The impact of baseline estimated glomerular filtration rate (eGFR) on the risk of adverse outcomes according to metabolic parameter variabilities in chronic kidney disease has rarely been investigated. Methods: We conducted a retrospective nationwide cohort study using the National Health Insurance System data in Korea from 2007 to 2013 to identify individuals with three or more health screenings. The metabolic components variability was defined as intraindividual variability between measurements using the variability independent of the mean. The metabolic variability score was defined as the total number of high-variability metabolic components. Multivariable-adjusted Cox regression analysis was conducted to evaluate the risks of all-cause mortality, myocardial infarction, and ischemic stroke. Results: During a mean follow-up of 6.0 ± 0.7 years, 223,531 deaths, 107,140 myocardial infarctions, and 116,182 ischemic strokes were identified in 9,971,562 patients. Low eGFR categories and higher metabolic variability scores were associated with a higher risk of adverse outcomes. The degree of association between metabolic variability and adverse outcomes was significantly larger in those with low eGFR categories than in those with preserved eGFR (p for interaction < 0.001). Representatively, those with high metabolic variability in the eGFR of <15 mL/min/1.73 m2 group showed a prominently higher risk for all-cause mortality (adjusted hazard ratio [aHR], 5.28; 95% confidence interval [CI], 4.02–6.94) when the degree was compared to the findings in those with preserved (eGFR of ≥60 mL/min/1.73 m2) kidney function (aHR, 2.55; 95% CI, 2.41–2.69). Conclusion: The degree of adverse association between metabolic variability and poor prognosis is accentuated in patients with impaired kidney function.

Chronic kidney disease (CKD) patients are hospitalized for various conditions. Hospitalization increases the readmission rate and mortality rate, seriously deteriorating patients’ quality of life. Consequently, it is crucial to analyze the reasons for hospitalization in CKD patients from a broader perspective according to CKD grade. Methods: This is a prospective cohort study of CKD patients entitled the KoreaN cohort study for Outcomes in patients With Chronic Kidney Disease (KNOW-CKD). A total of 2,238 patients were examined, and the reasons for hospitalization were classified into 16 disease categories. The incidence rate ratio (IRR) according to CKD stage was compared using negative bimodal regression analysis. Results: The all-cause hospitalization incidence was 184.96 per 1,000 person-years. The most common reason for hospitalization was circulatory system disease, followed by infection and digestive system disease. Among hospitalizations for acute kidney injury, endocrine-nutrition-metabolic–related illness, blood-related disease, and diseases of the nervous system and sensory organs, IRR increased as CKD grade advanced. The incidence of ophthalmologic surgery during hospitalization increased according to the CKD stage. The IRR of KNOW-CKD patients was 6.19 (95% confidence interval, 5.92–6.48; p < 0.001) compared with the general population. Conclusion: This in-depth analysis of hospitalizations among CKD patients confirmed that CKD patients were hospitalized for various reasons, such as metabolic, ophthalmic, and hematologic diseases. Early detection and intervention regarding causative diseases of CKD are important to reduce the hospitalization burden and improve patients’ quality of life.

Early-onset diabetes mellitus has a significant lifetime burden and is associated with higher morbidity and mortality. Since insulin resistance is one of the mechanisms of podocyte injury, we aimed to evaluate the effect of albuminuria on newly developed early-onset type 2 diabetes mellitus (T2DM). Methods: We screened 6,891,399 subjects aged ≥20 and <40 years without a history of prediabetes or diabetes from the Korean National Health Insurance Service database between 2009 and 2012. A multivariate Cox proportional hazard model was used to identify the impact of albuminuria on early-onset T2DM. Results: Among a total of 5,383,779 subjects, 62,148 subjects (1.2%) developed early-onset diabetes over 7.3 ± 1.2 years. Albuminuria was significantly associated with early-onset T2DM (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.55–1.70) after adjustment for age, sex, anthropometric data, physical exercise status, serum glucose, and total cholesterol. The risk of early-onset T2DM increased more in subjects with more components of metabolic syndrome (MetS). Among each component of MetS, hypertriglyceridemia was prominently associated with early-onset T2DM (aHR, 2.02; 95% CI, 1.81–2.25) in subjects with albuminuria. Conclusion: Dipstick albuminuria was significantly associated with early-onset T2DM in young adult populations. Close monitoring of albuminuria is warranted for disease risk modification, especially in subjects with MetS.

The activation of neurotrophic signaling pathways following the upregulation of glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor-β family, has a potential neuroprotective effect in the adult brain. Herein, we report that hippocampal transduction of adeno-associated virus serotype 1 (AAV1) with a constitutively active form of ras homolog enriched in brain [Rheb(S16H)], which can stimulate the production of brain-derived neurotrophic factor (BDNF) in hippocampal neurons, induces the increases in expression of GDNF and GDNF family receptor α-1 (GFRα-1), in neurons and astrocytes in the hippocampus of rat brain in vivo . Moreover, upregulation of GDNF and GFRα-1 contributes to neuroprotection against thrombin-induced neurotoxicity in the hippocampus. These results suggest that AAV1-Rheb(S16H) transduction of hippocampal neurons, resulting in neurotrophic interactions between neurons and astrocytes, may be useful for neuroprotection in the adult hippocampus.

We tested how adjuvants effect in a cancer vaccine model using an epitope derived from an autoactivation loop of membrane-type protease serine protease 14 (PRSS14; loop metavaccine) in mouse mammary tumor virus (MMTV)-polyoma middle tumor-antigen (PyMT) system and in 2 other orthotopic mouse systems. Earlier, we reported that loop metavaccine effectively prevented progression and metastasis regardless of adjuvant types and TH types of hosts in tail-vein injection systems. However, the loop metavaccine with Freund's complete adjuvant (CFA) reduced cancer progression and metastasis while that with alum, to our surprise, were adversely affected in 3 tumor bearing mouse models. The amounts of loop peptide specific antibodies inversely correlated with tumor burden and metastasis, meanwhile both TH1 and TH 2 isotypes were present regardless of host type and adjuvant. Tumor infiltrating myeloid cells such as eosinophil, monocyte, and neutrophil were asymmetrically distributed among 2 adjuvant groups with loop metavaccine. Systemic expression profiling using the lymph nodes of the differentially immunized MMTV-PyMT mouse revealed that adjuvant types, as well as loop metavaccine can change the immune signatures. Specifically, loop metavaccine itself induces TH2 and TH17 responses but reduces TH1 and Treg responses regardless of adjuvant type, whereas CFA but not alum increased follicular THresponse. Among the myeloid signatures, eosinophil was most distinct between CFA and alum. Survival analysis of breast cancer patients showed that eosinophil chemokines can be useful prognostic factors in PRSS14 positive patients. Based on these observations, we concluded that multiple immune parameters are to be considered when applying a vaccine strategy to cancer patients.

Gram-negative bacterial pathogens produce outer membrane vesicles (OMVs) and this secreted cargo plays a role in host-pathogen interactions. OMVs isolated from Burkholderia cepacia induce the cytotoxicity and pro-inflammatory responses both in vitro and in vivo, but OMV components associated with host pathology have not been characterized. This study analyzed the proteomes of OMVs produced by B. cepacia ATCC 25416 and investigated whether proteins in B. cepacia OMVs were responsible for host pathology in vitro. Proteomic analysis revealed that a total of 265 proteins were identified in B. cepacia OMVs. Of the 265 OMV proteins, 179 (67.5%), 32 (12.1%), 27 (10.2%), 17 (6.4%), and 10 (3.8%) were predicted to be located in the cytoplasm, inner membrane, periplasmic space, outer membrane, and extracellular compartment, respectively. Several putative virulence factors were also identified in B. cepacia OMVs. B. cepacia OMVs slightly induced the cytotoxicity in lung epithelial A549 cells, but there was no difference in cytotoxic activity between intact OMVs and proteinase K-treated OMVs. B. cepacia OMVs stimulated the expression of pro-inflammatory cytokine and chemokine genes in A549 cells, but the expression of these cytokine genes was significantly inhibited in A549 cells incubated with proteinase K-treated OMVs. In conclusion, our results suggest that proteins in B. cepaciaOMVs are directly responsible for pro-inflammatory responses in lung epithelial cells.

BACKGROUND: According to US-EPA report, the use of pyrethrins and pyrethroids has increased during the past decade, and their area of use included not only in agricultural settings, but in commerce, and individual household. It is known that urinary 3-PBA, major metabolite of pyrethroid, have some associations with health effect in nervous and endocrine system, however, there’s no known evidence that urinary 3-PBA have associations with obesity. METHOD: We used data of 3671 participants aged above 19 from the Korean National Environmental Health Survey in 2009–2011. In our analysis, multivariate piece-wise regression and logistic regression analysis were used to investigate the association between urinary 3-PBA (3-Phenoxybenzoic Acid) and BMI. RESULT: Log-transformed level of urinary 3-PBA had significantly positive association with BMI at the low-level range of exposure (p < 0.0001), and opposite associations were observed at the high level exposure (p = 0.04) after adjusting covariates. In piece-wise regression analysis, the flexion point that changes direction of the associations was at around 4 ug/g creatinine of urinary 3-PBA. As quintiles based on concentration of urinary 3-PBA increased to Q4, the ORs for prevalence of overweight (BMI ≥ 23 kg/m2) were increased, and the OR of Q5 was lower than that of Q4 (OR = 1.810 for Q4; OR = 1.483 for Q5). In the analysis using obesity (BMI ≥ 25 kg/m2) as outcome variable, significant associations were observed between obesity and quintiles of 3-PBA, however, there were no differences between the OR of Q5 and that of Q4 (OR = 1.659 for Q4; OR = 1.666 for Q5). CONCLUSION: Our analysis suggested that low-level of pyrethroid exposure has positive association with BMI, however, there is an inverse relationship above the urinary 3-PBA level at 4 ug/g creatinine. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40557-015-0079-7) contains supplementary material, which is available to authorized users.
Adult* ; Body Mass Index* ; Commerce ; Creatinine ; Endocrine System ; Environmental Health* ; Family Characteristics ; Humans ; Logistic Models ; Methods ; Multivariate Analysis ; Obesity ; Overweight ; Prevalence ; Pyrethrins

A method of detecting lead was developed using square wave anodic stripping voltammetry (SWASV) with DNA-carbon nanotube paste electrode (CNTPE). The results indicated a sensitive oxidation peak current of lead on the DNA-CNTPE. The curves were obtained within a concentration range of 50 ngL-1-20 mgL-1 with preconcentration time of 100, 200, and 400 sec at the concentration of mgL-1, microgL-1, and ngL-1, respectively. The observed relative standard deviation was 0.101% (n = 12) in the lead concentration of 30.0 microgL-1 under optimum conditions. The low detection limit (S/N) was pegged at 8 ngL-1 (2.6 x10-8 M). Results showed that the developed method can be used in real-time assay in vivo without requiring any pretreatment and pharmaceutical samples, and food samples, as well as other materials requiring water source contamination analyses.
Electrodes ; Limit of Detection ; Nanotubes ; Plants* ; Water