Anagliptin twice-daily regimen improves glycaemic variability in subjects with type 2 diabetes: A double-blind, randomized controlled trial.

AIM: To determine whether the twice-daily (BID) regimen is superior to the once-daily (QD) regimen for managing glycaemic variability by comparing the effects of anagliptin 100 mg BID versus sitagliptin 100 mg QD. MATERIALS AND METHODS: A double-blinded, randomized, multicentre study was performed in 89 patients with type 2 diabetes treated with metformin alone (6.5% < HbA1c < 8.5%). Subjects were randomly assigned to anagliptin 100 mg BID or sitagliptin 100 mg QD in a 1:1 ratio for 12 weeks. Continuous glucose monitoring was used to measure the mean amplitude of glycaemic excursion (MAGE) and postprandial time in range (TIR) before and after dipeptidyl peptidase-4 (DPP-4) inhibitor treatment to compare glycaemic variability. RESULTS: The decrease from baseline in MAGE at 12 weeks after DPP-4 inhibitor treatment was significantly greater in the anagliptin BID group than in the sitagliptin QD group (P < .05); -30.4 ± 25.6 mg/dl (P < .001) in the anagliptin group versus -9.5 ± 38.0 mg/dl (P = .215) in the sitagliptin group. The TIR after dinner increased by 33.0% ± 22.0% (P < .001) in the anagliptin group and by 14.6% ± 28.2% (P = .014) in the sitagliptin group, with a statistically significant difference (P = .009). No statistically significant differences were observed between the groups in the changes in HbA1c and fasting plasma glucose (FPG). CONCLUSIONS: The anagliptin BID regimen for the treatment of type 2 diabetes was superior in blood glucose control after dinner to improve glycaemic variability, as indicated by MAGE and TIR, but was equivalent to the QD regimen in terms of HbA1c and FPG.

The Protective Effects of Eicosapentaenoic Acid for Stress-induced Accelerated Senescence in Vascular Endothelial Cells.

Background: Eicosapentaenoic acid (EPA) is an omega-3 fatty acid that protects against cardiovascular diseases in patients with hypertriglyceridemia and may have pleotropic effects beyond lowering triglycerides. Many degenerative diseases, such as atherosclerosis and diabetes, are related to cellular senescence as a pathophysiological mechanism. We aimed to examine whether EPA could protect vascular endothelial cells under stress conditions against stress-induced accelerated senescence (SIAS). Methods: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to H2O2 as oxidative stress and a high glucose concentration with palmitate as a glucolipotoxic condition. Changes in cell viability, apoptosis, lactate dehydrogenase release, and cell cycle analysis were measured by cell counting kit-8 assay, annexin V/ propidium iodide staining, and enzyme-linked immunosorbent assay, respectively. EPA was applied in stress conditions. The degree of senescence was measured by senescence-associated beta-galactosidase staining and p16 staining using immunofluorescence. Apoptosis and cellular senescence-related proteins were measured by Western blotting. Results: Cultured HUVECs under oxidative and glucolipotoxic stresses revealed accelerated senescence and increased apoptosis. These changes were markedly reversed by EPA administration, and the expressions of apoptosis and cellular senescence-related proteins were reversed by EPA treatment. Conclusion: EPA effectively protects HUVECs against SIAS, which may be one of its pleotrophic effects.

Arterial stiffness is an independent predictor for risk of mortality in patients with type 2 diabetes mellitus: the REBOUND study.

BACKGROUND: This study aimed to evaluate the benefit of brachial-ankle pulse wave velocity (baPWV) as a noninvasive marker of arterial stiffness for the prediction of all-cause and cause-specific mortality in patients with type 2 diabetes. METHODS: This multicenter prospective observational study analyzed 2308 patients with type 2 diabetes between 2008 and 2018. The patients were categorized according to the quartiles of baPWV. Cause of mortality was determined using death certificates and patient clinical records. We estimated proportional mortality rates from all causes, cardiovascular, cancer, and other causes among adults with diabetic status according to their baPWV. Cox regression models were used to estimate hazard ratios (HRs). RESULTS: There were 199 deaths (8.6%) in the study population during a median follow-up duration of 8.6 years. When baPWV was assessed as quartiles, a significantly higher risk of all-cause mortality (HR = 5.39, P < 0.001), cardiovascular-mortality (HR = 14.89, P < 0.001), cancer-mortality (HR = 5.42, P < 0.001), and other-cause mortality (HR = 4.12, P < 0.001) was found in quartile 4 (Q4, ≥ 1830 cm/s) than in quartiles 1-3 (Q1-3). Adding baPWV to baseline model containing conventional risk factors such as age, sex, diabetes duration, body mass index, glycated hemoglobin, systolic blood pressure, glomerular filtration rate, smoking, and insulin improved the risk prediction for all-cause (net reclassification index (NRI) = 49%, P < 0.001) and cause-specific (cardiovascular NRI = 28%, P = 0.030; cancer NRI = 55%, P < 0.001; other-cause NRI 51%, P < 0.001) mortality. CONCLUSION: This long-term, large-scale, multicenter prospective observational cohort study provide evidence that increased arterial stiffness, as measured by baPWV, predicts the risk of all-cause and cause-specific mortality in type 2 diabetes, supporting the prognostic utility of baPWV. Trial registration Clinical Research Information Service (CRIS), KCT 0005010. Retrospectively Registered May 12, 2020. https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=16677.

Empowering hospital-associated infection prevention and control: A quasi-experimental study on the effect of scenario-based simulation training.

AIM: This study aimed to investigate the effect of scenario-based simulation training on infection control, specifically in terms of knowledge, self-efficacy and adherence to standard precautions. BACKGROUND: Hospital-associated infections can pose a threat to patient safety and are a critical public health issue that requires attention. DESIGN: This quasi-experimental study employed a pre-test/post-test design using a nonequivalent control group. METHODS: Infection control nurses were randomly assigned to two groups using lottery methods. The experimental group received scenario-based simulation training, whereas both the experimental and control groups received conventional education. Data were collected from 27 August to 1 December 1 2022. The chi-square test and t-test were used for data analysis. RESULTS: The mean scores for knowledge of infection prevention and control (t = 3.679, p < 0.001) and self-efficacy (t = 2.444, p = 0.018) were significantly higher in the experimental group than in the control group. Furthermore, the mean score for adherence to standard precautions was significantly higher in the experimental group than in the control group (t = 2.030, p = 0.048). CONCLUSION: Our results suggest that scenario-based simulation training for infection control might be effective in improving knowledge, self-efficacy and adherence to standard precautions. Scenario-based simulation training for infection control may be an effective educational intervention to enhance knowledge, self-efficacy and adherence to standard precautions, thus empowering nurses in infection prevention and control.

Enhancing competency in infection prevention and control: Identifying priorities for clinical nurse educational needs.

BACKGROUND: Healthcare-associated infections (HAIs) have become a significant concern globally, posing risks to patients and imposing social and economic burdens. Competency in infection prevention and control (IPC) practices is essential for nurses to effectively reduce the risk of transmission. However, there is a lack of research on educational needs for competency in IPC practices. OBJECTIVES: This study aimed to assess and prioritize educational needs for the development of educational content focused on the IPC practices of clinical nurses. DESIGN: A descriptive cross-sectional design was utilized. SETTINGS: This study was conducted at six general hospitals located in five urban regions in South Korea, each with 100 to 300 beds. PARTICIPANTS: A total of 226 nurses were recruited as participants for this study. METHODS: Data were collected from June to July 2021. A total of 226 nurses participated in this study. After examining the perceived importance and current performance of attributes related to IPC, educational needs were identified by paired-sample t-test, importance-performance analysis, Borich's needs analysis, and the Locus for Focus model. RESULTS: Items related to IPC were found to have lower performance than importance, highlighting the need for education. Educational needs were the highest for items in the "IPC practices according to microorganisms" category, such as MRSA, VRE, antimicrobial-resistant organisms, Clostridium difficile, scabies, and AIDS. Items in the "isolation precautions" category, including standard precautions, transmission-based precautions, management of isolation rooms, and wearing PPE, also demonstrated high priority in terms of educational needs. The findings suggest the need for training programs for clinical nurses with a focus on specific areas for improving IPC competency. CONCLUSIONS: The development and implementation of training modules tailored to the educational needs of clinical nurses may enhance their skills, knowledge, and attitudes, ultimately resulting in improved performance.

Effect of Pravastatin on Kidney Function in Patients with Dyslipidemia and Type 2 Diabetes Mellitus: A Multicenter Prospective Observational Study.

INTRODUCTION: Several studies have reported that pravastatin can mitigate the progression of kidney disease, but limited evidence exists regarding its effects on kidney function in Asian patients. This multicenter prospective observational study aimed to assess the effect of pravastatin on kidney function in Korean patients with dyslipidemia and type 2 diabetes mellitus (T2DM) in clinical practice. METHODS: This 48-week prospective multicenter study included 2604 of 2997 eligible patients with dyslipidemia and T2DM who had available estimated glomerular filtration rate (eGFR) measurements. The primary endpoint was eGFR percent change at week 24 from baseline. We also assessed secondary endpoints, which included percent changes in eGFR at weeks 12 and 48 from baseline, as well as changes in eGFR, metabolic profiles (lipid and glycemic levels) at 12, 24, and 48 weeks from baseline, and safety. RESULTS: We noted a significant improvement in eGFR, with mean percent changes of 2.5%, 2.5%, and 3.0% at 12, 24, and 48 weeks, respectively (all adjusted p < 0.05). The eGFR percent changes significantly increased in subgroups with baseline eGFR 30-90 mL/min/1.73 m2, glycated hemoglobin (HbA1c) ≥ 7 at baseline, no hypertension history, T2DM duration > 5 years, or previous statin therapy. Lipid profiles were improved and remained stable throughout the study, and interestingly, fasting glucose and HbA1c were improved at 24 weeks. CONCLUSION: Our findings suggest that pravastatin may have potential benefits for improving eGFR in Korean patients with dyslipidemia and T2DM. This could make it a preferable treatment option for patients with reduced kidney function. TRIAL REGISTRATION NUMBER: NCT05107063 submitted October 27, 2021.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. Conclusion: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Safety and Effectiveness of Empagliflozin in Korean Patients with Type 2 Diabetes Mellitus: Results from a Nationwide Post-Marketing Surveillance.

BACKGROUND: To evaluate the safety and effectiveness of empagliflozin in routine clinical settings, we collected and assessed the clinical profiles of Korean patients with type 2 diabetes mellitus. METHODS: This was a post-marketing surveillance study of empagliflozin 10 and 25 mg. Information on adverse events and adverse drug reactions (ADRs) was collected as safety data sets. Available effectiveness outcomes, including glycosylated hemoglobin (HbA1c) level, fasting plasma glucose, body weight, and blood pressure, were assessed. RESULTS: The incidence rate of ADRs was 5.14% in the safety dataset (n=3,231). Pollakiuria, pruritis genital, and weight loss were the most common ADRs. ADRs of special interest accounted for only 1.18%, and there were no serious events that led to mortality or hospitalization. In the effectiveness data set (n=2,567), empagliflozin significantly reduced the mean HbA1c level and body weight during the study period by -0.68%±1.39% and -1.91±3.37 kg (both P<0.0001), respectively. In addition, shorter disease duration, absence of dyslipidemia, and higher baseline HbA1c levels were identified as the clinical features characteristic of a "responder" to empagliflozin therapy. CONCLUSION: Empagliflozin is a safe and potent glucose-lowering drug in routine use among Korean patients with type 2 diabetes mellitus. It is expected to have better glycemic efficacy in Korean patients with poorly controlled type 2 diabetes mellitus.

Meteorin promotes the formation of GFAP-positive glia via activation of the Jak-STAT3 pathway.

Meteorin is an orphan ligand which has been previously reported to control neuritogenesis and angiogenesis, as well as gliogenesis. However, the precise function of this factor in CNS development and the underlying molecular mechanisms are poorly understood. Here, we demonstrate that meteorin is involved in GFAP-positive glial differentiation through activation of the Jak-STAT3 pathway, by using neurosphere and retinal explant culture systems. During embryonic brain development, meteorin is highly expressed in neural stem and radial glia cells of the ventricular zone and immature neurons outside the ventricular zone but its expression disappears spontaneously as development proceeds except in GFAP-positive astrocytes. In cultured neurospheres, meteorin activates STAT3, and in turn increases the transcriptional activity of GFAP by enhancing the binding of STAT3 to the promoter. By meteorin stimulation, differentiating neurospheres show increased numbers of GFAP-positive cells, but the effect is abrogated by a blockade of the Jak-STAT3 pathway using either a Jak inhibitor or STAT3 siRNA. Furthermore, we expand our findings to the retina, and show that meteorin increases GFAP expression in Müller glia. Together, our results suggest that meteorin promotes GFAP-positive glia formation by mediating the Jak-STAT3 signaling pathway during both cortical stem cell differentiation and retinal glia development.

S1 domain-containing STF modulates plastid transcription and chloroplast biogenesis in Nicotiana benthamiana.

• In this study, we examined the biochemical and physiological functions of Nicotiana benthamiana S1 domain-containing Transcription-Stimulating Factor (STF) using virus-induced gene silencing (VIGS), cosuppression, and overexpression strategies. • STF : green fluorescent protein (GFP) fusion protein colocalized with sulfite reductase (SiR), a chloroplast nucleoid-associated protein also present in the stroma. Full-length STF and its S1 domain preferentially bound to RNA, probably in a sequence-nonspecific manner. • STF silencing by VIGS or cosuppression resulted in severe leaf yellowing caused by disrupted chloroplast development. STF deficiency significantly perturbed plastid-encoded multimeric RNA polymerase (PEP)-dependent transcript accumulation. Chloroplast transcription run-on assays revealed that the transcription rate of PEP-dependent plastid genes was reduced in the STF-silenced leaves. Conversely, the exogenously added recombinant STF protein increased the transcription rate, suggesting a direct role of STF in plastid transcription. Etiolated seedlings of STF cosuppression lines showed defects in the light-triggered transition from etioplasts to chloroplasts, accompanied by reduced light-induced expression of plastid-encoded genes. • These results suggest that STF plays a critical role as an auxiliary factor of the PEP transcription complex in the regulation of plastid transcription and chloroplast biogenesis in higher plants.

Volatile Organic Compounds in Ambient Air at Four Residential Locations in Seoul, Korea.

To investigate the environmental behavior of volatile organic compounds (VOCs) in urban areas, their concentrations were measured at four urban monitoring sites (namely, N, S, E, and W) in Seoul, Korea (February to December 2009). A total of 27 compounds were quantified that consist of four chemical groups: aromatic (AR), halogenated aromatic, halogenated paraffin, and halogenated olefin. Results were evaluated by focusing on these four functional groups just mentioned and their summation term as total VOC (TVOC) along with several individual species (mainly AR species, that is, benzene, toluene, ethylbenzene, and xylene). The highest concentration of chemical groups was found from AR (71.1±42.1 ppbC), while that for individual species confirmed the dominance of toluene (7.48±3.88 ppb). The analysis of spatial distribution indicated that high TVOC levels were recorded at sites N and W, while it was not so significant such as S and E in terms of TVOC budget. Seasonal variation of these VOCs was characterized by the peak values in December to reflect the combined effects of pronounced source activities and meteorological conditions. Analysis of spatial variations in VOC levels between the four urban sites indicated that their distributions are tightly affected by local source processes in each area.

Cardiovascular outcomes with glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes: A meta-analysis.

BACKGROUND: According to available research, there have been no head-to-head studies comparing the effect of glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors on cardiovascular outcomes among patients with type 2 diabetes not reaching glycemic goal with metformin. METHODS: Relevant studies were identified through electronic searches of PubMed and EMBASE published up to January 15, 2020. Efficacy outcomes of interest included the composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, its individual components, all-cause death, and hospitalization for heart failure (HF). Safety outcomes included all suggested side effects of both agents previously reported. RESULTS: Eleven studies, including 94,727 patients were used for the analysis. The risk of composite end point was significantly lower in both groups compared to the control group (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.85-0.92, p < 0.001). The risk of hospitalization for HF was significantly lower in both groups but the magnitude of the effect was more pronounced in the SGLT-2 inhibitors group (HR 0.68, 95% CI 0.60-0.76, p < 0.001) than the GLP-1 agonists group (HR 0.92, 95% CI 0.84-0.99, p = 0.03). Patients treated with GLP-1 agonists discontinued trial medications more frequently compared to conventionally treated patients because of serious side effects. CONCLUSIONS: Both GLP-1 agonists and SGLT-2 inhibitors showed comparable cardiovascular outcomes in patients with type 2 diabetes. However, the SGLT-2 inhibitors were associated with more pronounced reduction of hospitalization for HF and lower risk of treatment discontinuation than GLP-1 agonists.

Effects of Online Learning on Nursing Students in South Korea during COVID-19.

Daily life has changed due to COVID-19. This has affected nursing education and caused a shift in online learning. This study examined the effects of online learning on nursing students' knowledge, self-regulation, and learning flow. We used a quasi-experimental design on a sample comprising 164 senior nursing students. We compared pre- and post-test scores to examine the educational effects. The pre-test was conducted a week before the educational intervention, and the post-test was conducted a week after it. We found a significant increase in knowledge (t = -14.85, p < 0.001) and learning flow (t = -2.15, p = 0.033) in the post-test. We also found an increase in self-regulation (t = -1.57, p = 0.119) from the pre- to the post-test that was not statistically significant. The results could help instructors to provide additional information in online learning. They highlight the need to assess learners' readiness for online learning and to prepare the learning environment with systematic educational planning, design, development, and evaluation for improving the effectiveness of online learning outcomes.

Testosterone Protects Pancreatic ß-cells from Apoptosis and Stress-Induced Accelerated Senescence.

PURPOSE: Androgens are steroid hormones that are very important in the sexual development and the maintenance of male reproductive system, and also have diverse actions in non-reproductive tissues, including potent antioxidant capacity. Type 2 diabetes mellitus is caused by tissue insulin resistance and insufficient insulin secretion from the pancreatic ß-cells. The progressive decline of pancreatic ß-cells in diabetes is closely related with the severity of disease. We wanted to know whether dihydrotestosterone (DHT) can protect insulin secreting pancreatic ß-cells from apoptosis and accelerated senescence induced by oxidative stress. MATERIALS AND METHODS: Cultured INS-1 cells were used. Various concentrations of H2O2 were applied to exert oxidative stresses. The degrees of apoptosis, accelerated senescence, and the changes of the expressions of related signaling molecules after the application of DHT were analyzed by CCK-8, p16 expression, SA-ß-Gal staining, reverse transcription polymerase chain reactions and Western blots. RESULTS: The application of H2O2 significantly increased (p<0.05) the degree of senescence and apoptosis of cultured INS-1 ß-cells. DHT not only showed anti-oxidant protective capacity, but also significantly reduced (p<0.05) the degree of accelerated senescence. CONCLUSIONS: DHT effectively protects pancreatic islet INS-1 ß-cells from H2O2 induced oxidative stress.

Effects of anagliptin on the stress induced accelerated senescence of human umbilical vein endothelial cells.

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) inhibitors have been used to treat type 2 diabetes mellitus (T2DM) via inhibition of the enzymatic activity of DPP-4 in degrading active circulating glucagon-like peptide-1. In addition to their glucose-lowering effect, DPP-4 inhibitors have pleiotropic effects. Cellular senescence regarded as important pathophysiological mechanism underlying many degenerative diseases, including atherosclerosis. This study was performed to examine whether the DPP-4 inhibitor, anagliptin, can directly protect against stress-induced accelerated senescence (SIAS) of vascular endothelial cells, regardless of changes in ambient glucose level. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to various concentrations of H2O2, and a fixed high concentration of glucose (25 mM) with varying concentrations of palmitate. Changes in cell viability, senescence-associated beta-galactosidase (SA-ß-Gal), p16 protein, markers of endoplasmic reticulum (ER) stress, NOX4, NLRP inflammasome, lactate dehydrogenase (LDH) release and interleukin (IL) 1ß levels were measured by Cell Counting Kit-8 assay, immunofluorescent staining, Western blotting, and enzyme-linked immunosorbent assay, respectively before and after application of anagliptin. RESULTS: The application of oxidative and glucolipotoxic stresses markedly increased the degree of SIAS of HUVECs, represented by increased SA-ß-Gal immunopositivity and p16 protein expression. Aggravation of ER stress and inflammatory response were also observed through increased levels of ATF4, CHOP, peIF2α, NOX4, NLRP inflammasome, LDH, and IL1ß. These changes were markedly reversed by the administration of anagliptin. CONCLUSIONS: The DPP-4 inhibitor anagliptin effectively protects HUVECs against SIAS, suggesting its potential use in the development of new treatment strategies for aging.

Neurofibromatosis Type 1 with the Development of Pheochromocytoma and Breast Cancer.

A 40-year-old woman presented with a left adrenal incidentaloma. Based on the presence of café-au-lait spots, cutaneous neurofibroma, and family history, she was diagnosed with neurofibromatosis type 1 (NF1). Adrenal incidentaloma screening showed an elevated normetanephrine level; the left adrenal mass showed the uptake of I-123 meta-iodobenzylguanidine. She underwent left adrenalectomy, and pheochromocytoma was diagnosed. One year later, the results of a biopsy of a palpable mass in the left breast suggested invasive ductal carcinoma. The patient underwent neoadjuvant chemotherapy followed by left breast-conserving surgery. We herein report a rare case of an NF1 patient who developed both pheochromocytoma and breast cancer.

Melatonin protects INS-1 pancreatic ß-cells from apoptosis and senescence induced by glucotoxicity and glucolipotoxicity.

INTRODUCTION: Melatonin is a hormone known as having very strong anti-oxidant property. Senescence is a biological state characterized by the loss of cell replication and the changes consisting of a pro-inflammatory phenotype, leading to Senescence Associated Secretory Phenotype (SASP) which is now regarded as one of the fundamental processes of many degenerative diseases. Increased cell division count induces cell senescence via DNA damage in response to elevated Reactive Oxygen Species (ROS). We wanted to test whether melatonin could reduce apoptosis and stress induced premature pancreatic ß-cell senescence induced by glucotoxicity and glucolipotoxicity. MATERIALS AND METHOD: Cultured rodent pancreatic ß-cell line (INS-1 cell) was used. Glucotoxicity (HG: hyperglycemia) and glucolipotoxicity (HGP: hyperglycemia with palmitate) were induced by hyperglycemia and the addition of palmitate. The degrees of the senescence were measured by SA-ß-Gal and P16lnk4A staining along with the changes of cell viabilities, cell cycle-related protein and gene expressions, endogenous anti-oxidant defense enzymes, and Glucose Stimulated Insulin Secretion (GSIS), before and after melatonin treatment. RESULTS: Cultured INS-1 cells in HG and HGP conditions revealed accelerated senescence, increased apoptosis, cell cycle arrest, compromised endogenous anti-oxidant defense, and impaired glucose-stimulated insulin secretion. Melatonin decreased apoptosis and expressions of proteins related to senescence, increase the endogenous anti-oxidant defense, and improved glucose-stimulated insulin secretion. CONCLUSION: Melatonin protected pancreatic ß-cell from apoptosis, decreased expressions of the markers related to the accelerated senescence, and improved the biological deteriorations induced by glucotoxicity and glucolipotoxicity.

Efficacy and Safety of Pioglitazone versus Glimepiride after Metformin and Alogliptin Combination Therapy: A Randomized, Open-Label, Multicenter, Parallel-Controlled Study.

BACKGROUND: There is limited information regarding the optimal third-line therapy for managing type 2 diabetes mellitus (T2DM) that is inadequately controlled using dual combination therapy. This study assessed the efficacy and safety of pioglitazone or glimepiride when added to metformin plus alogliptin treatment for T2DM. METHODS: This multicenter, randomized, active-controlled trial (ClinicalTrials.gov: NCT02426294) recruited 135 Korean patients with T2DM that was inadequately controlled using metformin plus alogliptin. The patients were then randomized to also receive pioglitazone (15 mg/day) or glimepiride (2 mg/day) for a 26-week period, with dose titration was permitted based on the investigator's judgement. RESULTS: Glycosylated hemoglobin levels exhibited similar significant decreases in both groups during the treatment period (pioglitazone: -0.81%, P<0.001; glimepiride: -1.05%, P<0.001). However, the pioglitazone-treated group exhibited significantly higher high density lipoprotein cholesterol levels (P<0.001) and significantly lower homeostatic model assessment of insulin resistance values (P<0.001). Relative to pioglitazone, adding glimepiride to metformin plus alogliptin markedly increased the risk of hypoglycemia (pioglitazone: 1/69 cases [1.45%], glimepiride: 14/66 cases [21.21%]; P<0.001). CONCLUSION: Among patients with T2DM inadequately controlled using metformin plus alogliptin, the addition of pioglitazone provided comparable glycemic control and various benefits (improvements in lipid profiles, insulin resistance, and hypoglycemia risk) relative to the addition of glimepiride.

Educational needs for new graduate nurses in Korea.

New nursing graduates often experience difficulty adjusting to clinical work environments, despite completing well-structured education programs. This study explored the educational needs of recent nursing graduates from the perspectives of new nurses and their clinical educators in Korea. Four focus-group interviews with 7 nurse educators and 8 new nurses were conducted. Data were analyzed using Patton's inductive content analysis. Five analytic categories emerged: communication skills that build good relationships, managing unexpected situations, prioritization, practical experiences, and different ways of delivering education. Educators and new nurses agreed that communication skills are essential in building and maintaining interpersonal relationships. Future educational programs for new graduate nurses should reflect the needs of nurses and their educators so new registered nurses can successfully make the transition to expert nurses.

The direct effect of lobeglitazone, a new thiazolidinedione, on pancreatic beta cells: A comparison with other thiazolidinediones.

AIMS: The direct effects of thiazolidinediones (TZDs) on pancreatic beta cells have been controversial. The aim of this study was to find out whether a novel TZD, lobeglitazone, has beneficial effects on pancreatic beta cells and db/db mice compared to those of other TZDs. METHODS: INS-1 cells were incubated at a high-glucose concentration with various concentrations of troglitazone, rosiglitazone, pioglitazone, and lobeglitazone. Apoptosis and proliferation of beta cells, markers for ER stress and glucose-stimulated insulin secretion (GSIS) were assessed. In addition, C57BL/6 db/db mice were treated with pioglitazone or lobeglitazone for 4 weeks, and metabolic parameters and the configuration of pancreatic islets were also examined. RESULTS: Lobeglitazone and other TZDs decreased INS-1 cell apoptosis in high-glucose conditions. Lobeglitazone and other TZDs significantly decreased hyperglycemia-induced increases in ER stress markers and increased GSIS. Metabolic parameters showed greater improvement in db/db mice treated with pioglitazone and lobeglitazone than in control mice. Islet size, cell proliferation, and beta cell mass were increased, and collagen surrounding the islets was decreased in treated mice. CONCLUSIONS: Lobeglitazone showed beneficial effects on beta cell survival and function against hyperglycemia. The prosurvival and profunction effects of lobeglitazone were comparable to those of other TZDs.