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Purpose This study aimed to identify the risk factors for diabetic foot ulceration (DFU) to develop and evaluate the performance of a DFU prediction model and nomogram among people with diabetes mellitus (DM). Methods This unmatched case-control study was conducted with 379 adult patients (118 patients with DM and 261 controls) from four general hospitals in South Korea. Data were collected through a structured questionnaire, foot examination, and review of patients' electronic health records. Multiple logistic regression analysis was performed to build the DFU prediction model and nomogram. Further, their performance was analyzed using the Lemeshow-Hosmer test, concordance statistic (C-statistic), and sensitivity/specificity analyses in training and test samples. Results The prediction model was based on risk factors including previous foot ulcer or amputation, peripheral vascular disease, peripheral neuropathy, current smoking, and chronic kidney disease. The calibration of the DFU nomogram was appropriate (χ² = 5.85, p = .321). The C-statistic of the DFU nomogram was .95 (95% confidence interval .93~.97) for both the training and test samples. For clinical usefulness, the sensitivity and specificity obtained were 88.5% and 85.7%, respectively at 110 points in the training sample. The performance of the nomogram was better in male patients or those having DM for more than 10 years. Conclusion The nomogram of the DFU prediction model shows good performance, and is thereby recommended for monitoring the risk of DFU and preventing the occurrence of DFU in people with DM.

Nuclear factor of activated T cells 5 (NFAT5) has been implicated in the pathogenesis of various human diseases, including cancer and arthritis. However, therapeutic agents inhibiting NFAT5 activity are currently unavailable. To discover NFAT5 inhibitors, a library of > 40,000 chemicals was screened for the suppression of nitric oxide, a direct target regulated by NFAT5 activity, through high-throughput screening. We validated the anti-NFAT5 activity of 198 primary hit compounds using an NFAT5-dependent reporter assay and identified the novel NFAT5 suppressor KRN2, 13-(2-fluoro)-benzylberberine, and its derivative KRN5. KRN2 inhibited NFAT5 upregulation in macrophages stimulated with lipopolysaccharide and repressed the formation of NF-κB p65-DNA complexes in the NFAT5 promoter region. Interestingly, KRN2 selectively suppressed the expression of pro-inflammatory genes, including Nos2 and Il6, without hampering high-salt-induced NFAT5 and its target gene expressions. Moreover, KRN2 and KRN5, the latter of which exhibits high oral bioavailability and metabolic stability, ameliorated experimentally induced arthritis in mice without serious adverse effects, decreasing pro-inflammatory cytokine production. Particularly, orally administered KRN5 was stronger in suppressing arthritis than methotrexate, a commonly used anti-rheumatic drug, displaying better potency and safety than its original compound, berberine. Therefore, KRN2 and KRN5 can be potential therapeutic agents in the treatment of chronic arthritis., Highlights • We identify a novel NFAT5 suppressor KRN2, 13-(2-fluoro)-benzylberberine, and its derivative KRN5 to inhibit NFAT5 activity. • KRN2 inhibits the transcriptional activation of NFAT5 and the pro-inflammatory responses. • KRN2 and KRN5 suppress experimentally induced arthritis in mice. NFAT5 has been implicated in the pathogenesis of arthritis. However, therapeutic agents specifically inhibiting NFAT5 activity are currently unavailable. To discover NFAT5 inhibitors, a library of > 40,000 chemicals was screened, leading to the discovery of novel berberine-based NFAT5 suppressors, KRN2 and its oral derivative KRN5. KRN2 inhibited the transcriptional activation of NFAT5 by blocking NF-κB binding to the NFAT5 promoter region, thereby reducing the expression of pro-inflammatory genes. Moreover, KRN2 and KRN5 ameliorated experimentally induced arthritis in mice without serious adverse effects. Therefore, we propose that KRN2 and KRN5 may be potential therapeutic agents in the treatment of chronic arthritis.

Governments and also local councils create and enforce their own regional public health care plans for the problem of overweight and obesity in the population. Public sports facilities can help these plans. In this paper, we investigated the contribution of public sports facilities to the reduction of the obesity of local residents. We used the data obtained from the Fifth Korea National Health and Nutrition Examination Surveys; and measured the degree of obesity using body mass index (BMI). We conducted various spatial regression analyses including the global Moran’s I test and local indicators of spatial autocorrelation analysis finding that there exists spatial dependence in the error term of spatial regression model for BMI. However, we also observed that the number of local public sports facilities is not significantly related to local BMI. This result can be caused by the low utilization ratio and an unbalanced spatial distribution of local public sports facilities. Based on our findings, we suggest that local councils need to improve the quality of public sports facilities encouraging the establishment of preferred types of pubic sports facilities.

NFAT5 (nuclear factor of activated T cells), a well-known osmoprotective factor, can be activated by isotonic stimuli such as Toll-like receptor (TLR) triggering. However, it is unclear how NFAT5 discriminates between isotonic and hypertonic stimuli to produce different functional and molecular outcomes. Here, we identified a novel XO-ROS-p38 MAPK-NFAT5 pathway (XO is xanthine oxidase, ROS is reactive oxygen species) that is activated in RAW 264.7 macrophages upon isotonic TLR stimulation. Unlike what is seen under hypertonic conditions, XO-derived ROS were selectively required for the TLR-induced NFAT5 activation and NFAT5 binding to the IL-6 promoter in RAW 264.7 macrophages under isotonic conditions. In mouse peritoneal macrophages and human macrophages, TLR ligation also induced NFAT5 activation, which was dependent on XO and p38 kinase. The involvement of XO in NFAT5 activation by TLR was confirmed in RAW 264.7 macrophages implanted in BALB/c mice. Moreover, allopurinol, an XO inhibitor, suppressed arthritis severity and decreased the expression of NFAT5 and IL-6 in splenic macrophages in C57BL/6 mice. Collectively, these data support a novel function of the XO-NFAT5 axis in macrophage activation and TLR-induced arthritis, and suggest that XO inhibitor(s) could serve as a therapeutic agent for chronic inflammatory arthritis.

Gonadotropin-releasing hormone (GnRH) agonist has been used in the treatment of a wide variety of sex-hormone-related diseases, as the administration of GnRH agonist can alter the secretion of gonadotropin and sex hormones. Recently, we found that the long-acting GnRH agonist aggravated hyperthyroidism and induced painless thyroiditis. This is the first report to demonstrate the association of thyroid dysfunction with GnRH agonist injection in Korea. Here, we report three cases and emphasize the clinical importance of this aggravating factor in autoimmune thyroid disease.

Children have become the target of intense and specialized food advertising efforts. This study examines the content of TV food advertising and discussed possible concerns from the perspective of children. A total of 102 ads were collected from two cable networks aimed at children. Most of the food ads used emotional appeals and did not provide information clues such as nutrition values. Ads with high sales pressure and celebrity endorsements appeared frequently and the ads for snack foods and high-carbohydrate bakery products were dominant. Understanding food ads can be a significant indicator to establish the orientation of consumer ad education and build educational programs appropriate for children. The issue that appears conspicuous in child targeted advertising and marketing is the childhood obesity and food advertising relation; subsequently, there is a need to evolve advertising that targets children into a positive educational information source.

SummaryObjective Overt and subclinical hypothyroidism are risk factors for atherosclerosis and cardiovascular diseases. It is unclear whether thyroid hormone levels within the normal range are also associated with atherosclerosis measured by coronary artery calcium (CAC). Context This study aimed to examine the relationship between normal variations in thyroid function and changes in CAC. Measurements We conducted a 4-year retrospective study of 2173 apparently healthy men and women with normal thyroid hormone levels. Their free thyroxin (FT4), free triiodothyronin (FT3) and thyroid-stimulating hormone (TSH) levels were measured by electrochemiluminescent immunoassay. The CAC score (CACS) of each subject was measured by multidetector computed tomography in both 2010 and 2014. Progression of CAC was defined as a CACS change over 4 years > 0. Results The mean CACS changes over 4 years by quartiles of baseline FT4 level (lowest to highest) were 12·9, 8·43, 7·82 and 7·81 (P = 0·028). CAC progression was not significantly associated with either the baseline FT3 or TSH levels. The odds ratios (OR) for CAC progression over 4 years (highest vs lowest quartile for baseline FT4) were 0·647 (95% confidence interval (CI) 0·472–0·886) after adjustment for confounding factor, which were attenuated with further adjustment for lipid profiles, homoeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein and hypertension [0·747 (95% CI 0·537–1·038)]. Quartiles of baseline FT3 or TSH level did not show any increased OR for CAC progression after adjustment for confounding factors. Conclusions In this cohort of euthyroid men and women, a low baseline FT4 level was associated with a high risk of CACS progression over 4 years.

Background: We investigated the association between the severity of non-alcoholic fatty liver disease (NAFLD) and the estimated 10-year risk of cardiovascular disease (CVD) calculated by Pooled Cohort Equation (PCE) and Framingham risk score (FRS). Methods: A total of 15,913 participants (mean age, 46.3 years) in a health screening program were selected for analysis. The presence and severity of fatty liver was assessed by abdominal ultrasonogram. Subjects who drank alcohol more than three times a week were excluded from the study. Results: Among the participants, 57.6% had no NAFLD, 35.4% had grade I, 6.5% had grade II, and 0.5% had grade III NAFLD. Mean estimated 10-year CVD risk was 2.59%, 3.93%, 4.68%, and 5.23% calculated using the PCE (P for trend

갑상선호르몬으로 치료를 받던 갑상선기능저하증 환자에서 임신을 하게 되면 50-85%의 환자에서 임신 중 갑상선호르몬의 요구량이 증가하며, 임신 전 용량의 약 30-50%가 증량된다고 알려져 있다. 그러나 저자들은 임신 전에 갑상선호르몬으로 치료되었던 기능저하 증 환자에서 임신 중에 혈액 내 갑상선호르몬의 농도가 증가되어, 치료를 중지하였음에도 혈액 내 갑상선호르몬 농도가 정상으로 유지되었고, 출산 후에 다시 심한 갑상선기능저하증이 발생되어 치료를 다시 시작하였던 1예를 경험하였기에 문헌고찰과 함께 보고하는 바이다.

Background/Aims Liver biopsy is a standard method for diagnosis of liver cirrhosis in patients with chronic hepatitis. Because liver biopsy is an invasive method, non-invasive methods have been used for diagnosis of compensated liver cirrhosis in patients with chronic hepatitis. The current study was designed to evaluate the usefulness of ultrasonography and routine blood tests for diagnosis of compensated liver cirrhosis in patients with chronic viral hepatitis. Methods Two hundred three patients with chronic viral hepatitis who underwent liver biopsy were included in this study and ultrasonography and routine blood tests were analyzed retrospectively. Ultrasonographic findings, including surface nodularity, parenchyma echogenecity, and spleen size, were evaluated. The diagnostic accuracy of ultrasonography and routine blood tests were examined. Results Discriminant analysis with forward stepwise selection of variables showed that liver surface nodularity, platelet count, and albumin level were independently associated with compensated liver cirrhosis (p95% specificity: platelet count 1.3; and surface nodularity. If at least one of the four variables exists in a patient with chronic viral hepatitis, we can predict liver cirrhosis with 90% specificity and 61% sensitivity. Conclusions These results suggest that four variables (platelet count 1.3, and surface nodularity) can be used for identification of liver cirrhosis in patients with chronic viral hepatitis with high specificity.