Plasma Biomarkers for Hypertension-Mediated Organ Damage Detection: A Narrative Review.

Hypertension (HT) is a disease that poses a serious threat to human health, mediating organ damage such as the cardiovascular (CV) system, kidneys, central nervous system (CNS), and retinae, ultimately increasing the risk of death due to damage to the entire vascular system. Thus, the widespread prevalence of hypertension brings enormous health problems and socioeconomic burdens worldwide. The goal of hypertension management is to prevent the risk of hypertension-mediated organ damage and excess mortality of cardiovascular diseases. To achieve this goal, hypertension guidelines recommend accurate monitoring of blood pressure and assessment of associated target organ damage. Early identification of organ damage mediated by hypertension is therefore crucial. Plasma biomarkers as a non-invasive test can help identify patients with organ damage mediated by hypertension who will benefit from antihypertensive treatment optimization and improved prognosis. In this review, we provide an overview of some currently available, under-researched, potential plasma biomarkers of organ damage mediated by hypertension, looking for biomarkers that can be detected by simple testing to identify hypertensive patients with organ damage, which is of great significance in clinical work. Natriuretic peptides (NPs) can be utilized as a traditional biomarker to detect hypertension-mediated organ damage, especially for heart failure. Nevertheless, we additionally may need to combine two or more plasma biomarkers to monitor organ damage in the early stages of hypertension.

Plasma biomarkers of Alzheimer's disease and related dementias in American Indians: The Strong Heart Study.

INTRODUCTION: Identification of Alzheimer's disease (AD) needs inexpensive, noninvasive biomarkers, with validation in all populations. METHODS: We collected plasma markers in older American Indian individuals: phosphorylated-tau181 (pTau181); amyloid-beta (Aß) 40,42; glial fibrillary acidic protein (GFAP); and neurofilament light chain (NfL). Plasma markers were analyzed for discriminant properties with cognitive status and etiology using receiver operating characteristic (ROC) analysis. RESULTS: PTau181, GFAP, NfL plasma values were significantly associated with cognition, but Aß were not. Discriminant performance was moderate for individual markers, with pTau181, GFAP, NfL performing best, but an empirically selected panel of markers (age, sex, education, pTau181, GFAP, NfL, Aß4240 ratio) had excellent discriminant performance (AUC > 0.8). DISCUSSION: In American Indian individuals, pTau181 and Aß values suggested more common pathology than in majority populations. Aß was less informative than in other populations; however, all four markers were needed for a best-performing dementia diagnostic model. These data validate utility of AD plasma markers, while suggesting population-specific diagnostic characteristics.

Alterations in circulating markers in HIV/AIDS patients with poor immune reconstitution: Novel insights from microbial translocation and innate immunity.

After long-term anti-retroviral therapy (ART) treatment, most human immunodeficiency virus (HIV)/Acquired Immure Deficiency Syndrome (AIDS) patients can achieve virological suppression and gradual recovery of CD4+ T-lymphocyte (CD4+ T cell) counts. However, some patients still fail to attain normal CD4+ T cell counts; this group of patients are called immune non-responders (INRs), and these patients show severe immune dysfunction. The potential mechanism of poor immune reconstitution (PIR) remains unclear and the identification of uniform biomarkers to predict the occurrence of PIR is particularly vital. But limited information is available on the relationship between circulating markers of INRs and immune recovery. Hence, this review summarises alterations in the intestine microbiota and associated markers in the setting of PIR to better understand host-microbiota-metabolite interactions in HIV immune reconstitution and to identify biomarkers that can predict recovery of CD4+ T cell counts in INRs.

Investigation of Long Non-coding RNAs H19 and LINC00675 in Colorectal Cancers in Terms of Histopathological Features and Correlations With Plasma Markers.

BACKGROUND/AIM: Functional and bioinformatic studies provide strong evidence that long non-coding RNAs (lncRNAs) can alter the molecular mechanisms of cancer through their interactions with DNA, RNAs, and proteins. This study aimed to evaluate the role of H19 and LINC00675 lncRNAs in colorectal cancers (CRCs) in terms of clinicopathological features. MATERIALS AND METHODS: Tumor and tumor-free surrounding tissue samples were obtained from 51 CRC cases. Total RNA isolation and cDNA synthesis were performed. qPCR was performed using the TaqMan non-coding lncRNA assay specific for H19 and LINC00675. Preoperative levels of plasma markers, lncRNA expression, and clinicopathological characteristics of the cases were evaluated statistically. RESULTS: Expression of H19 in tumor tissue was found to be 2.11 times higher than that of tumor-free surrounding tissue (p<0.001). LINC00675 levels were found to be approximately three times higher in colon tumors than tumors with rectal involvement (p=0.019). There was a correlation between H19 expression and creatinine (r=0.408; p=0.003). In addition, correlations were detected between LINC00675 with albumin (r=0.303; p=0.03), and between LINC00675 with globulin (r=0.332; p=0.02). CONCLUSION: H19 is a candidate biomarker that can be evaluated in terms of prognosis and antineoplastic treatment response, while LINC00675 may be an important marker of the microenvironment of advanced stage tumors, especially in tumors with rectal involvement.

Subacute cytokine changes after a traumatic brain injury predict chronic brain microstructural alterations on advanced diffusion imaging in the male rat.

INTRODUCTION: The process of neuroinflammation occurring after traumatic brain injury (TBI) has received significant attention as a potential prognostic indicator and interventional target to improve patients' outcomes. Indeed, many of the secondary consequences of TBI have been attributed to neuroinflammation and peripheral inflammatory changes. However, inflammatory biomarkers in blood have not yet emerged as a clinical tool for diagnosis of TBI and predicting outcome. The controlled cortical impact model of TBI in the rodent gives reliable readouts of the dynamics of post-TBI neuroinflammation. We now extend this model to include a panel of plasma cytokine biomarkers measured at different time points post-injury, to test the hypothesis that these markers can predict brain microstructural outcome as quantified by advanced diffusion-weighted magnetic resonance imaging (MRI). METHODS: Fourteen 8-10-week-old male rats were randomly assigned to sham surgery (n = 6) and TBI (n = 8) treatment with a single moderate-severe controlled cortical impact. We collected blood samples for cytokine analysis at days 1, 3, 7, and 60 post-surgery, and carried out standard structural and advanced diffusion-weighted MRI at day 60. We then utilized principal component regression to build an equation predicting different aspects of microstructural changes from the plasma inflammatory marker concentrations measured at different time points. RESULTS: The TBI group had elevated plasma levels of IL-1ß and several neuroprotective cytokines and chemokines (IL-7, CCL3, and GM-CSF) compared to the sham group from days 3 to 60 post-injury. The plasma marker panels obtained at day 7 were significantly associated with the outcome at day 60 of the trans-hemispheric cortical map transfer process that is a frequent finding in unilateral TBI models. DISCUSSION: These results confirm and extend prior studies showing that day 7 post-injury is a critical temporal window for the reorganisation process following TBI. High plasma level of IL-1ß and low plasma levels of the neuroprotective IL-7, CCL3, and GM-CSF of TBI animals at day 60 were associated with greater TBI pathology.

Cyclic GMP in Liver Cirrhosis-Role in Pathophysiology of Portal Hypertension and Therapeutic Implications.

The NO-cGMP signal transduction pathway plays a crucial role in tone regulation in hepatic sinusoids and peripheral blood vessels. In a cirrhotic liver, the key enzymes endothelial NO synthase (eNOS), soluble guanylate cyclase (sGC), and phosphodiesterase-5 (PDE-5) are overexpressed, leading to decreased cyclic guanosine-monophosphate (cGMP). This results in constriction of hepatic sinusoids, contributing about 30% of portal pressure. In contrast, in peripheral arteries, dilation prevails with excess cGMP due to low PDE-5. Both effects eventually lead to circulatory dysfunction in progressed liver cirrhosis. The conventional view of portal hypertension (PH) pathophysiology has been described using the "NO-paradox", referring to reduced NO availability inside the liver and elevated NO production in the peripheral systemic circulation. However, recent data suggest that an altered availability of cGMP could better elucidate the contrasting findings of intrahepatic vasoconstriction and peripheral systemic vasodilation than mere focus on NO availability. Preclinical and clinical data have demonstrated that targeting the NO-cGMP pathway in liver cirrhosis using PDE-5 inhibitors or sGC stimulators/activators decreases intrahepatic resistance through dilation of sinusoids, lowering portal pressure, and increasing portal venous blood flow. These results suggest further clinical applications in liver cirrhosis. Targeting the NO-cGMP system plays a role in possible reversal of liver fibrosis or cirrhosis. PDE-5 inhibitors may have therapeutic potential for hepatic encephalopathy. Serum/plasma levels of cGMP can be used as a non-invasive marker of clinically significant portal hypertension. This manuscript reviews new data about the role of the NO-cGMP signal transduction system in pathophysiology of cirrhotic portal hypertension and provides perspective for further studies.

A Community-Based Study Identifying Metabolic Biomarkers of Mild Cognitive Impairment and Alzheimer's Disease Using Artificial Intelligence and Machine Learning.

BACKGROUND: Currently, there is no objective, clinically available tool for the accurate diagnosis of Alzheimer's disease (AD). There is a pressing need for a novel, minimally invasive, cost friendly, and easily accessible tool to diagnose AD, assess disease severity, and prognosticate course. Metabolomics is a promising tool for discovery of new, biologically, and clinically relevant biomarkers for AD detection and classification. OBJECTIVE: Utilizing artificial intelligence and machine learning, we aim to assess whether a panel of metabolites as detected in plasma can be used as an objective and clinically feasible tool for the diagnosis of mild cognitive impairment (MCI) and AD. METHODS: Using a community-based sample cohort acquired from different sites across the US, we adopted an approach combining Proton Nuclear Magnetic Resonance Spectroscopy (1H NMR), Liquid Chromatography coupled with Mass Spectrometry (LC-MS) and various machine learning statistical approaches to identify a biomarker panel capable of identifying those patients with AD and MCI from healthy controls. RESULTS: Of the 212 measured metabolites, 5 were identified as optimal to discriminate between controls, and individuals with MCI or AD. Our models performed with AUC values in the range of 0.72-0.76, with the sensitivity and specificity values ranging from 0.75-0.85 and 0.69-0.81, respectively. Univariate and pathway analysis identified lipid metabolism as the most perturbed biochemical pathway in MCI and AD. CONCLUSION: A comprehensive method of acquiring metabolomics data, coupled with machine learning techniques, has identified a strong panel of diagnostic biomarkers capable of identifying individuals with MCI and AD. Further, our data confirm what other groups have reported, that lipid metabolism is significantly perturbed in those individuals suffering with dementia. This work may provide additional insight into AD pathogenesis and encourage more in-depth analysis of the AD lipidome.

Screening of long non-coding RNAs markers in plasma of children with chronic gastritis.

OBJECTIVE: The study aimed to detect and analyze long non-coding RNAs (lncRNAs) in plasma of children diagnosed with chronic gastritis, and to explore its biological functions and involved signaling pathways. METHODS: The plasma samples were collected from six children that were diagnosed with chronic gastritis by physical examination, gastroscopy, and pathological examination and six healthy children. The plasma samples were assayed for determining the expression profiles of lncRNA based upon the gen chip detection. The specific expression of lcnRNA in plasma of children with chronic gastritis was analyzed and its biological functions were speculated. RESULTS: Five lncRNAs (RP11-697M17.1, RP11-388M20.9, AFAP1-AS1, BC062758, and XLOC001406) were significantly up-regulated, and five lncRNAs (UNQ697, BX571672.5, CYP4F35P, ANKRD20A5P, and AL832737) were observed to be significantly down-regulated. The lncRNAs RP11-697M17.1, and UNQ697 were detected with the highest up-regulation and down-regulation, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that the up-regulated lncRNAs were significantly enriched in 20 signaling pathways such as phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) pathway, and the down-regulated lncRNAs target genes were significantly enriched in 20 signaling pathways such as the metabolic pathway. CONCLUSION: The analysis of the lncRNA expression profiles in plasma of children with chronic gastritis revealed that the lncRNA RP11-697M17.1, and lncRNA UNQ697 may act as plasma markers for predicting chronic gastritis in children.

Plasma IL-5 but Not CXCL13 Correlates With Neutralization Breadth in HIV-Infected Children.

Children may be the optimal target for HIV vaccine development as they generate substantially more frequent and more potent broadly HIV neutralizing antibodies (bnAbs) than adults. Development of a biomarker that correlates with neutralization breadth in this group could function as a powerful tool to facilitate the development of an HIV vaccine. Previously, we observed that this preferential ability in HIV-infected children over adults to generate bnAbs is associated with an enrichment of circulating follicular helper T-cells (TFH) with an effector phenotype, and the presence of IL-21 secreting HIV-specific TFH within lymphoid tissue germinal centers (GC). In adults, bnAbs development has been linked with high plasma levels of CXCL13, a chemoattractant for CXCR5-expressing TFH cells to the lymph node GC. We sought to test this relationship in HIV-infected children, but found no association between neutralization breadth and plasma levels of CXCL13, or with the Th2 cytokines IL-4 and IL-13, or the TFH associated factor Activin A. However, we did find an unexpected association between plasma IL-5 levels and bnAb development in these children. Importantly, although CXCL13 correlated with total circulating TFH cells, it was not associated with effector TFH. Additionally, raised CXCL13 expression was associated with a lower CD4 percentage, higher viral load and a loss of immune function, implying it is associated with progressive disease rather than HIV-specific GC activity in these subjects. Taken together, our data suggests that IL-5 should be evaluated further as a candidate plasma biomarker for HIV neutralization breadth and for monitoring vaccine responses in the pediatric age group.

CD44, TGM2 and EpCAM as novel plasma markers in endometrial cancer diagnosis.

BACKGROUND: Endometrial cancer (EC) is the most common malignancy of the female reproductive tract. Despite years of research, the accurate screening strategy is still not available in this disease and it is usually diagnosed only after the clinical signs are present. The recent technological advances in analytical methodologies enabled detection of multiple molecules in one, small sample of biological materials. Such approach was undertaken in the presented study. METHODS: Concentrations of aldehyde dehydrogenase 1 family, member A1 (ALDH1A1), carbonic anhydrase IX (CA9), CD44, epithelial cell adhesion molecule (EpCAM), hepsin, kallikrein-6, mesothelin, midkine, neural cell adhesion molecule L1 (L1CAM), and transglutaminase 2 (TGM2) were measured using MAGPIX®System in plasma samples of 45 EC, 20 healthy controls and 11 patients with endometriosis. RESULTS: Significantly increased concentration in EC as compared to healthy controls were found in case of CD44 (p <  0.001), EpCAM (p = 0.033) and TGM2 (p <  0.001). EpCAM and mesothelin concentrations differed based on FIGO stages. Regression analysis revealed marker panels with high accuracy in detection of EC. The highest AUC 0.937 was attributed to the 3-marker panel of CD44/TGM2/EpCAM (84% sensitivity, 100% specificity), FIGO IA samples were discriminated from more advanced stages of EC with the mesothelin/grade 1 model featuring AUC of 0.911 (95.24% sensitivity, 78.26% specificity). CONCLUSIONS: Novel plasma biomarkers presenting good accuracy in diagnosing EC were found with TGM2 reported for the first time as plasma marker. It was also revealed that endometriosis may share similarities in the pattern of markers alterations characteristic for EC.

Posttraumatic stress disorder and total amyloid burden and amyloid-ß 42/40 ratios in plasma: Results from a pilot study of World Trade Center responders.

INTRODUCTION: Chronic posttraumatic stress disorder (PTSD) is associated with poor memory and increased burden of various degenerative cerebral neuropathologies. The goal of this pilot study was to determine whether PTSD was associated with changes in plasma-based neuropathological biomarkers of neurodegeneration among World Trade Center (WTC) responders. METHODS: Thirty-four WTC responders had blood drawn and flash-frozen within 15 minutes of retrieval. PTSD symptoms were assessed at that time. Age, sex, and WTC exposure duration were obtained from medical records. Plasma was assayed in duplicate using an ultra-sensitive single-molecule enzyme-linked immunosorbent assay to examine the distribution of amyloid-ß (Aß) 42/40 ratios, total Aß, total tau, and neurofilament light (NfL). The comparison group was drawn from a bank of healthy controls collected and assayed at the same facility. RESULTS: The average age of WTC responders at blood draw was 53 years. Half were PTSD positive (PTSD+) as indicated by symptom severity. WTC responders had lower Aß42/Aß40 ratios but higher total tau and NfL levels in the plasma than healthy controls. PTSD+ status was associated with lower plasma Aß load and higher Aß42/Aß40 ratios. DISCUSSION: Findings suggest that PTSD may be associated with alterations in plasma markers related to Aß, tau, and NfL, highlighting the potential association between PTSD status and neurodegenerative neuropathology in WTC responders.

Identification of serological markers for pre- and postoperative fasting periods.

BACKGROUND & AIMS: Prolonged preoperative fasting periods lead to catabolic states and decelerate recovery after surgery. Valid plasma markers reflecting the patients' metabolic state may improve tailored nutrition support before surgery. Within this study, we sought to advance the knowledge on fasting time-sensitive plasma markers that allow the metabolic characterisation of surgical patients for an optimised preoperative metabolic preparation. METHODS: Patients scheduled for elective surgery of the upper (n = 23) or lower (n = 27) gastrointestinal tract participated in a prospective observational study. Patients' charateristics and nutritional status were recorded and blood samples were drawn on the day of admission. Further blood samples were collected before skin incision of the surgical procedure, on postoperative day 3 and on the day of discharge. Values of clinical chemistry, electrolytes, hemograms and plasma amino acids were determined and correlated with fasting times. RESULTS: Preoperative fasting times were positively correlated with plasma levels of valine, leucine, serine, α-amino butyric acid, free fatty acids, 3-hydroxy butyric acid and significantly negative correlated with chloride and glutamic acid. Postoperative fasting times were correlated with erythrocytes, leukocytes and plasma levels of albumin, CRP, HDL, asparagine and 3-methylhistidine. The multivariate regression analysis revealed glutamic acid and valine as significant independent predictors of preoperative fasting periods. The regression model showed best performance (sensitivity of 90.91% and specificity of 92.31%) to detect patients fasted for ≥20 h. CONCLUSION: Valine and glutamic acid appear as independent metabolic markers for accurate prediction of prolonged fasting periods, independent of the overall nutritional status, age or BMI of patients.

A comparison of biofluid cytokine markers across platform technologies: Correspondence or divergence?

BACKGROUND: Quantification of biofluid cytokines is a rapidly growing area of translational research. However, comparability across the expanding number of available assay platforms for detection of the same proteins remains to be determined. We aimed to directly compare a panel of commonly measured cytokines in plasma of typically aging adults across two high sensitivity quantification platforms, Meso Scale Discovery high performance electrochemiluminiscence (HPE) and single-molecule immunosorbent assays (Simoa) by Quanterix. METHODS: 57 community-dwelling older adults completed a blood draw, neuropsychological assessment, and brain MRI as part of a healthy brain aging study. Plasma samples from the same draw dates were analyzed for IL-10, IP-10, IL-6, TNFα, and IL-1ß on HPE and Simoa, separately. Reliable detectability (coefficient of variance (CV) < 20% and outliers 3 interquartiles above the median removed), intra-assay precision, absolute concentrations, reproducibility across platforms, and concurrent associations with external variables of interest (e.g., demographics, peripheral markers of vascular health, and brain health) were examined. RESULTS: The proportion of cytokines reliably measured on HPE (87.7-93.0%) and Simoa (75.4-93.0%) did not differ (ps > 0.32), with the exception of IL-1ß which was only reliably measured using Simoa (68.4%). On average, CVs were acceptable at <8% across both platforms. Absolute measured concentrations were higher using Simoa for IL-10, IL-6, and TNFα (ps < 0.05). HPE and Simoa shared only small-to-moderate proportions of variance with one another on the same cytokine proteins (range: r = 0.26 for IL-10 to r = 0.64 for IL-6), though platform agreement did not dependent on cytokine concentrations. Cytokine ratios within each platform demonstrated similar relative patterns of up- and down-regulation across HPE and Simoa, though still significantly differed (ps < 0.001). Supporting concurrent validity, all 95% confidence intervals of the correlations between cytokines and external variables overlapped between the two platforms. Moreover, most associations were in expected directions and consistently so across platforms (e.g., IL-6 and TNFα), though with several notable exceptions for IP-10 and IL-10. CONCLUSIONS: HPE and Simoa showed comparable detectability and intra-assay precision measuring a panel of commonly examined cytokine proteins, with the exception of IL-1ß which was not reliably detected on HPE. However, Simoa demonstrated overall higher concentrations and the two platforms did not show agreement when directly compared against one another. Relative cytokine ratios and associations demonstrated similar patterns across platforms. Absolute cytokine concentrations may not be directly comparable across platforms, may be analyte dependent, and interpretation may be best limited to discussion of relative associations.

A pilot study with flow mediated skin fluorescence: A novel device to assess microvascular endothelial function in coronary artery disease.

BACKGROUND: Endothelial dysfunction is one of the earliest vascular manifestations in the pathogen-esis of cardiovascular disease. Noninvasive, simple, and inexpensive methods of endothelial function assessment are therefore needed. METHODS: Microvascular endothelial function was assessed in coronary artery disease (CAD) patients by flow mediated skin fluorescence (FMSF), based on measurements of reduced form of nicotinamide adenine dinucleotide (NADH) fluorescence intensity during brachial artery occlusion (ischemic re-sponse [IRmax]) and immediately after occlusion (hyperemic response [HRmax]). Additionally, plasma levels of asymmetric dimethylarginine (ADMA) and endothelin-1 (ET-1) were measured to assess the association between biochemical markers and microvascular function evaluated in vivo by FMSF. RESULTS: A significant inverse correlation was found between ADMA levels and hyperemic response (r = -0.534, p = 0.003), while ET-1 levels were inversely related to the ischemic response (r= -0.575, p = 0.001). Both IR and HR were found lowest in patients with advanced CAD and diabetes. When the repeatability of the method was tested, the intraclass correlation coefficient for IRmax and HRmax were 0.985 (p < 0.001) and 0.914 (p < 0.001), respectively. Moreover, in Bland and Altman analysis, both variables IRmax and HRmax showed good agreement in repeated measurements. CONCLUSIONS: In this pilot study, it was demonstrated that NADH fluorescence measured by FMSF device in CAD patients was associated with established plasma endothelial markers, and that both ischemic and hyperemic response were blunted in patients with advanced disease and diabetes. Fur-thermore, FMSF device showed excellent repeatability and good agreement for repeated measurements. However, further study is warranted to confirm these results in a larger patient cohort. (Cardiol J 2018; 25, 1: 120-127).

Effect of protective mechanical ventilation on plasma markers of lung injury and inflammatory mediators during general anesthesia for liver transplantation surgery / 临床麻醉学杂志

Objective To approach the effect of protective mechanical ventilation on acute lung injury after orthotopic liver transplantation, by observing changes of plasma markers of lung injury and inflammatory mediators.Methods Sixty patients scheduled for liver transplantation under general anesthesia, 42 males and 18 females, aged 21-62 years, weighing 43-80 kg, ASA physical status Ⅱ-Ⅳ, were randomly divided into 2 groups: protective mechanical ventilation group (group P) and unprotective mechanical ventilation group (group U).Pulmonary artery blood for plasma markers of lung injury and inflammatory mediators were collected at the following time points: before operation (T1), 3 hours after mechanical ventilation (T2), 2 hours (T3) and 4 hours in neohepatic stage (T4).These mediators included clara cell secretory protein (CC16), surfactant proteins (SP-D), soluble receptor for advanced glycation end-products (sRAGE), TNF-α, IL-6 and IL-8.Moreover, blood gas results were recorded at these 7 time points: T1-T4, 2 hours after operation (T5), before tracheal extubation (T6) and 2 days after operation (T7).The postoperative awakening time, tracheal extubation time, ICU stay time and the incidence of ALI were recorded.Results Compared with T1, plasma level of CC16 in the two groups increased at T2 and T3 (P<0.05 or P<0.01), however, plasma level of SP-D, sRAGE, TNF-α, IL-6 and IL-8 did not increase until T3 (P<0.01).Moreover, plasma level of sRAGE, TNF-α, IL-6 and IL-8 at T4 were higher than those at T1 (P<0.05 or P<0.01).Compared with T1, OIs in the two groups increased at T2, T5 and T6 (P<0.05 or P<0.01), while decreased at T4 in group P (P<0.01) and at T3 and T4 in group U (P<0.01).In group P, patients showed a lower plasma level of CC16 at T2 and T3 (P<0.05 or P<0.01), a higher OI at T3 (P<0.05) and an earlier tracheal extubation after operation [(8.9±3.2) h vs (9.3±2.8) h, P<0.05] compared with group U.There was no significant difference of acute lung injury incidence between the two groups after operation, which was 5(16.6%) and 7 (23.3%), respectively.Conclusion Protective mechanical ventilation may promote oxygenation index, and shorten tracheal extubation time, thus protect lung function of patients in liver transplantation to some extend.

The association between plasma matrix metalloproteinase-9 concentration and endoleak after endovascular aortic aneurysm repair: a meta-analysis.

BACKGROUND: The most common complication after endovascular aneurysm repair (EVAR) is continued perfusion of the aneurysmal sac, known as endoleak. Assessment of markers released from the aneurysm wall into the circulation has been suggested as a possible alternative for detecting endoleaks. The aim of this meta-analysis was to examine if circulating concentrations of matrix metalloproteinase (MMP)-9 were higher in patients with endoleak after EVAR. METHODS: A systematic search of the MEDLINE, EMBASE, Scopus, Web of Science and Cochrane Library Databases was conducted. Studies reporting circulating MMP-9 concentrations in patients who did and did not have endoleaks after EVAR that met inclusion and exclusion criteria were included. A meta-analysis using a random effects model was performed to assess the association between circulating concentrations of MMP-9 and endoleak. Sensitivity analyses were performed using the one-study remove approach. Study quality was assessed using a quality assessment tool. RESULTS: Prior to EVAR, plasma concentrations of MMP-9 were similar in patients that did and did not subsequently develop an endoleak (Standardised mean difference: -0.13; 95% confidence interval, -0.63 to 0.37, p=0.60). 1 month after EVAR, plasma concentrations of MMP-9 were non-significantly higher in patients that had an endoleak (Standardized mean difference: 0.56; 95% CI -0.02 to 1.15, p=0.06). 3 months after EVAR, plasma concentrations of MMP-9 were higher in patients that had an endoleak (Standardised mean difference: 1.42; 95% confidence interval, 0.48-2.36, p<0.003). CONCLUSIONS: This meta-analysis suggests that plasma MMP-9 concentrations measured 3 months after EVAR are higher in patients that have an endoleak. It remains to be established whether plasma MMP-9 testing is sufficiently accurate for use as a surveillance test for endoleak after EVAR.

Pertinent plasma indicators of the ability of chickens to synthesize and store lipids.

Excessive deposition of body fat is detrimental to production efficiency. The aim of this study was to provide plasma indicators of chickens' ability to store fat. From 3 to 9 wk of age, chickens from 2 experimental lines exhibiting a 2.5-fold difference in abdominal fat content and fed experimental diets with contrasted feed energy sources were compared. The diets contained 80 vs. 20 g of lipids and 379 vs. 514 g of starch per kg of feed, respectively, but had the same ME and total protein contents. Cellulose was used to dilute energy in the high-fat diet. At 9 wk of age, the body composition was analyzed and blood samples were collected. A metabolome-wide approach based on proton nuclear magnetic resonance spectroscopy was associated with conventional measurements of plasma parameters. A metabolomics approach showed that betaine, glutamine, and histidine were the most discriminating metabolites between groups. Betaine, uric acid, triglycerides, and phospholipids were positively correlated (r > 0.3; P < 0.05) and glutamine, histidine, triiodothyronine, homocysteine, and ß-hydroxybutyrate were negatively correlated (r < -0.3; P < 0.05) with relative weight of abdominal fat and/or fat situated at the top of external face of the thigh. The combination of plasma free fatty acids, total cholesterol, phospholipid, ß-hydroxybutyrate, glutamine, and methionine levels accounted for 74% of the variability of the relative weight of abdominal fat. On the other hand, the combination of plasma triglyceride and homocysteine levels accounted for 37% of the variability of fat situated at the top of external face of the thigh. The variations in plasma levels of betaine, homocysteine, uric acid, glutamine, and histidine suggest the implication of methyl donors in the control of hepatic lipid synthesis and illustrate the interplay between AA, glucose, and lipid metabolisms in growing chickens.

Identifying cost-effective predictive rules of amyloid-ß level by integrating neuropsychological tests and plasma-based markers.

BACKGROUND: Detecting participants who are positive for amyloid-ß (Aß) pathology is germane in designing prevention trials by enriching for those cases that are more likely to be amyloid positive. Existing brain amyloid measurement techniques, such as the Pittsburgh Compound B-positron emission tomography and cerebrospinal fluid, are not reasonable first-line approaches limited by either feasibility or cost. OBJECTIVE: We aimed to identify simple and cost-effective rules that can predict brain Aß level by integrating both neuropsychological measurements and blood-based markers. METHOD: Several decision tree models were built for extracting the predictive rules based on the Alzheimer's Disease Neuroimaging Initiative cohort. RESULTS: We successfully extracted predictive rules of Aß level. For cognitive function variables, cases above the 45th percentile in total cognitive score (TOTALMOD), above the 52nd percentile of delayed word recall, and above the 70th percentile in orientation resulted in a group that was highly enriched for amyloid negative cases. Conversely scoring below the 15th percentile of TOTALMOD resulted in a group highly enriched for amyloid positive cases. For blood protein markers, scoring below the 57th percentile for apolipoprotein E (ApoE) levels (irrespective of genotype) enriched two fold for the risk of being amyloid positive. In the high ApoE cases, scoring above the 60th percentile for transthyretin resulted in a group that was >90% amyloid negative. A third decision tree using both cognitive and blood-marker data slightly improved the classification of cases. CONCLUSION: Our study demonstrated that the integration of the neuropsychological measurements and blood-based markers significantly improved prediction accuracy. The prediction model has led to several simple rules, which have a great potential of being naturally translated into clinical settings such as enrichment screening for AD prevention trials of anti-amyloid treatments.

Herpes virus in Alzheimer's disease: relation to progression of the disease.

Studies regarding different viruses of the herpes family, such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), or human herpes virus 6 (HHV-6) in Alzheimer's disease (AD) are scarce. DNA from peripheral blood leukocytes (PBL) and brain samples were analyzed for the presence of CMV, EBV, or HHV-6. All samples were negative for CMV. EBV positivity was 6% in AD brains, whereas 45% of PBL samples from AD patients and 31% from controls were positive for EBV (p = 0.05). HHV-6 showed a 23% positivity in PBL samples from AD and 4% from controls (p = 0.002). 17% of AD brains were HHV-6 positive. Within a group of elderly individuals, followed up for 5 years, EBV-positive or HHV-6-positive PBL increased in those who developed clinical AD. Virus serological positivity was also investigated, and IgG levels for CMV and EBV antigens were also increased in those subjects who developed AD during the follow-up. Our findings suggest that EBV and HHV-6 may be environmental risk factors for cognitive deterioration and progression to AD in elderly persons.

Circulating interleukin-8 and plasminogen activator inhibitor-1 are increased in women with ovarian carcinoma.

Elevated serum levels of several cytokines have been reported in ovarian cancer. We have previously found a diagnostic and prognostic value of hepatocyte growth factor (HGF). The aims of this study were to evaluate the diagnostic and prognostic value of multiple serum cytokines in women with ovarian tumors, and to examine possible associations between serum levels of cytokines and the previously analyzed HGF. Preoperative levels of multiple cytokines were quantified by serum-based immunoassays in 113 women with a pelvic mass: 57 carcinomas, 23 borderline tumors, and 33 benign ovarian tumors. The results were related to clinicopathological parameters. Univariate and multivariate analyses of five-year overall survival were performed. The women with ovarian carcinoma had significantly higher preoperative serum levels of cancer antigen 125 (CA 125), interleukin 8 (IL-8), and plasminogen activator inhibitor-1 (PAI-1) than women with benign ovarian tumors. Serum IL-8 and PAI-1 levels were positively correlated to serum levels of HGF. In a multivariate analysis of five-year overall survival, IL-8 had a prognostic impact. Serum levels of IL-8 and PAI-1 were elevated in women with ovarian carcinoma compared to women with benign ovarian tumors, and positively correlated to serum HGF levels in women with ovarian tumors. IL-8 also seemed to have a prognostic impact.