A Multicenter, Randomized, Open-Label Study to Compare the Effects of Gemigliptin Add-on or Escalation of Metformin Dose on Glycemic Control and Safety in Patients with Inadequately Controlled Type 2 Diabetes Mellitus Treated with Metformin and SGLT-2 Inhibitors (SO GOOD Study).

Background: We aimed to compare efficacy and safety between gemigliptin add-on and escalation of the metformin dose in patients with inadequately controlled type 2 diabetes mellitus (T2DM) despite treatment with metformin and SGLT2 inhibitors. Methods: This study was a multicenter, randomized, open-label, active-controlled, parallel-group comparative study. Patients with T2DM uncontrolled on metformin and SGLT2 inhibitors were randomized to receive gemigliptin 50 mg as an add-on (GEM group, n = 37) or escalation of the metformin dose (500 mg, MET group, n = 38) for 24 weeks. The primary endpoint was the change in glycosylated hemoglobin (HbA1c) from baseline to week 24. Results: At weeks 12 and 24, the reduction in HbA1c levels was significantly greater in the GEM group than in the MET group (GEM vs. MET = -0.64% ± 0.34% vs. -0.36% ± 0.50%, p = 0.009 at week 12; -0.61% ± 0.35% vs. -0.33% ± 0.70%, p = 0.045 at week 24). The proportions of patients who achieved target HbA1c levels of <7.0% at weeks 12 and 24 and <6.5% at week 12 were greater in the GEM group than in the MET group. An index of ß-cell function was also significantly improved in the GEM group. The safety profiles were similar between the two groups. Conclusions: Gemigliptin add-on therapy may be more effective than metformin dose escalation in patients with T2DM insufficiently controlled using metformin and SGLT2 inhibitors, without safety concerns. This trial is registered with CRIS_number: KCT0003520.

Nasopharyngeal lymphatic plexus is a hub for cerebrospinal fluid drainage.

Cerebrospinal fluid (CSF) in the subarachnoid space around the brain has long been known to drain through the lymphatics to cervical lymph nodes1-17, but the connections and regulation have been challenging to identify. Here, using fluorescent CSF tracers in Prox1-GFP lymphatic reporter mice18, we found that the nasopharyngeal lymphatic plexus is a major hub for CSF outflow to deep cervical lymph nodes. This plexus had unusual valves and short lymphangions but no smooth-muscle coverage, whereas downstream deep cervical lymphatics had typical semilunar valves, long lymphangions and smooth muscle coverage that transported CSF to the deep cervical lymph nodes. α-Adrenergic and nitric oxide signalling in the smooth muscle cells regulated CSF drainage through the transport properties of deep cervical lymphatics. During ageing, the nasopharyngeal lymphatic plexus atrophied, but deep cervical lymphatics were not similarly altered, and CSF outflow could still be increased by adrenergic or nitric oxide signalling. Single-cell analysis of gene expression in lymphatic endothelial cells of the nasopharyngeal plexus of aged mice revealed increased type I interferon signalling and other inflammatory cytokines. The importance of evidence for the nasopharyngeal lymphatic plexus functioning as a CSF outflow hub is highlighted by its regression during ageing. Yet, the ageing-resistant pharmacological activation of deep cervical lymphatic transport towards lymph nodes can still increase CSF outflow, offering an approach for augmenting CSF clearance in age-related neurological conditions in which greater efflux would be beneficial.

Heterogeneous reservoir computing in second-order Ta2O5/HfO2 memristors.

Multiple switching modes in a Ta2O5/HfO2 memristor are studied experimentally and numerically through a reservoir computing (RC) simulation to reveal the importance of nonlinearity and heterogeneity in the RC framework. Unlike most studies, where homogeneous reservoirs are used, heterogeneity is introduced by combining different behaviors of the memristor units. The chosen memristor for the reservoir units is based on a Ta2O5/HfO2 bilayer, in which the conductances of the Ta2O5 and HfO2 layers are controlled by the oxygen vacancies and deep/shallow traps, respectively, providing both volatile and non-volatile resistive switching modes. These several control parameters make the second-order Ta2O5/HfO2 memristor system present different behaviors in agreement with its history-dependent conductance and allow the fine-tuning of the behavior of each reservoir unit. The heterogeneity in the reservoir units improves the pattern recognition performance in the heterogeneous memristor RC system with a similar physical structure.

Protective effect of empagliflozin against palmitate-induced lipotoxicity through AMPK in H9c2 cells.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as novel cardioprotective agents. However, their direct impact on cardiomyocyte injury is yet to be studied. In this work, we investigate the underlying molecular mechanisms of empagliflozin (EMPA), an SGLT2 inhibitor, in mitigating palmitate (PA)-induced cardiomyocyte injury in H9c2 cells. We found that EMPA significantly attenuated PA-induced impairments in insulin sensitivity, ER stress, inflammatory cytokine gene expression, and cellular apoptosis. Additionally, EMPA elevated AMP levels, activated the AMPK pathway, and increased carnitine palmitoyl transferase1 (CPT1) gene expression, which collectively enhanced fatty acid oxidation and reduced stress signals. This study reveals a novel mechanism of EMPA's protective effects against PA-induced cardiomyocyte injury, providing new therapeutic insights into EMPA as a cardioprotective agent.

Optimization of ultrasound-assisted deep eutectic solvent extraction of bioactive compounds from pomegranate peel using response surface methodology.

The efficient extraction of polyphenols from pomegranate peels using a deep eutectic solvent (DES) and ultrasound-assisted extraction (UAE) was investigated. A Box-Behnken design was used to investigate the effects of four independent variables (water content, liquid-to-solid ratio, ultrasonic power, and extraction time) on total polyphenol content (TPC), punicalagin content (PC), and ellagic acid content (EC). Optimized DES-based UAE conditions were as follows: TPC (water content, 29.30%; liquid-to-solid ratio, 53.50 mL/g; ultrasonic power, 238.20 W; extraction time, 29.50 min), PC (water content, 25.65%; liquid-to-solid ratio, 44.20 mL/g; ultrasonic power, 120 W; extraction time, 20 min), and EC (water content, 33.13%; liquid-to-solid ratio, 60 mL/g; ultrasonic power, 300 W; extraction time, 20 min). Under these optimal conditions, the experimental values for TPC, PC, and EC were 67.50 mg GAE/g, 130.65 mg/g, and 2.04 mg/g, respectively; these values were consistent with the predicted values.

Amphiregulin Induces iNOS and COX-2 Expression through NF-κB and MAPK Signaling in Hepatic Inflammation.

Background: Inflammation is a major cause of hepatic tissue damage and accelerates the progression of nonalcoholic fatty liver disease (NAFLD). Amphiregulin (AREG), an epidermal growth factor receptor ligand, is associated with human liver cirrhosis and hepatocellular carcinoma. We aimed to investigate the effects of AREG on hepatic inflammation during NAFLD progression, in vivo and in vitro. Methods: AREG gene expression was measured in the liver of mice fed a methionine choline-deficient (MCD) diet for 2 weeks. We evaluated inflammatory mediators and signaling pathways in HepG2 cells after stimulation with AREG. Nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were analyzed using an enzyme-linked immunosorbent assay and western blotting. Nuclear transcription factor kappa-B (NF-κB) and mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase, were analyzed using western blotting. Results: Proinflammatory cytokines (interleukin (IL)-6, IL-1ß, and IL-8) and immune cell recruitment (as indicated by L3T4, F4/80, and ly6G mRNA expression) increased, and expression of AREG increased in the liver of mice fed the MCD diet. AREG significantly increased the expression of IL-6 and IL-1ß and the production of NO, PGE2, and IL-8 in HepG2 cells. It also activated the protein expression of iNOS and COX-2. AREG-activated NF-κB and MAPKs signaling, and together with NF-κB and MAPKs inhibitors, AREG significantly reduced the protein expression of iNOS and COX-2. Conclusion: AREG plays a role in hepatic inflammation by increasing iNOS and COX-2 expression via NF-κB and MAPKs signaling.

2023 Clinical Practice Guidelines for Diabetes Mellitus of the Korean Diabetes Association.

In May 2023, the Committee of Clinical Practice Guidelines of the Korean Diabetes Association published the revised clinical practice guidelines for Korean adults with diabetes and prediabetes. We incorporated the latest clinical research findings through a comprehensive systematic literature review and applied them in a manner suitable for the Korean population. These guidelines are designed for all healthcare providers nationwide, including physicians, diabetes experts, and certified diabetes educators who manage patients with diabetes or individuals at risk of developing diabetes. Based on recent changes in international guidelines and the results of a Korean epidemiological study, the recommended age for diabetes screening has been lowered. In collaboration with the relevant Korean medical societies, recently revised guidelines for managing hypertension and dyslipidemia in patients with diabetes have been incorporated into this guideline. An abridgment containing practical information on patient education and systematic management in the clinic was published separately.

ERG K+ channels mediate a major component of action potential repolarization in lymphatic muscle.

Smooth muscle cells in the walls of collecting lymphatic vessels fire spontaneous action potentials (APs), which conduct rapidly over the muscle layer to initiate contractions that propel lymph. Several ion channels have been implicated in the currents underlying the AP spike and the preceding diastolic depolarization, but the molecular identities of K+ channels involved in AP repolarization are unknown. Based on previous studies of other rhythmically active smooth muscles, we hypothesized that ether-a-go-go related gene (ERG) K+ channels (Kv11) play an important role in repolarization of the AP in lymphatic muscle. Message for one or more ERG channel isoforms was detected by RT-PCR analysis of lymphatic vessels from mice, rats and humans. Membrane potential recordings in smooth muscle cells of rat and human lymphatics revealed that nanomolar concentrations of ERG-1 inhibitors (E-4031 and BeKm-1) prolonged the duration of the AP plateau (normally ~ 1 s in duration) and induced multiple spikes, whereas ERG-1 activators (ICA-105574 and RPR-260243) shortened the plateau and could completely inhibit spontaneous APs. At relatively high inhibitor concentrations, the AP plateau duration lasted as long as 24 s. ERG activators reversed the effects of ERG inhibitors and vice-versa. In pressure myograph studies, ERG channel inhibition prolonged the diastolic repolarization phase of the contraction cycle and reduced the frequency of spontaneous contractions. This is the first evidence for a specific K+ channel contributing to the AP in lymphatic muscle. Our results imply that lymphatic contractile dysfunction may occur in long QT type II patients with mutations that result in ERG channel loss-of-function or impaired trafficking of the channel to the cell membrane.

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.

BACKGRUOUND: 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 ß-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.

Role of Chondroitin Sulfate Proteoglycan 5 in Steroid-Induced Cataract.

Steroid-induced cataracts (SIC) are defined as cataracts associated with the administration of corticosteroids. Long-term glucocorticoid treatment for inflammatory diseases reportedly increases the risk of SIC, and steroids can induce cataracts by disrupting ocular growth factor balance or homeostasis. In this study, we verified the effect of chondroitin sulfate proteoglycan 5 (CSPG5) using dexamethasone (dexa)-treated human lens epithelial (HLE-B3) cells and the lens epithelium from the anterior capsule of SIC patients obtained during cataract surgery. CSPG5 expression increased in the lens epithelium of SIC patients. The downregulation of CSPG5 suppressed the dexa-induced epithelial-mesenchymal transition (EMT)-related protein expression and motility in HLE-B3 cells. The disruption of the transcription factors EZH2 and B-Myb downregulated CSPG5, dexa-induced fibronectin expression, and cell migration in HLE-B3 cells, reaffirming that CSPG5 expression regulates EMT in lens epithelial cells. Taken together, these results indicate that the steroid-induced effects on lens epithelial cells are mediated via alterations in CSPG5 expression. Therefore, our study emphasizes the potential of CSPG5 as a therapeutic target for the prevention and treatment of SIC.

T18/S19 diphosphorylation of myosin regulatory light chain impairs pulmonary artery relaxation in monocrotaline-induced pulmonary hypertensive rats.

Phosphorylation of Ser19 (S19-p) on the myosin regulatory light chain (MLC2) is critical for arterial contraction. It has been shown that elevated RhoA-dependent kinase (ROCK) activity or decreased MLC phosphatase (MLCP) activity leads to further phosphorylation of Thr18 (T18/S19-pp), which has been linked to vasospastic diseases. However, this phenomenon has not yet been studied in the context of pulmonary arterial hypertension (PAH). In the monocrotaline-induced PAH (PAH-MCT) rat model, we observed a significant delay in pulmonary artery (PA) relaxation following high potassium-induced contraction, which persisted even with the use of an L-type calcium channel blocker or in a calcium-free solution. Immunoblot analysis showed increased levels of both S19-p and T18/S19-pp in unstimulated PAs from PAH-MCT rats. Proteomics analysis revealed a reduction in soluble guanylate cyclase (sGC) and protein kinase G (PKG) levels, and immunoblotting confirmed decreased levels of MYPT1 (a component of MLCP) and increased ROCK in PAH-MCT. In the control PAs, the pharmacological inhibition of sGC with ODQ resulted in a prominent delay of relaxation and increased T18/S19-pp as in PAH-MCT. The delayed relaxation and the T18/S19-pp in PAH-MCT were reversed by ROCK inhibitor, Y27632, while not by membrane permeable 8-Br-cGMP. The delayed relaxation and T18/S19-diP in the ODQ-treated control PA were also reversed by Y27632. Taken together, the decreased sGC and MLCP, and increased ROCK increased T18/S19-pp, which leads to the decreased ability of PA to relax in PAH-MCT rats. PA specific inhibition of ROCK or activation of MLCP are expected to serve as potential drugs in the treatment of PAH.

Lymphatic contractile dysfunction in mouse models of Cantú Syndrome with KATP channel gain-of-function.

Cantú Syndrome (CS) is an autosomal dominant disorder caused by gain-of-function (GoF) mutations in the Kir6.1 and SUR2 subunits of KATP channels. KATP overactivity results in a chronic reduction in arterial tone and hypotension, leading to other systemic cardiovascular complications. However, the underlying mechanism of lymphedema, developed by >50% of CS patients, is unknown. We investigated whether lymphatic contractile dysfunction occurs in mice expressing CS mutations in Kir6.1 (Kir6.1[V65M]) or SUR2 (SUR2[A478V], SUR2[R1154Q]). Pressure myograph tests of contractile function of popliteal lymphatic vessels over the physiological pressure range revealed significantly impaired contractile strength and reduced frequency of spontaneous contractions at all pressures in heterozygous Kir6.1[V65M] vessels, compared to control littermates. Contractile dysfunction of intact popliteal lymphatics in vivo was confirmed using near-infrared fluorescence microscopy. Homozygous SUR2[A478V] vessels exhibited profound contractile dysfunction ex vivo, but heterozygous SUR2[A478V] vessels showed essentially normal contractile function. However, further investigation of vessels from all three GoF mouse strains revealed significant disruption in contraction wave entrainment, decreased conduction speed and distance, multiple pacemaker sites, and reversing wave direction. Tests of 2-valve lymphatic vessels forced to pump against an adverse pressure gradient revealed that all CS-associated genotypes were essentially incapable of pumping under an imposed outflow load. Our results show that varying degrees of lymphatic contractile dysfunction occur in proportion to the degree of molecular GoF in Kir6.1 or SUR2. This is the first example of lymphatic contractile dysfunction caused by a smooth muscle ion channel mutation and potentially explains the susceptibility of CS patients to lymphedema.

Inhibition of DAMP actions in the tumoral microenvironment using lactoferrin-glycyrrhizin conjugate for glioblastoma therapy.

BACKGROUND: High-mobility group box-1 (HMGB1) released from the tumor microenvironment plays a pivotal role in the tumor progression. HMGB1 serves as a damaged-associated molecular pattern (DAMP) that induces tumor angiogenesis and its development. Glycyrrhizin (GL) is an effective intracellular antagonist of tumor released HMGB1, but its pharmacokinetics (PK) and delivery to tumor site is deficient. To address this shortcoming, we developed lactoferrin-glycyrrhizin (Lf-GL) conjugate. METHODS: Biomolecular interaction between Lf-GL and HMGB1 was evaluated by surface plasmon resonance (SPR) binding affinity assay. Inhibition of tumor angiogenesis and development by Lf-GL attenuating HMGB1 action in the tumor microenvironment was comprehensively evaluated through in vitro, ex vivo, and in vivo. Pharmacokinetic study and anti-tumor effects of Lf-GL were investigated in orthotopic glioblastoma mice model. RESULTS: Lf-GL interacts with lactoferrin receptor (LfR) expressed on BBB and GBM, therefore, efficiently inhibits HMGB1 in both the cytoplasmic and extracellular regions of tumors. Regarding the tumor microenvironment, Lf-GL inhibits angiogenesis and tumor growth by blocking HMGB1 released from necrotic tumors and preventing recruitment of vascular endothelial cells. In addition, Lf-GL improved the PK properties of GL approximately tenfold in the GBM mouse model and reduced tumor growth by 32%. Concurrently, various biomarkers for tumor were radically diminished. CONCLUSION: Collectively, our study demonstrates a close association between HMGB1 and tumor progression, suggesting Lf-GL as a potential strategy for coping with DAMP-related tumor microenvironment. HMGB1 is a tumor-promoting DAMP in the tumor microenvironment. The high binding capability of Lf-GL to HMGB1 inhibits tumor progression cascade such as tumor angiogenesis, development, and metastasis. Lf-GL targets GBM through interaction with LfR and allows to arrest HMGB1 released from the tumor microenvironment. Therefore, Lf-GL can be a GBM treatment by modulating HMGB1 activity.

Interfacial Capillary Spooling of Conductive Polyurethane-Silver Core-Sheath (PU@Ag) Microfibers for Highly Stretchable Interconnects.

Conductive fibers are core materials in textile electronics for the sustainable operation of devices under mechanical stimuli. Conventional polymer-metal core-sheath fibers were employed as stretchable electrical interconnects. However, their electrical conductivity is severely degraded by the rupture of metal sheaths at low strains. Because the core-sheath fibers are not intrinsically stretchable, designing a stretchable architecture of interconnects based on the fibers is essential. Herein, we introduce nonvolatile droplet-conductive microfiber arrays as stretchable interconnects by employing interfacial capillary spooling, motivated by the reversible spooling of capture threads in a spider web. Polyurethane (PU)-Ag core-sheath (PU@Ag) fibers were prepared by wet-spinning and thermal evaporation. When the fiber was placed on a silicone droplet, a capillary force was generated at their interface. The highly soft PU@Ag fibers were fully spooled within the droplet and reversibly uncoiled when a tensile force was applied. Without mechanical failures of the Ag sheaths, an excellent conductivity of 3.9 × 104 S cm-1 was retained at a strain of 1200% for 1000 spooling-uncoiling cycles. A light-emitting diode connected to a multiarray of droplet-PU@Ag fibers exhibited stable operation during spooling-uncoiling cycles.

Validation of the Dimensions of Anger Reactions Scale (the DAR-5) in non-clinical South Korean adults.

BACKGROUND: Posttraumatic anger is a commonly reported emotion among people who have experienced traumatic events. The current study aimed to demonstrate the reliability and validity of the South Korean version of the DAR-5 (DAR-5-K). The DAR-5 is a single scale with 5 items which measures posttraumatic anger. The DAR-5 is composed of five items that measure anger frequency, intensity, duration, aggression, and its interference with social relations. METHODS: Data were collected from 814 South Korean adults who had experienced traumatic events and participated in the study and analyzed via the combination of exploratory factor analysis (n = 405) and confirmatory factor analysis (n = 409). RESULTS: Results supported the one-factor structure, as reported in previous validation studies. The scale demonstrated robust internal reliability and concurrent validity with measures of posttraumatic stress disorder (PTSD) symptoms, depression, anxiety, and self-esteem. The DAR-5 cut-off score of 12 that was established in the original validation study successfully differentiated high from low scorers with regard to PTSD symptoms, depression, anxiety, and self-esteem. CONCLUSION: The results confirm that the DAR-5-K is a brief and psychometrically robust measure of anger that can be used to examine South Korean adults who have experienced traumatic events.

Highly parallel stateful Boolean logic gates based on aluminum-doped self-rectifying memristors in a vertical crossbar array structure.

The self-rectifying memristor with electronic bipolar resistive switching shows electroforming-free, highly rectifying properties and low operating power. Furthermore, configuring the memristors in a vertical array structure provides a higher memory density than in a planar array structure. These combined advantages can be exploited in in-memory computing, which may provide a new and efficient stateful logic gate with high parallelism compared to the conventional stateful logic gates in the planar array structure. The different switching mechanism compared to the previous logic gates based on filamentary-type switching is explained and exploited to realize the AND and OR Boolean logic gates. Since the AND and OR logic functions are the basic operations of sum-of-product (SoP) and product-of-sum (PoS) expressions, any canonical expression for Boolean logic can be implemented in the vertical crossbar array (CBA). Accordingly, the composite logic gate, such as an exclusive OR operation, is demonstrated. In addition, the implementation of the memristive priority encoder is proposed using parallel logic gates. Although the switching speed should be improved in further work, a higher parallelism with a larger number of layers in the vertical array structure can mitigate the low operation speed issue.

Cardiovascular Outcomes according to Comorbidities and Low-Density Lipoprotein Cholesterol in Korean People with Type 2 Diabetes Mellitus.

BACKGROUND: There are no clear data to support the cardiovascular (CV) risk categories and low-density lipoprotein cholesterol (LDL-C) treatment goals in Korean people with type 2 diabetes mellitus (T2DM). We evaluated the incidence of cardiovascular disease (CVD) according to comorbidities and suggested LDL-C treatment goals in Korean people with T2DM in nationwide cohort data. METHODS: Using the Korean National Health Insurance Service database, 248,002 people aged 30 to 90 years with T2DM who underwent routine health check-ups during 2009 were included. Subjects with previous CVD were excluded from the study. The primary outcome was incident CVD, defined as a composite of myocardial infarction and ischemic stroke during the follow-up period from 2009 to 2018. RESULTS: The mean age of the study participants was 59.6±10.9 years, and median follow-up period was 9.3 years. CVD incidence increased in the order of DM duration of 5 years or more (12.04/1,000 person-years), hypertension (HT) (12.27/1,000 personyears), three or more CV risk factors (14.10/1,000 person-years), and chronic kidney disease (18.28/1,000 person-years). The risk of incident CVD increased linearly from an LDL-C level of ≥70 mg/dL in most patients with T2DM. In T2DM patients without HT or with a DM duration of less than 5 years, the CVD incidence increased from LDL-C level of ≥100 mg/dL. CONCLUSION: For primary prevention of CVD in Korean adults with T2DM, it can be helpful to lower LDL-C targets when there are chronic kidney disease, HT, a long duration of diabetes mellitus, or three or more CV risk factors.

Association between Low-Density Lipoprotein Cholesterol Level and Cardiovascular Outcomes in Korean Adults: A Nationwide Cohort Study.

BACKGROUND: To validate the treatment target of low-density lipoprotein cholesterol (LDL-C) level according to the cardiovascular disease (CVD) risk which was recommended by Korean dyslipidemia guideline. METHODS: We used the Korean National Health Insurance Service database which included 3,958,048 people aged 20 to 89 years who underwent regular health screening. The primary outcome was incident CVD, defined as a composite of myocardial infarction and stroke during the follow-up period from 2009 to 2018. RESULTS: The risk of CVD increased from LDL-C level of 70 mg/dL in very high-risk and high-risk groups and from 130 mg/dL in moderate-risk and low-risk groups. Adjusted hazard ratios (HRs) of LDL-C ranges 70-99, 100-129, 130-159, 160-189, and ≥190 mg/dL were 1.20 (95% confidence interval [CI], 1.08-1.33), 1.27 (1.15-1.42), 1.39 (1.23-1.56), 1.69 (1.45-1.96), and 1.84 (1.49- 2.27) in very high-risk group, and 1.07 (1.02-1.13), 1.16 (1.10-1.21), 1.29 (1.22-1.36), 1.45 (1.36-1.55), and 1.73 (1.58-1.90) in high-risk group. Adjusted HRs (95% CI) of LDL-C ranges 130-159, 160-189, and ≥190 mg/dL were 1.15 (1.11-1.20), 1.28 (1.22- 1.34), and 1.45 (1.36-1.54) in moderate-risk group and 1.07 (1.02-1.13), 1.20 (1.13-1.26), and 1.47 (1.37-1.57) in low-risk group. CONCLUSION: We confirmed the incidence of CVD was increased in higher LDL-C range. The risk of CVD increased from ≥70 mg/dL of LDL-C in very high-risk and high-risk groups, and from ≥130 mg/dL of LDL-C in moderate-risk and low-risk groups in Korean adults.

Impact of Post-Transplant Diabetes Mellitus on Survival and Cardiovascular Events in Kidney Transplant Recipients.

BACKGRUOUND: Post-transplant diabetes mellitus (PTDM) is a risk factor for poor outcomes after kidney transplantation (KT). However, the outcomes of KT have improved recently. Therefore, we investigated whether PTDM is still a risk factor for mortality, major atherosclerotic cardiovascular events (MACEs), and graft failure in KT recipients. METHODS: We studied a retrospective cohort of KT recipients (between 1994 and 2017) at a single tertiary center, and compared the rates of death, MACEs, overall graft failure, and death-censored graft failure after KT between patients with and without PTDM using Kaplan-Meier analysis and a Cox proportional hazard model. RESULTS: Of 571 KT recipients, 153 (26.8%) were diagnosed with PTDM. The mean follow-up duration was 9.6 years. In the Kaplan- Meier analysis, the PTDM group did not have a significantly increased risk of death or four-point MACE compared with the non-diabetes mellitus group (log-rank test, P=0.957 and P=0.079, respectively). Multivariate Cox proportional hazard models showed that PTDM did not have a negative impact on death or four-point MACE (P=0.137 and P=0.181, respectively). In addition, PTDM was not significantly associated with overall or death-censored graft failure. However, patients with a long duration of PTDM had a higher incidence of four-point MACE. CONCLUSION: Patient survival and MACEs were comparable between groups with and without PTDM. However, PTDM patients with long duration diabetes were at higher risk of cardiovascular disease.

Safety, high-performing and effects of the N/P ratio of a solid lithium ion battery using PEGDME based polymer electrolytes.

In this study, we report on the electrochemical properties of a solid state lithium ion battery (LIB) using a poly (ethylene glycol) dimethyl ether (PEGDME)-based solid polymer electrolyte (P-SPE). The LIB is prepared using a LiFePO4 (LFP) cathode and graphite anode material with P-SPE, and the kinetic properties of the lithium ions in the P-SPE are investigated. The synthesized P-SPE is shown to be suitable solid polymer electrolyte candidate for LIB applications. LFP and graphite are selected as electrode materials to validate their effectiveness in different battery cells with respect to their high energy density and inherent safety. The five-layer stacked 5 × 6 cm2 pouch-type LIB demonstrates a high capacity of 90 mAh (0.6 mAh/cm2) or more in the initial cycle, and it shows cycle stability with a capacity decrease of 20% over 500 cycles. We test the manufactured pouch-type full cells under extreme conditions (e. g., cutting, crushing and exposure of the battery cell to the atmosphere). LIBs using the developed P-SPE are promising solid polymer electrolyte candidates for wearable LIB as well as high energy LIB applications.