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Background The role of mobile health care (mHealth) in glycemic control has been investigated, but its impact on self-management skills and its psychological aspects have not been studied. Objective We evaluated the efficacy of mHealth-based diabetes self-management education and the effect of voluntary participation on its effects. Methods This study was a randomized controlled open-label trial conducted for 6 months at Kangbuk Samsung Hospital. Participants in the control group (n=31) maintained their previous diabetes management strategies. Participants in the intervention group (n=41) additionally received mHealth-based diabetes self-management education through a mobile app and regular individualized feedback from health care professionals. The primary outcome was change in glycated hemoglobin (HbA1c) level over 6 months between the 2 groups (intervention versus control) and within each group (at 6 months versus baseline). The secondary outcomes were changes in body mass index, blood pressure, lipid profile, and questionnaire scores (the Korean version of the Summary of Diabetes Self-Care Activities Questionnaire, an Audit of Diabetes Dependent Quality of Life, the Appraisal of Diabetes Scale, and Problem Areas in Diabetes) over 6 months between groups and within each group. Results A total of 66 participants completed this study. HbA1c (P=.04), total cholesterol level (P=.04), and Problem Areas in Diabetes scores (P=.02) significantly decreased; total diet (P=.03) and self-monitoring of blood glucose level scores (P=.01), based on the Summary of Diabetes Self-Care Activities Questionnaire, markedly increased within the intervention group. These significant changes were observed in self-motivated participants who were recruited voluntarily via advertisements. Conclusions mHealth-based diabetes self-management education was effective at improving glycemic control and diabetes self-management skills and lowering diabetes-related distress in voluntary participants. Trial Registration ClinicalTrials.gov NCT03468283; http://clinicaltrials.gov/ct2/show/NCT03468283

Background Microfracture is a surgical technique that involves creating multiple holes of 3–4 mm depth in the subchondral bone to recruit stem cells in the bone marrow to the lesion, inducing fibrocartilage repair and knee cartilage regeneration. Recently, it has been reported that increasing the exposed area of the lower cartilaginous bone (drilling a lot of holes) increases the outflow of stem cells, which is expected to affect the physical properties of the subchondral bone when the exposed area is large. The purpose of this study was to analyse the effect of the distance between the holes in the microfracture procedure on the structural stability of the osteochondral bone using a finite element method. Methods In this study, lateral aspects of the femoral knee, which were removed during total knee arthroplasty were photographed using microtomography. The model was implemented using a solitary walks program, which is a three-dimensional simplified geometric representation based on the basic microtomography data. A microfracture model was created by drilling 4 mm-deep holes at 1, 1.5, 2, 2.5, 3, 4, and 5 mm intervals in a simplified three-dimensional (3D) geometric femoral model. The structural stability of these models was analysed with the ABAQUS program. We compared the finite element model (FEM) based on the microtomography image and the simplified geometric finite element model. Results Von Mises stress of the subchondral bone plate barely increased, even when the distance between holes was set to 1 mm. Altering the distance between the holes had little impact on the structural stability of the subchondral bone plate. Safety factors were all below 1. Conclusions Although we did not confirm an optimal distance between holes, this study does provide reference data and an epidemiological basis for determining the optimal distance between the holes used in the microfracture procedure.

This study aimed to investigate the effect of patient engagement in self-monitoring with a telemonitoring device on glycemic control among patients with type 2 diabetes. We conducted a subanalysis of the telemonitoring device study in Kaiser Permanente Northern California members. We divided the telemonitoring group into 53 frequent and 54 infrequent users based on self-monitoring of blood glucose (SMBG) frequency of the first 6 weeks. The frequency of SMBG transmitted from the telemonitoring device was examined over 24 weeks. Clinic and laboratory tests were collected at baseline, 6 weeks and 6 months. There was no significant difference in baseline HbA1c level between the two groups. After 6 months, change in HbA1c was −2.4 ± 1.6% among frequent users and −1.5 ± 1.5% among infrequent users (p = 0.003). The proportion of patients achieving target HbA1C level at 6 months was significantly higher among frequent users than among infrequent users. An increased frequency of SMBG was significantly correlated with a reduction in HbA1c at 6 months. In conclusion, initial active engagement in self-monitoring with a telemonitoring device could provide incremental improvement of glycemic control over 6 months.

Recently, mobile health care has been applied to manage diabetes requiring self-management. Health care by mobile applications (apps) has a great advantage when applied to patients with diabetes; the adherence to self-management activities for diabetes can be improved through mobile apps. The Food and Drug Administration (FDA) has cleared and approved the use of some mobile apps as medical devices for the management of diabetes since 2010. However, mobile apps may not be effective for all patients. We here report the effect of use of mobile-based diabetes care app (Healthy-note app) for 2 patients with diabetes, and discuss issues and strategies for effective mobile intervention. Further study is needed on improving patient's participation to increase the effect of management via a mobile app.

Limited information is available on the optimal cement thickness of monolithic zirconia crowns. This study was designed to evaluate the stress distribution in the posterior monolithic zirconia crowns with different cement thicknesses under masticatory force and maximum bite force using three-dimensional finite element analysis. The prepared and unprepared mandibular right first molar models were scanned and exported to the computer-aided design system. Solid models of monolithic zirconia crowns, which were cemented on prepared teeth were generated. Four models were fabricated applying different cement thicknesses (100 µm, 200 µm, 400 µm, and 600 µm). The solid models were imported into the finite element analysis software and meshed into tetrahedral elements. Four three-dimensional finite element models were simulated under masticatory force and maximum bite force: vertical (axial), angular (45°) and horizontal loads of 280 N at 5 points; vertical load of 700 N at 8 points were loaded, respectively. The stress distribution varied with the different cement thicknesses and directions of applied loads. The monolithic zirconia crowns with cement thicknesses exceeding 200 µm had wider distributions of peak maximum principal stress under the same loading conditions. Monolithic zirconia crowns have more stress concentrations on the occlusal surfaces, while the cement layers have more stress concentrations on the cervical areas. Thicker cement layers were associated with more concentrated stresses on the buccal and lingual cervical areas. The test results show that the cement thickness plays an essential role in the success of monolithic zirconia restorations in terms of reducing cement wash-out. Cement thickness of 100 µm is recommended for monolithic zirconia crowns.

The purpose of this study was to evaluate the effects of coping designs on the stress distributions in posterior zirconia crowns by non-linear three-dimensional finite element analysis. Three-dimensional finite element models of a mandibular right first molar with layers of veneering porcelain, zirconia coping, cement, and abutment tooth were designed by computer software (HyperWorks 10.0). Ten zirconia crowns with different designs were produced according to various shoulder positions and heights. The shoulders (1-mm width) exhibited incremental height increases of 1 mm, 2 mm, and 3 mm on the buccal, lingual, and proximal sides, respectively. An axial compressive dynamic load simulating the progressive load was applied until a stainless steel ball model (7 mm in diameter) deepened the veneer surface to 0.7 mm in depth. Loads were placed on the inner inclines of the mesiobuccal, distobuccal, and mesiolingual cusps. Residual maximum principal stresses (MPSs) at the veneer and coping under progressive loading were determined for each zirconia crown. Reinforcements with the shoulders on the buccal, lingual, and proximal axial walls resulted in lower MPSs in the veneering porcelain but higher MPSs in the zirconia coping. As the shoulder height increased, the tensile stresses decreased, while the compressive stresses increased in the veneering porcelains. It can be concluded that the shoulder height and position in the zirconia coping will affect the MPSs of the crown. Our findings conclusively reveal the critical role of the shoulder design of the coping in preventing veneer fracture on posterior zirconia restorations by reducing tensile stresses in veneering porcelain.

Background On September 27, 2012, at 3:43 pm, a hydrogen fluoride spill occurred in a manufacturing plant located at the 4th complex of the Gumi National Industrial Complex in Gumi City, South Korea. The present study aimed to evaluate the psychological effects of the hydrogen fluoride spill on the members of the community and to investigate their relationships with physical symptoms and changes in psychological effects occurring as time passed after the accident. Methods The 1st phase involved a survey of 1359 individuals that was conducted 1 month after the spill, and the 2nd phase involved a survey of 711 individuals that was conducted 7 months after the accident. The questionnaires included items for assessing demographic characteristics, hydrogen fluoride exposure level, physical symptoms, and psychological status. Physical symptoms were assessed to determine the persistence of irritations. Psychological status was assessed to investigate the impact of event level using the Impact of Event Scale – Revised Korean version (IES-R-K), and the anxiety level was assessed using the Beck Anxiety Inventory (BAI). Results As the hydrogen fluoride exposure level increased, the impact of event and anxiety levels increased significantly both 1 and 7 months after the accident (p

Phosphatidylinositol (PI) kinases are key molecules that participate in the phosphoinositide signaling in the cytoplasm. Despite the accumulating evidence that supports the existence and operation of independent PI signaling system in the nucleus, the exact location of the PI kinases inside the nucleus is not well defined. Here we show that PI4-kinases IIα and IIβ, which play central roles in PI(4,5)P2 synthesis and PI signaling, are localized in numerous small nucleoplasmic vesicles that function as inositol 1,4,5-trisphosphate (Ins(1,4,5)P3)-sensitive Ca(2+) stores. This is in accord with the past results that showed the localization of PI4(P)5-kinases that are essential in PI(4,5)P2 production and PI(4,5)P2 in nuclear matrix. Along with PI(4,5)P2 that also exists on the nucleoplasmic vesicle membranes, the localization of PI4-kinases IIα and IIβ in the nucleoplasmic vesicles strongly implicates the vesicles to the PI signaling as well as the Ins(1,4,5)P3-depenent Ca(2+) signaling in the nucleus. Accordingly, the nucleoplasmic vesicles indeed release Ca(2+) rapidly in response to Ins(1,4,5)P3. Further, the Ins(1,4,5)P3-induced Ca(2+) release studies suggest that PI4KIIα and IIβ are localized near the Ins(1,4,5)P3 receptor (Ins(1,4,5)P3R)/Ca(2+) channels on the Ca(2+) store vesicle membranes. In view of the widespread presence of the Ins(1,4,5)P3-dependent Ca(2+) store vesicles and the need to fine-control the nuclear Ca(2+) concentrations at multiple sites along the chromatin fibers in the nucleus, the existence of the key PI enzymes in the Ins(1,4,5)P3-dependent nucleoplasmic Ca(2+) store vesicles appears to be in perfect harmony with the physiological roles of the PI kinases in the nucleus.

Although early detection and successful gastrectomy have improved the survival of patients with gastric cancer, long-term health problems remain troubling. We evaluated the prevalence of osteoporosis and its risk factors in long-term survivors of gastric cancer after gastrectomy. We reviewed the medical records of a tertiary hospital between 2007 and 2014 to identify survivors of gastric cancer who had visited our center at around 5 years after gastrectomy. We evaluated their health status, including bone mineral density (BMD). Dual-energy X-ray absorptiometry was used to measure the BMD of the lumbar spine and femur (total and neck area). The prevalence of osteoporosis, defined by a BMD T score

PURPOSE The purpose of this study was to evaluate various core designs on stress distribution within zirconia crowns. MATERIALS AND METHODS Three-dimensional finite element models, representing mandibular molars, comprising a prepared tooth, cement layer, zirconia core, and veneer porcelain were designed by computer software. The shoulder (1 mm in width) variations in core were incremental increases of 1 mm, 2 mm and 3 mm in proximal and lingual height, and buccal height respectively. To simulate masticatory force, loads of 280 N were applied from three directions (vertical, at a 45° angle, and horizontal). To simulate maximum bite force, a load of 700 N was applied vertically to the crowns. Maximum principal stress (MPS) was determined for each model, loading condition, and position. RESULTS In the maximum bite force simulation test, the MPSs on all crowns observed around the shoulder region and loading points. The compressive stresses were located in the shoulder region of the veneer-zirconia interface and at the occlusal region. In the test simulating masticatory force, the MPS was concentrated around the loading points, and the compressive stresses were located at the 3 mm height lingual shoulder region, when the load was applied horizontally. MPS increased in the shoulder region as the shoulder height increased. CONCLUSION This study suggested that reinforced shoulder play an essential role in the success of the zirconia restoration, and veneer fracture due to occlusal loading can be prevented by proper core design, such as shoulder.

Introduction The aim of this study was to improve the quality of diabetes control and evaluate the efficacy of an Internet-based integrated healthcare system for diabetes management and safety. Methods We conducted a large-scale, multi-centre, randomized clinical trial involving 484 patients. Patients in the intervention group ( n = 244) were treated with the Internet-based system for six months, while the control group ( n = 240) received the usual outpatient management over the same period. HbA1c, blood chemistries, anthropometric parameters, and adverse events were assessed at the beginning of the study, after three months, and the end of the study. Results There were no initial significant differences between the groups with respect to demographics and clinical parameters. Upon six-month follow-up, HbA1c levels were significantly decreased from 7.86 ± 0.69% to 7.55 ± 0.86% within the intervention group ( p Discussion This e-healthcare system was effective for glucose control and body composition improvement without associated adverse events in a multi-centre trial. This system may be effective in improving diabetes control in the general population.

Cardiomyocytes contain secretory granules in which chromogranins and several types of natriuretic peptides and growth factors are stored in addition to high Ca(2+) concentrations. Yet the expression and serum levels of chromogranins and natriuretic peptides have been closely correlated with pathological cardiac hypertrophy and heart failure. Moreover, in distinction from the physiological cardiac hypertrophy that appears not to involve inositol 1,4,5-trisphosphate (IP3) production as the primary signaling step, accumulating evidence underscores the central role of IP3-induced intracellular Ca(2+) releases in cardiomyocytes in the development of pathological cardiac hypertrophy. Consistent with this observation, chronic treatment of cardiomyocytes with G-protein coupled receptor agonists endothelin-1, angiotensin II, or phenylephrine, agents that are known to produce intracellular IP3, leads to cardiomyopathy and heart failure. In particular, the IP3-induced Ca(2+) release inside the nucleus has been suggested to initiate a series of nuclear activities, including 1) Ca(2+)-calmodulin (CaM) mediated protein kinase II (CaMKII) activation, 2) activation of transcription factors such as myocyte enhancer factor-2 (MEF-2) and nuclear factor κB (NF-κB), and 3) increased production of chromogranins, natriuretic peptides, and growth factors, which eventually lead to pathological hypertrophy. Although secretory granules function as the major IP3-sensitive intracellular Ca(2+) store and the IP3-mediated Ca(2+) release from secretory granules in cardiomyocytes contributes to secretion of chromogranins and natriuretic peptides, the direct cause of pathological hypertrophy appears to be due to the IP3-induced Ca(2+) release from the small nucleoplasmic IP3-sensitive Ca(2+) store vesicles, thereby initiating the Ca(2+)-activated nuclear activities that lead to formation of more secretory granules, pathologic enlargement of cardiomyocytes, and heart failure.

Adipocyte fatty acid-binding protein (FABP4) is abundantly expressed in adipocytes and plays a role in glucose homeostasis. We analysed the relationship between serum FABP4 levels and the progression of metabolic syndrome in healthy adults.A total of 465 subjects were selected from participants in a medical check-up programme at a Health Promotion Center. Baseline serum FABP4 levels were measured, and the subjects were evaluated for the presence of metabolic syndrome (MetS) according to the recommendations of the American Heart Association/National Heart, Lung, and Blood Institute. The subjects were re-evaluated 4 years later. Baseline FABP4 concentrations were significantly higher in subjects with MetS than in those without MetS (P0.001). At the 4-year follow-up, subjects in the highest FABP4 tertile at baseline exhibited higher values for body mass index, fat mass and percent body fat, as well as blood pressure, fasting glucose, total cholesterol, triglycerides, low-density lipoprotein (LDL)-cholesterol, insulin, homeostasis model assessment of insulin resistance, monocyte chemoattractant protein-1 and tumor necrosis factor-α levels (all P0.05). The subjects with higher FABP4 levels had lower HDL-cholesterol concentrations (P0.05). After adjustment for age, sex, change in percent body fat and baseline values for other metabolic and inflammatory parameters, FABP4 levels at baseline were shown to be strongly associated with the development of MetS by year 4 (odds ratio (OR), 5.75; 95% confidence interval (CI), 2.71-12.23 for highest tertile vs. lowest tertile, P0.001)Baseline serum FABP4 levels appear to be a significant predictor for the future development of MetS, independent of pro-inflammatory cytokines.

The high capacity, low affinity Ca 2+ storage protein chromogranins are marker proteins of secretory granules that contain the most Ca 2+ in secretory cells. Along with the abundantly expressed chromogranins, the IP 3 R/Ca 2+ channels, the major intracellular Ca 2+ channels, are also expressed in secretory granules the most. Chromogranins not only induce formation of secretory granules but also are suggested to produce the small IP 3 -sensitive nucleoplasmic Ca 2+ store vesicles in the nucleus. Chromogranins A (CGA) and B (CGB) also directly bind the IP 3 Rs and activate the IP 3 R/Ca 2+ channels at the intragranular pH 5.5. But at a near physiological pH 7.5 only CGB interacts with the IP 3 Rs due to stronger interaction of CGB for the IP 3 Rs, which is several orders of magnitude stronger than that of CGA, and activates the IP 3 R/Ca 2+ channels. Therefore, the CGB-IP 3 R coupling is proposed to play key roles in the IP 3 -mediated Ca 2+ signaling mechanisms in the cytoplasm through both secretory granules and the ER, and in the nucleus through the small IP 3 -sensitive nucleoplasmic Ca 2+ store vesicles. Chromogranin B is further suggested to participate in transcription control and to target secretory granule components, including the IP 3 Rs, to newly formed secretory granules. Defects in secretory granule-related functions are directly linked to major human diseases such as Alzheimer's disease, secretory cell cancers, cystic fibrosis, acute pancreatitis, and cardiac hypertrophy. Therefore, realization of secretory granules as the major intracellular Ca 2+ storage and control organelle in secretory cells promises to open new horizon in understanding the Ca 2+ storage, signaling, and control mechanisms throughout the biokingdom.

BACKGROUND: We performed a retrospective longitudinal study on the effects of changes in weight, body composition, and homeostasis model assessment (HOMA) indices on glycemic progression in subjects without diabetes during a four-year follow-up period in a community cohort without intentional intervention. METHODS: From 28,440 non-diabetic subjects who participated in a medical check-up program in 2004, data on anthropometric and metabolic parameters were obtained after four years in 2008. Body composition analyses were performed with a bioelectrical impedance analyzer. Skeletal muscle index (SMI, %) was calculated with lean mass/weight×100. Subjects were divided into three groups according to weight change status in four years: weight loss (≤-5.0%), stable weight (-5.0 to 5.0%), weight gain (≥5.0%). Progressors were defined as the subjects who progressed to impaired fasting glucose or diabetes. RESULTS: Progressors showed worse baseline metabolic profiles compared with non-progressors. In logistic regression analyses, the increase in changes of HOMA-insulin resistance (HOMA-IR) in four years presented higher odds ratios for glycemic progression compared with other changes during that period. Among the components of body composition, a change in waist-hip ratio was the strongest predictor, and SMI change in four years was a significant negative predictor for glycemic progression. Changes in HOMA β-cell function in four years was a negative predictor for glycemic progression. CONCLUSION: Increased interval changes in HOMA-IR, weight gain and waist-hip ratio was associated with glycemic progression during a four-year period without intentional intervention in non-diabetic Korean subjects.

Chromogranins and secretogranins have traditionally been known as marker proteins of secretory granules that contain the highest concentrations of cellular calcium, reaching approximately 40 mM. In addition, chromogranin B was also shown to exist in the nucleus, localizing in the putative inositol 1,4,5-trisphosphate (IP3)-sensitive nucleoplasmic Ca2+ store vesicles. Chromogranins A (CGA) and B (CGB) are high-capacity, low-affinity Ca2+ binding proteins, binding 30-90 mol of Ca2+/mol with dissociation constants (Kd) of 1.5-4 mM. Yet the Ca2+-binding property of secretogranins has not been studied. Here, we show the localization of secretogranin II (SgII) in the nucleus, more specifically, in the IP3-sensitive nucleoplasmic Ca2+ store vesicles along with CGB and the IP3 receptors. We have also determined the Ca2+-binding property of SgII and found that SgII binds 61 mol of Ca2+/mol (910 nmol Ca2+/mg) with a Kd of 3.0 mM at the intragranular pH 5.5 and 30 mol of Ca2+/mol (440 nmol Ca2+/mg) with a Kd of 2.2 mM at a near-physiological pH 7.5. Chromogranin B also bound 50 mol of Ca2+/mol (670 nmol Ca2+/mg) with a Kd of 3.1 mM at pH 7.5. Given the high-capacity, low-affinity Ca2+-binding property of SgII and its presence in the IP3-sensitive nucleoplasmic Ca2+ store vesicles, these results suggest that SgII may function in the storage and control of Ca2+ in the nucleus through its interaction with CGB in the nucleoplasmic vesicles.

The nucleus also contains the inositol 1,4,5-trisphosphate receptor (IP3R)/Ca2+ channels in the nucleoplasm proper independent of the nuclear envelope or the cytoplasm. The nuclear IP3R/Ca2+ channels were shown to be present in small IP3-dependent nucleoplasmic Ca2+ store vesicles, yet no information is available regarding the IP3 sensitivity of nuclear IP3R/Ca2+ channels. Here, we show that nuclear IP3R/Ca2+ channels are 3-4-fold more sensitive to IP3 than cytoplasmic ones in both neuroendocrine PC12 cells and nonneuroendocrine NIH3T3 cells. Given the presence of phosphoinositides and phospholipase C and the importance of IP3-mediated Ca2+ signaling in the nucleus, the high IP3 sensitivity of nuclear IP3R/Ca2+ channels seemed to reflect the physiological needs of the nucleus to finely control the IP3-dependent Ca2+ concentrations. It was further shown that the IP3R/Ca2+ channels of secretory cells are 7-8-fold more sensitive to IP3 than those of nonsecretory cells. This difference appeared to result from the presence of secretory cell marker protein chromogranins (thus secretory granules) in secretory cells; expression of chromogranins in NIH3T3 cells increased the IP3 sensitivity of both nuclear and cytoplasmic IP3R/Ca2+ channels by approximately 4-6-fold. In contrast, suppression of chromogranin A expression in PC12 cells changed the EC50 of IP3 sensitivity for cytoplasmic IP3R/Ca2+ channels from 17 to 47 nM, whereas suppression of chromogranin B expression changed the EC50 of cytoplasmic IP3R/Ca2+ channels from 17 to 102 nM and the nuclear ones from 4.3 to 35 nM. Given that secretion is the major function of secretory cells and is under a tight control of intracellular Ca2+ concentrations, the high IP3 sensitivity appears to reflect the physiological roles of secretory cells.

Imatinib mesylate is the first molecule of targeted therapy in chronic myelogenous leukaemia inhibiting constitutively activated BCR-ABL kinase. There are no long-term follow-up studies of large sample sizes to assess the toxicity of the use of imatinib mesylate over 10 years. Several cases of hepatotoxicity, including fatal liver failure, have been associated with the long-term use of imatinib mesylate. We report here on a patient who experienced immediate dominant cholestatic damage of the liver and mild hepatocyte damage during imatinib mesylate therapy. This differs from most reports showing dominantly acute hepatitis with necrosis associated with the use of imatinib mesylate.

Background The aim of this study was to identify the relationships between borderline serum liver enzyme abnormalities and the incidence of impaired fasting glucose (IFG) and diabetes mellitus (DM) during a 7-year follow-up of workers, and to evaluate the quantitative level of risks. Methods A total of 749 workers in an electronics manufacturing company were divided into the normal fasting blood glucose (n = 633), IFG (n = 98), and DM (n = 18) groups, according to the results of their health checkup in 2006. Among 633 workers in the normal group, excluding 55 workers who were impossible to follow, incidence rate and relative risks of 578 workers to the IFG or DM in 2013 according to the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (γ-GTP) were investigated. The liver enzyme levels were categorized as A (normal), B (borderline elevation), and R (definite elevation) following the standard of the National Health Insurance Service of Korea. Results The incidence rate of IFG or DM based on ALT level was 9.7 % for the A, 30.0 % for B, and 15.4 % for R. According to γ-GTP, the incidence rate was 9.8 % for A, 34.5 % for B, and 25.0 % for R. The relative risk(RR) to the incidence of IFG or DM depending on the level of ALT were 3.09 in B and 1.59 in R compared to A. According to γ-GTP, RR was 3.52 in B and 2.55 in R compared to A. AST level was not related to the incidence of IFG or DM. A multiple logistic regression analysis with the incidence of IFG or DM as a dependent variable resulted in an odds ratio of 2.664(1.214–5.849) for B level ALT, 3.685(1.405–9.667) for B level of γ-GTP even after adjustment for other variables such as age, sex, body mass index, AUDIT score, systolic blood pressure, and triglyceride. Conclusions Even borderline elevations of ALT and γ-GTP, but not AST, increased the incidence and risk of IFG or DM after 7 years. Borderline elevation of ALT and γ-GTP was identified as an independent risk factor of IFG or DM.

Given the importance of inositol 1,4,5-trisphosphate receptor (IP(3)R)/Ca(2+) channels in the control of intracellular Ca(2+) concentrations, we determined the relative concentrations of the IP(3)R isoforms in subcellular organelles, based on serially sectioned electron micrographs. The endoplasmic reticulum (ER) was estimated to contain 15-20% of each of the three IP(3)R isoforms while secretory granules contained 58-69%. The nucleus contained approximately 15% each of IP(3)R-1 and -2, but 25% of IP(3)R-3, whereas the plasma membrane contained approximately 1% or less of each. These suggested that secretory granules, the nucleus and ER are at the center of IP(3)-dependent intracellular Ca(2+) control mechanisms in chromaffin cells.

Although the inositol 1,4,5-triphosphate (IP(3))-induced nuclear Ca(2+) release has been shown to play key roles in nuclear functions, the presence of IP(3) receptor (IP(3)R)/Ca(2+) channels in the nucleoplasm has not been found. Recently, the IP(3)R/Ca(2+) channels were reported to exist in the nucleoplasmic reticulum structure, an extension of the nuclear envelope. Here we investigated the potential existence of the IP(3)Rs in the nucleoplasm and found the presence of all three IP(3)R isoforms in neuroendocrine and non-neuroendocrine cells. The IP(3)Rs were widely scattered in the nucleoplasm, localizing in both the heterochromatin and euchromatin regions.

Chromogranins A (CGA) and B (CGB) are two major Ca(2+) storage proteins of the secretory granules of neuroendocrine cells. Nevertheless, we found in the present study that CGB was also localized in the nucleus. In immunogold electron microscopy using bovine adrenal medullary chromaffin cells, it was found that the number of CGB-labeled gold particles localized per microm(2) of the nucleus was equivalent to 20% that of CGB-labeled gold particles localized per microm(2) of the secretory granules. Considering that CGB is estimated to exist in the 0.1-0.2-mm range in the secretory granules of bovine chromaffin cells, 20% of these amounts to 20-40 microm. In addition, transfection of CGA and CGB into nonneuroendocrine COS-7 and NIH3T3 cells repeatedly indicated the nuclear localization of CGB in addition to its usual localization in the cytoplasm. Moreover, immunoblot and immunogold electron microscopy analyses of neuroendocrine PC12 cells also showed the existence of endogenous CGB in both the cytosol and the nucleus. Nuclear routing of CGB did not appear to depend entirely upon the nuclear localization signal as some of the nuclear localization signal mutant CGB were still targeted to the nucleus. In gene array assay, CGB was shown to either induce or suppress transcription of many genes including those of transcription factors. Of these we have analyzed eight genes, four induced (zinc finger protein, MEF2C, hCRP2, abLIM) and four suppressed (hcKrox, T3-receptor, troponin C, integrin) using the quantitative reverse transcription-PCR method and spectrophotometry to determine the transcription levels of each mRNA. CGB was shown to increase the transcription of zinc finger protein, MEF2C, hCRP2, and abLIM by 2.5-5-fold while suppressing that of hcKrox, T3-receptor, troponin C, and integrin by 60-75%. Given that MEF2C and hcKrox genes are transcription factors, these results pointed to the transcription control role of CGB in the nucleus.

Patient-specific guides have been introduced recently as a means of making accurate bone cuts through custom cutting blocks constructed based on pre-operative three-dimensional imaging. However, the controversy concerning the improved results of patient-specific guides have not been resolved yet; in addition, there have been no studies to investigate the causes of variable with inconsistent results and solutions for the causes.Thirty eight patients (38 knees) underwent total knee arthroplasty with patient-specific guides. The mean age of the patients was 68 years (SD ± 6.3), and all patients had a minimum 2-year follow-up. An intra-operative alignment using navigation and the causes of outliers were evaluated.An average coronal alignment of PSI jigs was 0.5° (SD ± 0.9°) in femur and 0.1° (SD ± 0.8°) in tibia, and the number of outliers was two and three cases, respectively. An average sagittal alignment was 0.6° (SD ± 0.9°) in femur and 5.5° (SD ± 1.1°) in tibia, and the number of outliers was three and five cases, respectively. All outliers resulted from large osteophytes near the contact point of patient-specific guides which disturb sitting of the guide.It was suggested that patient-specific guides were an effective and safe method to achieve accurate alignments, with no additional intra-operative complication. It is important to note that surgeons need to be precautious using the patient-specific instrumentation in patients with severe varus deformity. In addition, existing osteophytes which disturb sitting of the guides should be carefully evaluated pre-operatively and intra-operatively.IV.

Catecholamine secretory vesicle core proteins (chromogranins) contain an activity that inhibits catecholamine release, but the identity of the responsible peptide has been elusive. Size-fractionated chromogranins antagonized nicotinic cholinergic-stimulated catecholamine secretion; the inhibitor was enriched in processed chromogranin fragments, and was liberated from purified chromogranin A. Of 15 synthetic peptides spanning approximately 80% of chromogranin A, one (bovine chromogranin A344-364 [RSMRLSFRARGYGFRGPGLQL], or catestatin) was a potent, dose-dependent (IC50 approximately 200 nM), reversible secretory inhibitor on pheochromocytoma and adrenal chromaffin cells, as well as noradrenergic neurites. An antibody directed against this peptide blocked the inhibitory effect of chromogranin A proteolytic fragments on nicotinic-stimulated catecholamine secretion. This region of chromogranin A is extensively processed within chromaffin vesicles in vivo. The inhibitory effect was specific for nicotinic cholinergic stimulation of catecholamine release, and was shared by this chromogranin A region from several species. Nicotinic cationic (Na+, Ca2+) signal transduction was specifically disrupted by catestatin. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. This small domain within chromogranin A may contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release from chromaffin cells and neurons.

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson's disease (PD) is well known although the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derived mesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as well as late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as "PD", from patients with Parkin-defect PD as "Parkin" and from patients with pituitary adenomas as "non-PD" in short. The pGRN145 plasmid containing hTERT was introduced to establish telomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably over two-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondria of the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrial complex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defect PD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients with idiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understand the pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.

Chromogranins A and B have been known to undergo pH- and Ca(2+)-dependent aggregation, and this property is considered essential for the proper sorting of the vesicular matrix proteins. In the present study, purified native chromogranin B (CGB) from bovine adrenal medulla was used to study the pH- and Ca(2+)-dependent conformational changes and aggregation property. Similar to chromogranin A (CGA), which had been shown to undergo pH- and Ca(2+)-dependent conformational changes and to be composed of 60-65% random coil with 25-40% alpha-helicity, chromogranin B was also shown to consist of 65-70% random coil, 15-25% alpha-helix, and 10-15% beta-sheet structures. The high percentage of random coil suggests that CGB behaves hydrodynamically as an asymmetric molecule, thus explaining its anomalous migration on SDS-polyacrylamide gels. Further, CGB eluted from a gel filtration column in the volume indicative of a globular protein with molecular weight of approximately 200,000 at both the intravesicular pH of 5.5 and a near physiological pH of 7.5. Considering that dimeric CGA eluted from a gel filtration column in the position suggestive of a 300-kDa protein, this result indicated that CGB exists in a monomeric state at both pH levels. Like CGA, which exhibited greater aggregation at pH 5.5 than at pH 7.5 upon Ca2+ binding, CGB also aggregated much more readily at pH 5.5 than at pH 7.5. However, there was a marked difference in the aggregation properties of CGA and CGB with regard to their sensitivity to Ca2+: CGB was at least 2 orders of magnitude more sensitive to Ca2+ than CGA. This suggested that, in spite of the low concentration of CGB (approximately one-tenth that of CGA) in bovine adrenal chromaffin cells, CGB would start to aggregate well ahead of CGA in the trans-Golgi network. In view of the proposed importance of the pH- and Ca(2+)-induced chromogranin aggregation in vesicle biogenesis, the extreme sensitivity of CGB aggregation to Ca2+ appears to underline the potential importance of CGB aggregation in the early stages of vesicle biogenesis.

Seung-Hyun Yoo, Hyuk-Ju Kwon, Sun-Hee Kim, Jung-Ah Lee, Sung Sunwoo, Young-Sik Kim, Byung-Su Kim, Han-Jin Oh, Chul-Min Kim, Hee-Jeong Choi, Hee-Jin Hwang, Sun-Wha Ok Department of Family Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Psychiatry, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Department of Family Medicine, Vievis Namuh Hospital, Seoul, Korea Department of Family Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea School of Medicine, Seoul, Korea Department of Family Medicine, Eulji University School of Medicine, Daejeon, Korea Department of Family Medicine, Catholic Kwandong University International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Seoul, Korea Department of Child Development and Family Studies, Institute of Human Ecology, Seoul National University, Seoul, Korea

암의 조기발견과 암 치료의 발전에 따라 암 경험자의 수가 빠르게 증가하고 있다. 2015년 발표된 중앙암등록본부 암 통계에 따르면 암 진단 후 현재까지 생존해 있는 환자는 137 만 명이 넘어서고 있으며, 5년을 초과하여 생존한 암 경험자 의 수도 58만 5,000명에 달하고 있다[1]. 장기 생존한 암 경 험자들이 증가하면서, 암 치료를 시행하는 암 전문의료기관 뿐 아니라 지역사회의 일차의료기관에서도 암 경험자들을 보는 것이 점점 흔해지고 있다. 특히 위암은 우리나라에서 전통적으로 흔했던 암으로, 암 치료 후 5년 이상 경과한 암 경험자의 수는 2013년 말 현재 11만 명으로 모든 암 중 가장 많은 수를 차지하고 있다[1]. 암 경험자는 원발암에 대한 추적관리뿐 아니라, 이차암에 대한 예방 및 검진, 후기 합병증 및 암 이외의 동반 만성질 환에 대한 관리, 예방접종, 생활습관, 심리사회적 문제에 대 한 포괄적인 관리가 필요하다. 본고에서는 일차의료기관에 서 보게 될 수 있는 위암 치료 후 장기간 경과한 위암 경험 자의 흔한 건강문제와 이에 대한 관리방안을 다루고자 한다. 장기 위암 경험자의 관리

Chromogranin A is known to undergo pH induced conformational changes, and the difference in conformation is supposed to be responsible for the difference in Ca2+ binding property. To gain insight regarding the overall structure and the nature of pH-induced conformational changes of chromogranin A, limited trypsin digestions were carried out at pH 5.5 and pH 7.5. The resulting fragments were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and the amino acid sequences of the tryptic fragments were determined. From these analyses it was shown that the chromogranin A structure consists of an N-terminal compact core region and a rather loosely organized C-terminal region and that the change of pH from 7.5 to 5.5 loosened the overall structure of chromogranin A, exposing the C-terminal region. Since the conserved C-terminal region (residues 407–431) was shown to exist in monomer-dimer and monomer-tetramer equilibria at pH 7.5 and 5.5, respectively, the conformational changes of the region at pH 7.5 and 5.5 were studied by circular dichroism spectroscopy using a synthetic peptide representing the conserved C-terminal region. When the pH was changed from 7.5 to 5.5, the coil structure of the C-terminal peptide decreased with an accompanying increase of α-helicity.

Background: Diabetes self-management education and reinforcement are important for effective management of the disease. We investigated the effectiveness of interactive small-group education on glycemic, blood pressure, and lipid levels. Methods: For this study, 207 type 2 diabetes patients with suboptimal glycemic control (HbA1c levels >6.5%) were enrolled. The conventional education group received an existing education program from April to November in 2006, and the interactive education group received a new small-group education program from December 2006 to July 2007. The two groups were com-paratively analyzed for changes in blood sugar, glycated hemoglobin, lipid, and blood pressure at baseline, 3, 6, and 12 months and the proportion of patients achieving target goals at 12 months. Results: After 12 months of follow-up, HbA1c levels in the interactive education group were significantly lower than in the con-ventional education group (6.7% vs. 6.4%, P

During development, sympathetic neurons and chromaffin cells originate from bipotential sympathoadrenal (SA) progenitors arising from neural crests (NC) in the trunk regions. Recently, we showed that AP-2β, a member of the AP2 family, plays a critical role in the development of sympathetic neurons and locus coeruleus and their norepinephrine (NE) neurotransmitter phenotype. In the present study, we investigated the potential role of AP-2β in the development of NC-derived neuroendocrine chromaffin cells of the adrenal medulla and the epinephrine (EPI) phenotype determination. In support of its role in chromaffin cell development, AP-2β is prominently expressed in both embryonic and adult adrenal medulla. In adrenal chromaffin cells of the AP-2β(-/-) mouse, the expression levels of catecholamine biosynthesizing enzymes, dopamine β-hydroxylase (DBH) and phenylethanolamine-N-methyl-transferase (PNMT), as well as the SA-specific transcription factor, Phox2b, are significantly reduced compared to wild type. In addition, ultrastructural analysis demonstrated that the formation of large secretory vesicles, a hallmark of differentiated chromaffin cells, is defective in AP-2β(-/-) mice. Furthermore, the level of EPI content is largely diminished (>80%) in the adrenal gland of AP-2β(-/-) mice. Chromatin immunoprecipitation (ChIP) assays of rat adrenal gland showed that AP-2β binds to the upstream promoter of the PNMT gene in vivo; strongly suggesting that it is a direct target gene. Overall, our data suggest that AP-2β plays critical roles in the epinephrine phenotype and maturation of adrenal chromaffin cells.

Ca2+ signaling is an important determining factor in many cellular processes, especially in cancer cell proliferation, motility and invasion. Glioblastoma is the deadliest brain cancer with its average survival time of less than a year, with the most prominent cellular feature being the ability of these cells to migrate to and invade the neighboring tissue. We hypothesized that disturbing the Ca2+ signaling pathway would decrease the propensity for these cells to migrate. Thus, we investigated the detailed Ca2+ signaling pathway of the glioblastoma cells in response to various receptor tyrosine kinases (RTK) and G-protein coupled receptor (GPCR) agonists. Here we report that caffeine, which is a well-known activator of ryanodine receptors (RyRs), paradoxically inhibits inositol-1, 4, 5-triphospate receptor(IP3R)-mediated Ca2+ increase by selectively targeting IP3R subtype 3(IP3R3), whose mRNA expression is significantly increased in glioblastoma cells. Consequently, by inhibiting IP3R3-mediated Ca2+ release, caffeine was found to inhibit the invasion and migration of various glioblastoma cell lines in scrape motility, Matrigel invasion, soft agar, and brain slice implantation assays. In a mouse xenograft model of glioblastoma, caffeine intake via drinking water greatly increased mean survival duration of subject animals. These findings propose IP3R3 as a novel target for glioblastoma treatment and that caffeine may be a useful adjunct therapy that slows glioblastoma invasion and migration by selectively targeting IP3R3.

Human teeth system is one of the most important organs, plays vital role in mastication process. It consist 3 layers, outer hard and brittle cover enamel and porous dentine separated by very thin interfacial region called Dentine Enamel Junction (DEJ) or crown dentine. Dentine and enamel has almost isotropic material property while DEJ has different microstructure near enamel and dentine represented by functionally graded microstructure. Experimental evidences show that the crack initiated in the hard enamel region grows towards the crown dentine, it starts healing after 10–15 micron. Finite element analysis has been carried out and fracture toughness has been evaluated for layered model of human teeth with crack initiated at enamel region grows towards DEJ with its healing capabilities and graded structure. Comparison of the result with experimental value reported in literature shows acceptable matching suggests; FE results can be taken as basis for estimating Fracture toughness of human teeth system especially at interface of Enamel and Dentine, the DEJ.

Since Boucher technique used pedicle screw for the fixation of the spine in 1959, various kinds of pedicle screws have been developed continuously. The treatments of degenerative spine disease include spinal fusion and fixation using spinal devices. Spinal fusion surgery is classified into fusion and non fusion. The spine device market in which pedicle screws are used is getting bigger. However, it is one of the most challenging fields because of lack of the experimental and analytic data. In this study, a finite element model which includes non fusion device of human lumbar is developed and studied to understand the stability of the technique. The material property of the non fusion device is decided through comparison of intact model with fixed model. This result can be used as a basic source to new apparatus. This dynamic device offers a system that may alter the motion preservation and load sharing of a spinal segment without sacrificing stability.

The occlusal force of the tooth leads to loss of tooth tissue owing to attrition and abrasion, and may cause abfraction and pathological change of the dentine. Thus, we draw up finite element models, examine them applying ordinary occlusal force and analyze the stress distribution. Specimens used were mandibular first premolars from 15 Korean males and 13 females and were made into finite element models from medical images that were obtained using a micro-CT. We can find the fact that the irregular feature of the tooth is not useful only to masticating and pronouncing as well known, but that it is also suitable for protecting inner tissue by dispersing stress and delivering proper pressure to periodontal tissue to continue a physiological action. Also, image analysis can let us know the factor that is the cause of a disorder due to stress concentration in the cervical line. These results are expected to support the field of dental treatment planning, operating procedure and clinical trial, and the advance of technical expertise to develop implants and dentures.

Recently, secretory granule Ca(2+) storage protein chromogranin B (CGB) was shown to be present in the nucleoplasm proper in a complex structure that consists of the inositol 1,4,5-trisphosphate receptor (IP(3)R)/Ca(2+) channels and the phospholipids. Further, the amounts of IP(3)Rs present in the nucleus of bovine chromaffin cells were shown to be comparable to that of the endoplasmic reticulum. Therefore, we investigated here the potential contribution of nuclear CGB on the IP(3)-dependent Ca(2+) mobilization in the nucleus, using both neuroendocrine PC12 and nonneuroendocrine NIH3T3 cells. Chromogranin A (CGA) expression in the NIH3T3 cells, which do not contain intrinsic chromogranins, increased the IP(3)-induced Ca(2+) releases in the nucleus by 45%, while CGB expression in the same cells increased the IP(3)-induced Ca(2+) releases in the nucleus by 80%. Microinjection of IP(3) into the nucleus of CGB-expressing NIH3T3 cells increased the IP(3)-dependent nuclear Ca(2+) mobilization approximately 3-fold, whereas in CGA-expressing cells it remained the same as that of control cells. In contrast, inhibition of CGA expression in PC12 cells by siRNA treatment decreased the IP(3)-induced Ca(2+) releases in the nucleus by 17%, while inhibition of CGB expression decreased the IP(3)-induced Ca(2+) releases in the nucleus by 55%. Microinjection of IP(3) into the nucleus of siCGB-treated PC12 cells decreased the IP(3)-dependent nuclear Ca(2+) mobilization by approximately 75%, whereas in siCGA-treated cells it remained the same as that of control cells. Given the presence of CGB in the nucleus, these results further highlight the critical contribution of nuclear CGB in the IP(3)-induced Ca(2+) release in the nucleus.

We show here that expression of chromogranins in non-neuroendocrine NIH3T3 cells significantly increased the amount of IP 3 -mediated intracellular Ca 2 + mobilization in these cells, whereas suppression of them in neuroendocrine PC12 cells decreased the amount of mobilized Ca 2 + . We have therefore investigated the relationship between the IP 3 -induced intracellular Ca 2 + mobilization and secretory granules. The level of IP 3 -mediated Ca 2 + release in CGA-expressing NIH3T3 cells was 40% higher than in the control cells, while that of CGB-expressing cells was 134% higher, reflecting the number of secretory granules formed. Suppression of CGA and CGB expression in PC12 cells resulted in 41 and 78% reductions in the number of secretory granules, respectively, while the extents of IP 3 -induced Ca 2 + release in these cells were reduced 40 and 69%, respectively. The newly formed secretory granules of NIH3T3 cells contained all three isoforms of the IP 3 Rs. Comparison of the concentrations of the IP 3 R isoforms expressed in the ER and nucleus of chromogranin-expressing and nonexpressing NIH3T3 cells did not show significant differences, indicating that chromogranin expression did not affect the expression of endogenous IP 3 Rs. Nonetheless, the IP 3 R concentrations in secretory granules of chromogranin-expressing NIH3T3 cells were 3.5-4.7-fold higher than those of the ER, similar to the levels found in secretory granules of neuroendocrine chromaffin cells, thus suggesting that the IP 3 Rs targeted to the newly formed secretory granules are newly induced by chromogranins without affecting the expression of intrinsic IP 3 Rs. These results strongly suggest that the extent of IP 3 -induced intracellular Ca 2 + mobilization in secretory cells is closely related to the number of secretory granules.

It has been proposed that chromogranin A (CgA), a protein secreted by many normal and neoplastic neuroendocrine cells, can play a role as a positive or a negative modulator of cell adhesion. The mechanisms that regulate these extracellular functions of CgA are unknown. We show here that plasmin can regulate the anti/pro-adhesive activity of CgA by proteolytic cleavage of the N-terminal domain. Limited proteolytic processing decreased its anti-adhesive activity and induced pro-adhesive effects in fibronectin or serum-dependent fibroblast adhesion assays. Cleavage of Lys(77)-Lys(78) dibasic site in CgA(1-115) was relatively rapid and associated with an increase of pro-adhesive effect. In contrast, antibodies against the region 53-90 enhanced the anti-adhesive activity of CgA and CgA(1-115). Structure-activity relationship studies showed that the conserved region 47-64 (RILSILRHQNLLKELQDL) is critical for both pro- and anti-adhesive activity. These findings suggest that CgA might work on one hand as a negative modulator of cell adhesion and on the other hand as a precursor of positive modulators, the latter requiring proteolytic processing for activation. Given the importance of plasminogen activation in tissue invasion and remodeling, the interplay between CgA and plasmin could provide a novel mechanism for regulating fibroblast adhesion and function in neuroendocrine tumors.