Comprehensive Peroxidase-Based Hematologic Profiling for The Prediction of 1-Year Myocardial Infarction and Death

Background— Recognition of biological patterns holds promise for improved identification of patients at risk for myocardial infarction (MI) and death. We hypothesized that identifying high- and low-risk patterns from a broad spectrum of hematologic phenotypic data related to leukocyte peroxidase-, erythrocyte- and platelet-related parameters may better predict future cardiovascular risk in stable cardiac patients than traditional risk factors alone. Methods and Results— Stable patients (n=7369) undergoing elective cardiac evaluation at a tertiary care center were enrolled. A model (PEROX) that predicts incident 1-year death and MI was derived from standard clinical data combined with information captured by a high-throughput peroxidase-based hematology analyzer during performance of a complete blood count with differential. The PEROX model was developed using a random sampling of subjects in a derivation cohort (n=5895) and then independently validated in a nonoverlapping validation cohort (n=1474). Twenty-three high-risk (observed in ≥10% of subjects with events) and 24 low-risk (observed in ≥10% of subjects without events) patterns were identified in the derivation cohort. Erythrocyte- and leukocyte (peroxidase)-derived parameters dominated the variables predicting risk of death, whereas variables in MI risk patterns included traditional cardiac risk factors and elements from all blood cell lineages. Within the validation cohort, the PEROX model demonstrated superior prognostic accuracy (78%) for 1-year risk of death or MI compared with traditional risk factors alone (67%). Furthermore, the PEROX model reclassified 23.5% (P\u3c0.001) of patients to different risk categories for death/MI when added to traditional risk factors. Conclusion— Comprehensive pattern recognition of high- and low-risk clusters of clinical, biochemical, and hematologic parameters provided incremental prognostic value in stable patients having elective diagnostic cardiac catheterization for 1-year risks of death and MI

Comprehensive Peroxidase-Based Hematologic Profiling for The Prediction of 1-Year Myocardial Infarction and Death

Background— Recognition of biological patterns holds promise for improved identification of patients at risk for myocardial infarction (MI) and death. We hypothesized that identifying high- and low-risk patterns from a broad spectrum of hematologic phenotypic data related to leukocyte peroxidase-, erythrocyte- and platelet-related parameters may better predict future cardiovascular risk in stable cardiac patients than traditional risk factors alone. Methods and Results— Stable patients (n=7369) undergoing elective cardiac evaluation at a tertiary care center were enrolled. A model (PEROX) that predicts incident 1-year death and MI was derived from standard clinical data combined with information captured by a high-throughput peroxidase-based hematology analyzer during performance of a complete blood count with differential. The PEROX model was developed using a random sampling of subjects in a derivation cohort (n=5895) and then independently validated in a nonoverlapping validation cohort (n=1474). Twenty-three high-risk (observed in ≥10% of subjects with events) and 24 low-risk (observed in ≥10% of subjects without events) patterns were identified in the derivation cohort. Erythrocyte- and leukocyte (peroxidase)-derived parameters dominated the variables predicting risk of death, whereas variables in MI risk patterns included traditional cardiac risk factors and elements from all blood cell lineages. Within the validation cohort, the PEROX model demonstrated superior prognostic accuracy (78%) for 1-year risk of death or MI compared with traditional risk factors alone (67%). Furthermore, the PEROX model reclassified 23.5% (P\u3c0.001) of patients to different risk categories for death/MI when added to traditional risk factors. Conclusion— Comprehensive pattern recognition of high- and low-risk clusters of clinical, biochemical, and hematologic parameters provided incremental prognostic value in stable patients having elective diagnostic cardiac catheterization for 1-year risks of death and MI

MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases.

Low-grade systemic inflammation is often associated with metabolic syndrome, which plays a critical role in the development of the obesity-associated inflammatory diseases, including insulin resistance and atherosclerosis. Here, we investigate how Toll-like receptor-MyD88 signaling in myeloid and endothelial cells coordinately participates in the initiation and progression of high fat diet-induced systemic inflammation and metabolic inflammatory diseases. MyD88 deficiency in myeloid cells inhibits macrophage recruitment to adipose tissue and their switch to an M1-like phenotype. This is accompanied by substantially reduced diet-induced systemic inflammation, insulin resistance, and atherosclerosis. MyD88 deficiency in endothelial cells results in a moderate reduction in diet-induced adipose macrophage infiltration and M1 polarization, selective insulin sensitivity in adipose tissue, and amelioration of spontaneous atherosclerosis. Both in vivo and ex vivo studies suggest that MyD88-dependent GM-CSF production from the endothelial cells might play a critical role in the initiation of obesity-associated inflammation and development of atherosclerosis by priming the monocytes in the adipose and arterial tissues to differentiate into M1-like inflammatory macrophages. Collectively, these results implicate a critical MyD88-dependent interplay between myeloid and endothelial cells in the initiation and progression of obesity-associated inflammatory diseases

Complete genome sequence of “Enterobacter lignolyticus” SCF1

In an effort to discover anaerobic bacteria capable of lignin degradation, we isolated “Enterobacter lignolyticus”SCF1 on minimal media with alkali lignin as the sole source of carbon. This organism was isolated anaerobically from tropical forest soils collected from the Short Cloud Forest site in the El Yunque National Forest in Puerto Rico, USA, part of the Luquillo Long-Term Ecological Research Station. At this site, the soils experience strong fluctuations in redox potential and are net methane producers. Because of its ability to grow on lignin anaerobically, we sequenced the genome. The genome of “E. lignolyticus” SCF1 is 4.81 Mbp with no detected plasmids, and includes a relatively small arsenal of lignocellulolytic carbohydrate active enzymes. Lignin degradation was observed in culture, and the genome revealed two putative laccases, a putative peroxidase, and a complete 4-hydroxyphenylacetate degradation pathway encoded in a single gene cluster

Complete genome sequence of “Enterobacter lignolyticus” SCF1

In an effort to discover anaerobic bacteria capable of lignin degradation, we isolated “Enterobacter lignolyticus”SCF1 on minimal media with alkali lignin as the sole source of carbon. This organism was isolated anaerobically from tropical forest soils collected from the Short Cloud Forest site in the El Yunque National Forest in Puerto Rico, USA, part of the Luquillo Long-Term Ecological Research Station. At this site, the soils experience strong fluctuations in redox potential and are net methane producers. Because of its ability to grow on lignin anaerobically, we sequenced the genome. The genome of “E. lignolyticus” SCF1 is 4.81 Mbp with no detected plasmids, and includes a relatively small arsenal of lignocellulolytic carbohydrate active enzymes. Lignin degradation was observed in culture, and the genome revealed two putative laccases, a putative peroxidase, and a complete 4-hydroxyphenylacetate degradation pathway encoded in a single gene cluster

Complete genome sequence of “Enterobacter lignolyticus” SCF1

In an effort to discover anaerobic bacteria capable of lignin degradation, we isolated “Enterobacter lignolyticus”SCF1 on minimal media with alkali lignin as the sole source of carbon. This organism was isolated anaerobically from tropical forest soils collected from the Short Cloud Forest site in the El Yunque National Forest in Puerto Rico, USA, part of the Luquillo Long-Term Ecological Research Station. At this site, the soils experience strong fluctuations in redox potential and are net methane producers. Because of its ability to grow on lignin anaerobically, we sequenced the genome. The genome of “E. lignolyticus” SCF1 is 4.81 Mbp with no detected plasmids, and includes a relatively small arsenal of lignocellulolytic carbohydrate active enzymes. Lignin degradation was observed in culture, and the genome revealed two putative laccases, a putative peroxidase, and a complete 4-hydroxyphenylacetate degradation pathway encoded in a single gene cluster

Complete genome sequence of “Enterobacter lignolyticus” SCF1

In an effort to discover anaerobic bacteria capable of lignin degradation, we isolated “Enterobacter lignolyticus”SCF1 on minimal media with alkali lignin as the sole source of carbon. This organism was isolated anaerobically from tropical forest soils collected from the Short Cloud Forest site in the El Yunque National Forest in Puerto Rico, USA, part of the Luquillo Long-Term Ecological Research Station. At this site, the soils experience strong fluctuations in redox potential and are net methane producers. Because of its ability to grow on lignin anaerobically, we sequenced the genome. The genome of “E. lignolyticus” SCF1 is 4.81 Mbp with no detected plasmids, and includes a relatively small arsenal of lignocellulolytic carbohydrate active enzymes. Lignin degradation was observed in culture, and the genome revealed two putative laccases, a putative peroxidase, and a complete 4-hydroxyphenylacetate degradation pathway encoded in a single gene cluster

Complete genome sequence of “Enterobacter lignolyticus” SCF1

In an effort to discover anaerobic bacteria capable of lignin degradation, we isolated “Enterobacter lignolyticus”SCF1 on minimal media with alkali lignin as the sole source of carbon. This organism was isolated anaerobically from tropical forest soils collected from the Short Cloud Forest site in the El Yunque National Forest in Puerto Rico, USA, part of the Luquillo Long-Term Ecological Research Station. At this site, the soils experience strong fluctuations in redox potential and are net methane producers. Because of its ability to grow on lignin anaerobically, we sequenced the genome. The genome of “E. lignolyticus” SCF1 is 4.81 Mbp with no detected plasmids, and includes a relatively small arsenal of lignocellulolytic carbohydrate active enzymes. Lignin degradation was observed in culture, and the genome revealed two putative laccases, a putative peroxidase, and a complete 4-hydroxyphenylacetate degradation pathway encoded in a single gene cluster

Complete genome sequence of “Enterobacter lignolyticus” SCF1

In an effort to discover anaerobic bacteria capable of lignin degradation, we isolated “Enterobacter lignolyticus”SCF1 on minimal media with alkali lignin as the sole source of carbon. This organism was isolated anaerobically from tropical forest soils collected from the Short Cloud Forest site in the El Yunque National Forest in Puerto Rico, USA, part of the Luquillo Long-Term Ecological Research Station. At this site, the soils experience strong fluctuations in redox potential and are net methane producers. Because of its ability to grow on lignin anaerobically, we sequenced the genome. The genome of “E. lignolyticus” SCF1 is 4.81 Mbp with no detected plasmids, and includes a relatively small arsenal of lignocellulolytic carbohydrate active enzymes. Lignin degradation was observed in culture, and the genome revealed two putative laccases, a putative peroxidase, and a complete 4-hydroxyphenylacetate degradation pathway encoded in a single gene cluster

Complete genome sequence of “Enterobacter lignolyticus” SCF1

In an effort to discover anaerobic bacteria capable of lignin degradation, we isolated “Enterobacter lignolyticus”SCF1 on minimal media with alkali lignin as the sole source of carbon. This organism was isolated anaerobically from tropical forest soils collected from the Short Cloud Forest site in the El Yunque National Forest in Puerto Rico, USA, part of the Luquillo Long-Term Ecological Research Station. At this site, the soils experience strong fluctuations in redox potential and are net methane producers. Because of its ability to grow on lignin anaerobically, we sequenced the genome. The genome of “E. lignolyticus” SCF1 is 4.81 Mbp with no detected plasmids, and includes a relatively small arsenal of lignocellulolytic carbohydrate active enzymes. Lignin degradation was observed in culture, and the genome revealed two putative laccases, a putative peroxidase, and a complete 4-hydroxyphenylacetate degradation pathway encoded in a single gene cluster