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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.

To improve healing of pressure ulcer wounds, it is important to optimize the conditions of the area surrounding the wound. Negative pressure wound therapy (NPWT) promotes wound healing, however, the removal of NPWT can cause pain or focal bleeding, delaying wound healing or causing infection. In this study, we reviewed the efficacy of the lipidocolloid non-adherent dressing (Urgotul&reg, ) as a wound contact layer. A total of 38 patients from the same facility who applied NPWT from April 2016 to October 2019 were included and divided into two groups, NPWT with the lipidocolloid non-adherent dressing (group 1, experimental group, 19 patients) and NPWT only (group 2, control group, 19 patients). The condition of the wound was examined prior to NPWT application, at one week, and again at three weeks after application. No significant differences were found between groups for general characteristics, bacterial culture or photo analysis. However, when comparing groups based on the time of examination, there was a significant reduction of the wound size in group 1 (p = 0.001) but not in group 2 (p = 0.082). Therefore, the current study finds that using the lipidocolloid non-adherent dressing as a wound contact layer in NPWT stimulates healing by shrinking the size of the pressure ulcer wound.

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.

Objective.To investigate the expression of Gremlin 1 (GREM1), an antagonist of bone morphogenetic protein, in rheumatoid arthritis (RA) synovia and its involvement in the hyperplasia and invasiveness of fibroblast-like synoviocytes of RA (RA-FLS).Methods.Computational analysis was introduced to identify FLS-predominant regulators. GREM1 expression was examined by immunohistochemistry, real-time PCR, and ELISA. FLS proliferation and apoptosis were determined using tetrazolium-based colorimetric assay and APOPercentage assay, respectively. FLS migration and invasion were evaluated by wound migration and Matrigel invasion assay, respectively. Expressions of Bax, Bcl2, pErk1/2, and pAkt were detected by Western blot analysis.Results.Through global transcriptome profiling, we identified aGREM1gene predominantly expressed in RA-FLS. Indeed, the GREM1 expression was higher in synovia, synovial fluids, and FLS of patients with RA than in those of patients with osteoarthritis, and its levels correlated well with proinflammatory cytokine concentrations. Knockdown of GREM1 transcripts using short interfering RNA (siRNA) reduced the proliferation and survival of RA-FLS along with downregulation of pErk1/2, pAkt, and Bcl2 expressions, whereas it induced Bax expression. Conversely, the addition of recombinant GREM1 to RA-FLS showed the opposite results. Moreover, GREM1 siRNA decreased the migratory and invasive capacity of RA-FLS, whereas exogenous GREM1 increased it. The GREM1-induced FLS survival, migration, and invasion were completely blocked by neutralizing antibodies to ανβ3integrin on RA-FLS, suggesting that ανβ3integrin mediates the antiapoptotic and promigratory effects of GREM1.Conclusion.GREM1 is highly expressed in RA joints, and functions as a regulator of survival, proliferation, migration, and invasion of RA-FLS.

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