High remnant-cholesterol levels increase the risk for end-stage renal disease: a nationwide, population-based, cohort study.

BACKGROUND: The effect of remnant-cholesterol (remnant-C) on incident end-stage renal disease (ESRD) has not been studied longitudinally. This retrospective cohort study evaluated the association between remnant-C and the development of ESRD in a nationwide Korean cohort. METHODS: Participants in a National Health Insurance Service health examination (n = 3,856,985) were followed up until the onset of ESRD. The median duration of follow-up was 10.3 years. The Martin-Hopkins equation was used to determine low-density lipoprotein cholesterol (LDL-C) levels from directly measured triglyceride, high-density lipoprotein cholesterol (HDL-C), and total cholesterol levels. Remnant-C levels were determined by subtracting HDL-C and LDL-C from total cholesterol. The risk for incident ESRD was calculated for each quartile of remnant-C, adjusting for conventional risk factors such as baseline renal function, comorbidities, and total cholesterol levels. RESULTS: ESRD developed in 11,073 (0.29%) participants. The risk for ESRD exhibited a gradual increase according to higher levels of remnant-C, with a 61% increased risk in the highest quartile than in the lowest (hazard ratio [HR] 1.61 [95% confidence interval (CI) 1.50-1.72]). The elevated risk for ESRD in the highest quartile versus the lowest quartile was more prominent in younger than in older subjects (20-29 years, HR 4.07 [95% CI 2.85-5.83]; 30-39 years, HR 2.39 [95% CI 1.83-3.13]; ≥ 70 years, HR 1.32 [95% CI 1.16-1.51]). In addition, the increased risk for ESRD related to higher remnant-C levels was greater in females than in males. CONCLUSIONS: Independent of conventional risk factors, remnant-C levels were positively associated with incident ESRD, particularly in younger populations and adult females. Reducing remnant-C levels may be a novel preventive strategy against ESRD.

Van der Waals Colloidal Crystals.

A general guiding principle for colloidal crystallization is to tame the attractive enthalpy such that it slightly overwhelms the repulsive interaction. As-synthesized colloids are generally designed to retain a strong repulsive potential for the high stability of suspensions, encoding appropriate attractive potentials into colloids has been key to their crystallization. Despite the myriad of interparticle attractions for colloidal crystallization, the van der Waals (vdW) force remains unexplored. Here, it is shown that the implementation of gold cores into silica colloids and the resulting vdW force can reconfigure the pair potential well depth to the optimal range between -1 and -4 kBT at tens of nanometer-scale colloidal distances. As such, colloidal crystals with a distinct liquid gap can be formed, which is evidenced by photonic bandgap-based diffractive colorization.

Rapid and Reliable HLA-B*59:01 Genotyping to Prevent Carbonic Anhydrase Inhibitor-Induced Severe Cutaneous Adverse Reactions.

OBJECTIVE: Carbonic anhydrase inhibitors (CAIs) are intraocular pressure-reducing medications used in ophthalmology. Human leukocyte antigen-B*59:01 (HLA-B*59:01) is strongly associated with CAI-induced severe cutaneous adverse reactions (SCARs). This study aimed to develop and validate a rapid and economical screening method for HLA-B*59:01 to prevent carbonic anhydrase inhibitor-induced SCARs. METHODS: Duplex allele-specific polymerase chain reaction (PCR) with an internal control was performed for HLA-B*59:01 genotyping. The accuracy of duplex allele-specific PCR for HLA-B*59:01 genotyping was evaluated in 200 blood samples, using sequence-based typing (SBT) as the reference method. RESULTS: In total, 50 HLA-B*59:01-positive and 150 HLA-B*59:01-negative results obtained using duplex allele-specific PCR were in complete agreement with the SBT results. CONCLUSION: Duplex allele-specific PCR is a rapid, reliable, and economical assay for screening the HLA-B*59:01 allele.

Hydrogel design to overcome thermal resistance and ROS detoxification in photothermal and photodynamic therapy of cancer.

Responsive heat resistance (by heat shock protein upregulation) and spontaneous reactive oxygen species (ROS) detoxification have been regarded as the major obstacles for photothermal/photodynamic therapy of cancer. To overcome the thermal resistance and improve ROS susceptibility in breast cancer therapy, Au ion-crosslinked hydrogels including indocyanine green (ICG) and polyphenol are devised. Au ion has been introduced for gel crosslinking (by catechol-Au3+ coordination), cellular glutathione depletion, and O2 production from cellular H2O2. ICG can generate singlet oxygen from O2 (for photodynamic therapy) and induce hyperthermia (for photothermal therapy) under the near-infrared laser exposure. (-)-Epigallocatechin gallate downregulates heat shock protein to overcome heat resistance during hyperthermia and exerts multiple anticancer functions in spite of its ironical antioxidant features. Those molecules are concinnously engaged in the hydrogel structure to offer fast gel transformation, syringe injection, self-restoration, and rheological tuning for augmented photo/chemotherapy of cancer. Intratumoral injection of multifunctional hydrogel efficiently suppressed the growth of primary breast cancer and completely eliminated the residual tumor mass. Proposed hydrogel system can be applied to tumor size reduction prior to surgery of breast cancer and the complete remission after its surgery.

Clinical Link between the BARD Score at Diagnosis and Mortality during Follow-Up in Patients with Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

This study investigated whether the BARD score at diagnosis could predict all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). This study included 236 immunosuppressive drug-naïve patients without chronic liver diseases such as viral hepatitis, non-alcoholic fatty liver disease (NAFLD), and advanced liver diseases and their clinical data at diagnosis, such as age, sex, and the Birmingham Vasculitis Activity Score (BVAS). The BARD score was calculated by the sum of aspartate transaminase (AST)/alanine transaminase (ALT) ratio ≥ 0.8 (+2 points), body mass index (BMI) ≥ 28 kg/m2 (+1 point), and the presence of type 2 diabetes mellitus (T2DM) (+1 point). All-cause mortality was investigated as a poor outcome of AAV. The median age of AAV patients was 60.0 years, and 34.7% were men. Among AAV patients, 7, 50, and 187 scored 1, 1, and 2 points owing to having a BMI ≥ 28 kg/m2, T2DM, and an AST/ALT ratio ≥ 0.8, respectively. Patients with a BARD score ≥ 2 and those with a BARD score ≥ 3 exhibited significantly lower cumulative patient survival rates than those without (p = 0.038 and p = 0.003, respectively). In the multivariable Cox analysis, among the two cut-offs of the BARD scores, only a BARD score ≥ 3 (HR 2.866), along with age (HR 1.061), male sex (HR 2.327), and BVAS (HR 1.100), was independently associated with all-cause mortality during follow-up. In conclusion, this study was the first to demonstrate that the BARD score ≥ 3 at AAV diagnosis could predict all-cause mortality during follow-up in AAV patients.

Non-alcoholic fatty liver disease fibrosis score is a useful index for predicting all-cause mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Background: This study investigated whether the non-alcoholic fatty liver disease fibrosis score (NFS) could predict all-cause mortality during follow-up among patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: The medical records of 256 AAV patients were retrospectively reviewed. AAV patients with clinically critical chronic liver diseases were excluded. NFS was calculated using the following equation: NFS = -1.675 + 0.037 - age + 0.094 - body mass index +1.13 × impaired fasting glucose/diabetes mellitus +0.99 × aspartate aminotransferase/alanine aminotransferase ratio - 0.013 × platelet count - 0.66 × serum albumin. Results: The median age was 59.0 years, and 35.2% of the patients were male. The median Birmingham Vasculitis Activity Score (BVAS), five-factor score (FFS), and NFS were 12.0, 1.0, and - 4.7, respectively. Of the 256 patients, 33 (12.9%) died. Using the receiver operating characteristic curve, the optimal cut-off of NFS for all-cause mortality was obtained as-3.97. AAV patients with NFS at diagnosis ≥ - 3.97 exhibited a lower cumulative patients' survival rate than those with NFS at diagnosis <-3.97. The multivariable Cox analysis revealed that NFS at diagnosis ≥ - 3.97 (HR 2.232, 95% CI 1.011, 4.925) was independently associated with all-cause mortality in AAV patients. Conclusion: This study was the first to demonstrate that NFS at AAV diagnosis was clinically useful in predicting all-cause mortality during follow-up, regardless of both the degree of liver fibrosis and abnormal or normal liver function results.

Hepatic steatosis index at diagnosis has the potential for forecasting end-stage kidney disease in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Objective: This study evaluated whether the hepatic steatosis index (HSI) at antineutrophil cytoplasmic antibody-associated vasculitis (AAV) diagnosis could forecast poor outcomes during the disease course in AAV patients. Methods: This study included 260 AAV patients. The equation for HSI is as follows HSI=8×(alanine aminotransferase/aspartate aminotransferase)+body mass index+(2, diabetes mellitus)+(2, female). The cut-off of HSI was obtained using the receiver operating characteristic curve. Results: The median age of the 260 patients was 59.5 years, and 65.0% were female. Among the continuous variables excluding the parameters composing the equation for HSI, HSI was significantly correlated with Birmingham vasculitis activity score, five-factor score, haemoglobin, blood urea nitrogen, serum creatinine, and total cholesterol. Among poor outcomes, the area under the curve of HSI for end-stage renal disease (ESRD) was significant, and the cut-off of HSI for ESRD was set at ≤30.82. AAV patients with HSI ≤30.82 exhibited a significantly higher risk of ESRD (relative risk 3.489) and a significantly lower cumulative ESRD-free survival rate than those with HSI >30.82. Conclusion: This study is the first to demonstrate that HSI at AAV diagnosis could forecast ESRD during the disease course in AAV patients.

Cholecystectomy increases the risk of metabolic syndrome in the Korean population: a longitudinal cohort study.

Background: Cholecystectomy is a common surgical procedure to treat symptomatic gallstones; however, the long-term outcomes after cholecystectomy are unknown. Therefore, we aimed to investigate whether incident metabolic syndrome (MetS) is associated with cholecystectomy through a large, population-based, longitudinal study. Methods: Subjects aged ≥20 years who underwent cholecystectomy from 2010 to 2014 (n=76,485) and controls (n=76,485), matched for age and sex, were identified from the Korean National Health Insurance Corporation. Cox proportional hazards analyses were performed to evaluate the association between cases and incident MetS, and hazard ratios and 95% confidence intervals (CIs) were calculated. Results: A total of 152,970 patients were included. Mean age was 52.47±12.76 years, and 50.65% of participants were male. During the follow-up period, there were 38,979 (25.48%) newly diagnosed MetS cases in the study participants. The risk of MetS in the cholecystectomy group was approximately 20% higher than that in the control group [adjusted odds ratio (OR), 1.20; 95% CI: 1.17-1.23]. In the fully adjusted models, the corresponding ORs for new-onset high waist circumference (WC), low high-density lipoprotein cholesterol (HDL-C) levels, high triglycerides (TG) levels, high blood pressure (BP), and high blood glucose levels were 1.16 (1.13-1.19), 1.19 (1.16-1.22), 1.25 (1.22-1.28), 1.27 (1.23-1.31), and 1.21 (1.18-1.24), respectively. Cholecystectomy was an independent risk factor of incident MetS, after adjusting for potential confounding factors. In the subgroup analyses, the cholecystectomy group had a higher risk of MetS than the control group in subjects without hypertension or dyslipidemia, respectively. Conclusions: In this large, population-based study, cholecystectomy was associated with an increased risk of developing MetS, independent of other confounding factors. Therefore, careful monitoring of metabolic variables and long-term follow-up are required to evaluate MetS risk after cholecystectomy.

Long-term Effectiveness of the National Diabetes Quality Assessment Program in South Korea.

OBJECTIVE: This study examined the long-term effectiveness of the national diabetes quality assessment program (NDQAP) in diabetes. RESEARCH DESIGN AND METHODS: From the Health Insurance Review and Assessment Service database, 399,984 individuals with diabetes who visited a primary care clinic from 1 July 2012 to 30 June 2013 were included and followed up until 31 May 2021. The NDQAP included five quality assessment indicators: regular outpatient visits, continuity of prescriptions, regular testing of glycated hemoglobin and lipids, and regular fundus examination. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetes complications and all-cause mortality by the achievement of quality assessment indicators. RESULTS: During the mean follow-up duration of 7.6 ± 1.8 years, 20,054 cases (5.0%) of proliferative diabetic retinopathy (PDR), 6,281 end-stage kidney diseases (ESKD; 1.6%), 1,943 amputations (0.5%), 9,706 myocardial infarctions (MIs; 2.4%), 26,975 strokes (6.7%), and 35,799 all-cause mortality (8.9%) occurred. Each achievement of quality assessment indicator was associated with a decreased risk of diabetes complications and all-cause mortality. Individuals who were managed in high-quality institutions had a lower risk of PDR (HR 0.82; 95% CI 0.80-0.85), ESKD (HR 0.77; 95% CI 0.73-0.81), amputation (HR 0.75; 95% CI 0.69-0.83), MI (HR 0.85; 95% CI 0.82-0.89), stroke (HR 0.86; 95% CI 0.84-0.88), and all-cause mortality (HR 0.96; 95% CI 0.94-0.98) than those who were not managed in high-quality institutions. CONCLUSIONS: In Korea, the achievement of NDQAP indicators was associated with a decreased risk of diabetes complications and all-cause mortality.

Ruptured Fusiform Anterior Cerebral Artery Aneurysm in an Infant : Case Report and a Literature Review.

Ruptured intracranial aneurysms in infants are rare and infantile fusiform anterior cerebral artery (ACA) aneurysms are much rarer. In this report, we described the case of a 7-month-old infant with a ruptured fusiform ACA aneurysm who presented with seizure and underwent endovascular treatment. The patient was initially in a coma and the neurologic condition did not improve after treatment. The clinical characteristics of the case and literature review were discussed.

Strain and crystallographic identification of the helically concaved gap surfaces of chiral nanoparticles.

Identifying the three-dimensional (3D) crystal plane and strain-field distributions of nanocrystals is essential for optical, catalytic, and electronic applications. However, it remains a challenge to image concave surfaces of nanoparticles. Here, we develop a methodology for visualizing the 3D information of chiral gold nanoparticles ≈ 200 nm in size with concave gap structures by Bragg coherent X-ray diffraction imaging. The distribution of the high-Miller-index planes constituting the concave chiral gap is precisely determined. The highly strained region adjacent to the chiral gaps is resolved, which was correlated to the 432-symmetric morphology of the nanoparticles and its corresponding plasmonic properties are numerically predicted from the atomically defined structures. This approach can serve as a comprehensive characterization platform for visualizing the 3D crystallographic and strain distributions of nanoparticles with a few hundred nanometers, especially for applications where structural complexity and local heterogeneity are major determinants, as exemplified in plasmonics.

New index using triglyceride glucose-body mass index for predicting mortality in patients with antineutrophil cytoplasmic antibody-associated vasculitis.

Background: This study aimed to investigate whether triglyceride glucose-body mass index (TyG-BMI) and a new index using TyG-BMI (NITGB) could predict all-cause mortality in non-obese patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods: The medical records of 78 non-obese AAV patients (BMI < 23.0 kg/m2 for Asians) were retrospectively reviewed. TyG-BMI was calculated by the equation: Ln (triglyceride × fasting glucose/2) × BMI. To develop NITGB, we assigned a weight of a number close to an 0.1 decimal integer to each variable according to the slopes for independent variables with P-value < 0.1 in the multivariable Cox analysis. Results: The median age was 54.3 years and five patients died. When non-obese AAV patients were divided into two groups based on TyG-BMI ≥ 187.74, those with TyG-BMI ≥ 187.74 exhibited a significantly higher risk for all-cause mortality than those without (RR 9.450). Since age (HR 1.324), Birmingham vasculitis activity score (BVAS; HR 1.212), and TyG-BMI ≥ 187.74 (HR 12.168) were independently associated with all-cause mortality, NITGB was developed as follows: age + 0.2 × BVAS + 2.5 × TyG-BMI ≥ 187.74. When non-obese AAV patients were divided into two groups based on NITGB ≥ 27.36, those with NITGB ≥ 27.36 showed a significantly higher risk for all-cause mortality than those without (RR 284.000). Both non-obese AAV patients with TyG-BMI ≥ 187.74 and those with NITGB ≥ 27.36 exhibited significantly higher cumulative rates of all-cause mortality than those without. Conclusion: NITGB along with TyG-BMI could predict all-cause mortality in non-obese AAV patients.

Comparison of Newly Proposed LDL-Cholesterol Estimation Equations.

BACKGROUND: Low-density lipoprotein cholesterol is an important marker highly associated with cardiovascular disease. Since the direct measurement of it is inefficient in terms of cost and time, it is common to estimate through the Friedewald equation developed about 50 years ago. However, various limitations exist since the Friedewald equation was not designed for Koreans. This study proposes a new low-density lipoprotein cholesterol estimation equation for South Koreans using nationally approved statistical data. METHODS: This study used data from the Korean National Health and Nutrition Examination Survey from 2009 to 2019. The 18,837 subjects were used to develop the equation for estimating low-density lipoprotein cholesterol. The subjects included individuals with low-density lipoprotein cholesterol levels directly measured among those with high-density lipoprotein cholesterol, triglycerides, and total cholesterol measured. We compared twelve equations developed in the previous studies and the newly proposed equation (model 1) developed in this study with the actual low-density lipoprotein cholesterol value in various ways. RESULTS: The low-density lipoprotein cholesterol value estimated using the estimation formula and the actual low-density lipoprotein cholesterol value were compared using the root mean squared error. When the triglyceride level was less than 400 mg/dL, the root mean squared of the model 1 was 7.96, the lowest compared to other equations, and the model 2 was 7.82. The degree of misclassification was checked according to the NECP ATP III 6 categories. As a result, the misclassification rate of the model 1 was the lowest at 18.9%, and Weighted Kappa was the highest at 0.919 (0.003), which means it significantly reduced the underestimation rate shown in other existing estimation equations. Root mean square error was also compared according to the change in triglycerides level. As the triglycerides level increased, the root mean square error showed an increasing trend in all equations, but it was confirmed that the model 1 was the lowest compared to other equations. CONCLUSION: The newly proposed low-density lipoprotein cholesterol estimation equation showed significantly improved performance compared to the 12 existing estimation equations. The use of representative samples and external verification is required for more sophisticated estimates in the future.

Cuproptosis-Inducible Chemotherapeutic/Cascade Catalytic Reactor System for Combating with Breast Cancer.

Cascade hydroxyl radical generating hydrogel reactor structures including a chemotherapeutic agent are invented for multiple treatment of breast cancer. Glucose oxidase (GOx) and cupric sulfate (Cu) are introduced for transforming accumulated glucose (in cancer cells) to hydroxyl radicals for starvation/chemodynamic therapy. Cu may also suppress cancer cell growth via cuproptosis-mediated cell death. Berberine hydrochloride (BER) is engaged as a chemotherapeutic agent in the hydrogel reactor for combining with starvation/chemodynamic/cuproptosis therapeutic modalities. Moreover, Cu is participated as a gel crosslinker by coordinating with catechol groups in hyaluronic acid-dopamine (HD) polymer. Controlling viscoelasticity of hydrogel reactor can extend the retention time following local injection and provide sustained drug release patterns. Low biodegradation rate of designed HD/BER/GOx/Cu hydrogel can reduce dosing frequency in local cancer therapy and avoid invasiveness-related inconveniences. Especially, it is anticipated that HD/BER/GOx/Cu hydrogel system can be applied for reducing size of breast cancer prior to surgery as well as tumor growth suppression in clinical application.

Association between Sleep Duration and Incident Diabetes Mellitus in Healthy Subjects: A 14-Year Longitudinal Cohort Study.

BACKGROUND: This study aimed to investigate whether sleep duration and/or quality are associated with incident diabetes mellitus (DM). METHODS: A total of 8816 of 10,030 healthy participants were enrolled in a prospective cohort study. Sleep duration and quality questionnaires were completed. Sleep quality was assessed using the Epworth Sleepiness Scale (ESS), which measures excessive daytime sleepiness in individuals. RESULTS: During the 14-year follow-up period, 18% (1630/8816) were diagnosed with DM. A U-shaped relationship was observed between sleep duration and incident DM, with the highest risk observed when sleep duration was ≥10 h/day (hazard ratios (HR) 1.65 [1.25-2.17]). This group exhibited decreased insulin glycogenic index, a marker of insulin secretory function, during the study period. Among study participants who slept less than 10 h/day, the risk of incident DM increased when the ESS score was >10. CONCLUSIONS: We found that the association between sleep duration and incident DM was U-shaped; both short (≤5 h) and long (≥10 h) sleep durations were associated with an increased risk for the occurrence of incident DM. When sleep duration was 10 h or longer per day, there was a tendency to develop DM due to decreased insulin secretory function.

Ultralow-Loss Substrate for Nanophotonic Dark-Field Microscopy.

For the colloidal nanophotonic structures, a transmission electron microscope (TEM) grid has been widely used as a substrate of dark-field microscopy because a nanometer-scale feature can be effectively determined by TEM imaging following dark-field microscopic studies. However, an optically lossy carbon layer has been implemented in conventional TEM grids. A broadband scattering from the edges of the TEM grid further restricted an accessible signal-to-noise ratio. Herein, we demonstrate that the freely suspended, ultrathin, and wide-scale transparent nanomembrane can address such challenges. We developed a 1 mm by 600 µm scale and 20 nm thick poly(vinyl formal) nanomembrane, whose area is around 180 times wider than a conventional TEM grid, so that the possible broadband scattering at the edges of the grid was effectively excluded. Also, such nanomembranes can be formed without the assistance of carbon support; allowing us to achieve the highest signal-to-background ratio of scattering among other substrates.

Omega-3 fatty acids and atrial fibrillation.

Although some clinical trials have demonstrated reduced incidence of cardiovascular disease with the use of omega-3 fatty acids, others have found an increased risk of atrial fibrillation (AF). AF is the most common sustained cardiac arrhythmia worldwide. It is associated with high morbidity and mortality rates and significant public health burden. Previous studies of the effect of omega-3 fatty acids on AF occurrence have reported contradictory results. Here we reviewed the effect of omega-3 fatty acids on the risk of AF.

Remnant Cholesterol Is an Independent Predictor of Type 2 Diabetes: A Nationwide Population-Based Cohort Study.

OBJECTIVE: Although the atherogenic effect of remnant cholesterol (remnant-C) has been widely recognized, the relationship between remnant-C and glucose metabolism remains unclear. This retrospective, longitudinal study investigated the relationship between remnant-C and incident type 2 diabetes (T2D) in a nationwide cohort of Korean adults. RESEARCH DESIGN AND METHODS: A total of 8,485,539 Korean adults without diabetes participated in the national health screening in 2009 and were followed up until 2019. The relationship between remnant-C quartiles and incident T2D was examined by Cox regression models. The risk of incident T2D over the continuum of remnant-C was examined with cubic spline analysis. RESULTS: During the median follow-up period of 9.28 years, 584,649 individuals (6.8%) developed T2D. In multivariable-adjusted analyses, participants in the upper quartile of remnant-C had a higher risk of T2D, with hazard ratios of 1.25 (95% CI 1.24-1.27) in the second quartile, 1.51 (95% CI 1.50-1.53) in the third quartile, and 1.95 (95% CI 1.93-1.97) in the fourth quartile, compared with the lowest quartile. The increase in the risk of T2D owing to high remnant-C concentration was more profound in individuals with fewer traditional T2D risks, such as women, and absence of metabolic abnormalities, including impaired fasting glucose, hypertension, and atherogenic dyslipidemia. Moreover, the magnitude of the increased risk for incident T2D in individuals with higher remnant-C quartiles was higher in younger participants than older participants. CONCLUSIONS: These findings indicate that remnant-C profiles provide additional information in predicting future progression of T2D, independent of the conventional lipid parameters.