Differentially Expressed Potassium Channels Are Associated with Function of Human Effector Memory CD8+T cells

The voltage-gated potassium channel, Kv1.3, and the Ca2+-activated potassium channel, KCa3.1, regulate membrane potentials in T cells, thereby controlling T cell activation and cytokine production. However, little is known about the expression and function of potassium channels in human effector memory ( EM) CD8+ T cells that can be further divided into functionally distinct subsets based on the expression of the interleukin ( IL)-7 receptor alpha ( IL-7R alpha) chain. Herein, we investigated the functional expression and roles of Kv1.3 and KCa3.1 in EM CD8+ T cells that express high or low levels of the IL-7 receptor alpha chain ( IL-7R alpha(high) and IL-7R alpha(low), respectively). In contrast to the significant activity of Kv1.3 and KCa3.1 in IL-7Rahigh EM CD8+ T cells, IL-7Ralow EM CD8+ T cells showed lower expression of Kv1.3 and insignificant expression of KCa3.1. Kv1.3 was involved in the modulation of cell proliferation and IL-2 production, whereas KCa3.1 affected the motility of EM CD8+ T cells. The lower motility of IL-7Ralow EM CD8+ T cells was demonstrated using transendothelial migration and motility assays with intercellular adhesion molecule 1-and/or chemokine stromal cell-derived factor-1 alpha-coated surfaces. Consistent with the lower migration property, IL-7Ralow EM CD8+ T cells were found less frequently in human skin. Stimulating IL-7Ralow EM CD8+ T cells with IL-2 or IL-15 increased their motility and recovery of KCa3.1 activity. Our findings demonstrate that Kv1.3 and KCa3.1 are differentially involved in the functions of EM CD8+ T cells. The weak expression of potassium channels in IL-7Ralow EM CD8+ T cells can be revived by stimulation with IL-2 or IL-15, which restores the associated functions. This study suggests that IL-7Rahigh EM CD8+ T cells with functional potassium channels may serve as a reservoir for effector CD8+ T cells during peripheral inflammation.112Ysciescopu

Prospective Validation of FibroTest in Comparison with Liver Stiffness for Predicting Liver Fibrosis in Asian Subjects with Chronic Hepatitis B

Liver stiffness measurement (LSM) and FibroTest (FT) are frequently used as non-invasive alternatives for fibrosis staging to liver biopsy. However, to date, diagnostic performances of Enhanced Liver Fibrosis (ELF) test, which consists of hyaluronic acid, aminoterminal propeptide of procollagen type-III, and tissue inhibitor of matrix metalloproteinases-1, have not been compared to those of LSM and FT in Asian chronic hepatitis B (CHB) patients.Between June 2010 and November 2011, we prospectively enrolled 170 CHB patients who underwent liver biopsies along with LSM, FT, and ELF. The Batts system was used to assess fibrosis stages.Areas under receiver operating characteristic curves (AUROCs) to predict significant fibrosis (F≥2), advanced fibrosis (F≥3), and cirrhosis (F = 4) were 0.901, 0.860, and 0.862 for ELF, respectively; 0.937, 0.956, and 0.963 for LSM; and 0.896, 0.921, and 0.881 for FT. AUROCs to predict F≥2 were similar between each other, whereas LSM and FT had better AUROCs than ELF for predicting F≥3 (both p<0.05), and LSM predicted F4 more accurately than ELF (p<0.05). Optimized cutoffs of ELF to maximize sum of sensitivity and specificity were 8.5, 9.4, and 10.1 for F≥2, F≥3, and F = 4, respectively. Using suggested ELF, LSM and FT cutoffs to diagnose F1, F2, F3, and F4, 91 (53.5%), 117 (68.8%), and 110 (64.7%) patients, respectively, were correctly classified according to histological results.ELF demonstrated considerable diagnostic value in fibrosis staging in Asian CHB patients, especially in predicting F≥2. However, LSM consistently provided better performance for predicting F≥3 and F4

A Case of Multiple Endocrine Neoplasia Type 1 Combined with Papillary Thyroid Carcinoma

This is the first report of papillary thyroid carcinoma combined with multiple endocrine neoplasia type 1 (MEN1) in Korea. MEN1 is a hereditary disease comprising neoplastic disorders such as pituitary, parathyroid and pancreatic neuroendocrine tumor, such as gastrinoma. But papillary thyroid cancer was never regarded as its component before in Korea. Herein we present a 39-year-old woman who manifested typical features of MEN1 with a coincidental papillary thyroid carcinoma. Although the family history of MEN1 was definite, her genetic analysis of DNA had revealed no germline mutation in MEN1 gene locus. Unidentified culprit gene unable us further genetic study to find LOH (loss of heterogeneity) in 11q13, the possible explanation of papillary thyroid carcinoma as a new component of MEN1. As we have first experienced a case of MEN1 combined with papillary thyroid carcinoma in Korea, we report it with the review of literature

Multiple Endocrine Neoplasia Type 1 with Multiple Leiomyomas Linked to a Novel Mutation in the MEN1 Gene

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited syndrome. MEN1 is characterized by the presence of functioning and nonfunctioning tumors or hyperplasia of the pituitary gland, parathyroid glands, and pancreatic islet cells. In addition, MEN1 carriers can have adrenal or thyroid tumors and non-endocrine tumors, such as lipomas, angiofibromas, and leiomyomas. Although leiomyoma is not a major component of MEN1, it is thought to occur more frequently than expected. However, there has been no report of a case of MEN1 with leiomyoma in Korea so far. This report describes a patient with multiple leiomyomas in MEN1. A 50-year-old woman was referred for further evaluation of elevated calcium levels and osteoporosis. Biochemical abnormalities included hypercalcemia with elevated parathyroid hormone. There was hyperprolactinemia with pituitary microadenoma in sella MRI. An abdominal MRI demonstrated adrenal nodules and leiomyomas in the bladder and uterus. Endoscopic ultrasonography demonstrated esophageal leiomyoma and pancreatic islet cell tumor. A subtotal parathyroidectomy with thymectomy was performed. Sequencing of the MEN1 gene in this patient revealed a novel missense mutation (D350V, exon 7). This is the first case of MEN1 accompanied with multiple leiomyomas, parathyroid adenoma, pituitary adenoma, pancreatic tumor, and adrenal tumor

Efficacy and Safety of Evogliptin Add-on Therapy to Dapagliflozin/Metformin Combinations in Patients with Poorly Controlled Type 2 Diabetes Mellitus: A 24-Week Multicenter Randomized Placebo-Controlled Parallel-Design Phase-3 Trial with a 28-Week Extension

Background This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated

A Multiinstitutional Consensus Study on the Pathologic Diagnosis of Endometrial Hyperplasia and Carcinoma

BACKGROUND: The purpose of this study was to examine the reproducibility of both the diagnosis of endometrial hyperplasia (EH) or adenocarcinoma, and the histologic grading (HG) of endometrioid adenocarcinoma (EC). METHODS: Ninety-three cases of EH or adenocarcinomas were reviewed independently by 21 pathologists of the Gynecologic Pathology Study Group. A consensus diagnosis was defined as agreement among more than two thirds of the 21 pathologists. RESULTS: There was no agreement on the diagnosis in 13 cases (14.0%). According to the consensus review, six of the 11 EH cases (54.5%) were diagnosed as EH, 48 of the 57 EC cases (84.2%) were EC, and 5 of the 6 serous carcinomas (SC) (83.3%) were SC. There was no consensus for the 6 atypical EH (AEH) cases. On the HG of EC, there was no agreement in 2 cases (3.5%). According to the consensus review, 30 of the 33 G1 cases (90.9%) were G1, 11 of the 18 G2 cases (61.1%) were G2, and 4 of the 4 G3 cases (100.0%) were G3. CONCLUSIONS: The consensus study showed high agreement for both EC and SC, but there was no consensus for AEH. The reproducibility for the HG of G2 was poor. We suggest that simplification of the classification of EH and a two-tiered grading system for EC will be necessary.This study was partly supported by research fund of Chungnam National University in 2007

Lightweight Design for Active Small SAR S-STEP Satellite Using Multilayered High-Damping Carbon Fiber-Reinforced Plastic Patch

In the launch environment, satellites are subjected to severe dynamic loads. These dynamic loads in the launch environment can lead to the malfunction of the payload, or to mission failure. In order to improve the structural stability of satellites and enable the reliable execution of space missions, it is necessary to have a reinforcement structure that reduces structural vibrations. However, for active small SAR satellites, the mass requirements are very strict, and this makes it difficult to apply an additional structure for vibration reduction. Therefore, we have developed a carbon fiber-reinforced plastic (CFRP)-based laminated patch to obtain a vibration reduction structure with a lightweight design for improving the structural stability of an S-STEP satellite. To verify the vibration reduction performance of the CFRP-based patch, sine and random vibration tests were conducted at the specimen level. Finally, the structural stability of the S-STEP satellite with the proposed CFRP-based laminated patch was experimentally verified using sine and random vibration tests. The validation results indicate that the CFRP-based laminated patch is an efficient solution which can effectively reduce the vibration response without the need for major changes to the design of the satellite structure. The lightweight vibration reduction mechanism developed in this study is one of the best solutions for protecting vibration-sensitive components

Prevalence of stable coronary artery disease and its associated clinical factors among patients with chest pain and elevated cardiac troponin alone

Cardiac troponin is a useful test for diagnosing cardiogenic causes in patients with chest pain. However, cardiac troponin levels are often elevated in patients with chest pain due to non-cardiac causes other than coronary artery disease. The purpose of this study was to investigate the prevalence of coronary artery disease (CAD) and its associated factors in patients with chest pain and elevated cardiac troponin I (cTnI). 104 patients (mean age, 65 ± 11 years; 60 [58%] men) who underwent coronary angiography (CAG) for chest pain and elevated cTnI levels were enrolled in this study. All patients had a normal CK-MB range and did not show any ischemic changes on electrocardiography or echocardiography. Patients were classified into two groups according to the presence of CAD (Group 1, n = 62) and the absence of CAD (Group 2, n = 42). Patients were classified into subgroups according to the presence (Group 2a, microvascular angina [MVA], n = 18) and absence (Group 2b, non-angina [NA], n = 25) of angina. CAD was diagnosed in 62 (60%) patients and MVA was suspected in 18 (17%) patients without CAD. Patients with CAD showed elevated blood pressure and slightly decreased heart rate. Diabetes mellitus was more prevalent in patients with CAD and patients without CAD (esp. with MVA) were more likely to be common drinkers. Increased relative wall thickness (RWT) and reduced E’ velocity were associated with CAD. High-density lipoprotein (HDL) levels were reduced in patients with CAD and MVA but were higher in patients with NA. Lower HDL level was found to be independently associated with the presence of CAD. Elevated cTn1 levels without other evidence of myocardial ischemia are sufficient for performing CAG in patients with stable chest pain

Development of Deployable Reflector Antenna for the SAR-Satellite: Part 1. Design and Analysis of the Main Reflector Using Honeycomb Sandwich Composite Structure

The deployable reflector antenna based on the synthetic aperture radar is a satellite component that consists of a unit structure in the form of a folded reflector. During the launch process, this satellite antenna is in the stowed condition to improve storage efficiency. It is then deployed to perform the space mission in the on-orbit condition. Due to these structural characteristics of the deployable reflector antenna, the reflector is possible to be loaded in the limited volume of the launch vehicle with the reduced size. Additionally, because the deployable reflector antenna is made by the lightweight material of the carbon fiber reinforced polymer and honeycomb core, it can reduce the launching cost and improve the revisit interval. In this paper, the conceptual design of the main reflector of the deployable reflector antenna was conducted. The main reflector was designed as the honeycomb sandwich composite structure. To design the main reflector, the stacking sequence of the composite material and honeycomb core was investigated to maximize the structural stiffness and minimize the antenna’s mass. Subsequently, finite element analyses including modal, quasi-static, structural–thermal coupling, and transient response were performed to numerically evaluate the structural performance of the lightweight composite reflector antenna