Asia-Pacific Perspectives on the Role of Continuous Glucose Monitoring in Optimizing Diabetes Management.

Diabetes is prevalent, and it imposes a substantial public health burden globally and in the Asia-Pacific (APAC) region. The cornerstone for optimizing diabetes management and treatment outcomes is glucose monitoring, the techniques of which have evolved from self-monitoring of blood glucose (SMBG) to glycated hemoglobin (HbA1c), and to continuous glucose monitoring (CGM). Contextual differences with Western populations and limited regionally generated clinical evidence warrant regional standards of diabetes care, including glucose monitoring in APAC. Hence, the APAC Diabetes Care Advisory Board convened to gather insights into clinician-reported CGM utilization for optimized glucose monitoring and diabetes management in the region. We discuss the findings from a pre-meeting survey and an expert panel meeting regarding glucose monitoring patterns and influencing factors, patient profiles for CGM initiation and continuation, CGM benefits, and CGM optimization challenges and potential solutions in APAC. While CGM is becoming the new standard of care and a useful adjunct to HbA1c and SMBG globally, glucose monitoring type, timing, and frequency should be individualized according to local and patient-specific contexts. The results of this APAC survey guide methods for the formulation of future APAC-specific consensus guidelines for the application of CGM in people living with diabetes.

Asia-Pacific consensus recommendations for application of continuous glucose monitoring in diabetes management.

Glucose monitoring has evolved from self-monitoring of blood glucose to glycated hemoglobin, and the latest continuous glucose monitoring (CGM). A key challenge to adoption of CGM for management of diabetes in Asia is the lack of regional CGM recommendations. Hence, thirteen diabetes-specialists from eight Asia-Pacific (APAC) countries/regions convened to formulate evidence-based, APAC-specific CGM recommendations for individuals with diabetes. We defined CGM metrics/targets and developed 13 guiding-statements on use of CGM in: (1) people with diabetes on intensive insulin therapy, and (2) people with type 2 diabetes on basal insulin with/without glucose lowering drugs. Continual use of CGM is recommended in individuals with diabetes on intensive insulin therapy and suboptimal glycemic control, or at high risk of problematic hypoglycemia. Continual/intermittent CGM may also be considered in individuals with type 2 diabetes on basal insulin regimen and with suboptimal glycemic control. In this paper, we provided guidance for optimizing CGM in special populations/situations, including elderly, pregnancy, Ramadan-fasting, newly diagnosed type 1 diabetes, and comorbid renal disease. Statements on remote CGM, and stepwise interpretation of CGM data were also developed. Two Delphi surveys were conducted to rate the agreement on statements. The current APAC-specific CGM recommendations provide useful guidance for optimizing use of CGM in the region.

Daytime Glycemic Variability and Frailty in Older Patients with Diabetes: a Pilot Study Using Continuous Glucose Monitoring.

We investigated the relationship between glucose variability and frailty. Forty-eight type 2 diabetic patients aged ≥ 65 years were enrolled. The FRAIL scale was used for frailty assessment, and participants were classified into 'healthy & pre-frail' (n = 24) and 'frail' (n = 24) groups. A continuous glucose monitoring (CGM) system was used for a mean of 6.9 days and standardized CGM metrics were analyzed: mean glucose, glucose management indicator (GMI), coefficient of variation, and time in range, time above range (TAR), and time below range. The demographics did not differ between groups. However, among the CGM metrics, mean glucose, GMI, and TAR in the postprandial periods were higher in the frail group (all P < 0.05). After multivariate adjustments, the post-lunch TAR (OR = 1.12, P = 0.019) affected the prevalence of frailty. Higher glucose variability with marked daytime postprandial hyperglycemia is significantly associated with frailty in older patients with diabetes.

Modulation of Inflammatory Pathways and Adipogenesis by the Action of Gentisic Acid in RAW 264.7 and 3T3-L1 Cell Lines.

Gentisic acid (GA), a benzoic acid derivative present in various food ingredients, has been shown to have diverse pharmaceutical activities such as anti-carcinogenic, antioxidant, and hepatoprotective effects. In this study, we used a co-culture system to investigate the mechanisms of the anti-inflammatory and anti-adipogenic effects of GA on macrophages and adipocytes, respectively, as well as its effect on obesity-related chronic inflammation. We found that GA effectively suppressed lipopolysaccharide-stimulated inflammatory responses by controlling the production of nitric oxide and pro-inflammatory cytokines and modulating inflammation-related protein pathways. GA treatment also inhibited lipid accumulation in adipocytes by modulating the expression of major adipogenic transcription factors and their upstream protein pathways. Furthermore, in the macrophage-adipocyte co-culture system, GA decreased the production of obesity-related cytokines. These results indicate that GA possesses effective anti-inflammatory and anti-adipogenic activities and may be used in developing treatments for the management of obesity-related chronic inflammatory diseases.

Effect of Voluntary Participation on Mobile Health Care in Diabetes Management: Randomized Controlled Open-Label Trial.

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.

The effect of distance between holes on the structural stability of subchondral bone in microfracture surgery: a finite element model study.

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.

Neuroendocrine Targeting of Tissue Plasminogen Activator (t-PA).

t-PA has a widespread neuroendocrine distribution including prominent expression in chromaffin cells of the sympathoadrenal system. Chromaffin cell t-PA is sorted into catecholamine storage vesicles and co-released with catecholamines in response to sympathoadrenal activation, suggesting that catecholamine storage vesicles may serve as a reservoir for the rapid release of t-PA. Chromogranin A (CgA), a major core protein in secretory vesicles throughout the neuroendocrine system, may play a crucial role in targeting proteins into the regulated secretory pathway, by forming aggregated "granin" complexes to which other proteins destined for the regulated secretory vesicle bind and become separated from constitutively secreted proteins in the trans-Golgi network (TGN). Formation of such complexes is facilitated by conditions of the TGN (low pH, high Ca+2). We tested the hypothesis that t-PA interacts specifically with CgA and that this interaction is enhanced under conditions of the TGN. Immobilized t-PA was incubated with 125I-CgA. t-PA interacted specifically and saturably with CgA and the interaction was domain-specific, mediated by the EGF/finger and kringle 1 domains of t-PA and by a specific internal hydrophilic domain within CgA (KERTHQQKKHSSYEDELSEVL) as assessed by antibody and peptide competition studies. The interaction of t-PA with aggregated CgA complexes may play a role in the targeting of t-PA and its release from neurosecretory cells. These results may have broad implications for the regulation of local neurosecretory cell plasminogen activation under both normal physiological conditions and pathological conditions including cerebral ischemia.

Risk of osteoporosis after gastrectomy in long-term gastric cancer survivors.

INTRODUCTION: 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. METHODS: 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 <-2.5, was investigated, and clinical variables associated with the presence of osteoporosis were identified. RESULTS: A total of 250 survivors were included. The mean age was 54.6 years old, and the median follow-up was 6.0 years. The prevalence of osteoporosis was 34.0% (27.4% for men and 43.6% for women). Older age [odds ratio (OR) 5.50, 95% CI 2.33-13.00], higher alkaline phosphatase levels before gastrectomy (OR 5.67, 95% CI 1.36-23.64), and marked weight loss (≥20%) after gastrectomy (OR 3.59, 95% CI 1.32-9.77) were independently associated with the presence of osteoporosis. CONCLUSIONS: In our cohort, osteoporosis was commonly observed in long-term survivors of gastric cancer, and several risk factors for it were identified. To reduce the risk of osteoporosis after gastrectomy, maintaining adequate body weight may be necessary.

Psychological effects of a disastrous hydrogen fluoride spillage on the local community.

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 < 0.05). The mean score of the impact of event levels decreased significantly from 33.33 ± 14.64 at 1 month after the accident to 28.68 ± 11.80 at 7 months after the accident (p < 0.05). The mean score of the anxiety levels increased significantly from 5.16 ± 6.59 at 1 month after the accident to 6.79 ± 8.41 at 7 months after the accident (p < 0.05). The risk of persistent physical symptoms at 7 months after the accident was significantly higher in females. The risk of persistent physical symptoms also increased significantly, with increasing age, hydrogen fluoride exposure, and impact of event levels (p < 0.05). CONCLUSIONS: The present study found that the impact of event level and anxiety level increased with increasing hydrogen fluoride exposure. Anxiety levels persisted even after time passed. The risk of persistent physical symptoms at 7 months after the accident was higher in females, and it increased with increasing age, hydrogen fluoride exposure level, and impact of event levels.

Impact of initial active engagement in self-monitoring with a telemonitoring device on glycemic control among patients with type 2 diabetes.

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.

Diabetes Management via a Mobile Application: a Case Report.

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.

Comparison of clinical outcomes and second-look arthroscopic findings after ACL reconstruction using a hamstring autograft or a tibialis allograft.

PURPOSE: The purpose of this prospective randomized clinical study was to compare the clinical and radiological outcomes, including tibial tunnel widening and the progression of osteoarthritis after ACL reconstruction using a hamstring autograft or a tibialis allograft. In addition, we compared the graft tear and synovial coverage of grafts in patients that underwent the second-look arthroscopy. METHODS: Among 184 patients with an ACL injury who underwent ACL reconstruction, 68 patients of autograft group and 64 patients of tibialis allograft group were included for this study after minimum of 2-year follow-up. The Lachman and pivot-shift tests, Tegner activity score, Lysholm knee score, and IKDC score were compared between the two groups. The quadriceps and hamstring isokinetic strengths using dynamometer were also compared. Degree of OA was determined using the Kellgren-Lawrence grading system on the weight-bearing radiographs. In total, 51 patients (26 patients in autograft group and 25 in the tibialis allograft group) underwent the second-look arthroscopy, in which we compared the apparent tear of graft and synovial coverage of grafts. RESULTS: At the final follow-up, there were no statistical significances in the two groups in Lachman and pivot-shift tests (n.s.). The Tegner activity, Lysholm knee score, and IKDC scores were similar in the two groups. Moreover, no significant differences were observed in the muscle power (n.s.). Some patients showed the progression of OA (five in autograft and four in allograft groups) without intergroup difference (n.s.). Regarding the findings of second-look arthroscopy, although there was no significant difference in graft tear, synovial coverage was better in autograft group than in allograft group. CONCLUSION: Even though hamstring autografts and tibialis allografts provided good functional outcomes without significant differences, the second-look arthroscopy revealed that hamstring autografts produced better synovial coverage than tibialis allograft. LEVEL OF EVIDENCE: I.

An Internet-based health gateway device for interactive communication and automatic data uploading: Clinical efficacy for type 2 diabetes in a multi-centre trial.

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 < 0.001) compared to 7.81 ± 0.66% to 7.70 ± 0.88% within the control group. Postprandial glucose reduction was predominant. A subgroup with baseline HbA1c higher than 8% and good compliance achieved a reduction of HbA1c by 0.8 ± 1.05%. Glucose control and waist circumference reduction were more effective in females and subjects older than 40 years of age. There were no adverse events associated with the intervention. 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.

Risks of borderline liver enzyme abnormalities to the incidence of impaired fasting glucose and diabetes mellitus: a 7 year follow up study of workers.

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.

Assessing the accuracy of patient-specific guides for total knee arthroplasty.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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. LEVEL OF EVIDENCE: IV.

Distribution Profile of Inositol 1,4,5-Trisphosphate Receptor/Ca2+ Channels in α and ß Cells of Pancreas: Dominant Localization in Secretory Granules and Common Error in Identification of Secretory Granule Membranes.

OBJECTIVES: The α and ß cells of pancreatic islet release important hormones in response to intracellular Ca increases that result from Ca releases through the inositol 1,4,5-trisphoshate receptor (IP3R)/Ca channels. Yet no systematic studies on distribution of IP3R/Ca channels have been done, prompting us to investigate the distribution of all 3 IP3R isoforms. METHODS: Immunogold electron microscopy was performed to determine the presence and the relative concentrations of all 3 IP3R isoforms in 2 major organelles secretory granules (SGs) and the endoplasmic reticulum of α and ß cells of rat pancreas. RESULTS: All 3 IP3R isoforms were present in SG membranes of both cells, and the IP3R concentrations in SGs were ∼2-fold higher than those in the endoplasmic reticulum. Moreover, large halos shown in the electron microscope images of insulin-containing SGs of ß cells were gap spaces that resulted from separation of granule membranes from the surrounding cytoplasm. CONCLUSIONS: These results strongly suggest the important roles of SGs in IP3-induced, Ca-dependent regulatory secretory pathway in pancreas. Moreover, the accurate location of SG membranes of ß cells was further confirmed by the location of another integral membrane protein synaptotagmin V and of membrane phospholipid PI(4,5)P2.

Localization and projected role of phosphatidylinositol 4-kinases IIα and IIß in inositol 1,4,5-trisphosphate-sensitive nucleoplasmic Ca²âº store vesicles.

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 IIß, 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 IIß 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 IIß 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.

Polarization characteristics of semipolar (112̄2) InGaN/GaN quantum well structures grown on relaxed InGaN buffer layers and comparison with experiment.

Partial strain relaxation effects on polarization ratio of semipolar (112̄2) InxGa1−xN/GaN quantum well (QW) structures grown on relaxed InGaN buffers were investigated using the multiband effective-mass theory. The absolute value of the polarization ratio gradually decreases with increasing In composition in InGaN buffer layer when the strain relaxation ratio (ε0y'y'−εy'y')/ε0y'y' along y'-axis is assumed to be linearly proportional to the difference of lattice constants between the well and the buffer layer. Also, it changes its sign for the QW structure grown on InGaN buffer layer with a relatively larger In composition (x > 0.07). These results are in good agreement with the experiment. This can be explained by the fact that, with increasing In composition in the InGaN subsrate, the spontaneous emission rate for the y'-polarization gradually increases while that for x'-polarization decreases due to the decrease in a matrix element at the band-edge (k‖ = 0).

The influence of various core designs on stress distribution in the veneered zirconia crown: a finite element analysis study.

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.

Mitochondrial dysfunction of immortalized human adipose tissue-derived mesenchymal stromal cells from patients with Parkinson's disease.

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.