Disparities in cause-specific mortality by health insurance type and premium: evidence from Korean NHIS-HEALS cohort study, 2002-2019.

BACKGROUND: Although one's socioeconomic status affects health outcomes, limited research explored how South Korea's National Health Insurance (NHI) system affects mortality rates. This study investigated whether health insurance type and insurance premiums are associated with mortality. METHODS: Based on the National Health Insurance Service-Health Screening cohort, 246,172 men and 206,534 women aged ≥ 40 years at baseline (2002-2003) were included and followed until 2019. Health insurance type was categorized as employee-insured (EI) or self-employed-insured (SI). To define low, medium, and high economic status groups, we used insurance premiums at baseline. Death was determined using the date and cause of death included in the cohort. Cox proportional hazard models were used to analyze the association between insurance factors and the overall and cause-specific mortality. RESULTS: The SI group had a significantly higher risk of overall death compared to the EI group (adjusted hazard ratio (HR) [95% confidence interval]: 1.13 [1.10-1.15] for men and 1.18 [1.15-1.22] for women), after adjusting for various factors. This trend extended to death from the five major causes of death in South Korea (cancer, cardiovascular disease, cerebrovascular disease, pneumonia, and intentional self-harm) and from external causes, with a higher risk of death in the SI group (vs. the EI group). Further analysis stratified by economic status revealed that individuals with lower economic status faced higher risk of overall death and cause-specific mortality in both sexes, compared to those with high economic status for both health insurance types. CONCLUSION: This nationwide study found that the SI group and those with lower economic status faced higher risk of overall mortality and death from the five major causes in South Korea. These findings highlight the potential disparities in health outcomes within the NHI system. To address these gaps, strategies should target risk factors for death at the individual level and governments should incorporate such strategies into public health policy development at the population level. TRIAL REGISTRATION: This study was approved by the Institutional Review Board of Chungbuk National University Hospital (CBNUH-202211-HR-0236) and adhered to the principles of the Declaration of Helsinki (1975).

CU06-1004 alleviates vascular hyperpermeability in a murine model of hereditary angioedema by protecting the endothelium.

BACKGROUND: Over-release of the vasoactive peptide bradykinin (BK) due to mutation in the SERPING1 gene is the leading cause of hereditary angioedema (HAE). BK directly activates endothelial cells and increases vascular permeability by disrupting the endothelial barrier, leading to angioedema affecting face, lips, extremities, gastrointestinal tract, and larynx. Although various pharmacological treatment options for HAE became available during the last decade, they are presently limited and pose a major economic burden on patients. To identify additional therapeutic options for HAE, we evaluated the effect of CU06-1004, an endothelial dysfunction blocker, on BK-induced vascular hyperpermeability and the HAE murine model. METHODS: To investigate the effect of CU06-1004 on BK-induced vascular hyperpermeability in vivo, we pre-administrated WT mice with the drug and then induced vascular leakage through intravenous injection of BK and observed vascular alternation. Then, SERPING1 deficient mice were used for a HAE murine model. For an in vitro model, the HUVEC monolayer was pre-treated with CU06-1004 and then stimulated with BK. RESULTS: Bradykinin disrupted the endothelial barrier and formed interendothelial cell gaps, leading to hyperpermeability in vivo and in vitro. However, CU06-1004 treatment protected the endothelial barrier by suppressing Src and myosin light chain activation via BK and alleviated hyperpermeability. CONCLUSION: Our study shows that CU06-1004 oral administration significantly reduced vascular hyperpermeability in the HAE murine model by protecting the endothelial barrier function against BK stimulation. Therefore, protecting endothelium against BK with CU06-1004 could serve as a potential prophylactic/therapeutic approach for HAE patients.

Admixture of divergent genomes facilitates hybridization across species in the family Brassicaceae.

Hybridization and polyploidization are pivotal to plant evolution. Genetic crosses between distantly related species are rare in nature due to reproductive barriers but how such hurdles can be overcome is largely unknown. Here we report the hybrid genome structure of xBrassicoraphanus, a synthetic allotetraploid of Brassica rapa and Raphanus sativus. We performed cytogenetic analysis and de novo genome assembly to examine chromosome behaviors and genome integrity in the hybrid. Transcriptome analysis was conducted to investigate expression of duplicated genes in conjunction with epigenome analysis to address whether genome admixture entails epigenetic reconfiguration. Allotetraploid xBrassicoraphanus retains both parental chromosomes without genome rearrangement. Meiotic synapsis formation and chromosome exchange are avoided between nonhomologous progenitor chromosomes. Reconfiguration of transcription network occurs, and less divergent cis-elements of duplicated genes are associated with convergent expression. Genome-wide DNA methylation asymmetry between progenitors is largely maintained but, notably, B. rapa-originated transposable elements are transcriptionally silenced in xBrassicoraphanus through gain of DNA methylation. Our results demonstrate that hybrid genome stabilization and transcription compatibility necessitate epigenome landscape adjustment and rewiring of cis-trans interactions. Overall, this study suggests that a certain extent of genome divergence facilitates hybridization across species, which may explain the great diversification and expansion of angiosperms during evolution.

Activation and increased production of interleukin-17 and tumour necrosis factor-α of mucosal-associated invariant T cells in patients with periodontitis.

AIM: Mucosal-associated invariant T (MAIT) cells are known to be resident in oral mucosal tissue, but their roles in periodontitis are unknown. This study aimed to examine the level and function of MAIT cells in periodontitis patients. MATERIALS AND METHODS: Frequency, activation, and function of MAIT cells from 28 periodontitis patients and 28 healthy controls (HCs) were measured by flow cytometry. RESULTS: Circulating MAIT cells were numerically reduced in periodontitis patients. Moreover, they exhibited higher expression of CD69 and annexin V, together with more increased production of interleukin (IL)-17 and tumour necrosis factor (TNF)-α, in periodontitis patients than in HCs. Interestingly, periodontitis patients had higher frequencies of MAIT cells in gingival tissue than in peripheral blood. In addition, circulating MAIT cells had elevated expression of tissue-homing chemokine receptors such as CCR6 and CXCR6, and the corresponding chemokines (i.e., CCL20 and CXCL16) were more strongly expressed in inflamed gingiva than in healthy gingiva. CONCLUSIONS: This study demonstrates that circulating MAIT cells are numerically deficient with an activated profile toward the production of IL-17 and TNF-α in periodontitis patients. Furthermore, circulating MAIT cells have the potential to migrate to inflamed gingival tissues.

Positive association between the ratio of triglycerides to high-density lipoprotein cholesterol and diabetes incidence in Korean adults.

BACKGROUND: Insulin resistance is associated with the incidence of diabetes and cardiovascular diseases such as myocardial infarction. The ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG/HDL-C ratio) is positively correlated with insulin resistance. This study aimed to investigate the relationship between the TG/HDL-C ratio and the incidence of diabetes in Korean adults. METHODS: This retrospective study used data from the National Health Insurance Service-National Health Screening Cohort. The TG/HDL-C ratio was divided into three tertiles, the T1, T2, and T3 groups, based on sex. We estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) for diabetes using multivariate Cox proportional hazards regression analyses. RESULTS: A total of 80,693 subjects aged between 40 and 79 years were enrolled. The median follow-up period was 5.9 years. The estimated cumulative incidence of diabetes in the T1, T2, and T3 groups was 5.94%, 8.23%, and 13.50%, respectively, in men and 4.12%, 4.72%, and 6.85%, respectively, in women. Compared to T1, the fully adjusted HRs (95% CIs) of the T2 and T3 groups for new-onset diabetes were 1.17 (1.06-1.30) and 1.47 (1.34-1.62), respectively, in men and 1.20 (1.02-1.42) and 1.52 (1.30-1.78), respectively, in women. CONCLUSIONS: Increased TG/HDL-C ratio was significantly associated with a higher risk of new-onset diabetes in both sexes.

Metformin usage and the risk of colorectal cancer: a national cohort study.

PURPOSE: This study aimed to investigate the association between metformin usage and the risk of colorectal cancer (CRC) using data from the Korean National Health Insurance Service-National Health Screening Cohort database. METHODS: Data from the NHIS-HEALS cohort between 2002 and 2015 were longitudinally analyzed. Subjects were divided into three groups: metformin non-users with diabetes mellitus (DM), metformin users with DM, and no DM group. CRC was defined using the ICD-10 code (C18.0-C20.0) at the time of admission. Cox proportional hazard regression models were adopted after stepwise adjustment for confounders to investigate the association between metformin usage and colorectal cancer risk. RESULTS: During the follow-up period, of the total 323,430 participants, 2341 (1.33%) of the 175,495 males and 1204 (0.81%) of the 147,935 females were newly diagnosed with CRC. The estimated cumulative incidence of CRC was significantly different among the three groups based on Kaplan-Meier's survival curve (p values < 0.05 in both sexes). Compared with metformin non-users, hazard ratios (95% CIs) of metformin users and the no DM group were 0.66 (0.51-0.85) and 0.72 (0.61-0.85) in males and 0.59 (0.37-0.92) and 0.93 (0.66-1.29) in females, respectively, after being fully adjusted. CONCLUSIONS: Metformin users with diabetes appear to have a significantly lower risk of CRC compared with metformin non-users.

Association between Second-hand Smoke Exposure and Urinary NNAL Level in Korean Adolescents.

BACKGROUND: The 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) is a metabolite of tobacco-specific lung carcinogen that can be found in both smokers and non-smokers. Particularly, NNAL levels of children with a history of exposure to second-hand smoke (SHS) are higher than those of adults. Thus, we aimed to investigate the association between SHS exposure and urine NNAL levels in Korean adolescents. METHODS: This cross-sectional study used data from the Korea National Health and Nutrition Examination Survey VII. Overall, 648 never-smoking adolescents (425 boys and 223 girls) aged 12 to 18 were included in this study. Logistic regression analyses identified the relationship between SHS exposure and elevated urine NNAL levels. RESULTS: The mean urine NNAL levels of the no exposure and exposure group in boys were 1.39 and 2.26 ng/mL, respectively, whereas they were 1.01 and 2.45 ng/mL in girls, respectively (P < 0.001). Among the adolescents exposed to SHS, the confounder-adjusted odds ratio (95% confidence intervals) for elevated urine NNAL levels according to exposure area as overall, home, and public area were 2.68 (1.58-4.53), 31.02 (9.46-101.74), and 1.89 (1.12-3.17) in boys; and 6.50 (3.22-13.11), 20.09 (7.08-57.04), and 3.94 (1.98-7.77) in girls, respectively. CONCLUSION: SHS exposure was significantly associated with elevated urine NNAL levels in Korean adolescents, particularly in female adolescents and in those with home exposure. These findings remind us of the need to protect adolescents from SHS.

Metformin use reduced the overall risk of cancer in diabetic patients: A study based on the Korean NHIS-HEALS cohort.

BACKGROUND AND AIM: Several studies have reported the preventive effect of metformin on cancer development. This study aimed to investigate the relationship between use of metformin and risk of cancer in Koreans. METHODS AND RESULTS: This study was designed retrospectively using the National Health Insurance Service-National Health Screening Cohort conducted between 2002 and 2015. 40 to 69-year-old subjects who received a health screening examination from 2002 to 2003 were enrolled. Hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer were estimated in a multivariate Cox proportional regression analysis. A total of 323,430 subjects was enrolled (301,905 individuals without diabetes [No DM], 8643 diabetic patients with metformin treatment [metformin users], and 12,882 diabetic patients without metformin treatment [metformin non-users]). The median follow-up period was 12.7 years. Cumulative incidence of overall cancer was 7.9% (7.7, 10.3, and 11.1% in No DM, metformin users and non-users, respectively). Compared to metformin non-users, the fully adjusted HRs (95% CIs) of metformin users and No DM for overall cancer incidence were 0.73 (0.66-0.81) and 0.75 (0.64-0.88), respectively, in men and 0.83 (0.78-0.89) and 0.81 (0.72-0.92) in women. CONCLUSIONS: Diabetic patients receiving metformin treatment, and individuals without diabetes were at lower risk for cancer incidence than diabetic patients without metformin treatment.

Association between statin use and all-cause mortality in cancer survivors, based on the Korean health insurance service between 2002 and 2015.

BACKGROUND AND AIMS: Cancer is the number one cause of death in Korea. This study aimed to investigate if statin use in cancer survivors was inversely associated with all-cause mortality. METHODS AND RESULTS: Data from the 2002 to 2015 National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) were used. The Kaplan-Meier estimator was used to estimate the survival function according to statin usage. Cox proportional hazards regression models were adopted after stepwise adjustment for potential confounders to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. The median follow-up duration was 10.0 years. Statin users had a higher percentage of diabetes and hypertension in both sexes. Survival rates of statin users were higher than non-users (p-values <0.001 in men and 0.021 in women). Compared to non-users, the HRs (95% CIs) of statin users for all-cause mortality were 0.327 (0.194-0.553) in men and 0.287 (0.148-0.560) in women after adjustment for potential confounding factors. CONCLUSIONS: Statin users in cancer survivors had higher survival rate than non-users in both sexes.

Experimental rat prostatitis caused by Trichomonas vaginalis infection.

BACKGROUND: Trichomonas vaginalis (T. vaginalis) is the most common sexually transmitted parasite. It has been detected in prostatic tissue of patients with prostatitis and reported to be associated with chronic prostatitis and benign prostatic hyperplasia as well as prostate cancer. Recently, experimental rodent models of prostatitis induced by pathogen infection have been developed. However, there have so far been no reports of prostatitis caused by T. vaginalis infection in animals. Here, we investigated whether infection with T. vaginalis via the rat urethra could cause prostatitis. METHODS: T. vaginalis was injected into prostate through urethra of rat (Wistar rats), and the rats were killed 1, 2, or 4 weeks later. The presence of T. vaginalis trophozoites in the rat prostates was examined by immunohistochemistry, and pathological changes of the prostate were observed by hematoxylin-eosin staining and evaluated by grading from 0 to 5 for inflammatory cell infiltration, acinar changes, and interstitial fibrosis. Infiltrated mast cells were observed by toluidine blue staining of rat prostate tissue. Chemokine C-C motif ligand 2 (CCL2) levels of the rat prostates were measured by ELISA. RESULTS: T. vaginalis trophozoites were observed in acini in the prostates of the injected rats. The prostate tissues had higher pathological scores, and 83% (5/6) and 100% (6/6) of the ventral and dorsolateral lobes (n = 6), respectively, were inflamed. Infiltration and degranulation of mast cells were observed at higher rates in prostate sections of the T. vaginalis-infected rats. Also, prostate tissues of the injected rats had increased CCL2 levels. CONCLUSIONS: Injection of T. vaginalis in rats caused prostatitis as revealed by pathologic changes, mast cell infiltration and increased CCL2 production. Therefore, this study provides the first evidence that T. vaginalis infection in rats causes prostatitis.

Comparison study of reconstruction algorithms for prototype digital breast tomosynthesis using various breast phantoms.

Digital breast tomosynthesis (DBT) is a recently developed system for three-dimensional imaging that offers the potential to reduce the false positives of mammography by preventing tissue overlap. Many qualitative evaluations of digital breast tomosynthesis were previously performed by using a phantom with an unrealistic model and with heterogeneous background and noise, which is not representative of real breasts. The purpose of the present work was to compare reconstruction algorithms for DBT by using various breast phantoms; validation was also performed by using patient images. DBT was performed by using a prototype unit that was optimized for very low exposures and rapid readout. Three algorithms were compared: a back-projection (BP) algorithm, a filtered BP (FBP) algorithm, and an iterative expectation maximization (EM) algorithm. To compare the algorithms, three types of breast phantoms (homogeneous background phantom, heterogeneous background phantom, and anthropomorphic breast phantom) were evaluated, and clinical images were also reconstructed by using the different reconstruction algorithms. The in-plane image quality was evaluated based on the line profile and the contrast-to-noise ratio (CNR), and out-of-plane artifacts were evaluated by means of the artifact spread function (ASF). Parenchymal texture features of contrast and homogeneity were computed based on reconstructed images of an anthropomorphic breast phantom. The clinical images were studied to validate the effect of reconstruction algorithms. The results showed that the CNRs of masses reconstructed by using the EM algorithm were slightly higher than those obtained by using the BP algorithm, whereas the FBP algorithm yielded much lower CNR due to its high fluctuations of background noise. The FBP algorithm provides the best conspicuity for larger calcifications by enhancing their contrast and sharpness more than the other algorithms; however, in the case of small-size and low-contrast microcalcifications, the FBP reduced detectability due to its increased noise. The EM algorithm yielded high conspicuity for both microcalcifications and masses and yielded better ASFs in terms of the full width at half maximum. The higher contrast and lower homogeneity in terms of texture analysis were shown in FBP algorithm than in other algorithms. The patient images using the EM algorithm resulted in high visibility of low-contrast mass with clear border. In this study, we compared three reconstruction algorithms by using various kinds of breast phantoms and patient cases. Future work using these algorithms and considering the type of the breast and the acquisition techniques used (e.g., angular range, dose distribution) should include the use of actual patients or patient-like phantoms to increase the potential for practical applications.

The unified ICE-CBF pathway provides a transcriptional feedback control of freezing tolerance during cold acclimation in Arabidopsis.

During cold acclimation, C-repeat binding factors (CBFs) activate downstream targets, such as cold-regulated genes, leading to the acquisition of freezing tolerance in plants. Inducer of CBF expression 1 (ICE1) plays a key role by activating CBF3 expression in shaping the cold-induced transcriptome. While the ICE1-CBF3 regulon constitutes a major cold acclimation pathway, gene regulatory networks governing the CBF signaling are poorly understood. Here, we demonstrated that ICE1 and its paralog ICE2 induce CBF1, CBF2, and CBF3 by binding to the gene promoters. ICE2, like ICE1, was ubiquitinated by the high expression of osmotically responsive gene 1 (HOS1) E3 ubiquitin ligase. Whereas ICE2-defective ice2-2 mutant did not exhibit any discernible freezing-sensitive phenotypes, ice1-2 ice2-2/+ plant, which is defective in ICE1 and has a heterozygotic ice2 mutation, exhibited significantly reduced freezing tolerance. Accordingly, all three CBF genes were markedly down-regulated in the ice1-2 ice2-2/+ plant, indicating that ICE1 and ICE2 are functionally redundant with different implementations in inducing CBF genes. Together with the negative regulation of CBF3 by CBF2, we propose that the unified ICE-CBF pathway provides a transcriptional feedback of freezing tolerance to sustain plant development and survival during cold acclimation.

Brazilin Isolated from Caesalpinia sappan suppresses nuclear envelope reassembly by inhibiting barrier-to-autointegration factor phosphorylation.

To date, many anticancer drugs have been developed by directly or indirectly targeting microtubules, which are involved in cell division. Although this approach has yielded many anticancer drugs, these drugs produce undesirable side effects. An alternative strategy is needed, and targeting mitotic exit may be one alternative approach. Localization of phosphorylated barrier-to-autointegration factor (BAF) to the chromosomal core region is essential for nuclear envelope compartment relocalization. In this study, we isolated brazilin from Caesalpinia sappan Leguminosae and demonstrated that it inhibited BAF phosphorylation in vitro and in vivo. Moreover, we demonstrated direct binding between brazilin and BAF. The inhibition of BAF phosphorylation induced abnormal nuclear envelope reassembly and cell death, indicating that perturbation of nuclear envelope reassembly could be a novel approach to anticancer therapy. We propose that brazilin isolated from C. sappan may be a new anticancer drug candidate that induces cell death by inhibiting vaccinia-related kinase 1-mediated BAF phosphorylation.

Bisphenol A and nonylphenol have the potential to stimulate the migration of ovarian cancer cells by inducing epithelial-mesenchymal transition via an estrogen receptor dependent pathway.

Epithelial-mesenchymal transition (EMT) is an important process appearing in embryo development and tumor migration or progression, which is influenced by 17ß-estradiol (E2). Bisphenol A (BPA) and nonylphenol (NP) are suspected as endocrine disrupting chemicals (EDCs) because they can exert estrogenic properties. In this study, we examined whether E2, BPA, and NP can lead to the EMT process in BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To confirm the effect of E2, BPA, and NP, BG-1 cells were cultured under treatment with E2, BPA, or NP, and the alteration of EMT markers such as vimentin was examined at mRNA levels by using real-time and reverse-transcription (RT)-PCR. The expressions of snail, slug, and vimentin were enhanced by the treatment of E2, BPA, or NP compared to a control (DMSO). In protein levels, vimentin protein was increased by E2 and two EDCs, while E-cadherin was decreased. In addition, the expression of snail protein was enhanced by the treatment of E2 and the two EDCs in comparison with that of the control. Since EMT response in cancer cells can affect metastasis, we also performed a scratch assay and Western blot assay to show the migration ability caused by E2, BPA, or NP. Consequently, E2, BPA, and NP enhanced the migration capability of BG-1 cells and increased the expression of MMP-9 protein. Furthermore, to examine whether EMT and migration of BG-1 cancer cells are induced by BPA or NP via the ER dependent pathway, we cotreated the cells with ER-antagonist, ICI 182,780, in the presence of E2, BPA, or NP. As a result, the expressions of E-cadherin, vimentin, snail, and slug were reversed following treatment with an ER antagonist. Moreover, we confirmed that ICI 182,780 reduced the migration ability of BPA and NP to the control level. Taken together, these results indicate that BPA and NP, the potential EDCs, may have the ability to influence ovarian cancer metastasis via regulating EMT markers and migration in ER-expressing BG-1 ovarian cancer cells.

NVP-BEZ235, a dual PI3K/mTOR inhibitor, induces cell death through alternate routes in prostate cancer cells depending on the PTEN genotype.

Deregulation of the PI3K-AKT/mTOR pathway due to mutation of the tumor suppressor gene PTEN frequently occurs in human prostate cancer and is therefore considered to be an attractive therapeutic target. Here, we investigated how the PTEN genotype affected the antitumor effect of NVP-BEZ235 in human prostate cancer cells. In this setting, NVP-BEZ235 induced cell death in a PTEN-independent manner. NVP-BEZ235 selectively induced apoptotic cell death in the prostate cancer cell line DU145, which harbors wild-type PTEN; however, in the PC3 cell line, which is PTEN-null, treatment with NVP-BEZ235 resulted in autophagic cell death. Consistently, NVP-BEZ235 treatment did not result in the cleavage of caspase-3; instead, it resulted in the conversion of LC3-I to LC3-II, indicating autophagic cell death; these results suggest that an alternate mechanism of cell death is induced by NVP-BEZ235 in PTEN-null prostate cancer cells. Based on our findings, we conclude that the PTEN/PI3K/Akt pathway is critical for prostate cancer survival, and targeting PI3K signaling by NVP-BEZ235 may be beneficial in the treatment of prostate cancer, independent of the PTEN genotype.

Effective DQE (eDQE) and dose to optimize radiographic technical parameters: a survey of pediatric chest X-ray examinations in Korea.

OBJECTIVE: The purpose of this study was to investigate the effect of various technical parameters for dose optimization in pediatric chest radiological examinations by evaluating effective dose and effective detective quantum efficiency (eDQE). MATERIALS AND METHODS: For tube voltages ranging from 40 to 90 kV in 10 kV increments at the focus-to-detector distance (FDD) of 100, 110, 120, 150, 180 cm, the eDQE was evaluated at same effective dose. RESULTS: The eDQE was considerably higher without the use of the grid on equivalent effective dose. This indicates that the reduction of scatter radiation did not compensate for the loss of absorbed effective photons in the grid. The eDQE increased with increasing FDD because of the greater effective modulation transfer function (eMTF) with lower focal spot blurring. However, most of the major hospitals in Korea employed a short FDD of 100 cm with the grid. The entrance surface air kerma values for the hospitals of this survey exceeded the Korean reference level of 100 µGy. CONCLUSIONS: The different reference levels might be appropriate for the same examination conducted on children of different ages. Also, it is necessary to refine the technical parameters to perform pediatric chest examinations.

Higher high-density lipoprotein cholesterol levels increased vertebral osteoporotic fracture, but reduced hip fracture in men based on the National Health Insurance Service-National Health Screening Cohort.

BACKGROUND CONTEXT: Lipids are currently known to play an important role in bone metabolism. PURPOSE: This study aimed to investigate the effect of high-density lipoprotein cholesterol (HDL-C) on osteoporotic fractures beyond its beneficial effects on the cardiovascular system. STUDY DESIGN/SETTING: This was a retrospective, observational study that used data from the National Health Insurance Service-Health Screening cohort database. PATIENT SAMPLE: This study included 318,237 participants who were 50 years or older and with HDL-C levels of 10 to 200 mg/dL. OUTCOMES MEASURES: Physiologic measure-Diagnosis of osteoporotic fracture during the follow-up period. METHODS: The study participants were categorized into four quartiles according to baseline HDL-C levels. The Cox proportional hazards model was used to assess osteoporotic fracture risk according to HDL-C levels. RESULTS: After full adjustment and with the Q1 group as the reference group, estimates of hazard ratios (HRs; 95% confidence intervals [CIs]) for any osteoporotic fracture in men were 1.03 (0.94-1.12), 1.02 (0.93-1.11), and 1.07 (0.98-1.18) for the Q2, Q3, and Q4 groups, respectively. After classifying osteoporotic fractures according to the body location, the fully adjusted HRs for vertebral and hip fractures in the men's Q4 groups were 1.16 (1.02-1.31) and 0.74 (0.57-0.96), respectively. In women, fully adjusted HRs (95% CIs) of the female Q4 group for any osteoporotic, vertebral, and hip fractures were 1.03 (0.95-1.11), 0.96 (0.86-1.07), and 1.06 (0.80-1.41), respectively. CONCLUSION: In this study, HDL-C levels were positively associated with vertebral fractures in both men and women but inversely related to hip fractures in men. Therefore, monitoring the lipid profiles of patients with osteoporosis may be beneficial for the prevention of osteoporotic fractures.

The potential bone regeneration effects of leptin- and osteolectin-coated 3D-printed PCL scaffolds: anin vivostudy.

This study investigated the effectiveness of bone regeneration upon the application of leptin and osteolectin to a three-dimensional (3D) printed poly(ϵ-caprolactone) (PCL) scaffold. A fused deposition modeling 3D bioprinter was used to fabricate scaffolds with a diameter of 4.5 mm, a height of 0.5 mm, and a pore size of 420-520 nm using PCL (molecular weight: 43 000). After amination of the scaffold surface for leptin and osteolectin adhesion, the experimental groups were divided into the PCL scaffold (control), the aminated PCL (PCL/Amine) scaffold, the leptin-coated PCL (PCL/Leptin) scaffold, and the osteolectin-coated PCL (PCL/Osteo) scaffold. Next, the water-soluble tetrazolium salt-1 (WST-1) assay was used to assess cell viability. All groups exhibited cell viability rates of >100%. Female 7-week-old Sprague-Dawley rats were used forin vivoexperiments. Calvarial defects were introduced on the rats' skulls using a 5.5 mm trephine bur. The rats were divided into the PCL (control), PCL/Leptin, and PCL/Osteo scaffold groups. The scaffolds were then inserted into the calvarial defect areas, and the rats were sacrificed after 8-weeks to analyze the defect area. Micro-CT analysis indicated that the leptin- and osteolectin-coated scaffolds exhibited significantly higher bone regeneration. Histological analysis revealed new bone and blood vessels in the calvarial defect area. These findings indicate that the 3D-printed PCL scaffold allows for patient-customized fabrication as well as the easy application of proteins like leptin and osteolectin. Moreover, leptin and osteolectin did not show cytotoxicity and exhibited higher bone regeneration potential than the existing scaffold.

Reduced Alcohol Consumption and Major Adverse Cardiovascular Events Among Individuals With Previously High Alcohol Consumption.

Importance: Cardiovascular benefits of mild to moderate alcohol consumption need to be validated in the context of behavioral changes. The benefits of reduced alcohol consumption among people who drink heavily across different subtypes of cardiovascular disease (CVD) are unclear. Objective: To investigate the association between reduced alcohol consumption and risk of major adverse cardiovascular events (MACEs) in individuals who drink heavily across different CVD subtypes. Design, Setting, and Participants: This cohort study analyzed data from the Korean National Health Insurance Service-Health Screening database and self-reported questionnaires. The nationally representative cohort comprised Korean citizens aged 40 to 79 years who had national health insurance coverage on December 31, 2002, and were included in the 2002 to 2003 National Health Screening Program. People who drank heavily who underwent serial health examinations over 2 consecutive periods (first period: 2005-2008; second period: 2009-2012) were included and analyzed between February and May 2023. Heavy drinking was defined as more than 4 drinks (56 g) per day or more than 14 drinks (196 g) per week for males and more than 3 drinks (42 g) per day or more than 7 drinks (98 g) per week for females. Exposures: Habitual change in heavy alcohol consumption during the second health examination period. People who drank heavily at baseline were categorized into 2 groups according to changes in alcohol consumption during the second health examination period as sustained heavy drinking or reduced drinking. Main Outcomes and Measures: The primary outcome was the occurrence of MACEs, a composite of nonfatal myocardial infarction or angina undergoing revascularization, any stroke accompanied by hospitalization, and all-cause death. Results: Of the 21 011 participants with heavy alcohol consumption at baseline (18 963 males [90.3%]; mean [SD] age, 56.08 [6.16] years) included in the study, 14 220 (67.7%) sustained heavy drinking, whereas 6791 (32.2%) shifted to mild to moderate drinking. During the follow-up of 162 378 person-years, the sustained heavy drinking group experienced a significantly higher incidence of MACEs than the reduced drinking group (817 vs 675 per 100 000 person-years; log-rank P = .003). Reduced alcohol consumption was associated with a 23% lower risk of MACEs compared with sustained heavy drinking (propensity score matching hazard ratio [PSM HR], 0.77; 95% CI, 0.67-0.88). These benefits were mostly accounted for by a significant reduction in the incidence of angina (PSM HR, 0.70; 95% CI, 0.51-0.97) and ischemic stroke (PSM HR, 0.66; 95% CI, 0.51-0.86). The preventive attributes of reduced alcohol intake were consistently observed across various subgroups of participants. Conclusions and Relevance: Results of this cohort study suggest that reducing alcohol consumption is associated with a decreased risk of future CVD, with the most pronounced benefits expected for angina and ischemic stroke.

Changes in alcohol consumption habits and risk of atrial fibrillation: a nationwide population-based study.

AIMS: Heavy alcohol consumption is an established risk factor for atrial fibrillation (AF). However, the association between habitual changes in heavy habitual drinkers and incident AF remains unclear. The aim of this study was to evaluate whether absolute abstinence or reduced drinking decreases incident AF in heavy habitual drinkers. METHODS AND RESULTS: Atrial fibrillation-free participants with heavy alcohol consumption registered in the Korean National Health Insurance Service database between 2005 and 2008 were enrolled. Habitual changes in alcohol consumption between 2009 and 2012 were classified as sustained heavy drinking, reduced drinking, and absolute abstinence. The primary outcome measure was new-onset AF during the follow-up. To minimize the effect of confounding variables on outcome events, inverse probability of treatment weighting (IPTW) analysis was performed. Overall, 19 425 participants were evaluated. The absolute abstinence group showed a 63% lower incidence of AF (IPTW hazard ratio: 0.379, 95% confidence interval: 0.169-0.853) than did the sustained heavy drinking group. Subgroup analysis identified that abstinence significantly reduced incident AF in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease (all P-value <0.05). There was no statistical difference in incident AF in participants with reduced drinking compared with sustained heavy alcohol group. CONCLUSION: Absolute abstinence could reduce the incidence of AF in heavy alcohol drinkers. Comprehensive clinical measures and public health policies are warranted to motivate alcohol abstinence in heavy drinkers.

In this study of 19 425 participants, we investigated whether alcohol consumption reduction was associated with lower risk of incident atrial fibrillation (AF) in individuals with chronic heavy alcohol consumption. The absolute abstinence significantly reduced incident AF, but reducing alcohol consumption was not associated with a lower incident AF. The benefit of absolute abstinence for incidence of AF was significantly identified in participants with normal body mass index and without hypertension, diabetes, dyslipidaemia, heart failure, stroke, chronic kidney disease, or coronary artery disease.