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We investigated cardiovascular risk due to proton pump inhibitor (PPI) treatment using a self-controlled case series (SCCS) study design, a type of case-only design and an approach to overcome between-person confounding in which individuals act as their own control.We conducted an SCCS study using the National Health Insurance Service-Health Screening cohort in Korea (2002-2015). The cohort included 303,404 adult participants without prior cardiovascular events, who were followed up until December 2015. The primary outcome was a composite of stroke or myocardial infarction. The SCCS method estimated the age-adjusted incidence rate ratio between periods with and without exposure to PPI among patients with primary outcomes. As sensitivity analysis, conventional multivariable Cox proportional regression analyses were performed, which treated the exposure to PPI and H2 blocker during follow-up as time-dependent variables.In the SCCS design, 10,952 (3.6%) patients with primary outcomes were included. There was no association between PPI exposure and primary outcome (incidence rate ratio 0.98, 95% confidence interval [CI] 0.89-1.09). In the time-dependent Cox regression analyses, both PPI (adjusted hazard ratio 1.36, 95% CI 1.24-1.49) and H2 blocker (adjusted hazard ratio 1.46, 95% CI 1.38-1.55) were associated with an increased risk of the primary outcome.Negative findings in the SCCS design suggest that association between increased cardiovascular risk and PPI, frequently reported in prior observational studies, is likely due to residual confounding related to conditions with PPI treatment, rather than a true relationship.

Infection is associated with the occurrence, recurrence, and progression of atrial fibrillation (AF), and is also closely related to poor prognosis. However, studies of the relationship between infectivity and severe complications of coronavirus infectious disease-19 (COVID-19) with a history of AF are limited. To estimate infectivity and severity of complications in COVID-19 patients with a history of AF, this study was done. From the Korean nationwide COVID-19 dataset, 212 678 participants with at least one severe acute respiratory syndrome coronavirus 2 (COVID-19) test were included between January 1 and June 4, 2020. AF was defined according to at least two outpatient hospital visits or one admission with an ICD-10 code of "I48" before the COVID-19 test. To investigate the association of AF with infectivity and severe complications of COVID-19, 1:4 ratio propensity score matching (PSM) was performed. Severe complications of COVID-19 were defined as a composite outcome of mechanical ventilation, intensive care unit admission, and death within 2 months after COVID-19 diagnosis. Among 212 678 participants who underwent the COVID-19 test, there were 7713 COVID-19 positive patients. After PSM, COVID-19 PCR positivity did not show a significant difference according to the presence of AF (odds ratio [OR]: 0.79, 95% confidence interval [CI]: [0.60-1.04]). Of 7713 COVID-19 patients, 62 (0.8%) had a history of AF and severe complications occurred in 444 (5.7%) patients. After PSM, AF was associated with the development of severe complications (OR: 2.04, 95% CI: [1.10-3.79]) and mortality (OR: 2.09, 95% CI: [1.01-4.31]) of COVID-19. We found that AF was associated with an increased risk of severe complications in COVID-19 infected patients.

Retinal vascular occlusions are a common cause of visual loss. The association between oral health and the risk of retinal vascular occlusions remains unknown. We investigated whether oral health was associated with the risk of retinal vascular occlusions. We conducted a retrospective cohort study including 138,484 participants who completed a national health screening program with an oral health examination from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS) 2002–2015. Oral health markers, such as the presence of periodontitis, tooth loss, and dental caries, and the frequency of daily tooth brushing, were evaluated. The primary outcome was the occurrence of retinal vascular occlusions up to December 2015. In total, 2533 participants developed retinal vascular occlusions (215 with retinal artery occlusion, 1686 with retinal vein occlusion, 632 with unspecified retinal vascular occlusion). In the multivariable Cox regression analysis, periodontitis was an independent risk factor for retinal vascular occlusions (adjusted hazard ratio: 1.18; 95% confidence interval: 1.02–1.36; p = 0.024). Frequent tooth brushing was negatively associated with the risk of retinal vascular occlusions (adjusted hazard ratio: 0.89; 95% confidence interval: 0.80–0.98; p = 0.022). Improving oral hygiene may contribute to the attenuation of the risk of retinal vascular occlusions.

OBJECTIVE Studies on the association of oral hygiene indicators with cardiovascular disease in hypertensive patients have been lacking. Oral hygiene is directly or indirectly associated with systemic inflammation, one of the essential mechanisms of cardiovascular disease. Therefore, we hypothesized that oral hygiene would be related to the risk of cardiovascular diseases in hypertensive patients. METHODS We included 52 677 hypertensive participants who completed oral health checkups from the Korean National Health Insurance Service-National Health Screening Cohort between 2003 and 2004. We collected data on periodontitis diagnosis and treatment history, number of teeth loss, number of dental caries, and frequency of tooth brushing from medical records of health claims and oral health examination. The primary outcome was defined as composite outcomes of stroke and myocardial infarction. Follow-up was done until the date of primary outcome, or 31 December 2015. RESULTS During the 11.26 ± 2.39 years (mean ± standard deviation) of the study follow-up, 3292 participants developed primary outcomes [stroke (n = 2430), myocardial infarction (n = 862)]. In multivariable Cox regression analyses, participants with dental caries (≥ 5) were independently associated with occurrence of a primary outcome [adjusted hazard ratio: 1.37; 95% confidence interval (CI):1.10-1.72; P = 0.006]. Frequent tooth brushing (≥ 2 times/day) was significantly related to lower risk of primary outcomes (adjusted hazard ratio: 0.88; 95% CI: 0.81-0.96; P = 0.002). CONCLUSION Our study demonstrated that multiple dental caries were related to the risk of cardiovascular diseases in hypertensive patients. Better oral hygiene may attenuate the risk of cardiovascular events in hypertensive patients.

Seomae mugwort, a Korean native variety of Artemisia argyi, exhibits physiological effects against various diseases. However, its effects on osteoarthritis (OA) are unclear. In this study, a Seomae mugwort extract prevented cartilage destruction in an OA mouse model. In vitro and ex vivo analyses revealed that the extract suppressed MMP3, MMP13, ADAMTS4 and ADAMTS5 expression induced by IL‐1β, IL‐6 and TNF‐α and inhibited the loss of extracellular sulphated proteoglycans. In vivo analysis revealed that oral administration of the extract suppressed DMM‐induced cartilage destruction. We identified jaceosidin in Seomae mugwort and showed that this compound decreased MMP3, MMP13, ADAMTS4 and ADAMTS5 expression levels, similar to the action of the Seomae mugwort extract in cultured chondrocytes. Interestingly, jaceosidin and eupatilin combined had similar effects to Seomae mugwort in the DMM‐induced OA model. Induction of IκB degradation by IL‐1β was blocked by the extract and jaceosidin, whereas JNK phosphorylation was only suppressed by the extract. These results suggest that the Seomae mugwort extract and jaceosidin can attenuate cartilage destruction by suppressing MMPs, ADAMTS4/5 and the nuclear factor‐κB signalling pathway by blocking IκB degradation. Thus, the findings support the potential application of Seomae mugwort, and particularly jaceosidin, as natural therapeutics for OA.

Background: Identification of patients at high susceptibility and high risk of developing serious complications related to coronavirus disease 2019 (COVID-19) infection is clinically important in the face of the COVID-19 pandemic. Objective: To investigate whether patients with Alzheimer’s disease (AD) are more susceptible to COVID-19 infection and whether they have a higher risk of developing serious complications. Methods: We retrospectively reviewed the Korean nationwide population-based COVID-19 dataset for participants who underwent real-time reverse transcription polymerase chain reaction assays for COVID-19 between January 1 and June 4, 2020. A 1 : 3 ratio propensity score matching and binary logistic regression analysis were performed to investigate the association between AD and the susceptibility or severe complications (i.e., mechanical ventilation, intensive care unit admission, or death) of COVID-19. Results: Among 195,643 study participants, 5,725 participants had AD and 7,334 participants were diagnosed with COVID-19. The prevalence of participants testing positive for COVID-19 did not differ according to the presence of AD (p = 0.234). Meanwhile, AD was associated with an increased risk of severe COVID-19 complications (OR 2.25 [95% CI 1.54–3.28]). Secondary outcome analyses showed that AD patients had an increased risk for mortality (OR 3.09 [95% CI 2.00–4.78]) but were less likely to receive mechanical ventilation (OR 0.42 [95% CI 0.20–0.87]). Conclusion: AD was not associated with increased susceptibility to COVID-19 infection, but was associated with severe COVID-19 complications, especially with mortality. Early diagnosis and active intervention are necessary for patients with AD suspected COVID-19 infection.

Problem Infection is associated with occurrence and worsening of heart failure (HF). However, studies on the association of susceptibility and severe complications of coronavirus disease 2019 (COVID-19) with HF history are limited. Method of study From the Korean nationwide COVID-19 dataset, 212,678 participants with at least one severe acute respiratory syndrome coronavirus 2 real-time reverse transcription polymerase chain reaction (RT PCR) test were included between Jan 1 and June 4, 2020. To investigate the association of HF with susceptibility and severe complications of COVID-19, 1:5 ratio propensity score matching (PSM) and logistic regression analysis were performed. The primary outcome was a composite outcome of mechanical ventilation, intensive care unit admission, and death. Results After PSM, COVID-19 PCR positivity did not show a significant difference according to HF history in multivariable analysis (odds ratio (OR): 0.91, 95% confidence interval (CI) (0.79 - 1.04), p = 0.146). Of 7,630 individuals with confirmed COVID-19 infection, 310 (4.1%) had HF history. The overall primary outcome occurred in 426 (5.6%) individuals, including 159 (2.1%) cases of mechanical ventilation, 254 (3.3%) cases of intensive care unit admission, and 215 (2.8%) cases of death. In multivariate logistic analysis, presence of HF history was associated independently with primary outcome (OR: 1.99, 95% CI: 1.42 - 2.79, p Conclusions Our study demonstrated that HF history is associated poor prognosis, particularly mortality, in COVID-19. Patients with HF can have severe complication if infected with COVID-19; therefore, careful management are necessary. This article is protected by copyright. All rights reserved.

Periodontitis is a common chronic inflammatory disease and one of oral complications in diabetes. Diabetes-related microvascular complications and periodontitis are also closely related to systemic inflammation. We hypothesized that periodontitis and oral hygiene markers might increase the risk of microvascular complications in diabetes mellitus.We enrolled 11,353 diabetes participants without prior microvascular complications who received complete oral health checkups in the National Health Insurance Service-National Health Screening Cohort in 2003-2004. The primary outcome was the first development of diabetes-related microvascular complications, including nephropathy, neuropathy, and retinopathy.The age of all participants was 55.27 ± 9.46 years, and 7833 (68.99%) participants were male. Periodontitis was noted in 8.37%. During the 7.03 ± 4.30 year of the mean follow-up period, 7227 patients experienced diabetes-related microvascular complications (2645 with nephropathy, 2513 with neuropathy, 2069 with retinopathy). Multivariable Cox regression analyses revealed that periodontitis was an independent risk factor for diabetes-related microvascular complications (adjusted hazard ratio (HR):1.13; 95% confidence interval (CI):1.04-1.23; p = 0.004). In the secondary analysis for individual microvascular complications, periodontitis was an independent risk factor for retinopathy (adjusted HR: 1.21; 95% CI: 1.04-1.40; p = 0.013).The presence of periodontitis was associated with an increased risk of microvascular complications in diabetes patients.

Background Research on the association of non-alcoholic fatty liver disease (NAFLD) with prognosis in COVID-19 has been limited. We investigated the association between the fatty liver index (FLI), a non-invasive and simple marker of NAFLD, and the severe complications of COVID-19 patients in South Korea. Methods We included 3122 COVID-19-positive patients from the nationwide COVID-19 cohort dataset in South Korea between January and June 2020. The FLI was calculated using triglyceride, body mass index, glutamyl transpeptidase, and waist circumference, which were obtained from the national health screening program data. Severe complications related to COVID-19 were defined as the composite of mechanical ventilation, intensive care unit treatment, high-oxygen flow therapy, and death within 2 months after a COVID-19 infection. We performed a multivariate logistic regression analysis for the development of severe complications in COVID-19 patients. Results The mean ± standard deviation of FLI were 25.01 ± 22.64. Severe complications from COVID-19 occurred in 223 (7.14%) patients, including mechanical ventilation in 82 (2.63%) patients, ICU admission in 126 (4.04%), high-flow oxygen therapy in 75 (2.40%), and death in 94 (3.01%) patients, respectively. The multivariate analysis indicated that the highest tertile (T3) of FLI was positively associated with severe complications from COVID-19 (adjusted odds ratio (OR): 1.77, 95% confidence interval (CI) (1.11–2.82), P = 0.017) compared with the lowest tertile (T1). Conclusions Our study demonstrated that FLI, which represents NAFLD, was positively associated with an increased risk of severe complications from COVID-19. FLI might be used as a prognostic marker for the severity of COVID-19.

Oral diseases, such as periodontitis and dental caries, can cause systemic inflammation as well as local effects, which is an important contributing factor for obesity. We aimed to investigate the change in body mass index (BMI) according to the presence of periodontitis and oral hygiene indicators. This study enrolled 110,068 participants from the national health screening cohort in Korea from 2009–2010 who underwent an oral health checkup. As oral hygiene indicators, the presence of periodontitis, dental caries, tooth loss, and tooth brushing were assessed. We constructed a linear mixed model for BMI. BMI was repeatedly measured in the health examination until 2015. In the multivariate linear mixed model for BMI, the presence of periodontitis (β = 0.0687, standard error (SE) = 0.0225, p = 0.002), dental caries (β = 0.0735, SE = 0.0152, p &lt, 0.001), and tooth loss (β = 0.1328, SE = 0.0175, p &lt, 0.001) were positively associated with BMI. In contrast, frequent tooth brushing (≥3 times/day) was negatively associated with BMI (β = −0.2610, SE = 0.0306, p &lt, 0.001). The presence of periodontitis, dental caries, and tooth loss may be associated with higher BMI, whereas frequent tooth brushing may be related to lower BMI. Better oral hygiene might be associated with lower BMI. Further study is needed to determine the effect of oral health behavior and dental disease on obesity.

Background and ObjectivesThe goal of this work was to evaluate whether patients with epilepsy were more susceptible to coronavirus disease 2019 (COVID-19) infection and at greater risk of severe complications when infected with COVID-19 compared with patients without epilepsy.MethodsWe included participants who underwent at least 1 severe acute respiratory syndrome coronavirus 2 real-time reverse-transcription PCR test between January 1 and June 4, 2020, from the Korean nationwide COVID-19 dataset. Epilepsy was defined according to the presence of diagnostic code in health claims data before the COVID-19 diagnosis. To investigate the association between epilepsy and the susceptibility for or severe complications of COVID-19, a 1:6 ratio propensity score matching (PSM) and logistic regression analysis were performed. Severe complications with COVID-19 infection were defined as a composite of the incidence of mechanical ventilation, intensive care unit admission, and death within 2 months after COVID-19 diagnosis.ResultsAmong 212,678 study participants who underwent a COVID-19 test, 3,919 (1.8%) had a history of epilepsy. After PSM, there was no significant difference in COVID-19 PCR positivity according to epilepsy history (odds ratio [OR] 0.86, 95% CI 0.67–1.11). Of the 7,713 individuals with confirmed COVID-19 infection, 72 (0.9%) had a history of epilepsy. Among the patients with COVID-19, severe complications occurred in 444 (5.8%) individuals. After PSM, the presence of epilepsy was associated with the occurrence of severe complications after COVID-19 infection (OR 2.05, 95% CI 1.04–4.04). Mortality after COVID-19 infection did not differ according to the presence of epilepsy history (OR 1.55, 95% CI 0.65–3.70).DiscussionThe presence of epilepsy was not associated with increased susceptibility to COVID-19 infection or mortality related to the infection. However, there was an increased risk of severe complications with COVID-19 in patients with epilepsy; therefore, careful management and monitoring may be necessary.

Although Hif‐2α is a master regulator of catabolic factor expression in osteoarthritis development, Hif‐2α inhibitors remain undeveloped. The aim of this study was to determine whether Cirsium japonicum var. maackii (CJM) extract and one of its constituents, apigenin, could attenuate the Hif‐2α‐induced cartilage destruction implicated in osteoarthritis progression. In vitro and in vivo studies demonstrated that CJM reduced the IL‐1β‐, IL‐6, IL‐17‐ and TNF‐α‐induced up‐regulation of MMP3, MMP13, ADAMTS4, ADAMTS5 and COX‐2 and blocked osteoarthritis development in a destabilization of the medial meniscus mouse model. Activation of Hif‐2α, which directly up‐regulates MMP3, MMP13, ADAMTS4, IL‐6 and COX‐2 expression, is inhibited by CJM extract. Although cirsimarin, cirsimaritin and apigenin are components of CJM and can reduce inflammation, only apigenin effectively reduced Hif‐2α expression and inhibited Hif‐2α‐induced MMP3, MMP13, ADAMTS4, IL‐6 and COX‐2 expression in articular chondrocytes. IL‐1β induction of JNK phosphorylation and IκB degradation, representing a critical pathway for Hif‐2α expression, was completely blocked by apigenin in a concentration‐dependent manner. Collectively, these effects indicate that CJM and one of its most potent constituents, apigenin, can lead to the development of therapeutic agents for blocking osteoarthritis development as novel Hif‐2α inhibitors.

Background Cardiovascular risk increases following herpes zoster. We investigated whether treatment with antiviral agents, steroids, and common cardiovascular medications was associated with the risk of postherpetic cardiovascular events. Methods This was a nationwide population-based, retrospective, cohort study using the National Health Insurance Service health claims data in Korea. We included patients with a first-ever diagnosis of herpes zoster in 2003–2014 and no prior cardiovascular event. The primary outcome was the occurrence of composites of myocardial infarction (International Statistical Classification of Diseases, Tenth Revision, code I21) and stroke (codes I60–I63) since the herpes zoster. We analyzed the exposure (intravenous or oral administration) to antiviral agents, steroids, antithrombotics, and statins within ±7 days from the index date of herpes zoster diagnosis. Follow-up was performed until occurrence of the primary outcome, death, or 31 December 2015, whichever came first. Results Of 84 993 patients with herpes zoster, the proportions of patients who received the treatment with antiviral agents, steroids, antithrombotics, and statins were 90.5%, 48.0%, 9.1%, and 7.9%, respectively. During the mean (standard deviation) follow-up period of 5.4 (3.1) years, 1523 patients experienced the primary outcome. Multivariate Cox regression analysis demonstrated that treatment with antiviral agents (adjusted hazard ratio, 0.82; 95% confidence interval, .71–.95) and statins (0.71; .59–.85) were significantly associated with the lower risk of primary outcome. Use of antithrombotics and steroids were not associated with the risk. Conclusions After herpes zoster, treatment with antiviral agents was significantly associated with lower risk of cardiovascular events. We need more information on the cardiovascular protective role of herpes zoster treatments.

3′-Sialyllactose (3′-SL), a natural prebiotic, maintains immune homeostasis and exerts anti-inflammatory and anti-arthritic effects. Although regulatory T cells (Tregs) prevent excessive inflammation and maintain immune tolerance, the effect of 3′-SL on Treg regulation is unclear. This study aimed to investigate the effect of 3′-SL on Treg responses in atopic dermatitis (AD) pathogenesis. Oral administration of 3′-SL reduced AD-like symptoms such as ear, epidermal, and dermal thickness in repeated topical application of house dust mites (HDM) and 2,4-dinitrochlorobenzene (DNCB). 3′-SL inhibited IgE, IL-1β, IL-6, and TNF-α secretion and markedly downregulated AD-related cytokines including IL-4, IL-5, IL-6, IL-13, IL-17, IFN-γ, TNF-α, and Tslp through regulation of NF-κB in ear tissue. Additionally, in vitro assessment of Treg differentiation revealed that 3′-SL directly induced TGF-β-mediated Treg differentiation. Furthermore, 3′-SL administration also ameliorated sensitization and elicitation of AD pathogenesis by suppressing mast cell infiltration and production of IgE and pro-inflammatory cytokines in mouse serum by mediating the Treg response. Furthermore, Bifidobacterium population was also increased by 3′-SL administration as prebiotics. Our data collectively show that 3′-SL has therapeutic effects against AD progression by inducing Treg differentiation, downregulating AD-related cytokines, and increasing the Bifidobacterium population.

Background and purpose 3'-Sialyllactose (3'-SL) is a safe compound that is present in high levels in human milk. Although it has anti-inflammatory properties and supports immune homeostasis, its effect on collagen-induced arthritis (CIA) is unknown. In this study, we investigated the prophylactic and therapeutic effect of 3'-SL on the progression of rheumatoid arthritis (RA) in in vitro and in vivo models. Experimental approach The anti-arthritic effect of 3'-SL was analysed with fibroblast-like synoviocytes in vitro and an in vivo mouse model of CIA. RT-PCR, Western blotting and ELISA were performed to evaluate its effects in vitro. Histological analysis of ankle and knee joints of mice with CIA was performed using immunohistochemistry, as well as safranin-O and haematoxylin staining. Key results 3'-SL markedly alleviated the severity of CIA in the mice by reducing paw swelling, clinical scores, incidence rate, serum levels of inflammatory cytokines and autoantibody production. Moreover, 3'-SL reduced synovitis and pannus formation and suppressed cartilage destruction by blocking secretion of chemokines, pro-inflammatory cytokines, matrix metalloproteinases and osteoclastogenesis via NF-κB signalling. Notably, phosphorylation of p65, which is a key protein in the NF-κB signalling pathway, was totally blocked by 3'-SL in the RA models. Conclusions and implications 3'-SL ameliorated pathogenesis of CIA by suppressing catabolic factor expression, proliferation of inflammatory immune cells and osteoclastogenesis. These effects were mediated via blockade of the NF-κB signalling pathway. Therefore, 3'-SL exerted prophylactic and therapeutic effects and could be a novel therapeutic agent for the treatment of RA.

Patients with myocardial infarction (MI) are at high risk of developing pneumonia. Proton pump inhibitors (PPI) and H2-receptor antagonists (H2RA) are commonly used acid-suppressive medications to the patients with MI for gastrointestinal (GI) protection, which may increase the risk for pneumonia. We evaluated whether PPI, H2RA, and mucoprotective agents without anti-acid properties increase the risk of post-MI pneumonia. We performed a retrospective cohort study based on the National Health Insurance Service—National Sample Cohort in Korea. The study included 3701 patients discharged with MI without prior history of pneumonia. During follow-up, treatments with PPI, H2RA, and mucoprotective agents were collected as time-dependent variables based on the prescription records. We performed multivariate time-dependent Cox regression analyses for the development of post-MI pneumonia. During the mean 4.85 ± 3.75 years follow-up, 999 participants developed pneumonia. In the multivariate analyses (adjusted hazard ratio; 95% confidence interval), the risk for pneumonia was significantly increased in treatment with PPI (2.25; 1.57–3.21) and H2RA (1.50; 1.16–1.93). Meanwhile, the risk for pneumonia was not increased in treatment with mucoprotective agents. When we evaluated GI bleeding event according to the medications as a secondary outcome analysis, mucoprotective agents were associated with increased GI bleeding risk, but PPI and H2RA were not. In the use of the GI medications in the treatment of patients with MI, the influence of these drugs on bleeding and pneumonia should be considered.

Aim Periodontitis is a common chronic inflammatory disease prevalent in diabetes. The aim of this study was to evaluate periodontitis and poor oral hygiene as independent risk factors for either cerebral or myocardial infarction in the diabetes population. Methods This retrospective cohort study included 17,009 patients with diabetes who had participated in a nationwide health-screening programme, including oral health examination, during 2002–2003 in South Korea. Presence of periodontitis, tooth loss and carious teeth were assessed by professional dentists, and the number of tooth brushings per day was evaluated through self-reported questionnaires. The primary study outcome was the development of cerebral or myocardial infarction, based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision (ICD-10) codes, up to 31 December 2015. Results The study enrolled 17,009 patients with diabetes. Over the mean 11.64 years of follow-up, 1341 patients presented with either cerebral or myocardial infarction. On multivariable Cox proportional hazards regression analysis, presence of periodontitis was an independent risk factor for either cerebral or myocardial infarction [adjusted hazard ratio (HR): 1.17, 95% confidence interval (CI): 1.02–1.34; P = 0.030]. An increased number of carious teeth (≥5) was also associated with risk of cerebral or myocardial infarction (adjusted HR: 1.67, 95% CI: 1.20–2.32; P = 0.002), whereas frequent tooth brushing (≥2 times/day) was negatively associated with risk of cerebral or myocardial infarction (adjusted HR: 0.79, 95% CI: 0.70–0.90; P Conclusion Early identification and intervention of periodontal disease may be effective in reducing cardiovascular complications in the diabetes population, and improved oral hygiene would probably be associated with lower cardiovascular risk in diabetes.

The Hongseong area in the southwestern Gyeonggi Massif in South Korea is considered to represent the eastward extension of the Qinling–Dabie–Sulu collision belt in China. We have carried out zircon U–Pb SHRIMP dating and P–T estimations of the gneisses and amphibolites in the eastern Wolhyeonri complex within the Hongseong area in order to constrain their metamorphic and tectonic evolutions. The protoliths of the migmatitic biotite gneisses formed during the Neoproterozoic and underwent granulite-facies metamorphism (750–880 °C, 12–15 kbar) at 442–413 Ma. These rocks subsequently experienced amphibolite-facies retrograde metamorphism at 585–660 °C and 7.5–10.3 kbar. Mylonitic biotite gneiss, hornblende gneiss, and folded amphibolite in the study area yield metamorphic ages that range from 429 to 420 Ma. The protoliths of some garnet amphibolites that formed at 470–456 Ma are arc magmatic rocks; they experienced metamorphism at the boundary between amphibolite- and eclogite-facies (ca. 625–700 °C and 13–15.5 kbar) before 418 Ma and underwent retrograde amphibolite-facies metamorphism (ca. 625–700 °C and 8–9 kbar) at 418–405 Ma. These data suggest that a regional intermediate-P/T metamorphic event occurred during the Middle Paleozoic. In contrast, Paleoproterozoic augen gneiss blocks enclosed in the Deokjeongri gneiss complex preserve evidence of high-pressure (HP) metamorphism (840–960 °C, 17–21.8 kbar) at 234–230 Ma, which are similar to the previously reported results from eclogite blocks in this area. The occurrence of Middle Paleozoic regional metamorphism before the Permo-Triassic HP metamorphism in the Hongseong area may be correlated with the Middle Paleozoic metamorphism in the Qinling belt in China; such regional metamorphic events were caused by the collision of microcontinents with the North or South China Cratons prior to the collision between the North and South China Cratons in the Permo-Triassic.

3′‐Sialyllactose has specific physiological functions in a variety of tissues; however, its effects on osteoarthritic development remain unknown. Here, we demonstrated the function of 3′‐sialyllactose on osteoarthritic cartilage destruction. In vitro and ex vivo, biochemical and histological analysis demonstrated that 3′‐sialyllactose was sufficient to restore the synthesis of Col2a1 and accumulation of sulphated proteoglycan, a critical factor for cartilage regeneration in osteoarthritic development, and blocked the expression of Mmp3, Mmp13 and Cox2 induced by IL‐1β, IL‐6, IL‐17 and TNF‐α, which mediates cartilage degradation. Further, reporter gene assays revealed that the activity of Sox9 as a transcription factor for Col2a1 expression was accelerated by 3′‐sialyllactose, whereas the direct binding of NF‐κB to the Mmp3, Mmp13 and Cox2 promoters was reduced by 3′‐sialyllactose in IL‐1β‐treated chondrocytes. Additionally, IL‐1β induction of Erk phosphorylation and IκB degradation, representing a critical signal pathway for osteoarthritic development, was totally blocked by 3′‐sialyllactose in a dose‐dependent manner. In vivo, 3′‐sialyllactose protected against osteoarthritic cartilage destruction in an osteoarthritis mouse model induced by destabilization of the medial meniscus, as demonstrated by histopathological analysis. Our results strongly suggest that 3′‐sialyllactose may ameliorate osteoarthritic cartilage destruction by cartilage regeneration via promoting Col2a1 production and may inhibit cartilage degradation and inflammation by suppressing Mmp3, Mmp13 and Cox2 expression. The effects of 3′‐sialyllactose could be attributed in part to its regulation of Sox9 or NF‐κB and inhibition of Erk phosphorylation and IκB degradation. Taken together, these effects indicate that 3′‐sialyllactose merits consideration as a natural therapeutic agent for protecting against osteoarthritis.

Although the biological mechanisms underlying the beneficial effects of vitamin B6 on cardiovascular disease (CVD) have been reported on, epidemiological studies have yielded controversial results, and data on the Korean population are limited. This study examined the association between dietary vitamin B6 intake and CVD incidence in Koreans. A total of 9142 participants of the Korean Genome and Epidemiology Study, aged 40&ndash, 69 years, who did not have CVD or cancer at the baseline were included in the analysis. Dietary data were assessed using a validated semi-quantitative food frequency questionnaire. CVD incidence was assessed using biennial questionnaires and confirmed through repeated personal interviews. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard regression models. After multivariate adjustment, a higher vitamin B6 intake was significantly associated with a decreased CVD risk in men (HR: 0.44, 95% CI: 0.25&ndash, 0.78), no such association was observed in women. Dose-response analysis confirmed the presence of inverse linearity between vitamin B6 intake and CVD incidence in men (p for nonlinearity = 0.3). A higher dietary intake level of vitamin B6 was associated with a reduced CVD risk in Korean men. These observations require further verification in other populations.

Background Although previous studies have shown that short-term exposure to mercury is associated with obesity, it should be noted that mercury is not easily released and that it constantly accumulates in the body. However, few studies have explored the association between chronic mercury exposure and obesity. This study aimed to examine the association between chronic mercury exposure and obesity in Korean adults. Methods The study used baseline data from the Trace Element Study of Korean Adults in Yeungnam area. A total of 495 participants aged 40–69 years who provided the required information (demographic, diet, lifestyle, toenail mercury levels, and health examination results) were included. Toenail mercury levels were measured using neutron-activation analysis. Body mass index and waist circumference were obtained from medical examination. Multivariable-adjusted logistic regression and restricted cubic spline regression were used in the analysis. Results In the fully adjusted logistic regression models, participants with the highest toenail mercury levels had a higher prevalence of obesity (odds ratio [OR]: 3.26, 95 % confidence interval [CI]: 1.79–5.93) and abdominal obesity (OR: 2.30, 95 % CI: 1.15–4.59). In the cubic spline regression model, linear relationships were confirmed between increased toenail mercury levels and higher prevalence of obesity and abdominal obesity (all p > 0.05 for nonlinearity). Conclusions In summary, chronic mercury exposure was associated with higher prevalence of obesity and abdominal obesity in Korean adults. Therefore, the development of public health interventions against environmental exposure of foods is required to manage and prevent obesity.

The eastern Wolhyeonri complex in the southwestern Gyeonggi Massif, South Korea, which has a close affinity with the northern margin of the South China Craton, primarily consists of Neoproterozoic igneous and sedimentary rocks that were metamorphosed by the middle Paleozoic thermal event. In this study, we present the results from thermobarometry, whole-rock chemistry, and zircon geochronology of rocks in the eastern Wolhyeonri complex near Gwangcheon. The main rock type, such as the migmatitic biotite gneisses, was deposited after ca. 722–680 Ma, and the associated foliated amphibolites exhibit a rift-related Neoproterozoic origin. The ca. 845–820 Ma arc-related metadolerite and mafic layer in the metavolcanic-sedimentary unit are also exposed. Two Neoproterozoic magmatic events support the idea that the southwestern Gyeonggi Massif developed along the northern margin of the South China Craton. These Neoproterozoic rocks experienced upper amphibolite-facies (7–10.5 kbar and 710–735 °C) to low-pressure granulite-facies metamorphism (10.5–12.0 kbar and 810–830 °C) during 424–412 Ma, were associated with ca. 418 Ma leucogranite formation, and then underwent retrograde amphibolite-facies metamorphism. Combined with the results from previous studies, the early-middle Paleozoic orogeny in the southern Gyeonggi Massif is characterized by 470–456 Ma subduction associated with a high P/T metamorphism, and the initiation of intermediate P/T metamorphism from ca. 445 Ma followed by low-pressure granulite-facies metamorphism at 432–403 Ma, and high-pressure granulite-facies metamorphism at 392–381 Ma, indicating that the tectonic setting transitioned from a continental collision to a post-collisional setting between 432 Ma and 392 Ma. These events and the absence of Paleozoic ultrahigh-pressure metamorphism strongly correlated with the Wuyi-Yunkai orogen in the South China Craton, rather than the Qinling belt in the North China Craton. Therefore, the early-middle Paleozoic orogeny in the southern Gyeonggi Massif was caused by the subduction and subsequent collision within the South China Craton.