Blood sphingolipid as a novel biomarker in patients with neuromyelitis optica spectrum disorder.

BACKGROUND: Sphingolipids are signaling molecules and structural components of the axolemma and myelin sheath. Plasma sphingolipid levels may reflect disease status of neuromyelitis optica spectrum disorder (NMOSD). We aimed to examine plasma sphingolipids as disease severity biomarkers for NMOSD and compare their characteristics with those of serum neurofilament light chain (sNfL) and glial fibrillary acidic protein (sGFAP). METHODS: We measured plasma sphingolipids, sNfL, and sGFAP levels in NMOSD cases with anti-aquaporin-4-antibody. An unbiased approach, partial least square discriminant analysis (PLS-DA), was utilized to determine whether sphingolipid profiles differ according to the disease state of NMOSD (presence, moderate-to-severe disability [Expanded Disease Severity Scale, (EDSS) > 3.0], and relapses). RESULTS: We investigated 81 patients and 10 controls. PLS-DA models utilizing sphingolipids successfully differentiated patients with EDSS > 3.0, but failed to identify the presence of disease and relapses. Ceramide-C14-a significant contributor to differentiating EDSS > 3.0-positively correlated with EDSS, while its levels were independent of age and the presence of relapses. This characteristic was unique from those of sNfL and sGFAP, which were affected by age and relapses as well as EDSS. CONCLUSION: Plasma sphingolipids may be useful NMOSD biomarkers for disability with distinct characteristics compared to sNfL and sGFAP.

Association of ambient air pollution with hemoglobin levels and anemia in the general population of Korean adults.

BACKGROUND: Emerging evidence has suggested significant associations between ambient air pollution and changes in hemoglobin levels or anemia in specific vulnerable groups, but few studies have assessed this relationship in the general population. This study aimed to evaluate the association between long-term exposure to air pollution and hemoglobin concentrations or anemia in general adults in South Korea. METHODS: A total of 69,830 Korean adults from a large-scale nationwide survey were selected for our final analysis. Air pollutants included particulate matter with an aerodynamic diameter less than or equal to 10 micrometers (PM10), particulate matter with an aerodynamic diameter less than or equal to 2.5 micrometers, nitrogen dioxide, sulfur dioxide (SO2), and carbon monoxide (CO). We measured the serum hemoglobin concentration to assess anemia for each participant. RESULTS: In the fully adjusted model, exposure levels to PM10, SO2, and CO for one and two years were significantly associated with decreased hemoglobin concentrations (all p < 0.05), with effects ranging from 0.15 to 0.62% per increase in interquartile range (IQR) for each air pollutant. We also showed a significant association of annual exposure to PM10 with anemia (p = 0.0426); the odds ratio (OR) [95% confidence interval (CI)] for anemia per each increase in IQR in PM10 was estimated to be 1.039 (1.001-1.079). This association was also found in the 2-year duration of exposure (OR = 1.046; 95% CI = 1.009-1.083; adjusted Model 2). In addition, CO exposure during two years was closely related to anemia (OR = 1.046; 95% CI = 1.004-1.091; adjusted Model 2). CONCLUSIONS: This study provides the first evidence that long-term exposure to air pollution, especially PM10, is significantly associated with reduced hemoglobin levels and anemia in the general adult population.

Transcriptional Changes in Radiation-Induced Lung Injury: A Comparative Analysis of Two Radiation Doses for Preclinical Research.

In a recent stereotactic body radiation therapy animal model, radiation pneumonitis and radiation pulmonary fibrosis were observed at around 2 and 6 weeks, respectively. However, the molecular signature of this model remains unclear. This study aimed to examine the molecular characteristics at these two stages using RNA-seq analysis. Transcriptomic profiling revealed distinct transcriptional patterns for each stage. Inflammatory response and immune cell activation were involved in both stages. Cell cycle processes and response to type II interferons were observed during the inflammation stage. Extracellular matrix organization and immunoglobulin production were noted during the fibrosis stage. To investigate the impact of a 10 Gy difference on fibrosis progression, doses of 45, 55, and 65 Gy were tested. A dose of 65 Gy was selected and compared with 75 Gy. The 65 Gy dose induced inflammation and fibrosis as well as the 75 Gy dose, but with reduced lung damage, fewer inflammatory cells, and decreased collagen deposition, particularly during the inflammation stage. Transcriptomic analysis revealed significant overlap, but differences were observed and clarified in Gene Ontology and KEGG pathway analysis, potentially influenced by changes in interferon-gamma-mediated lipid metabolism. This suggests the suitability of 65 Gy for future preclinical basic and pharmaceutical research connected with radiation-induced lung injury.

Eucommia ulmoides Leaves Alleviate Cognitive Dysfunction in Dextran Sulfate Sodium (DSS)-Induced Colitis Mice through Regulating JNK/TLR4 Signaling Pathway.

Ulcerative colitis (UC) is one of the inflammatory bowel diseases (IBD) that is characterized by systemic immune system activation. This study was performed to assess the alleviative effect of administering an aqueous extract of Eucommia ulmoides leaves (AEEL) on cognitive dysfunction in mice with dextran sulfate sodium (DSS)-induced colitis. The major bioactive compounds of AEEL were identified as a quinic acid derivative, caffeic acid-O-hexoside, and 3-O-caffeoylquinic acid using UPLC Q-TOF/MSE. AEEL administration alleviated colitis symptoms, which are bodyweight change and colon shortening. Moreover, AEEL administration protected intestinal barrier integrity by increasing the tight junction protein expression levels in colon tissues. Likewise, AEEL improved behavioral dysfunction in the Y-maze, passive avoidance, and Morris water maze tests. Additionally, AEEL improved short-chain fatty acid (SCFA) content in the feces of DSS-induced mice. In addition, AEEL improved damaged cholinergic systems in brain tissue and damaged mitochondrial and antioxidant functions in colon and brain tissues caused by DSS. Also, AEEL protected against DSS-induced cytotoxicity and inflammation in colon and brain tissues by c-Jun N-terminal kinase (JNK) and the toll-like receptor 4 (TLR4) signaling pathway. Therefore, these results suggest that AEEL is a natural material that alleviates DSS-induced cognitive dysfunction with the modulation of gut-brain interaction.

Pro-Hemorrhagic Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Associated with NOTCH3 p.R75P Mutation with Low Vascular NOTCH3 Aggregation Property.

OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024.

The impact of MEIS1 TALE homeodomain transcription factor knockdown on glioma stem cell growth.

Myeloid ecotropic virus insertion site 1 (MEIS1) is a HOX co-factor necessary for organ development and normal hematopoiesis. Recently, MEIS1 has been linked to the development and progression of various cancers. However, its role in gliomagenesis particularly on glioma stem cells (GSCs) remains unclear. Here, we demonstrate that MEIS1 is highly upregulated in GSCs compared to normal, and glioma cells and to its differentiated counterparts. Inhibition of MEIS1 expression by shRNA significantly reduced GSC growth in both in vitro and in vivo experiments. On the other hand, integrated transcriptomics analyses of glioma datasets revealed that MEIS1 expression is correlated to cell cycle-related genes. Clinical data analysis revealed that MEIS1 expression is elevated in high-grade gliomas, and patients with high MEIS1 levels have poorer overall survival outcomes. The findings suggest that MEIS1 is a prognostic biomarker for glioma patients and a possible target for developing novel therapeutic strategies against GBM.

DNAJB1-PRKACA fusion neoantigens elicit rare endogenous T cell responses that potentiate cell therapy for fibrolamellar carcinoma.

Fibrolamellar carcinoma (FLC) is a liver tumor with a high mortality burden and few treatment options. A promising therapeutic vulnerability in FLC is its driver mutation, a conserved DNAJB1-PRKACA gene fusion that could be an ideal target neoantigen for immunotherapy. In this study, we aim to define endogenous CD8 T cell responses to this fusion in FLC patients and evaluate fusion-specific T cell receptors (TCRs) for use in cellular immunotherapies. We observe that fusion-specific CD8 T cells are rare and that FLC patient TCR repertoires lack large clusters of related TCR sequences characteristic of potent antigen-specific responses, potentially explaining why endogenous immune responses are insufficient to clear FLC tumors. Nevertheless, we define two functional fusion-specific TCRs, one of which has strong anti-tumor activity in vivo. Together, our results provide insights into the fragmented nature of neoantigen-specific repertoires in humans and indicate routes for clinical development of successful immunotherapies for FLC.

360° immersive virtual reality-based mirror therapy for upper extremity function and satisfaction among stroke patients: a randomized controlled trial.

BACKGROUND: Stroke is a leading cause of long-term disability worldwide; therefore, an effective rehabilitation strategy is fundamental. Mirror therapy (MT) has been a popular approach for upper extremity rehabilitation, but it presents some limitations. Recent advancements in virtual reality (VR) technology have introduced immersive VR-based MT, potentially overcoming these limitations and enhancing rehabilitation outcomes. AIM: This study aimed to evaluate the effectiveness of a novel 360° immersive virtual reality-based MT (360MT) in upper extremity rehabilitation for stroke patients, comparing it to traditional MT (TMT) and conventional physical therapy control group (CG). DESIGN: A prospective, active control, assessor blinded, parallel groups, randomized controlled trial. POPULATION: Forty-five participants with chronic stroke within six months of onset. METHODS: The participants were randomly allocated to 360MT, TMT, or CG groups. Outcome measures included Fugl-Meyer Assessment for Upper Extremity (FMA-UE), Box and Block Test (BBT), and Manual Function Test (MFT). Additionally, patient experience and satisfaction in the groups of 360MT and TMT were assessed through questionnaires and interviews. RESULTS: Results revealed that the 360MT group showed significantly greater improvements in FMA-UE, MFT and BBT compared to TMT (P<0.05) and CG (P<0.001) groups. Patient experience and satisfaction were more favorable in the 360MT group, with participants reporting higher engagement and motivation. CONCLUSIONS: 360MT appears to be a promising approach for upper extremity rehabilitation in stroke patients, providing better outcomes and higher patient satisfaction. However, further research is needed to confirm these findings and strengthen the evidence base for 360MT in stroke rehabilitation. CLINICAL REHABILITATION IMPACT: 360MT demonstrated notably enhanced upper extremity rehabilitation outcomes as well as better patient satisfaction among chronic stroke patients within six months of onset compared to traditional MT and conventional physical therapy. This novel approach not only fostered functional improvements but also elevated levels of engagement and motivation among participants, suggesting a promising future application in stroke rehabilitation framework.

Association between Combustible Cigarettes and Noncombustible Nicotine or Tobacco Products and Generalized Anxiety Disorder Based on Data from the 8th Korea National Health and Nutrition Examination Survey 2021.

Background: Despite the increasing prevalence of anxiety disorders in Korea, there have been no nationwide studies on the association between tobacco status and generalized anxiety disorder (GAD). Furthermore, despite the increasing number of people using noncombustible nicotine or tobacco products (NNTPs), the association between NNTP use and GAD remains unclear. Therefore, this study investigated the association between tobacco use and GAD. Methods: This nationwide study used data from the 8th Korea National Health and Nutrition Examination Survey (2021) and included 5,454 adults aged ≥19 years who self-reported on the tobacco use and mental health sections. Multivariable logistic regression analysis was performed to investigate the odds ratios (ORs) of GAD (Generalized Anxiety Disorder-7 score ≥10) according to tobacco status among Korean adults. The severity of anxiety was assessed using the Generalized Anxiety Disorder-7 scale. Results: Compared to never tobacco users, the ORs of GAD for combustible cigarette smokers and NNTP users were 2.74 (95% confidence interval [CI], 1.66-4.50) and 2.11 (95% CI, 1.16-3.83), respectively. The OR of GAD for former tobacco users was 1.63 (95% CI, 0.98-2.72). Conclusion: Tobacco use (combustible cigarettes and NNTP) was positively associated with GAD. However, in former tobacco users, there was no significant association with GAD when compared with never tobacco users. Given the OR of GAD among tobacco users, it is crucial to pay attention to screening for GAD and implement appropriate early interventions.

Left Atrial Strain Insights in Atrial Fibrillation and the Interplay with Metabolic Syndrome.

INTRODUCTION: Understanding the interplay between metabolic syndrome and left atrial (LA) function is crucial, especially in patients newly diagnosed with atrial fibrillation (AF). We evaluated the association between subclinical atrial function and metabolic syndrome in patients diagnosed with new-onset AF. METHODS: A retrospective analysis was conducted on 220 patients, aged between 20 and 100 years, who were newly diagnosed with AF. These patients were divided into two groups based on the presence or absence of metabolic syndrome. LA reservoir strain, a measure of LA function, was assessed using transthoracic echocardiography. Statistical methods, including receiver operating characteristic (ROC) curve and logistic regression analyses, were employed to evaluate the association between LA strain and metabolic syndrome. RESULTS: Among the 220 patients, 108 had metabolic syndrome and displayed more adverse clinical characteristics. The LA reservoir strain was significantly lower in this group (9.7% ± 5.2% vs. 12.0% ± 5.8%, p = 0.003). ROC curve analysis identified 9.3% as the optimal cutoff value for predicting metabolic syndrome, with a sensitivity of 50.9% and specificity of 70.5%. Further, multivariate analysis confirmed that an LA reservoir strain below 9.3% was independently linked to metabolic syndrome (odds ratio 4.261, 95% confidence interval 1.134-16.009, p = 0.032). CONCLUSIONS: The findings reveal a significant association between lower LA reservoir strain values and the presence of metabolic syndrome in patients newly diagnosed with AF. An LA strain value below 9.3% serves as a critical diagnostic and prognostic indicator, highlighting its clinical importance in managing patients with AF.

Ductile Copolyesters Prepared Using Succinic Acid, 1,4-Butanediol, and Bis(2-hydroxyethyl) Terephthalate with Minimizing Generation of Tetrahydrofuran.

Poly(1,4-butylene succinate) (PBS) is a promising sustainable and biodegradable synthetic polyester. In this study, we synthesized PBS-based copolyesters by incorporating 5-20 mol% of -O2CC6H4CO2- and -OCH2CH2O- units through the polycondensation of succinic acid (SA) with 1,4-butanediol (BD) and bis(2-hydroxyethyl) terephthalate (BHET). Two different catalysts, H3PO4 and the conventional catalyst (nBuO)4Ti, were used comparatively in the synthesis process. The copolyesters produced using the former were treated with M(2-ethylhexanoate)2 (M = Mg, Zn, Mn) to connect the chains through ionic interactions between M2+ ions and either -CH2OP(O)(OH)O- or (-CH2O)2P(O)O- groups. By incorporating BHET units (i.e., -O2CC6H4CO2- and -OCH2CH2O-), the resulting copolyesters exhibited improved ductile properties with enhanced elongation at break, albeit with reduced tensile strength. The copolyesters prepared with H3PO4/M(2-ethylhexanoate)2 displayed a less random distribution of -O2CC6H4CO2- and -OCH2CH2O- units, leading to a faster crystallization rate, higher Tm value, and higher yield strength compared to those prepared with (nBuO)4Ti using the same amount of BHET. Furthermore, they displayed substantial shear-thinning behavior in their rheological properties due to the presence of long-chain branches of (-CH2O)3P=O units. Unfortunately, the copolyesters prepared with H3PO4/M(2-ethylhexanoate)2, and hence containing M2+, -CH2OP(O)(OH)O-, (-CH2O)2P(O)O- groups, did not exhibit enhanced biodegradability under ambient soil conditions.

Development of a Korean version of simple, intuitive descriptions for clinical use of the generic functioning domains in the ICD-11 Chapter V.

PURPOSE: To develop a Korean version of simple, intuitive descriptions (SIDs) for clinical use of the generic functioning domains in the International Classification of Disease 11th revision (ICD-11) Chapter V. METHODS: The initial Korean SID version proposal for the International Classification of Functioning, Disability, and Health (ICF) Rehabilitation set was translated following the Italian version. The remaining 17 codes were developed using original ICF descriptions; WHO Disability Assessment Schedule, Model Disability Survey, Korean Classification of Functioning, Disability, and Health; and previous studies. The final proposal for the Korean version of SIDs was selected through virtual conferences and three rounds of voting. RESULTS: This study developed SIDs for the 47 generic functioning domains in the Chapter V of ICD-11. However, the SID for 20 of the 47 codes was confirmed in vote A, for 23 codes in vote B and for the remaining 4 in the final vote. All experts agreed with the final SID proposal. CONCLUSIONS: This is the first study in South Korea to attempt the development of SIDs for ICD-11 Chapter V. Therefore, the findings of this study could be used to evaluating of disability, functioning when ICD-11 is adopted for use in Korean clinical settings.

Simple, intuitive descriptions (SIDs) highlight the core concepts of the ICF category definitions in a user-friendly manner and enhance the utility of the ICF for routine clinical practice.The 11^th revision of the International Classification of Disease (ICD-11) was developed in 2019 with the addition of Chapter V which reflects functioning domains and better explains the association between functioning and disease.In addition, Chapter V is based on ICF, so the concept of ICF must be included, and concept definition is required for use in clinical practice.This study developed a Korean version of SIDs for clinical use of the generic functioning domains in the ICD-11 Chapter V.

Emerging Frontiers in Multichannel Membrane Capacitive Deionization: Recent Advances and Future Prospects.

Capacitive deionization (CDI) has emerged as a promising desalination technology and recently promoted the development of multichannel membrane capacitive deionization (MC-MCDI). In MC-MCDI, the independent control of multiflow channels, including the feed and electrolyte channels, enables the optimization of electrode operation in various modes, such as concentration gradients and reverse voltage discharge, facilitating semicontinuous operation. Moreover, the integration of redox couples into MC-MCDI has led to advancements in redox-mediated desalination. Specifically, the introduction of redox-active species helps enhance the ion removal efficiency and reduce energy consumption during desalination. This systematic approach, combining principles from CDI and electrodialysis, results in more sustainable and efficient desalination. These advancements have contributed to improved desalination performance and practical feasibility, rendering MC-MCDI an increasingly attractive option for addressing water scarcity challenges. Despite the considerable interest in and potential of this process, there is currently no comprehensive review available that covers the operational features and applications of MC-MCDI. Therefore, this Review provides an overview of recent research progress, focusing on the unique cell configuration, vital operation principles, and potential advantages over conventional CDI. Additionally, innovative applications of MC-MCDI are discussed. The Review concludes with insights into future research directions, potential opportunities in industrial desalination technology, and the fundamental and practical challenges for successful implementation.

CREB5 promotes the proliferation and self-renewal ability of glioma stem cells.

Glioblastoma multiforme (GBM) is the most fatal form of brain cancer in humans, with a dismal prognosis and a median overall survival rate of less than 15 months upon diagnosis. Glioma stem cells (GSCs), have recently been identified as key contributors in both tumor initiation and therapeutic resistance in GBM. Both public dataset analysis and direct differentiation experiments on GSCs have demonstrated that CREB5 is more highly expressed in undifferentiated GSCs than in differentiated GSCs. Additionally, gene silencing by short hairpin RNA (shRNA) of CREB5 has prevented the proliferation and self-renewal ability of GSCs in vitro and decreased their tumor forming ability in vivo. Meanwhile, RNA-sequencing, luciferase reporter assay, and ChIP assay have all demonstrated the closely association between CREB5 and OLIG2. These findings suggest that targeting CREB5 could be an effective approach to overcoming GSCs.

Loss of hepatic Sirt7 accelerates diethylnitrosamine (DEN)-induced formation of hepatocellular carcinoma by impairing DNA damage repair.

The mammalian sirtuin family (SIRT1-SIRT7) has shown diverse biological roles in the regulation and maintenance of genome stability under genotoxic stress. SIRT7, one of the least studied sirtuin, has been demonstrated to be a key factor for DNA damage response (DDR). However, conflicting results have proposed that Sirt7 is an oncogenic factor to promote transformation in cancer cells. To address this inconsistency, we investigated properties of SIRT7 in hepatocellular carcinoma (HCC) regulation under DNA damage and found that loss of hepatic Sirt7 accelerated HCC progression. Specifically, the number, size, and volume of hepatic tumor colonies in diethylnitrosamine (DEN) injected Sirt7-deficient liver were markedly enhanced. Further, levels of HCC progression markers and pro-inflammatory cytokines were significantly elevated in the absence of hepatic Sirt7, unlike those in the control. In chromatin, SIRT7 was stabilized and colocalized to damage site by inhibiting the induction of γH2AX under DNA damage. Together, our findings suggest that SIRT7 is a crucial factor for DNA damage repair and that hepatic loss-of-Sirt7 can promote genomic instability and accelerate HCC development, unlike early studies describing that Sirt7 is an oncogenic factor [BMB Reports 2024; 57(2): 98-103].

Harnessing Metabolic Indices as a Predictive Tool for Cardiovascular Disease in a Korean Population without Known Major Cardiovascular Event.

Background: This study evaluated the usefulness of indices for metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), and insulin resistance (IR), as predictive tools for cardiovascular disease in middle-aged Korean adults. Methods: The prospective data obtained from the Ansan-Ansung cohort database, excluding patients with major adverse cardiac and cerebrovascular events (MACCE). The primary outcome was the incidence of MACCE during the follow-up period. Results: A total of 9,337 patients were included in the analysis, of whom 1,130 (12.1%) experienced MACCE during a median follow-up period of 15.5 years. The metabolic syndrome severity Z-score, metabolic syndrome severity score, hepatic steatosis index, and NAFLD liver fat score were found to significantly predict MACCE at values above the cut-off point and in the second and third tertiles. Among these indices, the hazard ratios of the metabolic syndrome severity score and metabolic syndrome severity Z-score were the highest after adjusting for confounding factors. The area under the receiver operating characteristic curve (AUC) of the 10-year atherosclerotic cardiovascular disease (ASCVD) score for predicting MACCE was 0.716, and the metabolic syndrome severity Z-score had an AUC of 0.619. Conclusion: The metabolic syndrome severity score is a highly reliable indicator and was closely associated with the 10-year ASCVD risk score in predicting MACCE in the general population. Given the specific characteristics and limitations of metabolic syndrome severity scores as well as the indices of NAFLD and IR, a more practical scoring system that considers these factors is essential to achieve greater accuracy in forecasting cardiovascular outcomes.

Blood pressure and variability responses to the down-titration of antihypertensive drugs.

OBJECTIVES: Several recent guidelines have proposed the gradual reduction of antihypertensive drugs for patients with well controlled blood pressure (BP). However, no studies have examined alterations in BP variability (BPV) during the down-titration of antihypertensives. This study aims to investigate changes in home BPV during the down-titration of antihypertensives. METHODS: We analyzed 83 hypertensive patients who underwent down-titration of antihypertensives and had available home BP data during the down-titration. Down-titration was performed when home SBP was less than 120 mmHg, regardless of the clinic SBP. Primary exposure variable was the standard deviation (SD) of home BP. RESULTS: Among 83 patients (mean age 66.3 ±â€Š11.9 years; 45.8% men), down-titration led to increase home SBP (from 110.5 to 118.7 mmHg; P  < 0.001), and home DBP (from 68.8 to 72.8 mmHg; P  = 0.001) significantly. There were no significant differences in SDs of SBP [from 6.02 ±â€Š3.79 to 5.76 ±â€Š3.09 in morning, P  = 0.570; from 6.13 ±â€Š3.32 to 6.63 ±â€Š3.70 in evening, P  = 0.077; and from 6.54 (4.80, 8.31) to 6.37 (4.65, 8.76) in home SBP, P  = 0.464] and SDs of DBP during the down-titration of antihypertensive drugs. CONCLUSION: Down-titration of antihypertensive drugs did not have notable impact on clinic BP and home BPV, while significantly increasing home BP. These findings provide important insights indicating that the potential concern related to an increase in BPV in the planned strategy of reducing antihypertensive drugs is not substantial.

Preparation of Well-Defined Double-Metal Cyanide Catalysts for Propylene Oxide Polymerization and CO2 Copolymerization.

Reevaluating the composition of the double metal cyanide catalyst (DMC) as a salt of (NC)6Co3- anions with 1:1 Zn2+/(X)Zn+ cations (X = Cl, RO, AcO), we prepared a series of well-defined DMCs, [ClZn+][Zn2+][(NC)6Co3-][ROH], [(RO)Zn+][Zn2+][(NC)6Co3-], [(AcO)Zn+][Zn2+][(NC)6Co3-], [(RO)Zn+]p[ClZn+](1-p)[Zn2+][(NC)6Co3-], [(AcO)Zn+]p[(tBuO)Zn+]q[Zn2+][(NC)6Co3-], and [(AcO)Zn+]p[(tBuO)Zn+]q[ClZn+]r[Zn2+][(NC)6Co3-]. The structure of [(MeOC3H6O)Zn+][Zn2+][(NC)6Co3-] was precisely determined at the atomic level through Rietveld refinement of the synchrotron X-ray powder diffraction data. By evaluating the catalyst's performance in both propylene oxide (PO) polymerization and PO/CO2 copolymerization, a correlation between structure and performance was established on various aspects including activity, dispersity, unsaturation level, and carbonate fraction in the resulting polyols. Ultimately, our study identified highly efficient catalysts that outperformed the state-of-the-art benchmark DMC not only in PO polymerization [DMC-(OAc/OtBu/Cl)(0.59/0.38/0.15)] but also in PO/CO2 copolymerization [DMC-(OAc/OtBu)(0.95/0.08)].

Association between Estimated Pulse Wave Velocity and Incident Nonalcoholic Fatty Liver Disease in Korean Adults.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is associated with vascular dysfunction, one of the signs of which is arterial stiffness. Carotid-femoral pulse wave velocity (PWV), which is considered the gold standard measure of arterial stiffness, can be estimated using two commonly assessed clinical variables: age and blood pressure. This study aimed to evaluate the association between estimated PWV (ePWV) and the prevalence and incidence of NAFLD among Korean adults. Methods: This study used data from the Ansan-Ansung cohort study, a subset of the Korean Genome and Epidemiology Study, and included 8,336 adult participants with and without NAFLD at baseline. The participants were subdivided into three tertile groups according to ePWV. Results: At baseline, the prevalence of NAFLD was 10.5, 27.5, and 35.0% in the first (lowest), second, and third (highest) tertiles of ePWV, respectively. During the 18-year follow-up period, 2,467 (42.9%) incident cases of NAFLD were identified among 5,755 participants who did not have NAFLD at baseline. After adjustment for clinically relevant variables, participants in the second (adjusted hazard ratio [HR], 1.25; 95% confidence interval [CI], 1.12-1.40) and third (adjusted HR, 1.42; 95% CI, 1.24-1.64) tertiles of ePWV had a significantly higher risk of incident NAFLD than those in the first tertile. Conclusion: Higher ePWV is independently associated with an elevated risk of NAFLD in the general population.