Involvement of IL-17 A/IL-17 Receptor A with Neutrophil Recruitment and the Severity of Coronary Arteritis in Kawasaki Disease.

PURPOSE: To assess the role of the interleukin (IL)-17 A/IL-17 receptor A (IL-17RA) in Kawasaki disease (KD)-related coronary arteritis (CA). METHODS: In human study, the plasma levels of IL-17 A and coronary arteries were concurrently examined in acute KD patients. In vitro responses of human coronary endothelial cells to plasma stimulation were investigated with and without IL-17RA neutralization. A murine model of Lactobacillus casei cell-wall extract (LCWE)-induced CA using wild-type Balb/c and Il17ra-deficient mice were also inspected. RESULTS: The plasma levels of IL-17 A were significantly higher in KD patients before intravenous immunoglobulin therapy, especially in those with coronary artery lesion. The pre-IVIG IL-17 A levels positively correlated with maximal z scores of coronary diameters and plasma-induced endothelial mRNA levels of chemokine (C-X-C motif) ligand-1, IL-8, and IL-17RA. IL-17RA blockade significantly reduced such endothelial upregulations of aforementioned three genes and inducible nitric oxide synthase, and neutrophil transmigration. IL-17RA expression was enhanced on peripheral blood mononuclear cells in pre-IVIG KD patients, and in the aortic rings and spleens of the LCWE-stimulated mice. LCWE-induced CA composed of dual-positive Ly6G- and IL-17 A-stained infiltrates. Il17ra-deficient mice showed reduced CA severity with the fewer number of neutrophils and lower early inducible nitric oxide synthase and chemokine (C-X-C motif) ligand-1 mRNA expressions than Il17ra+/+ littermates, and absent IL-17RA upregulation at aortic roots. CONCLUSION: IL-17 A/IL-17RA axis may play a role in mediating aortic neutrophil chemoattraction, thus contributory to the severity of CA in both humans and mice. These findings may help to develop a new therapeutic strategy toward ameliorating KD-related CA.

Elevated C-Reactive Protein Levels Modify the Effect of Magnesium on Depressive Symptoms: A Population-Based Study.

Depression is a profound public health concern, yet its etiology remains unclear. A body's magnesium status and low-grade systemic inflammation are associated with depression. However, the interaction of magnesium status and inflammation on depression/depressive symptoms is unknown. We assessed the association between serum magnesium levels and depressive symptoms by analyzing data from the Nutrition and Health Survey in Taiwan 2005-2008. In total, 2196 participants aged ≥20 years were included. Depressive symptoms were assessed using the 5-item Brief-Symptom Rating Scale. We performed logistic regression and multiple linear regression analyses to examine the association. A dose-response analysis was performed using restricted cubic spline models, and stratification by chronic inflammation was also performed. We found that higher serum magnesium levels were associated with lower depression scores and a lower risk of depression. In the subgroup analysis, serum magnesium levels were inversely associated with depressive symptoms more prominently among people with higher CRP levels, with a threshold at 5 mg/L (≥5 vs. <5) showing a greater difference than at 3 mg/L (≥3 vs. <3). Conclusions: Serum magnesium levels were inversely associated with depressive symptoms. This inverse association was affected by inflammation level. A dose-response relationship was also observed.

The Association of Serum and Dietary Magnesium with Depressive Symptoms.

Depression is a leading cause of the global burden of disease and has a multifactorial etiology that includes nutrients. Magnesium status has been associated with depression with inconclusive results. The impact of chronic latent magnesium deficiency (CLMD, 0.75 ≤ serum magnesium < 0.85 mmol/L) on depression has not yet been investigated. We assessed the association between serum magnesium levels/dietary magnesium intake and depressive symptoms by analyzing nationally representative data from Taiwan (Nutrition and Health Survey in Taiwan, NAHSIT). We used the 5-item Brief Symptom Rating Scale to measure depressive symptoms. Subgroup analysis by sex was also performed. Serum magnesium levels had a low correlation with dietary magnesium intake. Higher serum magnesium levels were associated with lower depressive scores and a lower risk of depressive symptoms, but dietary magnesium intake showed no association. Sex differences were found. Compared with subjects with serum magnesium <0.75 mmol/L, those with ≥0.85 mmol/L had lower depressive scores. In conclusion, serum magnesium was inversely associated with depressive symptoms, but dietary magnesium intake was not. Subjects with CLMD showed similar depressive scores and were at a similar risk of depressive symptoms to those with serum magnesium < 0.75 mmol/L. CLMD should be considered while assessing the association between magnesium status and depressive symptoms.

Estimate dynamic changes of dysfunction and lifelong spent for psychiatric care needs in patients with schizophrenia.

BACKGROUND: Disturbance of functionality is one of the core features of schizophrenia, and has deleterious effects on a patient's employment, increased healthcare costs, and a large societal burden. Thus, if a patient's disability status could be predicted, and interventions needed identified in advance, poor outcomes could be prevented. To achieve this aim, we developed a method by which to assess dynamic changes of dysfunction and estimate the lifetime duration of disability in patients with schizophrenia, as a proxy for assessing their specialized healthcare needs. METHODS: The proposed method was developed based on a nationwide database and a cross-sectional survey. The primary analysis investigated the dynamic change in the proportion of patients with manifested disability over time, while the secondary analysis estimated the lifetime duration of disability, obtained as the proportion of patients with manifested disability multiplied by the survival probability throughout the life of patients. RESULTS: The average lifetime duration of manifested disability of global functioning was estimated to be 20.9 years, which represents approximately 73% of the whole lifetime of patients. The duration of disability in socially-useful activities was estimated to be 15.6 years, while that in personal and social relationships was 17.5 years. The female patients had a longer duration of manifested disability (22.9 years) than the male patients (19.5 years). CONCLUSIONS: The developed method of analysis indicated that the longest lifetime durations of manifest disability were observed in the areas of socially-useful activities and personal and social relationships, and the proportions of patients with these disabilities rapidly increased at 200 months after diagnosis.

Estimation of life expectancy, loss-of-life expectancy, and lifetime healthcare expenditures for schizophrenia in Taiwan.

By employing a novel semi-parametric extrapolation method, the life expectancies after the first hospitalization for schizophrenia and the associated lifetime healthcare expenditures were both estimated. Based on the linkage between the National Health Insurance Research Database and the National Mortality Registry of Taiwan, we have established a schizophrenic cohort for 2000-2010 and followed up to 2011. Survival function was estimated through Kaplan-Meier's method and extrapolated throughout life. We applied a simple linear regression to the logit-transformed survival ratio between the schizophrenic cohort and the sex-, age-matched referents via Monte Carlo simulation from the national life table. The monthly survival probability was multiplied by the average healthcare expenditures and summed throughout life to estimate the lifelong cost reimbursed by the National Health Insurance. The results showed that patients diagnosed at age 20-29 had the highest expected years of life lost (EYLL), 15 and 9years, in men and women, respectively, with corresponding lifetime healthcare expenditures of USD 48,000 and 53,000. Males generally had higher health cost per life-year than their female counterparts across their lifespan. We applied the same method to the first 6years of the cohort and extrapolated to 12years, which showed that the relative biases for different age strata were less than 5%. We thus concluded that the semi-parametric extrapolation method might provide a timely estimation of lifetime outcomes for health care planning of schizophrenia.

CXC chemokine ligand 12/stromal cell-derived factor-1 regulates cell adhesion in human colon cancer cells by induction of intercellular adhesion molecule-1.

BACKGROUND: The CXC chemokine ligand 12 (CXCL12)/stromal cell-derived factor-1 (SDF-1) and CXC receptor 4 (CXCR4) axis is involved in human colorectal cancer (CRC) carcinogenesis and can promote the progression of CRC. Interaction between CRC cells and endothelium is a key event in tumor progression. The aim of this study was to investigate the effect of SDF-1 on the adhesion of CRC cells. METHODS: Human CRC DLD-1 cells were used to study the effect of SDF-1 on intercellular adhesion molecule-1 (ICAM-1) expression and cell adhesion to endothelium. RESULTS: SDF-1 treatment induced adhesion of DLD-1 cells to the endothelium and increased the expression level of the ICAM-1. Inhibition of ICAM-1 by small interfering RNA (siRNA) and neutralizing antibody inhibited SDF-1-induced cell adhesion. By using specific inhibitors and short hairpin RNA (shRNA), we demonstrated that the activation of ERK, JNK and p38 pathways is critical for SDF-1-induced ICAM-1 expression and cell adhesion. Promoter activity and transcription factor ELISA assays showed that SDF-1 increased Sp1-, C/EBP-ß- and NF-κB-DNA binding activities in DLD-1 cells. Inhibition of Sp1, C/EBP-ß and NF-κB activations by specific siRNA blocked the SDF-1-induced ICAM-1 promoter activity and expression. The effect of SDF-1 on cell adhesion was mediated by the CXCR4. CONCLUSION: Our findings support the hypothesis that ICAM-1 up-regulation stimulated by SDF-1 may play an active role in CRC cell adhesion.

Association between somatization subscale score and serotonin transporter availability in healthy volunteers--a single photon emission computed tomography study with [¹²³I] ADAM.

RATIONALE AND OBJECTIVE: Serotonin is one of the key neuromodulators involved in fundamental cerebral functions and behaviors. Previous study has demonstrated that somatization symptoms are probably associated with central serotonergic circuits, which are implicated in anxiety and nociception regulation. This study aims to examine the correlation between somatization subscale score and serotonin transporter (SERT) availability in healthy volunteers. METHODS: Sixty-four healthy participants, 26 males and 38 females, were enrolled from the community and were administered the single somatization subscale of the Chinese symptom checklist 90 revised (SCL90-R). Single photon emission computed tomography with [(123)I] 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine was also performed to examine SERT availability. RESULTS: The somatization scores were negatively correlated with SERT availability (Spearman's ρ = -0.35, p = 0.005), particularly in males (Spearman's ρ = -0.54, p = 0.004). CONCLUSION: This result reconfirmed the correlation between central serotonergic activity and the intensity of somatization symptoms, even in healthy participants. However, a gender difference exists in this correlation.