Acute Kidney Injury Biomarkers for Patients in a Coronary Care Unit: A Prospective Cohort Study

Background: Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU) patients and evaluated several biomarkers of acute kidney injury (AKI), including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and cystatin C (CysC) on the first day of CCU admission. Methodology/Principal Findings: Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%). According to Acute Kidney Injury Network criteria, 28.7 % (43/150) of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p,0.05) between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC) (0.89560.031, p,0.001). The overall 180-day survival rate was 88.7 % (133/150). Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II) and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction

Alzheimer's patient activity assessment using different sensors

International audiencePurpose: Older people population is expected to grow dramatically over the next 20 years (including Alzheimer's patients), while the number of people able to provide care will decrease. We present the development of medical and information and communication technologies to support the diagnosis and evaluation of dementia progress in early stage Alzheimer disease (AD) patients.Method: We compared video and accelerometers activity assessment for the estimation of older people performance in instrumental activities of daily living (IADL) and physical tests in the clinical protocol developed by the Memory Center of the Nice Hospital and the Department of Neurology at National Cheng Kung University Hospital - Taiwan. This clinical protocol defines a set of IADLs (e.g., preparing coffee, watching TV) that could provide objective information about dementia symptoms and be realistically achieved in the two sites observation room. Previous works studied accelerometers activity assessment for the detection of changes in older people gait patterns caused by dementia progress, or video-based event detection for personal self-care activities (ADLs)[1, 2, 3], but none has used both sensors for IADLs analysis. The proposed system uses a constraint-based ontology to model and detect events based on different sensors readings (e.g., 2D video stream data is converted to 3D geometric information that is combined with a priori semantic information, like defined spatial zones or posture estimations given by accelerometer). The ontology language is declarative and intuitive (as it uses natural terminology), allowing medical experts to define and modify the IADL models. The proposed system was tested with 44 participants (healthy=21, AD=23). A stride detection algorithm was developed by the Taiwanese team for the automatic acquisition of patients gait parameters (e.g., stride length, stride frequency) using a tri-axial accelerometer embedded in a wearable device. It was tested with 33 participants (healthy=17, Alzheimer = 16) during a 40 meters walking test. Results & Discussion: The proposed system detected the full set of activities of the first part of our clinical protocol (e.g., repeated transfer test, walking test) with a true positive rate of 96.9 % to 100%. Extracted gait parameters and automatically detected IADLs will be future analyzed for the evaluation of differences between Alzheimer patients at mild to moderate stages and healthy control participants, and for the monitoring of patients motor and cognitive abilities

Association between genetic variant on chromosome 12p13 and stroke survival and recurrence: a one year prospective study in Taiwan

<p>Abstract</p> <p>Background</p> <p>The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample.</p> <p>Methods</p> <p>We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke.</p> <p>Results</p> <p>There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively.</p> <p>Conclusions</p> <p>This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.</p

Rhamnose Binding Protein as an Anti-Bacterial Agent-Targeting Biofilm of Pseudomonas aeruginosa

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Transcriptome Changes in Relation to Manic Episode

Bipolar disorder (BD) is highly heritable and well known for its recurrent manic and depressive episodes. The present study focused on manic episode in BD patients and aimed to investigate state-specific transcriptome alterations between acute episode and remission, including messenger RNAs (mRNAs), long noncoding RNAs (lncRNAs), and micro-RNAs (miRNAs), using microarray and RNA sequencing (RNA-Seq) platforms. BD patients were enrolled with clinical information, and peripheral blood samples collected at both acute and remission status spanning for at least 2 months were confirmed by follow-ups. Symptom severity was assessed by Young Mania Rating Scale. We enrolled six BD patients as the discovery samples and used the Affymetrix Human Transcriptome Array 2.0 to capture transcriptome data at the two time points. For replication, expression data from Gene Expression Omnibus that consisted of 11 BD patients were downloaded, and we performed a mega-analysis for microarray data of 17 patients. Moreover, we conducted RNA sequencing (RNA-Seq) in additional samples of 7 BD patients. To identify intraindividual differentially expressed genes (DEGs), we analyzed data using a linear model controlling for symptom severity. We found that noncoding genes were of majority among the top DEGs in microarray data. The expression fold change of coding genes among DEGs showed moderate to high correlations (∼0.5) across platforms. A number of lncRNAs and two miRNAs (MIR181B1 and MIR103A1) exhibited high levels of gene expression in the manic state. For coding genes, we reported that the taste function-related genes, including TAS2R5 and TAS2R3, may be mania state-specific markers. Additionally, four genes showed a nominal p-value of less than 0.05 in all our microarray data, mega-analysis, and RNA-Seq analysis. They were upregulated in the manic state and consisted of MS4A14, PYHIN1, UTRN, and DMXL2, and their gene expression patterns were further validated by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR). We also performed weight gene coexpression network analysis to identify gene modules for manic episode. Genes in the mania-related modules were different from the susceptible loci of BD obtained from genome-wide association studies, and biological pathways in relation to these modules were mainly related to immune function, especially cytokine–cytokine receptor interaction. Results of the present study elucidated potential molecular targets and genomic networks that are involved in manic episode. Future studies are needed to further validate these biomarkers for their roles in the etiology of bipolar illness

Purification and Characterization of Enterovirus 71 Viral Particles Produced from Vero Cells Grown in a Serum-Free Microcarrier Bioreactor System

[[abstract]]Background: Enterovirus 71 (EV71) infections manifest most commonly as a childhood exanthema known as hand-foot-and-mouth disease (HFMD) and can cause neurological disease during acute infection. Principal Finding: In this study, we describe the production, purification and characterization of EV71 virus produced from Vero cells grown in a five-liter serum-free bioreactor system containing 5 g/L Cytodex 1 microcarrier. The viral titer was >106 TCID50/mL by 6 days post infection when a MOI of 10?5 was used at the initial infection. Two EV71 virus fractions were separated and detected when the harvested EV71 virus concentrate was purified by sucrose gradient zonal ultracentrifugation. The EV71 viral particles detected in the 24–28% sucrose fractions had an icosahedral structure 30–31 nm in diameter and had low viral infectivity and RNA content. Three major viral proteins (VP0, VP1 and VP3) were observed by SDS-PAGE. The EV71 viral particles detected in the fractions containing 35–38% sucrose were 33–35 nm in size, had high viral infectivity and RNA content, and were composed of four viral proteins (VP1, VP2, VP3 and VP4), as shown by SDS-PAGE analyses. The two virus fractions were formalin-inactivated and induced high virus neutralizing antibody responses in mouse immunogenicity studies. Both mouse antisera recognized the immunodominant linear neutralization epitope of VP1 (residues 211–225). Conclusion:These results provide important information for cell-based EV71 vaccine development, particularly for the preparation of working standards for viral antigen quantification

Orexin-A levels in relation to the risk of metabolic syndrome in patient with schizophrenia taking antipsychotics

Background The role of orexin-A in regulating metabolic homeostasis has been recognized, but its association with antipsychotic-induced metabolic abnormalities remains unclear. We investigated the association between orexin-A levels and metabolic syndrome in patients with schizophrenia treated with clozapine or less obesogenic antipsychotics compared with nonpsychiatric controls. Methods Plasma orexin-A levels and metabolic parameters were determined in 159 patients with schizophrenia: 109 taking clozapine; 50 taking aripiprazole, amisulpride, ziprasidone, or haloperidol; and 60 nonpsychiatric controls. Results Orexin-A levels were significantly higher in the group taking less obesogenic antipsychotics, followed by the clozapine group and the controls (F=104.6, P&lt;.01). Higher orexin-A levels were correlated with better metabolic profiles in the patient groups but not in the controls. Regression analyses revealed that the patients with higher orexin-A levels had significantly lower risk of metabolic syndrome (adjusted odds ratio [OR]=0.04, 95% CI: 0.01–0.38 for the 2nd tertile; OR=0.04, 95% CI: 0.01–0.36 for the 3rd tertile, compared with the first tertile), after adjustment for age, sex, smoking history, types of antipsychotics (clozapine vs less obesogenic antipsychotics), duration of antipsychotic treatment, and disease severity. Conclusions Our results revealed that the orexin-A level was upregulated in patients with schizophrenia treated with antipsychotics, especially for the group taking less obesogenic antipsychotics. Furthermore, higher orexin-A levels were independently associated with better metabolic profiles. These observations suggest that an upregulation of orexin-A has a protective effect against the development of metabolic abnormalities in patients with schizophrenia receiving antipsychotic treatment

C-reactive protein concentration as a significant correlate for metabolic syndrome: a Chinese population-based study. Endocrine 43

Abstract Increasing evidence suggests that chronic, lowgrade inflammation may be a common soil involving the pathogenesis of metabolic syndrome (MetS) and cardiovascular disease. We examined the association between C-reactive protein (CRP) concentration, an extensively studied biomarker of low-grade inflammation, and the MetS in a representative sample of Chinese adults in Taiwan. We performed a cross-sectional analysis of data from 4234 subjects [mean (±SD) age, 47.1 (±18.2) years; 46.4 % males] who participated in a population-based survey on prevalences of hypertension, hyperglycemia, and hyperlipidemia in Taiwan. CRP levels were measured by the immunoturbidimetric CRP-latex high-sensitivity assay. The MetS was defined by an unified criteria set by several major organizations. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated with logistic regression model. Overall, there were 938 subjects with MetS among 4,234 participants, resulting in a prevalence rate of 22.1 %. A significantly progressive increase in the prevalence of MetS across quartiles of CRP was observed (p for trend \0.001). Participants in the second, third, and upper quartiles of CRP had significantly higher risk of having MetS when compared with those in the lowest quartile [adjusted ORs (95 % CIs) were 2.18 (1.62-2.94), 4.39 (3.31-5.81), and 7.11 (5.39-9.38), respectively; p for trend \0.001]. Furthermore, there was a strong stepwise increase in CRP levels as the number of components of the MetS increased. The prevalence of MetS showed a graded increase according to CRP concentrations. The possible utility of CRP concentration as a marker for MetS risk awaits further evaluation in prospective studies