The FVIII:Ag contents of the rFVIII Kogenate, and Advate and a pd-FVIII-pd-VWF (Fanhdi) were measured by ELISA. The FX activation was initiated by adding 1.0 IU of FVIII:C of each FVIII-containing product to a coagulant phospholipids suspension
containing 1.0 nm FIXa, 100 nm FX, 1 mu m hirudin and 2 mm calcium chloride and measured after 1, 5 and 10 min. The same approach was followed after adding 2.0 IU of pd-VWF to1.0 IU of FVIII:C of Kogenate or Advate. The FVIII:Ag content/IU of FVIII:C of Kogenate, Advate and Fanhdi were 1.80 +/- 0.05, 1.31 +/- 0.9 and 0.84 +/- 1.5 IU respectively. Only Kogenate and Advate effectively enhanced FX activation 1 min after adding each FVIII:C to the coagulant suspension containing FIXa and FX. Thus, the FXa initially generated by FIXa readily activated FVIII:C in control Kogenate and Advate to thereby effectively enhance FX activation while the VWF in Fanhdi continued to suppress FX activation see more for up to 10 min. AZD8186 datasheet Addition of pd-VWF to Kogenate or Advate effectively decreased their enhancements of FX activation to the same level as Fanhdi over 10 min. The FVIII:Ag fraction in Kogenate and Advate that cannot bind VWF appears to be inactive as it has no measureable FVIII:C activity in the presence of added VWF in vitro.”
“The ectodermal neural
cortex (ENC) gene family, whose members are implicated in neurogenesis, is part of the kelch repeat superfamily. To date, ENC genes have been identified only in osteichthyans, although other kelch repeat-containing genes are prevalent throughout bilaterians. The lack of elaborate molecular phylogenetic analysis with exhaustive taxon sampling has obscured the possible link of the establishment of this gene family with vertebrate novelties. In this study, we identified ENC homologs in diverse vertebrates by means of database mining and polymerase chain reaction screens. Our analysis revealed that the ENC3 ortholog was lost in the basal eutherian lineage through single-gene deletion and that the C188-9 manufacturer triplication between ENC1, -2, and -3 occurred
early in vertebrate evolution. Including our original data on the catshark and the zebrafish, our comparison revealed high conservation of the pleiotropic expression pattern of ENC1 and shuffling of expression domains between ENC1, -2, and -3. Compared with many other gene families including developmental key regulators, the ENC gene family is unique in that conventional molecular phylogenetic inference could identify no obvious invertebrate ortholog. This suggests a composite nature of the vertebrate-specific gene repertoire, consisting not only of de novo genes introduced at the vertebrate origin but also of long-standing genes with no apparent invertebrate orthologs. Some of the latter, including the ENC gene family, may be too rapidly evolving to provide sufficient phylogenetic signals marking orthology to their invertebrate counterparts.
The piperidine ring in the dithiocarbamate fragment is in the normal chair conformation.”
“In Central Europe, traditional management of oak coppice forest was abandoned at the beginning of the last century, leaving large tracts of forest developing into aged coppice stands. Since the increasing importance and use of biomass as a renewable energy source, resumption of coppice management in these forests is being considered. However, there are uncertainties about the re-sprouting ability of large and old oak stumps. In this study we determined the re-sprouting ability of sessile oak (Quercus
petraea (Mattuschka) Liebl.) stumps 80-100 years after the last coppice cut. Stump mortality and re-sprouting intensity were analyzed in relation to three different harvesting methods (harvester; conventional chainsaw cut; very low chainsaw cut), browsing intensity, vitality of parent trees
and stump parameters. LY411575 In addition, the extent to which stump mortality may be compensated by generative regeneration was quantified.\n\nOn average, 16% of all sessile oak stools died within two vegetation periods after coppicing. Stump mortality was higher in unfenced areas compared to areas protected against browsing. No clear KU-57788 research buy relationships were observed between stump mortality and harvesting method or parent tree characteristics.\n\nTwo vegetation periods after coppicing, numerous new stump sprouts were recorded. In unfenced areas, average maximum sprout height was reduced by nearly 80%. Maximum sprout height (used as an indicator for re-sprouting intensity) was found to be unaffected by harvesting method and not related to stump height or parent tree characteristics. When stumps were cut close to the soil surface the majority of the most vigorous oak sprouts originated below ground.\n\nOur
results indicate that SB203580 in vivo the re-sprouting ability of 80-100 year old oak trees originating from former coppice management is still high and little influenced by harvesting methods. (C) 2012 Elsevier B.V. All rights reserved.”
“Exotic animals are becoming increasingly popular and more exotic pet owners are seeking veterinary care. This has led to a demand for properly trained veterinarians who are capable of providing quality, up-to-date medical and surgical treatments. Many surgeries are now performed on exotic pets, and selection of the appropriate suture material is an important part of the treatment protocol. An understanding of different available suture materials, healing times of different tissues, and knowledge of different anatomic and physiologic characteristics in different species is important in the selection of the most appropriate suture material. This review will summarize important aspects of suture selection in exotic animals. Copyright 2011 Elsevier Inc. All rights reserved.”
“Interleukin (IL)-22, a relatively new member of the IL-10 family, has been implicated in inflammation and tumorigenesis.
Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes
their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses BEZ235 order target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2.\n\nResults: We engineered a C4-2B PCa sub-line called C4-2B/Rx2(dox), in which Doxycycline (Dox) treatment stimulates Runx2 expression from very low to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer associated functions. They included secreted factors (CSF2, SDF-1), proteolytic enzymes check details (MMP9, CST7), cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A), intracellular signaling molecules (DUSP1, SPHK1, RASD1) and transcription factors (wSox9, SNAI2, SMAD3) functioning in epithelium to mesenchyme transition (EMT), tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during
cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels
declined after Dox withdrawal.\n\nConclusions: The effects of Runx2 in C4-2B/Rx2dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is therefore an attractive target for the development of novel diagnostic, prognostic and therapeutic approaches to PCa management. Targeting Runx2 may prove more effective than focusing on its individual www.selleckchem.com/products/ro-3306.html downstream genes and pathways.”
“Esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances because of its high frequency of metastasis. Given the associations of MUC1 with ESCC and tumor metastasis, we explored a potential role of MUC1 in ESCC metastasis. Among 40 ESCC and 20 paired normal tissue specimens examined, we found a significant increase of MUC1 expression in ESCC and more importantly, that expression of MUC1 and MMP13 are strongly correlated in patients who had lymph node metastasis. Studies with cell models indicated that overexpression of MUC1 upregulates the expression of MMP13, leading to increased cell migration. In support of a mode of transcriptional regulation, promoter analysis revealed that MUC1 stimulates MMP13 expression through the Runx-2-binding site.
(C) 2013 Elsevier B.V. All rights reserved.”
“Background Tendinopathy is a clinical diagnosis of localised tendon pain often confirmed by imaging findings. The pathophysiological cause of the pain is unknown and the sympathetic nervous system (SNS) may be implicated. Objective To review what is known regarding the role of the SNS in human tendinopathy. Study selection Published data describing sympathetic innervation or an index of sympathetic activity in human tendons were eligible for inclusion. Data sources Bibliographical databases (AMED, Biological Abstracts, CINAHL Plus, EMBASE, MEDLINE, Scopus, SPORTDiscus and Web of Science) were searched for relevant
articles. AZD1390 price Reference lists from included articles were screened for additional articles. Study appraisal Studies were scored with a quality assessment tool to identify potential sources of bias. Each question had an explicit decision rule to guide assessment. Results Nine case-control and four cross-sectional studies examined
sympathetic innervation of tendons. There was evidence suggesting a lack of difference in sympathetic innervation learn more of tendon proper between tendinopathy biopsies and healthy controls. In contrast, the paratendinous tissue showed evidence of increased sympathetic innervation in painful tendons. The most notable increase in SNS markers was seen in abnormal tenocytes from painful tendons. Data from two studies were suitable for metaanalysis. These heterogeneous studies revealed no difference in sympathetic innervation between painful and painfree tendons. No studies recorded SNS activity in vivo. Conclusion Sympathetic innervation in painful tendons depends on tissue type. Abnormal tenocytes may have increased capacity for self-production of sympathetic neurotransmitters. Future insight may be gained by measuring global in vivo sympathetic drive in tendinopathy.”
“IntroductionHysterectomy is the most common major gynecologic operation, together Akt activity with bilateral salpingo-oophorectomy
in the majority of women over the age of 45. AimTo investigate whether surgical menopause affects female sexual performance differently from natural menopause. MethodsThe study included 121 women who had undergone surgical menopause and 122 women who had undergone natural menopause. All the women had similar economic, sociocultural, and personal demographic profiles, had been postmenopausal for at least 1 year, and were between the ages of 45 and 65. The women were asked to complete a six-question survey of sexual performance parameters (sexual desire, coital frequency, arousal, orgasm frequency, dyspareunia, and vaginal lubrication). These sexual performance parameters were compared between the surgical and natural menopause groups.
Our results suggest that cognitive tonal expectations can influence pitch perception at several steps of processing, starting with early attentional selection of pitch.”
“The optical absorption of Au quantum dots (QDs) was studied by applying the photoacoustic (PA) spectroscopic technique, which is useful for optically opaque samples. The characteristic bands of Au QDs were observed Wnt inhibitor at around 2.4 eV for electrodes consisting of 15 nm TiO2 nanoparticles and at around 2.3 eV for those consisting of 37 nm ones, which correspond to the characteristic surface plasmon
resonance bands in the visible region. The electrode thickness dependence of the PA signal intensity around the characteristic band showed a tendency toward saturation in both cases. There was a great difference in the saturation characteristics of the PA signal intensity
between the electrodes made with different sized TiO2 nanoparticles, even though the preparation conditions for the Au QDs were the same. The saturation time for electrodes made with 37 nm TiO2 nanoparticles https://www.selleckchem.com/products/gm6001.html was shorter than those made with 15 nm particles, indicating that the penetration of the QDs into the electrodes made with 37 nm nanoparticles was less than those made with 15 nm nanoparticles, although the porous area observed was high. Also, the PA signal intensity around the peak of electrodes with 15 nm nanoparticles is larger than that with 37 nm ones, indicating a higher adsorption rate for the smaller nanoparticles due to the lower surface activation energy of larger nanoparticles. There was no photoelectrochemical current response although the characteristic optical absorption bands of the Au QDs were observed by surface plasmon
“Asian sea bass immunoglobulin M (IgM) was purified from the sera of Lates calcarifer by affinity chromatography. p38 MAPK activation Analysis of the purified IgM on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing and non-reducing conditions revealed that the sea bass IgM was a tetrameric protein with a molecular weight of 896 kDa; it contained an equimolar heavy chain and light chain with molecular weight of 83 kDa and 27 kDa respectively. However, besides the covalently linked tetrameric IgM, noncovalently linked tetramer dissociated into dimeric and monomeric forms also demonstrated by non-reducing SDS-PAGE. Carbohydrate moieties were found to be linked with both heavy and light chains. A polyclonal rabbit anti-Asian sea bass IgM was prepared which showed a specific reaction of anti-fish IgM antibody with IgM of sea bass. Sea bass IgM concentration was determined in the serum by indirect ELISA. The average IgM concentration in the sera of the healthy sea bass was 5.4 +/- 1.8 mg ml(-1); it amounted to 16.7% of the total serum protein.
The resulting nuclease maps were 86% consistent with the predicted 3′SL structure, suggesting that it can form in solution. We used a well-defined reverse genetic system for launch of NoV replication in yeast cells to test the function of the 3′SL in the viral life cycle. Deletion of the nucleotides that comprise the 3′SL from a NoV2-GFP chimeric
replicon resulted in a severe defect in RNA2 replication. A minimal replicon containing the 5′-terminal 17 nt and the 3′-terminal 54 nt of RNA2 (including the predicted 3′SL) retained the ability to replicate in yeast, suggesting that this region is able to direct replication of a heterologous mRNA. These data suggest that the 3′SL plays an essential role in replication of NoV RNA2. The conservation of the predicted 3′SL suggests that this common motif may play a role in selleck inhibitor RNA replication for the other members of the Nodaviridae. (C) 2010 Elsevier B.V. All rights reserved.”
“A 12-year-old girl with hypoplastic right heart, double inlet left ventricle, and transposition of the great arteries had a lateral tunnel Fontan operation 8 years previously. She developed symptoms related to a combination of stenosis in the inferior caval venous pathway, a fenestration,
and leak in the lateral tunnel. These were successfully treated with a custom-made stent graft.”
“The abundance of denitrifying bacteria in soil has been determined primarily by the conventional QNZ most probable number (MPN) method. We have developed a single-cell identification technique that is culture-independent, direct in situ PCR, to enumerate denitrifying bacteria in soils. The specificity of this method was evaluated with six species of denitrifying bacteria using nirK as the target gene; Escherichia coli was used as a negative control. Almost all (97.3%-100%) of the nirK-type denitrifying bacteria (Agromonas oligotrophica, Alcaligenes faecalis, Achromobacter denitrificans, Bradyrhizobium
japonicum, and Pseudomonas chlororaphis) were detected by direct in situ PCR, whereas no E. coli cells and only a few cells (2.4%) of nirS-type denitrifying bacteria (Pseudomonas aeruginosa) were detected. Ferroptosis phosphorylation Numbers of denitrifying bacteria in upland and paddy soil samples quantified by this method were 3.3 x 10(8) to 2.6 x 10(9) cells g(-1) dry soil. These values are approximately 1,000 to 300,000 times higher than those estimated by the MPN method. These results suggest that direct in situ PCR is a better tool for quantifying denitrifying bacteria in soil than the conventional MPN method.”
“This study explores the variability in concentrations of dissolved CH(4) and annual flux estimates in the pelagic zone in a statistically defined sample of 207 lakes in Finland. The lakes were situated in the boreal zone, in an area where the mean annual air temperature ranges from – 2.8 to 5.9 degrees C. We examined how lake CH(4) dynamics related to regional lake types assessed according to the EU water framework directive.
Upon T- or B-cell receptor engagement human (h) A20 is cleaved by MALT1 after arginine 439, yielding an N-terminal fragment (hA20p50) and a C-terminal one (hA20p37). The hA20p50 fragment has never been detected directly, thus limiting insight into the functional consequences of MALT1-mediated cleavage of A20. Here, various antibodies were tested, including newly generated hA20p50 and hA20p37 specific antibodies, leading BAY 73-4506 cell line to detection of the hA20p50 fragment
produced after MALT1-mediated cleavage of ectopically expressed as well as endogenous A20 proteins. The properties of both A20 fragments, generated upon co-expression with a constitutively active MALT1 protein, were further studied by sub-cellular fractionation and fluorescence microscopy. In contrast to full-length A20 which is particulate and insoluble, we found hA20p50 to be soluble and readily released into the cytosol whereas hA20p37 was partially soluble, thus suggesting loss of compartmentalization
as a possible mechanism for MALT1-mediated dampening of A20 function. (C) 2010 Elsevier Inc. All rights reserved.”
“We developed a method for coupling protein to its coding DNA on magnetic microbeads using emulsion PCR and cell-free protein synthesis in emulsion. A PCR mixture containing streptavidin-coated microbeads was compartmentalized by water-in-oil (w/o) emulsion with estimated 0.5 template molecules per droplet. The template molecules were amplified and immobilized on beads via bead-linked FK228 supplier reverse primers and biotinylated forward primers. After amplification, the templates were sequentially labeled with streptavidin and biotinylated
anti-glutathione S-transferase (GST) antibody. The pool of beads was then subjected to cell-free protein synthesis compartmentalized in another w/o emulsion, in which templates were coupled to their coding proteins. We mixed two types of DNA AZD1480 cost templates of Histidine6 tag (His6)-fused and FLAG tag-fused GST in a ratio of 1:1,000 (His6: FLAG) for use as a model DNA library. After incubation with fluorescein isothiocyanate (FITC)-labeled anti-His6 (C-term) antibody, the beads with the His6 gene were enriched 917-fold in a single-round screening by using flow cytometry. A library with a theoretical diversity of 10(6) was constructed by randomizing the middle four residues of the His6 tag. After a two-round screening, the randomized sequences were substantially converged to peptide-encoding sequences recognized by the anti-His6 antibody.”
“Abiotic stresses are major environmental factors that affect agricultural productivity worldwide. NAC transcription factors play pivotal roles in abiotic stress signaling in plants. As a staple crop, wheat production is severely constrained by abiotic stresses whereas only a few NAC transcription factors have been characterized functionally. To promote the application of NAC genes in wheat improvement by biotechnology, a novel NAC gene designated TaNAC67 was characterized in common wheat.
MEDs and symptoms were collected from food challenge studies and each reaction was graded using the integrated grading system. Peanut allergic patients who experienced severe reactions had significantly higher MEDs and threshold
distribution doses than those who experienced mild and moderate reactions. No significant differences in threshold distributions according to the severity grading were found for milk, egg and soy. The relationship between threshold dose distribution and reaction severity based on these grading criteria differed between peanut and other allergens, and severe reactions were found to occur in some patients at low MEDs for all of these food allergens. Published Vorinostat chemical structure by Elsevier Ltd.”
“In the present study, we designed and synthesized a novel 1,5-diarylpyrazole derivative, 2-amino-N-(2-methyl-5-(1-(4-sulfamoylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)phenyl)
selleck chemicals acetamide hydrochloride (CC06), which was intended to act as a prodrug and would exert potent anti-inflammatory activity after being converted to its parent compound in vivo. In vitro cell-based biological assay, CC06 showed decreased inhibitory effects on cyclooxygenase (COX)-1 and COX-2 compared with its parent compounds, but it exhibited potent anti-inflammatory activity in vivo. The anti-inflammatory effect was evaluated in a carrageenan-induced rat paw edema model and CC06 (15, 30, 60 mg/kg, intragastrically) reduced rat paw edema in a dose-dependent
manner. CC06 is also a selective inhibitor of Apoptosis inhibitor COX-2 since it can reduce prostaglandin E(2) (PGE(2)) production in the inflamed pouch dose-dependently without affecting PGE(2) production in stomach in rat air pouch model. Furthermore, preliminary pharmacokinetics experiments were conducted using high performance liquid chromatography/mass spectrometry (HPLU/MS) to detect whether CC06 can convert to its parent compound or not. Our results supported the hypothesis that CC06 was actually converted to its parent compound. These suggested that CC06 served as an anti-inflammatory prodrug and actually converted to its parent compound to exert its anti-inflammatory effect. This finding will be of great benefit in carrying out structural modifications of prodrug-like selective COX-2 inhibitors.”
“Regulated nucleocytoplasmic transport is of vital importance for maintaining the physiology of the cell, and disturbed nucleocytoplasmic shuttling of certain proteins has been found in a variety of diseases including cancer.
5, 15, or 30 ml/kg, respectively). Saline or HES was treated before the construction of left colonic anastomosis and on a regular daily basis. Anastomotic bursting pressures
were measured in vivo on day 5. Tissue samples were obtained for analyses of hydroxyproline (HP) contents, myeloperoxidase (MPO) acivity, malondialdehyde (MDA), reduced glutathione (GSH) levels, and nuclear factor-kappa B (NF-kappa B) activation. The plasma levels of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 were also measured. Results: Intra-abdominal sepsis led to significant decreases CH5424802 chemical structure in colonic anastomotic bursting pressures, and perianastomotic tissue HP contents and GSH levels, along with increases in perianastomotic tissue MPO
activity, MDA levels and NF-kappa B activation and plasma levels of TNF-alpha and IL-6. After treated with HES, these provoked perianastomotic tissue MPO activity, MDA levels, NF-kappa B activation, and plasma levels of TNF-a and IL-6 were suppressed and GSH levels were restored, especially in 15 ml/kg HES group. Without obvious influence on systemic nutritional condition, HES 15 ml/kg but not HES 7.5 ml/kg significantly increased anastomotic bursting pressures, and perianastomotic tissue HP contents. However, HES 30 ml/kg even led to adverse effects on anastomotic bursting pressures. Conclusions: This study showed that moderate doses (15 ml/kg) of HES 130/0.4 administration significantly prevented this intraperitoneal sepsis-induced check details impaired anastomotic healing of the left colon. It also suggested the possibility of poorer anastomotic healing receiving HES at higher doses (30 ml/kg). Clearly, HES 130/0.4 now should not be recommended to use at a high doses 4EGI-1 postoperatively in sepsis.”
“A sodium hypochlorite accident is a rare event
in adults, but even more so in children. The purposes of this paper were to: report the case of a one-year, 10-month-old toddler who was treated under general anesthesia for early childhood caries, incurred a sodium hypochlorite accident following attempted pulpectomy in his primary maxillary central incisors, but made a full recovery without any sequelae after a typical four to six weeks course of disease; review the pertinent literature; and give recommendations on how to minimize the potential occurrence of such incidents.”
“Background: The inconsistent epidemiological results of the endocrine disrupting effects of DDT fuel a harsh debate on its global ban. Objectives: We tested the hypothesis that occupational exposure to dichloro-diphenyl-trichloroethane (DDT) causes impairment in male fertility in a cohort of DDT exposed workers, in Sardinia, Italy. Methods: We accessed official records on date of marriage and date of birth of the first child to estimate time to pregnancy (UP) in the spouses of 1223 workers employed in a 1946-1950 anti-malarial campaign.
The experimental design was completely randomized with six treatments and four replications. Plants of Tifton 85 bermudagrass with 38 days were ensiled in experimental silos with Bunsen valves, with compacting density of 236 kg silage per m(3) for Tifton NU7441 cost 85 bermudagrass, which was pre-dried in the sun; the average silage was 294 kg m(-3) for the other treatments. The ratios between soybean hulls and corn grits, added to the silage, were calculated
based on the initial DM content from Tifton 85 bermudagrass in order to obtain 320 g/kg DM of the material to be ensiled. There was an increase of lactic bacteria and Clostridium as well as an absence of enterobacteria after the silo opening. Fungi developed only in Tifton 85 bermudagrass and its treatments before the ensilage and yeasts developed in silages of Tifton 85 bermudagrass when they received soybean hulls or corn grits after silo opening. There was no breach regarding aerobic stability of silages during the studied period. The pH reached the highest
values within 48 hours after opening the silos, but there were variations during this period.”
“Objectives: Calprotectin, also known as S100A8/A9 complex, is currently considered as a valid biomarker for diagnosis, follow-up and therapeutic monitoring of inflammatory bowel diseases. The attractive evidence that this protein may be actively produced and released by leukocytes (especially neutrophils) and by nonmyeloid VS-6063 concentration cardiovascular cell types has paved the way to a series of studies that have assessed its biology in the setting of cardiovascular disease. The aim of this review was thus to investigate the diagnostic
and prognostic utility of this biomarker in cardiovascular disease and in particular click here in myocardial infarction. Design and methods: We performed a systematic, electronic search on Medline, Scosus and Web of Science, using the keywords “calprotectin” or “S100A8/A9″ or “MRP-8/14″ and “myocardial infarction” or “acute coronary syndrome” or “cardiovascular disease”, from inception to June 2013. The bibliographic references of articles published in English, French and Italian were reviewed for additional relevant studies. Results: The data of the current scientific literature seems to confirm that calprotectin is actively secreted in the setting of cardiac ischemia and its concentration is significantly associated with the prognosis. Nevertheless, the evidence provided by recent articles that have assessed its performance for diagnosing acute myocardial infarction, either alone or in combination with troponin, supports the hypothesis that this biomarker may be of limited value for enabling a better or faster diagnosis of cardiac ischemia. Even its putative role as an independent prognostic biomarker of cardiovascular morbidity and death is still largely uncertain.