 100 mg/d aspirin (ASA) group for 6 months. The primary endpoint was change in plaque volume measured by carotid three‐dimensional ultrasonography. The secondary endpoints were changes in carotid intima–media thickness (IMT) and endothelial function, assessed by laser Doppler. Results: Twenty‐four patients in the CTZ group and 23 in the ASA group were included in the final analysis. The mean ± SD age of male (n = 20) and female (n = 16) patients was 62.2 and 59.1 years, respectively. The total plaque volume was slightly decreased in the CTZ group (from 183.8 ± 52.5 to 181.5 ± 54.0 mm3; P =.567), but significantly increased in the ASA group (from 112.9 ± 21.2 to 128.5 ± 23.3 mm3; P =.043). A significant regression in the maximum IMT was observed only in the CTZ group (right: from 2.19 ± 0.17 to 1.96 ± 0.12 mm; left: from 2.02 ± 0.20 to 1.72 ± 0.19 mm). The CTZ group exhibited an increase in HDL cholesterol and a decrease in triglycerides and liver enzymes. Conclusions: Cilostazol treatment for 6 months significantly attenuated the progression of carotid plaque compared with aspirin in patients with T2D (NCT03248401). [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to investigate the association between the transcription factor 7-like 2 gene (TCF7L2) rs7903146 polymorphism and peripheral arterial disease in type 2 diabetes. Methods: In total, 1818 Korean type 2 diabetes patients were enrolled from January 2013 to December 2017. Subjects were categorized into two groups according to their duration of type 2 diabetes: long (⩾10 years, n = 771) and short (<10 years, n = 1047) durations. A multivariate logistic regression model was used for assuming an additive effect on peripheral arterial disease for the presence of a variant allele in TCF7L2 rs7903146. Results: The frequency of the minor T-allele was 7.6% (n = 139), and this allele was significantly associated with a 2.6-fold higher risk of peripheral arterial disease (odds ratio = 2.595, 95% confidence interval = 1.177–5.722, p = 0.018) in patients exhibiting a long duration of type 2 diabetes (⩾10 years). This result was significant after adjusting for age, sex, body mass index, familial history of diabetes, smoking, duration of diabetes and laboratory measurements, which included glycated haemoglobin, fasting plasma glucose and lipid profiles. In patients with diabetes < 10 years, there was no significant association between TCF7L2 rs7903146 and peripheral arterial disease (odds ratio = 1.233, 95% confidence interval = 0.492–3.093, p = 0.655). Conclusion: Our results provide evidence that genetic variation in TCF7L2 rs7903146 could increase risk for peripheral arterial disease in patients exhibiting long-standing type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Active surveillance (AS) has been considered one of the management options in patients with low-risk papillary thyroid microcarcinoma (PTMC). It is important to evaluate clinical lymph node (LN) metastasis to select appropriate candidates with low-risk disease. We investigated the predictive accuracy of computed tomography (CT) for cervical LN metastasis in patients who have PTMC with tumor characteristics appropriate for AS. Methods: This was a retrospective study. Medical records from December 2014 to the end of 2016 were reviewed. Patients who underwent thyroidectomy and who had pathologically confirmed PTMC were included. A total of 464 patients who had tumors with ultrasound (US) characteristics appropriate for AS and who underwent preoperative CT were included in the analysis. Results: CT showed higher diagnostic values especially in positive predictive value (PPV) than US. In patient-based analyses, CT showed low sensitivity and negative predictive value (NPV) (16.0% and 58.5%, respectively), but high specificity and PPV (99.6% and 97.1%, respectively) for detecting cervical LN metastasis. Similar trends were observed for the results of the central neck-level by CT (sensitivity, 14.9%; specificity, 97.4%; PPV, 82.9%; and NPV, 57.4%) in level-by-level analyses. When restricted to lateral neck levels, CT showed high diagnostic accuracy of 95.4% for detecting LN metastasis. In all analyses, CT showed better diagnostic values for cervical LN metastasis than US. Combining US and CT did not improve the diagnostic accuracy compared with CT. Conclusions: In patients with PTMC whose tumor has characteristics suitable for AS, CT had additional benefit after cervical LN assessment by US. Further studies are needed to evaluate routine initial CT scanning for patients who are candidates for AS. [ABSTRACT FROM AUTHOR]

Aim: To perform a prospective study to evaluate the effect of cilostazol (CTZ) compared with aspirin (acetylsalicylic acid; ASA) in Korean people with diabetes and subclinical coronary atherosclerosis. Materials and methods: A total of 100 people with diabetes who had mild to moderate coronary atherosclerosis, assessed by coronary computed tomographic angiography (CCTA), were randomly assigned to either 200 mg/d CTZ or 100 mg/d ASA (n = 50 each group). The primary outcome was change in coronary artery stenosis assessed by CCTA after 12 months of treatment. Secondary outcomes included changes in plaque composition, coronary artery calcium score and cardiac markers. Results: The mean age, body mass index and glycated haemoglobin concentration were 61.5 years, 25.0 kg/m2 and 56.8 mmol/mol, respectively, and were well matched between the two groups. Coronary artery stenosis decreased in the CTZ group (from 44.0 ± 2.1% to 40.4 ± 2.5%) but remained unchanged in the ASA group (from 38.9 ± 2.1% to 40.6 ± 2.1%). In the CTZ group, the non‐calcified portion of plaques decreased significantly (from 20.6 ± 3.0 to 17.3 ± 3.0 mm3), whereas it did not change significantly in the ASA group (15.2 ± 2.8 vs 16.6 ± 2.9 mm3). Increases in HDL cholesterol, decreases in triglycerides, liver enzyme and high‐sensitivity C‐reactive protein levels, and reductions in abdominal visceral fat area and insulin resistance were observed only in the CTZ group. Conclusion: CTZ treatment for 12 months decreased coronary artery stenosis and the non‐calcified plaque component. These results suggest that CTZ treatment may be an option for preventing the progression of coronary atherosclerosis in people with diabetes. [ABSTRACT FROM AUTHOR]

This open‐label, prospective study evaluated the effectiveness and safety of empagliflozin as add‐on therapy in inadequately controlled type 2 diabetes (T2D) patients (glycated haemoglobin [HbA1c], 7.5‐12%) who were already using three other types of orally active antidiabetic agents. A total of 268 T2D patients were enrolled and divided into two groups, empagliflozin (EMPA 25 mg/d, n = 142) or insulin glargine (INS, n = 126), respectively. After the treatment period of 24 weeks, HbA1c and fasting plasma glucose (FPG) were significantly reduced (HbA1c, P = 0.004; FPG, P = 0.008, respectively) in the EMPA group compared to the INS group. Also, EMPA treatment evoked a significant reduction in body weight (P < 0.001) and systolic blood pressure (P = 0.017) compared to the INS group. Hypoglycaemic adverse events were significantly higher in the INS group compared to the EMPA group (P = 0.001). In conclusion, this study demonstrated that a regimen comprising four different orally active antidiabetic agents, including EMPA, was effective and safe as a therapeutic strategy for treating T2D patients for glycaemic control and improvement of other cardiovascular and metabolic indices. [ABSTRACT FROM AUTHOR]

Background: There are inconsistent results for the effectiveness of using smartphone applications (apps) or websites on weight loss. We investigated the efficacy of a smartphone intervention using a designated app that utilizes a lifestyle intervention-focused approach, including a human coaching element, toward weight loss in overweight or obese Korean adults. Methods: One hundred four adults aged 20-60 years with a body mass index ≥23 kg/m2, who signed up for a smartphone program for weight loss (using the Noom app), were recruited. Participants received an in-person orientation about the study and app use, and a baseline blood sample was obtained. The in-app intervention with daily behavior and nutrition education content and coaching lasted 15 weeks. The primary endpoint of the study was a change in weight. The secondary endpoints were changes in metabolic risk factors such as blood pressure, waist circumference, and glucose and lipid profiles. Body composition changes were also assessed, and body weight at 52 weeks was measured to ascertain long-term effects. Results: Participants showed a clinically significant weight loss effect of −7.5% at the end of the 15-week program ( P < 0.001), and at a 52-week follow-up, a weight loss effect of −5.2% was maintained. At 15 weeks, percent body fat and visceral fat decreased by −6.0 ± 5.4% and −3.4 ± 2.7 kg, respectively (both P < 0.001). Fasting glucose level also decreased significantly by −5.7 ± 14.6 mg/dL at 15 weeks. Lipid parameters showed significant improvements, except for high-density lipoprotein cholesterol. The frequency of logging meals and exercise was associated with body fat loss. Conclusions: This advanced smartphone app was a useful tool to maintain weight loss in overweight or obese people. [ABSTRACT FROM AUTHOR]

Human dual-specificity phosphatase 26 (DUSP26) is a novel target for anticancer therapy because its dephosphorylation of the p53 tumor suppressor regulates the apoptosis of cancer cells. DUSP26 inhibition results in neuroblastoma cell cytotoxicity through p53-mediated apoptosis. Despite the previous structural studies of DUSP26 catalytic domain (residues 61–211, DUSP26-C), the high-resolution structure of its catalytically active form has not been resolved. In this study, we determined the crystal structure of a catalytically active form of DUSP26 (residues 39–211, DUSP26-N) with an additional N-terminal region at 2.0 Å resolution. Unlike the C-terminal domain-swapped dimeric structure of DUSP26-C, the DUSP26-N (C152S) monomer adopts a fold-back conformation of the C-terminal α8-helix and has an additional α1-helix in the N-terminal region. Consistent with the canonically active conformation of its protein tyrosine phosphate-binding loop (PTP loop) observed in the structure, the phosphatase assay results demonstrated that DUSP26-N has significantly higher catalytic activity than DUSP26-C. Furthermore, size exclusion chromatography-multiangle laser scattering (SEC-MALS) measurements showed that DUSP26-N (C152S) exists as a monomer in solution. Notably, the crystal structure of DUSP26-N (C152S) revealed that the N-terminal region of DUSP26-N (C152S) serves a scaffolding role by positioning the surrounding α7-α8 loop for interaction with the PTP-loop through formation of an extensive hydrogen bond network, which seems to be critical in making the PTP-loop conformation competent for phosphatase activity. Our study provides the first high-resolution structure of a catalytically active form of DUSP26, which will contribute to the structure-based rational design of novel DUSP26-targeting anticancer therapeutics. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the relationships among hip geometry, bone mineral density, and the risk of hip fracture in premenopausal women.Methods: The participants in this case-control study were 16 premenopausal women with minimal-trauma hip fractures (fracture group) and 80 age-and BMI-adjusted controls. Subjects underwent dual-energy X-ray absorptiometry (DXA) to assess BMD at the proximal femur and to obtain DXA-derived hip geometry measurements.Results: The fracture group had a lower mean femoral neck and total hip BMD than the control group (0.721 ± 0.123 vs. 0.899 ± 0.115, p <0.001 for the femoral neck BMD and 0.724 ± 0.120 vs. 0.923 ± 0.116, p <0.001 for the total hip BMD). In addition, participants in the fracture group had a longer hip axis length (HAL; p = 0.007), narrower neck shaft angle (NSA; p = 0.008), smaller cross sectional area (CSA; p < 0.001) and higher cross sectional moment of inertia (CSMI; p = 0.004) than those in control group. After adjusting for BMD, the fracture group still had a significantly longer mean HAL (p = 0.020) and narrower NSA (p = 0.006) than the control group.Conclusions: BMD is an important predictor of hip fracture in premenopausal women. Furthermore, HAL and NSA are BMD-independent predictors of hip fracture in premenopausal women. Hip geometry may be clinically useful for identification of premenopausal women for whom active fracture prevention should be considered. [ABSTRACT FROM AUTHOR]

Liriope platyphyllahas been reported to possess various biological activities, including anti-asthma, anti-inflammation, anti-diabetes, and neuriotogenic properties. In this study, we evaluated the effects of prosapogenin III isolated from the roots ofL. platyphylla(Liriopis Tuber) on inflammatory responses in lipopolysaccharide (LPS) stimulated RAW264.7 mouse macrophages. We investigated LPS-induced production/expression of inflammatory mediators such as nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxigenase-2 (COX-2), and proinflammatory cytokines, including interleukin-1β (IL-1β) and interleukin (IL)-6 in RAW264.7 cells. We also performed Western blot analysis for determination of the phosphorylation of mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) 1/2, p38, and c-Jun N-terminal kinase (JNK), and nuclear translocation of nuclear factor-κB (NF-κB) in LPS-stimulated cells. Treatment with prosapogenin III resulted in significant inhibition of NO production in LPS-stimulated Raw264.7 cells through suppression of iNOS expression. Treatment with prosapogenin III resulted in a significant decrease in expressions of COX-2, IL-1β, and IL-6 through down-regulation of their mRNA or protein in LPS-stimulated cells. In addition, treatment with prosapogenin III resulted in potently inhibited phosphorylation of three MAPKs, including ERK1/2, p38, and JNK in LPS-stimulated cells. Treatment with prosapogenin III also resulted in suppression of the nuclear translocation of NF-κB in LPS-stimulated cells. These results indicate that prosapogenin III of Liriopis Tuber has anti-inflammatory effects in activated macrophages through inhibition of production of inflammatory mediators by blockade of the MAPK/NF-κB pathway. [ABSTRACT FROM PUBLISHER]

Abstract: Clusterin (CLU) is a multifunctional glycoprotein that is overexpressed in prostate and breast cancers. Although CLU is known to be involved in the regulation of apoptosis and cell survival, the precise molecular mechanism underlying the pro-apoptotic function of nuclear CLU (nCLU) remains unclear. In this study, we identified a conserved BH3 motif in C-terminal coiled coil (CC2) region of nCLU by sequence analysis and characterized the molecular interaction of the putative nCLU BH3 domain with anti-apoptotic Bcl-2 family proteins by nuclear magnetic resonance (NMR) spectroscopy. The chemical shift perturbation data demonstrated that the nCLU BH3 domain binds to pro-apoptotic BH3 peptide-binding grooves in both Bcl-XL and Bcl-2. A structural model of the Bcl-XL/nCLU BH3 peptide complex reveals that the binding mode is remarkably similar to those of other Bcl-XL/BH3 peptide complexes. In addition, mutational analysis confirmed that Leu323 and Asp328 of nCLU BH3 domain, absolutely conserved in the BH3 motifs of BH3-only protein family, are critical for binding to Bcl-XL. Taken altogether, our results suggest a molecular basis for the pro-apoptotic function of nCLU by elucidating the residue specific interactions of the BH3 motif in nCLU with anti-apoptotic Bcl-2 family proteins. [Copyright &y& Elsevier]