Halenaquinol Blocks Staphylococcal Protein A Anchoring on Cell Wall Surface by Inhibiting Sortase A in Staphylococcus aureus.

Sortase A (SrtA) is a cysteine transpeptidase that binds to the periplasmic membrane and plays a crucial role in attaching surface proteins, including staphylococcal protein A (SpA), to the peptidoglycan cell wall. Six pentacyclic polyketides (1-6) were isolated from the marine sponge Xestospongia sp., and their structures were elucidated using spectroscopic techniques and by comparing them to previously reported data. Among them, halenaquinol (2) was found to be the most potent SrtA inhibitor, with an IC50 of 13.94 µM (4.66 µg/mL). Semi-quantitative reverse transcription PCR data suggest that halenaquinol does not inhibit the transcription of srtA and spA, while Western blot analysis and immunofluorescence microscopy images suggest that it blocks the cell wall surface anchoring of SpA by inhibiting the activity of SrtA. The onset and magnitude of the inhibition of SpA anchoring on the cell wall surface in S. aureus that has been treated with halenaquinol at a value 8× that of the IC50 of SrtA are comparable to those for an srtA-deletion mutant. These findings contribute to the understanding of the mechanism by which marine-derived pentacyclic polyketides inhibit SrtA, highlighting their potential as anti-infective agents targeting S. aureus virulence.

A novel marine-derived mitophagy inducer ameliorates mitochondrial dysfunction and thermal hypersensitivity in paclitaxel-induced peripheral neuropathy.

BACKGROUND AND PURPOSE: Mitochondrial dysfunction contributes to the pathogenesis and maintenance of chemotherapy-induced peripheral neuropathy (CIPN), a significant limitation of cancer chemotherapy. Recently, the stimulation of mitophagy, a pivotal process for mitochondrial homeostasis, has emerged as a promising treatment strategy for neurodegenerative diseases, but its therapeutic effect on CIPN has not been explored. Here, we assessed the mitophagy-inducing activity of 3,5-dibromo-2-(2',4'-dibromophenoxy)-phenol (PDE701), a diphenyl ether derivative isolated from the marine sponge Dysidea sp., and investigated its therapeutic effect on a CIPN model. EXPERIMENTAL APPROACH: Mitophagy activity was determined by a previously established mitophagy assay using mitochondrial Keima (mt-Keima). Mitophagy induction was further verified by western blotting, immunofluorescence, and electron microscopy. Mitochondrial dysfunction was analysed by measuring mitochondrial superoxide levels in SH-SY5Y cells and Drosophila larvae. A thermal nociception assay was used to evaluate the therapeutic effect of PDE701 on the paclitaxel-induced thermal hyperalgesia phenotype in Drosophila larvae. KEY RESULTS: PDE701 specifically induced mitophagy but was not toxic to mitochondria. PDE701 ameliorated paclitaxel-induced mitochondrial dysfunction in both SH-SY5Y cells and Drosophila larvae. Importantly, PDE701 also significantly ameliorated paclitaxel-induced thermal hyperalgesia in Drosophila larvae. Knockdown of ATG5 or ATG7 abolished the effect of PDE701 on thermal hyperalgesia, suggesting that PDE701 exerts its therapeutic effect through mitophagy induction. CONCLUSION AND IMPLICATIONS: This study identified PDE701 as a novel mitophagy inducer and a potential therapeutic compound for CIPN. Our results suggest that mitophagy stimulation is a promising strategy for the treatment of CIPN and that marine organisms are a potential source of mitophagy-inducing compounds.

Oral Hormone Replacement Therapy and Uterine Volume in Korean Adolescents with Turner Syndrome: A Retrospective Case-Control Study.

STUDY OBJECTIVE: We aimed to identify critical factors for uterine development by comparing uterine volume (UV) among patients with Turner syndrome (TS) who underwent pubertal induction (PI), patients with TS who had natural menarche (NM), and patients in a non-TS control group. METHODS: This retrospective case-control study included patients with TS who had undergone PI with oral estrogen in a PI group (n = 31) and an NM group (n = 7). The control group included patients without TS with spontaneous puberty who underwent pelvic ultrasound at 16 years of age. For TS patients, both the UV from the first ultrasound performed at age 16 or older (1st-UV) and the UV from the most recent final ultrasound (final-UV) were obtained. RESULTS: The 1st-UV was larger for patients in the NM group than those in the PI group (P < .001), but did not differ significantly between the NM and control groups (P = .375). The final-UV of the PI group was larger than their 1st-UV (P < .001), but still smaller than the NM group (P = .021). Hormone replacement therapy (HRT) duration and 1st-UV of PI group were positively correlated (P = .048). There were no variables that were significantly correlated with final-UV of PI group. CONCLUSION: Patients with TS who experienced NM showed normal uterine development, but TS patients who underwent PI showed significantly smaller, undeveloped UV. While HRT duration and UV are positively correlated at the beginning of HRT, it is unclear what determines the final UV; however, late PI initiation and use of oral estrogen probably contributed to the lack of UV development.

Characterization of Yeast Protein Hydrolysate for Potential Application as a Feed Additive.

Yeast protein can be a nutritionally suitable auxiliary protein source in livestock food. The breakdown of proteins and thereby generating high-quality peptide, typically provides nutritional benefits. Enzyme hydrolysis has been effectively uesed to generate peptides; however, studies on the potential applications of different types of enzymes to produce yeast protein hydrolysates remain limited. This study investigated the effects of endo- (alcalase and neutrase) and exotype (flavourzyme and prozyme 2000P) enzyme treatments on yeast protein. Endotype enzymes facilitate a higher hydrolysis efficiency in yeast proteins than exotype enzymes. The highest degree of hydrolysis was observed for the protein treated with neutrase, which was followed by alcalase, prozyme 2000P, and flavourzyme. Furthermore, endotype enzyme treated proteins exhibited higher solubility than their exotype counterparts. Notably, the more uniform particle size distribution was observed in endotype treated yeast protein. Moreover, compared with the original yeast protein, the enzymatic protein hydrolysates possessed a higher content of ß-sheets structures, indicating their higher structural stability. Regardless of enzyme type, enzyme treated protein possessed a higher total free amino acid content including essential amino acids. Therefore, this study provides significant insights into the production of protein hydrolysates as an alternative protein material.

Characterization of TGFß1-induced tendon-like structure in the scaffold-free three-dimensional tendon cell culture system.

The biological mechanisms regulating tenocyte differentiation and morphological maturation have not been well-established, partly due to the lack of reliable in vitro systems that produce highly aligned collagenous tissues. In this study, we developed a scaffold-free, three-dimensional (3D) tendon culture system using mouse tendon cells in a differentially adherent growth channel. Transforming Growth Factor-ß (TGFß) signaling is involved in various biological processes in the tendon, regulating tendon cell fate, recruitment and maintenance of tenocytes, and matrix organization. This known function of TGFß signaling in tendon prompted us to utilize TGFß1 to induce tendon-like structures in 3D tendon constructs. TGFß1 treatment promoted a tendon-like structure in the peripheral layer of the constructs characterized by increased thickness with a gradual decrease in cell density and highly aligned collagen matrix. TGFß1 also enhanced cell proliferation, matrix production, and morphological maturation of cells in the peripheral layer compared to vehicle treatment. TGFß1 treatment also induced early tenogenic differentiation and resulted in sufficient mechanical integrity, allowing biomechanical testing. The current study suggests that this scaffold-free 3D tendon cell culture system could be an in vitro platform to investigate underlying biological mechanisms that regulate tenogenic cell differentiation and matrix organization.

Impact of socioeconomic status on biologics utilization in rheumatoid arthritis: revealing inequalities and healthcare efficiency.

BACKGROUND/AIMS: This cross-sectional study aimed to investigate biologics treatment disparities in rheumatoid arthritis (RA) patients based on socioeconomic status (SES). METHODS: Data from the KOrean Observational Study Network for Arthritis (KORONA) database were analyzed to assess various factors associated with SES, health behaviors, and biologics use. Logistic regression and structured equation modeling (SEM) were utilized for data analysis. RESULTS: Among 5,077 RA patients included, 393 (7.7%) patients were identified as biologics users. Within the entire cohort, 31.8% of the participants were in the low-income and low-education groups, and 39.3% of the participants were in the high-income and high-education groups. Despite the patients with low income or low education experienced higher disease activity at diagnosis, had more comorbidities, exhibited higher medication compliance, underwent more check-ups, and had more hospital admissions than their counterparts, the odds of patients with low-income receiving biologics were 34% lower (adjusted odds ratio = 0.76, 95% confidence interval: 0.60-0.96, p = 0.021) after adjustment for demographics and comorbidities. SEM and pathway analyses confirmed the negative impact of low SES on biologics use. CONCLUSION: The findings suggest that SES plays a significant role in biologics use among RA patients, indicating potential healthcare inefficiencies for low SES patients. Moreover, adverse healthcare habits negatively affect biologics use in RA patients. The study highlights the importance of considering socioeconomic factors while discussing biologics use and promoting equitable access to biologics for optimal RA management.

Norterpene Cyclic Peroxides from the Marine Sponge Diacarnus spinipoculum, Inhibitors of Transient Receptor Potential Ankyrin 1.

Bioassay-guided isolation of the extract from the marine sponge Diacarnus spinipoculum showing inhibitory activity against human transient receptor potential ankyrin 1 (hTRPA1) resulted in the isolation of 12 norditerpene cyclic peroxides (1-12) and eight norsesterterpene cyclic peroxides (13-20). Among these, 10 (5-7, 11, 12, 16-20) are unprecedented analogs. Compounds with either a hydroxy (5, 11) or a methoxy (6, 12) group attached to the cyclohexanone moiety were obtained as epimeric mixtures at C-11, while compounds 4, 6, 10, and 12 are likely the artifacts of isolation. The absolute configurations of the new compounds were established based on an NMR-based empirical method and comparison of specific rotation values. Mosher ester analysis revealed the absolute configurations of compounds 17-20. The inhibitory activity of the isolated compounds against hTRPA1 varied significantly depending on their structures, with the norsesterterpenoid 19 displaying the most potent activity (IC50 2.0 µM).

Enhancing the dispersibility of Gelidium amansii-derived microfibrillated cellulose through centrifugal fractionation.

Hydrothermal pretreatment is useful for microfibrillated cellulose (MFC) preparation due to its safety, but the remaining hemicellulose might affect MFC properties. This study aimed to investigate the effect of centrifugation time on hemicellulose removal and the physicochemical properties of MFC obtained after hydrothermal pretreatment and micro-fibrillation. In this study, centrifugation was applied to the MFC suspension at varying duration times. Composition analysis and Fourier transform infrared spectra indicated that fractionated MFC has no hemicellulose content after 10, 20, and 30 min centrifugation. It also showed an approximately 5 times higher than 0.5 % g/g of initial solid concentration, indicated by a lower gel concentration point, than unfractionated MFC. Scanning electron microscope images of the fractionated MFC for 30 min (MFC2C) presented thin, long cellulose fibrils of 517 nm in average diameter and 635-10,000 nm in length that induced a slower sedimentation rate. MFC2C dispersion was also improved by autoclave sterilization by regulating cellulose structure, rheology, and crystallinity. As a result, MFC dispersibility can be enhanced by removing hemicellulose through simple centrifugation.

Antioxidant Properties of Kombucha Made with Tartary Buckwheat Tea and Burdock Tea.

Kombucha is a beverage fermented by SCOBY, which is a symbiotic culture of bacteria and yeast. Recently, kombucha has received significant attention due to its health benefits, which include antioxidant and anti-obesity effects. In this study, we investigated the characteristics of kombucha made with Tartary buckwheat and burdock, both known for their high polyphenols content. First, the total polyphenol content and antioxidant activity were measured by 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assays, which revealed a polyphenol content of 180 ug/mL in Tartary buckwheat kombucha and a high radical scavenging ability of over 90% in both kombucha preparations. Analysis of the changes in the organic acid content during fermentation revealed increases in various organic acid contents, such as glucuronic acid, lactic acid, and acetic acid. Glucuronic acid, especially, which has many functional properties in health, was found to be produced at a concentration of 4.03 g/L in Tartary buckwheat kombucha. Pancreatic lipase inhibitory ability analysis revealed inhibitory effects of 40.47% and 57.68% for Tartary buckwheat and burdock kombucha, respectively. The results of this study confirmed the antioxidant and anti-obesity effects of kombucha made from Tartary buckwheat and burdock, indicating the potential value of these ingredients as functional kombucha ingredients.

A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.

Despite advances in precision oncology, cancer remains a global public health issue. In this report, proof-of-principle evidence is presented that a cell-penetrable peptide (ACP52C) dissociates transcription factor CP2c complexes and induces apoptosis in most CP2c oncogene-addicted cancer cells through transcription activity-independent mechanisms. CP2cs dissociated from complexes directly interact with and degrade YY1, leading to apoptosis via the MDM2-p53 pathway. The liberated CP2cs also inhibit TDP2, causing intrinsic genome-wide DNA strand breaks and subsequent catastrophic DNA damage responses. These two mechanisms are independent of cancer driver mutations but are hindered by high MDM2 p60 expression. However, resistance to ACP52C mediated by MDM2 p60 can be sensitized by CASP2 inhibition. Additionally, derivatives of ACP52C conjugated with fatty acid alone or with a CASP2 inhibiting peptide show improved pharmacokinetics and reduced cancer burden, even in ACP52C-resistant cancers. This study enhances the understanding of ACP52C-induced cancer-specific apoptosis induction and supports the use of ACP52C in anticancer drug development.

Decreasing Hydrogen Content within Zirconium Using Au and Pd Nanoparticles as Sacrificial Agents under Pressurized Water at High Temperature.

Decreasing hydride-induced embrittlement of zirconium-based cladding is a significant challenge for the successful dry storage of spent nuclear fuel. Herein, to radically minimize hydride-induced embrittlement, we used nanoparticles as sacrificial agents with a greater affinity than zirconium for hydrogen. Corrosion experiments in the presence of gold (Au) and palladium (Pd) nanoparticles under simulated pressurized water reactor (PWR) conditions revealed that the hydrogen content of the zirconium samples was remarkably reduced, with a maximum decrease efficiency of 53.9% using 65 nm Au and 53.8% using 50 nm Pd nanoparticles. This approach provides an effective strategy for preventing hydride-induced embrittlement of zirconium-based cladding.

Coscinoderines A-J: Trisubstituted Pyridinium-Containing Norterpenoids Isolated from Coscinoderma bakusi, a Tropical Marine Sponge.

Ten new norterpene alkaloids, coscinoderines A-J (1-10), were isolated from the marine sponge Coscinoderma bakusi. Each coscinoderine contains a 1,2,5-trisubstituted pyridinium moiety bearing a terpene unit at the C-2 position. Their structures were elucidated by analysis of NMR and HRMS data, and the absolute stereochemistry of 4 with a 2-methylbutyl group attached to the nitrogen was determined from a comparison of the calculated and measured ECD spectra. The isolation of coscinoderines expands the repertoire of pyridinium alkaloids isolated from marine sponges.

Anti-cancer Effect of Unique Cartilage Matrix-associated Protein in Breast Cancer Cells Depends on γ-Carboxylation.

BACKGROUND/AIM: Unique cartilage matrix-associated protein (UCMA), a recently discovered vitamin K-dependent protein (VKDP) with a large number of γ-carboxyglutamic acid (Gla) residues, is associated with ectopic calcifications. Although the function of VKDPs is related to their γ-carboxylation status, the carboxylation status of UCMA in breast cancer is still unknown. Here, we investigated the inhibitory effect of UCMA with differing γ-carboxylation status on breast cancer cell lines, such as MDA-MB-231, 4T1, and E0771 cells. MATERIALS AND METHODS: Undercarboxylated UCMA (ucUCMA) was generated by mutating the γ-glutamyl carboxylase (GGCX) recognition sites. The ucUCMA and carboxylated UCMA (cUCMA) proteins were collected from culture media of HEK293-FT cells that had been transfected with mutated GGCX and wild-type UCMA expression plasmids, respectively. Boyden Transwell and colony formation assays were performed to evaluate cancer cell migration, invasion, and proliferation. RESULTS: Culture medium containing cUCMA protein inhibited the migration, invasion, and colony formation of MDA-MB-231 and 4T1 cells to a greater degree than medium containing ucUCMA protein. Significant reductions in the migration, invasion, and colony formation were also observed in cUCMA-treated E0771 cells compared to those in ucUCMA-treated cells. CONCLUSION: The inhibitory role of UCMA in breast cancer is closely related to its γ-carboxylation status. The results of this study may be a basis for the development of UCMA-based anti-cancer drugs.

Systemic C-peptide supplementation ameliorates retinal neurodegeneration by inhibiting VEGF-induced pathological events in diabetes.

Diabetic retinopathy (DR) is caused by retinal vascular dysfunction and neurodegeneration. Intraocular delivery of C-peptide has been shown to be beneficial against hyperglycemia-induced microvascular leakage in the retina of diabetes; however, the effect of C-peptide on diabetes-induced retinal neurodegeneration remains unknown. Moreover, extraocular C-peptide replacement therapy against DR to avoid various adverse effects caused by intravitreal injections has not been studied. Here, we demonstrate that systemic C-peptide supplementation using osmotic pumps or biopolymer-conjugated C-peptide hydrogels ameliorates neurodegeneration by inhibiting vascular endothelial growth factor-induced pathological events, but not hyperglycemia-induced vascular endothelial growth factor expression, in the retinas of diabetic mice. C-peptide inhibited hyperglycemia-induced activation of macroglial and microglial cells, downregulation of glutamate aspartate transporter 1 expression, neuronal apoptosis, and histopathological changes by a mechanism involving reactive oxygen species generation in the retinas of diabetic mice, but transglutaminase 2, which is involved in retinal vascular leakage, is not associated with these pathological events. Overall, our findings suggest that systemic C-peptide supplementation alleviates hyperglycemia-induced retinal neurodegeneration by inhibiting a pathological mechanism, involving reactive oxygen species, but not transglutaminase 2, in diabetes.

Dopamine ameliorates hyperglycemic memory-induced microvascular dysfunction in diabetic retinopathy.

Dopamine is a neurotransmitter that mediates visual function in the retina and diabetic retinopathy (DR) is the most common microvascular complication of diabetes and the leading cause of blindness; however, the role of dopamine in retinal vascular dysfunction in DR remains unclear. Here, we report a mechanism of hyperglycemic memory (HGM)-induced retinal microvascular dysfunction and the protective effect of dopamine against the HGM-induced retinal microvascular leakage and abnormalities. We found that HGM induced persistent oxidative stress, mitochondrial membrane potential collapse and fission, and adherens junction disassembly and subsequent vascular leakage after blood glucose normalization in the mouse retinas. These persistent hyperglycemic stresses were inhibited by dopamine treatment in human retinal endothelial cells and by intravitreal injection of levodopa in the retinas of HGM mice. Moreover, levodopa supplementation ameliorated HGM-induced pericyte degeneration, acellular capillary and pericyte ghost generation, and endothelial apoptosis in the mouse retinas. Our findings suggest that dopamine alleviates HGM-induced retinal microvascular leakage and abnormalities by inhibiting persistent oxidative stress and mitochondrial dysfunction.

Scalarane Sesterterpenoids Isolated from the Marine Sponge Hyrtios erectus and their Cytotoxicity.

Eighteen scalarane sesterterpenoids (1-18), including eight new derivatives (1-8), were isolated from the sponge Hyrtios erectus (family Thorectidae), the extract of which showed cytotoxicity against the HeLa and MCF-7 cell lines. Of the new derivatives, six compounds (1-6) were found to contain a γ-hydroxybutenolide moiety capable of reversible stereoinversion at the hydroxylated carbon center. Under the influence of other adjacent functional groups, each derivative exhibited a different stereochemical behavior, which was fully deduced by ROESY experiments. All the isolated compounds were examined for their cytotoxicity by MTS assay using staurosporine as a positive control (IC50 0.18 and 0.13 µΜ against HeLa and MCF-7 cells, respectively), and they were found to show weak growth inhibitory activities against HeLa and MCF-7 cells, with a minimal IC50 value of 20.0 µΜ. The compounds containing a γ-hydroxybutenolide moiety (1-3, 10, 12) showed cytotoxicity, with IC50 values ranging from 24.3 to 29.9 µΜ, and the most potent derivative was heteronemin (16). Although the cytotoxicities of isolated compounds were insufficient to discuss the structure-activity relationship, this research could contribute to expanding the structural diversity of scalaranes and understanding the stereochemical behavior of γ-hydroxybutenolides.

Transcriptional and toxic responses to saxitoxin exposure in the marine copepod Tigriopus japonicus.

Saxitoxin (STX) is a highly toxic marine neurotoxin produced by phytoplankton and a growing threat to ecosystems worldwide due to the spread of toxic algae. Although STX is an established sodium channel blocker, the overall profile of transcriptional levels in STX-exposed organisms has yet to be described. Here, we describe a toxicity assay and transcriptome analysis of the copepod Tigriopus japonicus exposed to STX. The half-maximal lethal concentration of STX was 12.35 µM, and a rapid mortality slope was evident at concentrations between 12 and 13 µM. STX induced changes in swimming behavior among the copepods after 10 min of exposure. In transcriptome analysis, gene ontology revealed that the genes involved in nervous system and gene expression were highly enriched. In addition, the congenital neurological disorder and nuclear factor erythroid 2-related factor 2-mediated oxidative stress pathways were identified to be the most significant in network analysis and toxicity pathway analysis, respectively. This study provides valuable information about the effects of STX and related transcriptional responses in T. japonicus.

Body fat distribution and insulin resistance among Korean middle-aged women: a Korean National Health and Nutrition Examination Survey.

OBJECTIVE: To evaluate menopause-related changes in body fat distribution and their relationship with insulin resistance in middleaged Korean women. METHODS: We analyzed women aged 40-60 years using data from the National Health and Nutrition Examination Survey conducted from 2008 to 2011. Body fat was measured using dual-energy X-ray absorptiometry. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Among 3,468 participants, menopausal women (n=1,489) had a higher body mass index (BMI) and higher trunk, arm, and head fat percentages than premenopausal women (n=1,979). However, no significant difference was found in the leg fat percentage according to menopausal status. Multivariable regression analysis for HOMA-IR showed that trunk fat percentage, BMI, and waist circumference positively correlated with insulin resistance and leg fat percentage negatively correlated after adjusting for several confounding factors, whereas menopausal status was not associated with HOMAIR. CONCLUSION: Middle-aged women not only have different body weights and BMI but also have different body fat distributions according to menopausal status. Each fat percentage change in the trunk and leg is differently associated with metabolic health, particularly insulin resistance. To evaluate the metabolic health of middle-aged women, BMI is generally noted; however, body fat distribution, which can be easily assessed using dual-energy X-ray absorptiometry, should also be considered.

Three-dimensional linear and volumetric computed tomography analysis of the frontal sinus.

The frontal sinus is one of the four paranasal sinuses in humans, and knowledge of its anatomy is important when performing surgery involving the frontal bone or sinus. Although many studies have measured the frontal sinus using radiography and computed tomography (CT), few studies have evaluated by using three-dimensional (3D) analysis. The purpose of this study was to analyze the frontal sinus using 3D reconstruction analysis and determine the differences in linear and volumetric measurements between sexes, sides, and ages. The sample comprised 281 facial CT scans: 173 and 108 from males and females, respectively. The width, height, and length of each frontal sinus and total volume were all larger in males than in females. Almost all linear and volumetric measurements were larger in young adults than in older for both sexes, but not all of the differences were statistically significant. Linear and volumetric measurements were larger for males than females regardless of age group. There were no statistically significant differences between the right and left sides except the width in males. The size of the frontal sinus was strongly influenced by sex and age. The measurements reported here might be useful for improving surgical procedures involving the frontal sinus.

Vasomotor symptoms and carotid artery intima-media thickness among Korean midlife women.

OBJECTIVES: To evaluate the association between vasomotor symptoms (VMS) and carotid intima-media thickness (CIMT) in Korean midlife women. STUDY DESIGN: This cross-sectional study included 918 Korean women aged 45-65 years who attended their routine health checkup at a single institution between 2013 and 2016. MAIN OUTCOME MEASURES: All participants' results on the Menopause Rating Scale were used to assess the VMS. Severe and very severe VMS were combined into severe VMS. CIMT and blood flow velocities were measured on the common carotid arteries using duplex ultrasound. RESULTS: All participants' mean age was 54.73 ± 5.37 years, and 627 (68.3%) were postmenopausal. A total of 401 (43.7%) women reported VMS: 217 (23.6%), mild; 109 (11.9%), moderate; and 75 (8.2%), severe. The mean CIMT was 0.062 ± 0.017 mm and 0.064 ± 0.019 mm in premenopausal and menopausal women, respectively. In the multivariate linear regression analysis, the CIMT of women with moderate VMS was 0.102 mm (95% confidence interval [CI] = 0.002-0.009) more than that of women with no VMA, and the CIMT of women with severe VMS was 0.246 mm (95% CI = 0.012-0.021) more than that of women with no VMS, after adjusting for several confounders, including age, body mass index, and lifestyle factors. Severe VMS were associated with the risk of thickened CIMT (≥0.075 mm) and/or plaques (odds ratio = 2.90, 95% CI = 1.74-4.84) in the logistic regression analysis after adjusting for the same variables. CONCLUSIONS: Moderate and severe VMS are independently associated with increased CIMT in otherwise healthy Korean midlife women. Clinicians managing midlife women with bothersome VMS should consider screening for subclinical cardiovascular diseases.