Collagen Meniscal Scaffold Implantation Can Provide Meniscal Regeneration in Asian Patients with Partial Meniscal Defects: A Prospective Randomized Controlled Study with Three-Dimensional Volume Analysis of the Meniscus.

Background: To date, the efficiency of collagen meniscal scaffold implantation in Asian patients with partial meniscal defects has not been evaluated. In addition, no study has quantitatively analyzed meniscal regeneration using three-dimensional (3D) volume analysis after collagen scaffold implantation. We aimed to compare meniscal regeneration using 3D volume analysis between Asian patients undergoing collagen-based meniscal scaffold implantation after partial meniscectomy and those undergoing only partial meniscectomy. Methods: Nineteen patients who underwent collagen-based meniscal scaffold implantation and 14 who underwent partial meniscectomy were analyzed with a prospective randomized control design for 12 months postoperatively. The demographic characteristics, Kellgren-Lawrence grade, and location of the injury lesion (medial or lateral meniscus) were not significantly different between the groups. Using 3D volume analysis with magnetic resonance imaging (MRI), the meniscus-removing ratio during the operative procedure and the meniscus defect-filling ratio were measured during the 12-month postoperative period. Clinically, the visual analog scale, International Knee Documentation Committee score, and Knee Injury and Osteoarthritis Outcome Score were evaluated. The Whole-Organ Magnetic Resonance Imaging Score (WORMS) and Genovese grade were also evaluated using MRI. Results: In the 3D volume analysis, the average meniscus-removing ratio during surgery was not significantly different between the groups (-9.3% vs. -9.2%, p = 0.984). The average meniscus defect-filling ratio during the postoperative 12-month period was 7.5% in the scaffold group and -0.4% in the meniscectomy group (p < 0.001). None of the clinical results were significantly different between the scaffold and meniscectomy groups at 12 months postoperatively. The average change in the total WORMS score was not significantly different between the groups (0 vs. 1.9, p = 0.399). The Genovese grade of the implanted collagen scaffold did not significantly change during the follow-up period in terms of morphology and size (p = 0.063); however, the grade significantly improved in terms of signal intensity (p = 0.001). Conclusions: Definite meniscal regeneration and stable scaffold incorporation were observed after collagen-based meniscal scaffold implantation in Asian patients during 12 months of follow-up. A long-term follow-up study with a larger cohort is required to determine the advantages of collagenous meniscal scaffold implantation in Asian patients.

Morroniside Protects C2C12 Myoblasts from Oxidative Damage Caused by ROS-Mediated Mitochondrial Damage and Induction of Endoplasmic Reticulum Stress.

Oxidative stress contributes to the onset of chronic diseases in various organs, including muscles. Morroniside, a type of iridoid glycoside contained in Cornus officinalis, is reported to have advantages as a natural compound that prevents various diseases. However, the question of whether this phytochemical exerts any inhibitory effect against oxidative stress in muscle cells has not been well reported. Therefore, the current study aimed to evaluate whether morroniside can protect against oxidative damage induced by hydrogen peroxide (H2O2) in murine C2C12 myoblasts. Our results demonstrate that morroniside pretreatment was able to inhibit cytotoxicity while suppressing H2O2-induced DNA damage and apoptosis. Morroniside also significantly improved the antioxidant capacity in H2O2-challenged C2C12 cells by blocking the production of cellular reactive oxygen species and mitochondrial superoxide and increasing glutathione production. In addition, H2O2-induced mitochondrial damage and endoplasmic reticulum (ER) stress were effectively attenuated by morroniside pretreatment, inhibiting cytoplasmic leakage of cytochrome c and expression of ER stress-related proteins. Furthermore, morroniside neutralized H2O2-mediated calcium (Ca2+) overload in mitochondria and mitigated the expression of calpains, cytosolic Ca2+-dependent proteases. Collectively, these findings demonstrate that morroniside protected against mitochondrial impairment and Ca2+-mediated ER stress by minimizing oxidative stress, thereby inhibiting H2O2-induced cytotoxicity in C2C12 myoblasts.

Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial.

PURPOSE: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. RESULTS: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4-18.3], while the placebo group had a PFS of 10.9 months (9.0-13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide. CONCLUSIONS: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).

Continuous glucose monitoring with structured education in adults with type 2 diabetes managed by multiple daily insulin injections: a multicentre randomised controlled trial.

AIMS/HYPOTHESIS: The aim of this study was to compare the effectiveness of stand-alone intermittently scanned continuous glucose monitoring (isCGM) with or without a structured education programme and blood glucose monitoring (BGM) in adults with type 2 diabetes on multiple daily insulin injections (MDI). METHODS: In this 24 week randomised open-label multicentre trial, adults with type 2 diabetes on intensive insulin therapy with HbA1c levels of 58-108 mmol/mol (7.5-12.0%) were randomly assigned in a 1:1:1 ratio to isCGM with a structured education programme on adjusting insulin dose and timing according to graphical patterns in CGM (intervention group), isCGM with conventional education (control group 1) or BGM with conventional education (control group 2). Block randomisation was conducted by an independent statistician. Due to the nature of the intervention, blinding of participants and investigators was not possible. The primary outcome was change in HbA1c from baseline at 24 weeks, assessed using ANCOVA with the baseline value as a covariate. RESULTS: A total of 159 individuals were randomised (n=53 for each group); 148 were included in the full analysis set, with 52 in the intervention group, 49 in control group 1 and 47 in control group 2. The mean (± SD) HbA1c level at baseline was 68.19±10.94 mmol/mol (8.39±1.00%). The least squares mean change (± SEM) from baseline HbA1c at 24 weeks was -10.96±1.35 mmol/mol (-1.00±0.12%) in the intervention group, -6.87±1.39 mmol/mol (-0.63±0.13%) in control group 1 (p=0.0367 vs intervention group) and -6.32±1.42 mmol/mol (-0.58±0.13%) in control group 2 (p=0.0193 vs intervention group). Adverse events occurred in 28.85% (15/52) of individuals in the intervention group, 26.42% (14/53) in control group 1 and 48.08% (25/52) in control group 2. CONCLUSIONS/INTERPRETATION: Stand-alone isCGM offers a greater reduction in HbA1c in adults with type 2 diabetes on MDI when education on the interpretation of graphical patterns in CGM is provided. TRIAL REGISTRATION: ClinicalTrials.gov NCT04926623. FUNDING: This study was supported by Daewoong Pharmaceutical Co., Ltd.

ID1high/activin Ahigh glioblastoma cells contribute to resistance to anti-angiogenesis therapy through malformed vasculature.

Although bevacizumab (BVZ), a representative drug for anti-angiogenesis therapy (AAT), is used as a first-line treatment for patients with glioblastoma (GBM), its efficacy is notably limited. Whereas several mechanisms have been proposed to explain the acquisition of AAT resistance, the specific underlying mechanisms have yet to be sufficiently ascertained. Here, we established that inhibitor of differentiation 1 (ID1)high/activin Ahigh glioblastoma cell confers resistance to BVZ. The bipotent effect of activin A during its active phase was demonstrated to reduce vasculature dependence in tumorigenesis. In response to a temporary exposure to activin A, this cytokine was found to induce endothelial-to-mesenchymal transition via the Smad3/Slug axis, whereas prolonged exposure led to endothelial apoptosis. ID1 tumors showing resistance to BVZ were established to be characterized by a hypovascular structure, hyperpermeability, and scattered hypoxic regions. Using a GBM mouse model, we demonstrated that AAT resistance can be overcome by administering therapy based on a combination of BVZ and SB431542, a Smad2/3 inhibitor, which contributed to enhancing survival. These findings offer valuable insights that could contribute to the development of new strategies for treating AAT-resistant GBM.

Does the use of tranexamic acid intraoperatively reduce postoperative blood loss and complications following biportal endoscopic lumbosacral decompression?

Background: Biportal endoscopic spine surgery is an effective minimally invasive technique for treating common lumbar pathologies. We aim to evaluate the impact of intraoperative tranexamic acid (TXA) use on postoperative blood loss in biportal endoscopic decompression surgery. Methods: Patients undergoing biportal endoscopic lumbar discectomies and decompressions either by same day surgery or overnight stay at a single institution beginning in October 2021 were prospectively enrolled. This study was non-randomized, non-blinded with the first cohort of consecutive patients receiving 1 g of intravenous TXA intra-operatively before closure and the second cohort of consecutive patients receiving no TXA. Exclusion criteria included any revision surgery, any surgery for the diagnosis of spinal instability, infection, tumor, or trauma, any contraindication for TXA. Results: Eighty-four patients were included in the study, with 45 (54%) receiving TXA and 39 (46%) not receiving TXA. Median follow-up was 168 days [interquartile range (IQR), 85-368 days]. There were no differences in patient or surgical characteristics between cohorts. Estimated blood loss (EBL) was similar (P=0.20), while post-operative drain output was significantly lower in the TXA cohort (P=0.0028). Single level discectomies had significantly less drain output as compared to 2 level unilateral laminotomy, bilateral decompression (ULBD) cases (P<0.005). Post-operative complications were similar, with low rates of wound complication (1.2%) and transient postoperative weakness (2.4%, P>0.99 for both). Oswestry disability index (ODI), visual analog scale (VAS) back and VAS leg scores decreased significantly; the absolute decrease in scores did not differ between groups (P=0.71, 0.22, 0.86, respectively). Conclusions: Systemic intraoperative TXA administration is associated with a significant decrease in post-operative blood loss in biportal spinal endoscopy, with no impact on the improvement in patient-reported outcomes (PROs) or rate of post-operative complications. Single level biportal discectomies had significantly less postoperative drainage with TXA and may not need drains postoperatively. Larger, randomized studies are necessary to evaluate the cost-effectiveness of TXA use in biportal spinal endoscopy.

Activation of Heme Oxygenase-1 by Mangiferin in Human Retinal Pigment Epithelial Cells Contributes to Blocking Oxidative Damage.

Mangiferin is a kind of natural xanthone glycosides and is known to have various pharmacological activities. However, since the beneficial efficacy of this compound has not been reported in retinal pigment epithelial (RPE) cells, this study aimed to evaluate whether mangiferin could protect human RPE ARPE-19 cells from oxidative injury mimicked by hydrogen peroxide (H2O2). The results showed that mangiferin attenuated H2O2-induced cell viability reduction and DNA damage, while inhibiting reactive oxygen species (ROS) production and preserving diminished glutathione (GSH). Mangiferin also antagonized H2O2-induced inhibition of the expression and activity of antioxidant enzymes such as manganese superoxide dismutase and GSH peroxidase, which was associated with inhibition of mitochondrial ROS production. In addition, mangiferin protected ARPE-19 cells from H2O2-induced apoptosis by increasing the Bcl-2/Bax ratio, decreasing caspase-3 activation, and blocking poly(ADP-ribose) polymerase cleavage. Moreover, mangiferin suppressed the release of cytochrome c into the cytosol, which was achieved by interfering with mitochondrial membrane disruption. Furthermore, mangiferin increased the expression and activity of heme oxygenase-1 (HO-1) and nuclear factor-erythroid-2 related factor 2 (Nrf2). However, the inhibition of ROS production, cytoprotective and anti-apoptotic effects of mangiferin were significantly attenuated by the HO-1 inhibitor, indicating that mangiferin promoted Nrf2-mediated HO-1 activity to prevent ARPE-19 cells from oxidative injury. The results of this study suggest that mangiferin, as an Nrf2 activator, has potent ROS scavenging activity and may have the potential to protect oxidative stress-mediated ocular diseases.

Nonlinear Hall Effect from Long-Lived Valley-Polarizing Relaxons.

The nonlinear Hall effect has attracted much attention due to the famous, widely adopted interpretation in terms of the Berry curvature dipole in momentum space. Using ab initio Boltzmann transport equations, we find a 60% enhancement in the nonlinear Hall effect of n-doped GeTe and its noticeable frequency dependence, qualitatively different from the predictions based on the Berry curvature dipole. The origin of these differences is long-lived valley polarization in the electron distribution arising from electron-phonon scattering. Our findings await immediate experimental confirmation.

Atypical post-infectious glomerulonephritis with c-ANCA positivity followed by endocarditis.

Post-infectious glomerulonephritis (PIGN), an uncommon variety of glomerulonephritis (GN), is characterized by emergence of nephritic syndrome within a few weeks following an infectious event. PIGN typically presents as a mild condition and tends to resolve by the time of diagnosis for GN. Aggregatibacter actinomycetemcomitans belongs to the HACEK group of bacteria, which constitutes less than 3% of bacteria responsible for community-acquired infective endocarditis. We present a case of 29-year-old man suspected of lymphoma with B-symptoms along with severe splenomegaly and nephromegaly. Shortly after, he developed an episode of nephritic syndrome accompanied by acute kidney injury (AKI) and high titers of cytoplasmic ANCA (c-ANCA)-positivity. Kidney biopsy revealed PIGN with tubulointerstitial nephritis. Despite treatment with antibiotics and corticosteroid, he visited the emergency room due to worsening dyspnea and multi-organ failure. An echocardiogram showed a bicuspid aortic valve with vegetation unseen on previous echocardiogram. He underwent aortic valve replacement immediately without adverse events. Four months after valve replacement, his renal function and cardiac performance have remained stable. We report a case of PIGN with AKI and high titers of c-ANCA appearing later as an infective endocarditis due to Aggregatibacter actinomycetemcomitans. With careful clinical observation and appropriate and timely management, satisfactory outcomes for patient health are possible.

ARF4-mediated retrograde trafficking as a driver of chemoresistance in GBM.

BACKGROUND: Cellular functions hinge on the meticulous orchestration of protein transport, both spatially and temporally. Central to this process is retrograde trafficking, responsible for targeting proteins to the nucleus. Despite its link to many diseases, the implications of retrograde trafficking in glioblastoma (GBM) are still unclear. METHODS: To identify genetic drivers of TMZ resistance, we conducted comprehensive CRISPR-knockout screening, revealing ADP-ribosylation factor 4 (ARF4), a regulator of retrograde trafficking, as a major contributor. RESULTS: Suppressing ARF4 significantly enhanced TMZ sensitivity in GBM patient-derived xenograft (PDX) models, leading to improved survival rates (p<0.01) in both primary and recurrent lines. We also observed that TMZ exposure stimulates ARF4-mediated retrograde trafficking. Proteomics analysis of GBM cells with varying levels of ARF4 unveiled the influence of this pathway on EGFR signaling, with increased nuclear trafficking of EGFR observed in cells with ARF4 overexpression and TMZ treatment. Additionally, spatially-resolved RNA-sequencing of GBM patient tissues revealed substantial correlations between ARF4 and crucial nuclear EGFR (nEGFR) downstream targets, such as MYC, STAT1, and DNA-PK. Decreased activity of DNA-PK, a DNA repair protein downstream of nEGFR signaling that contributes to TMZ resistance, was observed in cells with suppressed ARF4 levels. Notably, treatment with DNA-PK inhibitor, KU57788, in mice with a recurrent PDX line resulted in prolonged survival (p<0.01), highlighting the promising therapeutic implications of targeting proteins reliant on ARF4-mediated retrograde trafficking. CONCLUSION: Our findings demonstrate that ARF4-mediated retrograde trafficking contributes to the development of TMZ resistance, cementing this pathway as a viable strategy to overcome chemoresistance in GBM.

Exploring the role of loop tunnels in enhancing termite food transport efficiency: A simulation approach.

Subterranean termites construct a network of tunnels beneath the ground, comprising a main tunnel and branch tunnels. While termites do not construct tunnels that turn back in a "U" shape, the intersection of main and branch tunnels often forms closed curved structures (a loop). The loop structure can have either a positive or negative effect on the transport efficiency of termites in food transportation. However, little research has been conducted on the impact of loop tunnels on transport efficiency (E) due to the technical difficulties associated with direct observation. In this study, we used an individual-based model to simulate termite behavior during food transportation within a tunnel composed of a main tunnel and a loop tunnel. The model incorporates four control variables: the number of introduced simulated termites (k1), the probability of a simulated termite using a loop tunnel when walking towards a food or nest site (k2 or k3), and the length of the loop tunnel (k4). The simulation results reveal that the E value is high for (k2, k3) = (high, high), (low, low), (high, low), and (low, high) when the length of the loop tunnel is relatively short. However, when the length of the loop tunnel is relatively long, E is high only for (k2, k3) = (high, low) and (low, high). We found that these results are primarily influenced by the frequency of traffic jams. Therefore, termites would benefit from adopting strategies that reduce the occurrence of traffic jams during food transportation. In the Discussion section, we briefly touch on the strategy from an ecological perspective.

Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study.

OBJECTIVE: To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM). DESIGN: Nationwide population based study. SETTING: Longitudinal cohort study in Korea. PARTICIPANTS: 7 796 763 participants in the National Health Screening Programme in 2009 were divided into three groups based on NAFLD status: no NAFLD (fatty liver index<30); grade 1 NAFLD (30≤fatty liver index<60); and grade 2 NAFLD (fatty liver index≥60). Median follow-up was 8.13 years. MAIN OUTCOME MEASURES: The primary outcome was incident cardiovascular disease (myocardial infarction, ischaemic stroke) or all cause death. RESULTS: Of 7 796 763 participants, 6.49% (n=505 763) had T2DM. More patients with T2DM had grade 1 NAFLD (34.06%) and grade 2 NAFLD (26.73%) than those without T2DM (grade 1 NAFLD: 21.20%; grade 2 NAFLD: 10.02%). The incidence rate (per 1000 person years) of cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD, and the incidence rates in patients with T2DM were higher than those in patients without T2DM. The five year absolute risk for cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD in patients without and with T2DM (no NAFLD, without T2DM: 1.03, 95% confidence interval 1.02 to 1.04, and 1.25, 1.24 to 1.26, respectively; grade 1 NAFLD, without T2DM: 1.23, 1.22 to 1.25, and 1.50, 1.48 to 1.51, respectively; grade 2 NAFLD, without T2DM: 1.42, 1.40 to 1.45, and 2.09, 2.06 to 2.12, respectively; no NAFLD, with T2DM: 3.34, 3.27 to 3.41, and 3.68, 3.61 to 3.74, respectively; grade 1 NAFLD, with T2DM: 3.94, 3.87 to 4.02, and 4.25, 4.18 to 4.33, respectively; grade 2 NAFLD, with T2DM: 4.66, 4.54 to 4.78, and 5.91, 5.78 to 6.05, respectively). Patients with T2DM and without NAFLD had a higher five year absolute risk for cardiovascular disease and all cause death than those without T2DM and with grade 2 NAFLD. Risk differences for cardiovascular disease and all cause death between no NAFLD and grade 1 or grade 2 NAFLD were higher in patients with T2DM than in those without T2DM. CONCLUSIONS: NAFLD in patients with T2DM seems to be associated with a higher risk of cardiovascular disease and all cause death, even in patients with mild NAFLD. Risk differences for cardiovascular disease and all cause death between the no NAFLD group and the grade 1 or grade 2 NAFLD groups were higher in patients with T2DM than in those without T2DM.

A Study on the Impact of Financial Literacy and Digital Capabilities on Entrepreneurial Intention: Mediating Effect of Entrepreneurship.

In the post-COVID-19 era, the content of work and the necessary skills are rapidly changing due to the digital transformation of the way people work. Entrepreneurial adaptability and digital capability are the most necessary competencies for exploring opportunities and quickly turning them into a professional career amid a crisis. Financial literacy is also essential for expanding skills in economic and social life. The purpose of this study is to verify the influence of university students' financial literacy and digital capability on entrepreneurial intention and the mediating effect of entrepreneurship. To this end, a survey was conducted on university students in Busan and Gyeongnam, and a sample of 162 respondents was verified using SPSS 28.0. As a result of the study, it was found that financial literacy had a partially positive effect on entrepreneurship and entrepreneurial intention. Digital capability was found to have a positive effect on entrepreneurship and entrepreneurial intention. It was found that entrepreneurship had a partially positive effect on entrepreneurial intention. It was found that entrepreneurship had a partially positive mediating effect between financial literacy and entrepreneurial intention. It was found that entrepreneurship had a positive mediating effect between digital capability and entrepreneurial intention. As a result of this study, it was confirmed that financial literacy, digital capability, and entrepreneurship are very important competencies for university students to adapt to new trends and promote start-ups in a rapidly changing job environment after COVID-19, suggesting the need for further education.

Designing lightweight neutron absorbing composites using a comprehensive absorber areal density metric.

Efforts to lightweight neutron absorbing composites are limited by incomplete understandings of the interaction between absorbing particles and their matrices. In this study, analytical models and a more physically representative simulation evaluated the penalty to neutron absorbing performance due to neutron channeling between large absorbing particles. Models and simulation agreed that B4C particles smaller than 100µm and especially those smaller than 10µm did not cause excessive neutron channeling. A more comprehensive neutron absorbing composite design metric - boron-10 equivalent areal density, which considers the particle size penalty and the matrix contribution to absorptivity - was introduced and used to estimate lightweighting via matrix substitution. Calculations using this new metric showed that a non-absorbing Mg matrix reduced mass by up to 35% over Al, constrained by the difference in mass density, while an absorbing Mg-Li matrix reduced mass by up to 60%, exceeding the difference in mass densities alone. Measurement of apparent absorber areal density through two experimental techniques - foil activation and direct counting - validated estimated absorber areal density as a neutron absorbing composite design metric. This updated understanding of the particle size penalty, newly introduced design metric, and experimental validation demonstrate a path to lightweight neutron absorbing composites.

Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials.

BACKGROUND: We assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials. METHODS: Data from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223). RESULTS: In the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (- 0.94% vs. -0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs. CONCLUSIONS: The glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function. TRIAL REGISTRATION: Not applicable (pooled analysis).

Kidney Health Plan 2033 in Korea: bridging the gap between the present and the future.

In response to the increase in the prevalence of chronic kidney disease (CKD) in Korea, the growth of patients requiring renal replacement therapy and the subsequent increase in medical costs, the rapid expansion of patients with end-stage kidney disease (ESKD), and the decrease in patients receiving home therapy, including peritoneal dialysis, the Korean Society of Nephrology has proclaimed the new policy, Kidney Health Plan 2033 (KHP 2033). KHP 2033 would serve as a milestone to bridge the current issues to a future solution by directing the prevention and progression of CKD and ESKD, particularly diabetic kidney disease, and increasing the proportion of home therapy, thereby reducing the socioeconomic burden of kidney disease and improving the quality of life. Here, we provide the background for the necessity of KHP 2033, as well as the contents of KHP 2033, and enlighten the Korean Society of Nephrology's future goals. Together with patients, healthcare providers, academic societies, and national policymakers, we need to move forward with goal-oriented drive and leadership to achieve these goals.

Enhancement of denitrification by sulfur-based carrier in sequencing batch reactor (SBR) for advanced wastewater treatment.

This study was to enhance the nitrogen removal efficiency in the sequencing batch reactor (SBR) process by adding sulfur-based carriers. The nitrogen removal efficiency of the control group was compared with that of the experimental group through a two-series operation of SBR1 without carrier and SBR2 with the carrier under the condition of no external carbon source. A total nitrogen (T-N) removal efficiency of 6.6%, 72.6%, and 79.9% was observed in SBR1, SBR2 (5%), and (10%), respectively. The T-N removal efficiency was improved in the system with carriers, which showed an increase in the removal efficiency of approximately 91.7%. The results suggest that the inclusion of the carrier led to an elevation in the sulfur ratio, implying an augmented surface area for sulfur-based denitrifying microorganisms. Additionally, CaCO3 contributed essential alkalinity for sulfur denitrification, thereby preventing a decline in pH. Regardless of the carrier, the efficiency of organic matter removal surpassed 89%, indicating that the sulfur-based carrier did not adversely affect the biological reaction associated with organic matter. Therefore, autotrophic denitrification was successfully performed using a sulfur carrier in the SBR process without an external carbon source, improving the nitrogen removal efficiency.

Clinical Characteristics of Patients With Statin Discontinuation in Korea: A Nationwide Population-Based Study.

Objective: To investigate the clinical characteristics of patients with statin discontinuation in Korea, using a nationwide database. Methods: We analyzed 1,308,390 patients treated with statin for the first time in their life between 2016 and 2017 using the Korean National Health Information Database. The patients participated in the Korean National Health Screening Program within two years before taking statin. Patients with statin discontinuation were defined as those who were not prescribed statin between 365 days and 730 days after the initial statin prescription. Results: The overall prevalence of statin discontinuation was 39.44%. Patients with statin discontinuation were younger, had lower body mass index (BMI), included a higher number of smokers and drinkers, did not exercise regularly, with fewer cases of hypertension and diabetes mellitus than those without statin discontinuation (p<0.001). Compared with patients aged 20-29 years, the risk of statin discontinuation showed a U-shaped relationship with age (odds ratios [ORs]: 0.619 in 30-39 years; 0.454 in 40-49 years; 0.345 in 50-59 years; 0.307 in 60-69 years; 0.324 in 70-79 years; and 0.415 in ≥80 years). In addition, increased BMI was associated with decreased risk of statin discontinuation (ORs: 0.969 with 25.0-29.9 kg/m2, and 0.890 with ≥30.0 kg/m2). Patients with hypertension and diabetes mellitus were at a lower risk of statin discontinuation (OR: 0.414 for hypertension; 0.416 for diabetes mellitus). Conclusion: The prevalence of patients with statin discontinuation in Korea was 39.44% at 1 to 2 years after initial statin treatment.