Factors in the emergence of serious human infections associated with highly pathogenic strains of shiga toxin-producing Escherichia coli.

The appearance of highly pathogenic strains of Shiga toxin (Stx)-producingEscherichia. coli (STEC) has owed largely to the acquisition of Stx-encoding prophages by strains of E. coli that have pre-existing potential as enteric pathogens, such as atypical enteropathogenic E.

Emerging Public Health Challenges of Shiga Toxin-Producing Escherichia coli Related to Changes in the Pathogen, the Population, and the Environment.

Emerging public health challenges of Shiga toxin (stx)-producing Escherichia coli (STEC) include the occurrence of more frequent or severe disease and risk factors shifts associated with changes, often interconnected, in the pathogen, the population, and the environment. In 3 outbreaks with heightened severity attributed to enhanced pathogen virulence, including the acquisition of an stx2 phage in 1 outbreak, population and environmental factors likely contributed significantly to disease outcomes. Evolving population risk factors that are associated with more severe disease include consumption of fresh produce, contact with STEC-contaminated environments, demographics, socioeconomic status, and immunity.

Plasma 25-hydroxyvitamin D, hormonal contraceptive use, and cardiometabolic disease risk in an ethnically diverse population of young adults.

Objectives: The relationship between vitamin D and cardiometabolic disease risk across ethnic groups is unclear, and it is not known whether the use of hormonal contraceptives (HCs), which affect vitamin D metabolism and are also associated with cardiometabolic disease risk, modifies this relationship. Our objectives were to determine the prevalence of vitamin D deficiency (plasma 25-hydroxyvitamin D [25(OH)D] < 30 nmol/L) to assess seasonal variation in concentrations of 25(OH)D, and to examine whether 25(OH)D is associated with cardiometabolic biomarkers across ethnic groups and across men, female HC nonusers, and female HC users in an ethnically diverse population of young adults living in Canada.

Methods: The study population consisted of Caucasian, East Asian, and South Asian individuals (n = 1384, 69% female) aged 20-29 years.

Plasma vitamin D and biomarkers of cardiometabolic disease risk in adult Canadians, 2007-2009.

Introduction: Vitamin D may modulate cardiometabolic disease risk, although the relationship has not been investigated in the general Canadian population. Understanding this relationship may inform public health strategies to curb the incidence of cardiometabolic disease in Canada and elsewhere. The objectives of this study were to examine the association between vitamin D and traditional and novel biomarkers of cardiometabolic disease and to describe the extent of the month-to-month fluctuations of vitamin D in the Canadian population.

Common variants of the vitamin D binding protein gene and adverse health outcomes.

The vitamin D binding protein (DBP) is the major plasma carrier for vitamin D and its metabolites, but it is also an actin scavenger, and is the precursor to the immunomodulatory protein, Gc-MAF. Two missense variants of the DBP gene - rs7041 encoding Asp432Glu and rs4588 encoding Thr436Lys - change the amino acid sequence and alter the protein function. They are common enough to generate population-wide constitutive differences in vitamin D status, based on assay of the serum metabolite, 25-hydroxyvitamin D (25OHD).

The association between obesity, cardiometabolic disease biomarkers, and innate immunity-related inflammation in Canadian adults.

Introduction: Obesity is associated with a state of chronic inflammation, and increased cardiometabolic disease risk. The present study examined the relationship between body mass index (BMI) and cardiometabolic and inflammatory biomarkers among normal weight, overweight, and obese Canadian adults.

Methods: Subjects (n = 1805, aged 18 to 79 years) from the Canadian Health Measures Survey (CHMS) were examined for associations between BMI, cardiometabolic markers (apolipoprotein [Apo] A1, ApoB, low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol, total cholesterol/HDL ratio [total:HDL-C ratio], triglycerides, and glycosylated hemoglobin [HbA(1c)]), inflammatory factors (C-reactive protein [CRP], fibrinogen, and homocysteine), and 25-hydroxyvitamin D [25(OH)D].

Novel repressor of Escherichia coli O157:H7 motility encoded in the putative fimbrial cluster OI-1.

Escherichia coli O157:H7 is a gastrointestinal pathogen that has become a serious public health concern, as it is associated with outbreaks and severe diseases such as hemolytic-uremic syndrome. The molecular basis of its greater virulence than that of other serotypes is not completely known. OI-1 is a putative fimbria-encoding genomic island that is found almost exclusively in O157:H7 Shiga toxin-producing E.

Effects of polymorphisms in nucleotide-binding oligomerization domains 1 and 2 on biomarkers of the metabolic syndrome and type II diabetes.

The innate immune receptor toll-like receptor 4 (TLR4) has been implicated in mediating some of the effects of dietary lipids on inflammation and type 2 diabetes (T2D). Similar to TLR4, the nucleotide-binding oligomerization domains (Nods) 1 and 2 are also proteins of innate immunity, which can respond to lipids and initiate pro-inflammatory signalling that plays a role in the aetiology of T2D. The objective was to determine the effect of Nod1 (Glu266Lys) and Nod2 (Ser268Pro) genotypes on factors associated with the metabolic syndrome (MetS), and whether they modify the association between dietary lipids and biomarkers of the MetS.

A common polymorphism near the interleukin-6 gene modifies the association between dietary fat intake and insulin sensitivity.

Background: Increasing evidence suggests a role for inflammation in the development of type 2 diabetes. Elevated levels of inflammatory cytokines, including interleukin-6, have been associated with insulin resistance, and dietary lipids can increase cytokine production. The objective of this study was to determine whether a single nucleotide polymorphism near the IL6 gene (rs7801406) modifies the relationship between dietary fat and markers of insulin sensitivity.

Dietary patterns and ethnicity are associated with distinct plasma proteomic groups.

Background: High-abundance plasma proteins are involved in disease-associated pathways and are useful in the diagnosis of nutritional and disease states. However, little is known about how concentrations of many plasma proteins vary between individuals from different ethnocultural groups with different dietary habits.

Objective: We explored the association between plasma proteomic groups, dietary patterns, and ethnicity in the Toronto Nutrigenomics and Health Study, an ethnically diverse population of healthy young adults.

Plasma vitamin D levels and risk of metabolic syndrome in Canadians.

Purpose: Vitamin D deficiency has been implicated in susceptibility to the development of metabolic syndrome, obesity and type 2 diabetes mellitus. The present study aimed to quantify the association between vitamin D plasma level, the number of metabolic syndrome components and insulin resistance in Canadians.

Methods: Vitamin D plasma level and clinical data were determined from 1,818 subjects from the Canadian Health Measures Survey; a representative health survey of the general population of Canada conducted from 2007 to 2009.

Genetic polymorphisms of innate immunity-related inflammatory pathways and their association with factors related to type 2 diabetes.

Background: Type 2 diabetes mellitus (T2DM) has been linked to a state of pre-clinical chronic inflammation resulting from abnormalities in the innate immune pathway. Serum levels of pro-inflammatory cytokines and acute-phase proteins, collectively known as 'inflammatory network', are elevated in the pre-, or early, stages of T2DM and increase with disease progression. Genetic variation can affect the innate immune response to certain environmental factors, and may, therefore, determine an individual's lifetime risk of disease.

Rapid genoserotyping tool for classification of Salmonella serovars.

We have developed a Salmonella genoserotyping array (SGSA) which rapidly generates an antigenic formula consistent with the White-Kauffmann-Le Minor scheme, currently the gold standard for Salmonella serotyping. A set of 287 strains representative of 133 Salmonella serovars was assembled to validate the array and to test the array probes for accuracy, specificity, and reproducibility. Initially, 76 known serovars were utilized to validate the specificity and repeatability of the array probes and their expected probe patterns.

Characterization of Escherichia coli isolated from gut biopsies of newly diagnosed patients with inflammatory bowel disease.

Background: Mucosal-associated Escherichia coli may play a role in the pathogenesis of inflammatory bowel diseases (IBDs). In this study we assessed mucosal-associated E. coli in adults at the time of first diagnosis.

Serological response of Shiga toxin-producing Escherichia coli type III secreted proteins in sera from vaccinated rabbits, naturally infected cattle, and humans.

Escherichia coli O157:H7 is an important zoonotic pathogen, causing hemolytic uremic syndrome (HUS). The colonization of cattle and human hosts is mediated through the action of effectors secreted via a type III secretion system (T3SS). The structural genes for the T3SS and many of the secreted effectors are located on a pathogenicity island called the locus of enterocyte effacement (LEE).

Vitamins D, C, and E in the prevention of type 2 diabetes mellitus: modulation of inflammation and oxidative stress.

The incidence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and certain population subgroups are especially vulnerable to the disease. To reduce T2DM risk and progression at the population level, preventative strategies are needed that can be implemented on a population-wide scale with minimal cost and effort. Chronic low-grade inflammation resulting from oxidative stress and imbalances in the innate immune system has been associated with obesity, metabolic syndrome, and insulin resistance - critical stages in the development and progression of T2DM.

Polymorphisms in Toll-like receptor 4 are associated with factors of the metabolic syndrome and modify the association between dietary saturated fat and fasting high-density lipoprotein cholesterol.

Toll-like receptor 4 (TLR4) is a protein of the innate immune system hypothesized to mediate some of the effects of a high-fat diet on inflammation and insulin resistance. As both these factors are associated with the metabolic syndrome (MetS), genetic variation in TLR4 may affect the relationship between dietary lipids and MetS. The objective of the study was to determine whether 2 polymorphisms in TLR4 (rs4986790 Asp299Gly and rs5030728 G>A) modify the relationship between dietary fat and markers of the MetS.

Extending the reach of public health genomics: what should be the agenda for public health in an era of genome-based and “personalized” medicine?

The decade following the completion of the Human Genome Project has been marked by divergent claims about the utility of genomics for improving population health. On the one hand, genomics is viewed as the harbinger of a brave new world in which novel treatments rectify known causes of disease. On the other hand, genomics may have little practical relevance to the principal causes or remedies of diseases which are predominantly social or environmental in origin, particularly in low- and middle-income countries.

Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes.

Background: Adherent and invasive Escherichia coli (AIEC) are commonly found in ileal lesions of Crohn's Disease (CD) patients, where they adhere to intestinal epithelial cells and invade into and survive in epithelial cells and macrophages, thereby gaining access to a typically restricted host niche. Colonization leads to strong inflammatory responses in the gut suggesting that AIEC could play a role in CD immunopathology. Despite extensive investigation, the genetic determinants accounting for the AIEC phenotype remain poorly defined.

Type 2 diabetes mellitus and inflammation: Prospects for biomarkers of risk and nutritional intervention.

Obesity is a major risk factor for type 2 diabetes mellitus (T2DM), which is a significant health problem worldwide. Active disease is associated with low-grade chronic inflammation resulting in part from the activation of the innate immune system. In obesity, this activation leads to the release of pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β and interleukin-6 that block major anabolic cascades downstream of insulin signaling and thus disrupt insulin homeostasis and action.

Lineage and host source are both correlated with levels of Shiga toxin 2 production by Escherichia coli O157:H7 strains.

Escherichia coli O157:H7 strains fall into three major genetic lineages that differ in their distribution among humans and cattle. Several recent studies have reported differences in the expression of virulence factors between E. coli O157:H7 strains from these two host species.

In silico genomic analyses reveal three distinct lineages of Escherichia coli O157:H7, one of which is associated with hyper-virulence.

Background: Many approaches have been used to study the evolution, population structure and genetic diversity of Escherichia coli O157:H7; however, observations made with different genotyping systems are not easily relatable to each other. Three genetic lineages of E. coli O157:H7 designated I, II and I/II have been identified using octamer-based genome scanning and microarray comparative genomic hybridization (mCGH).

Verocytotoxin-producing Escherichia coli (VTEC).

Escherichia coli O157:H7 and other Verocytotoxin-producing E. coli (VTEC) are zoonotic pathogens associated with food and waterborne illness around the world. E.

Enterohemorrhagic Escherichia coli O157:H7 gene expression profiling in response to growth in the presence of host epithelia.

Background: The pathogenesis of enterohemorrhagic Escherichia coli (EHEC) O157:H7 infection is attributed to virulence factors encoded on multiple pathogenicity islands. Previous studies have shown that EHEC O157:H7 modulates host cell signal transduction cascades, independent of toxins and rearrangement of the cytoskeleton. However, the virulence factors and mechanisms responsible for EHEC-mediated subversion of signal transduction remain to be determined.

Host and pathogen determinants of verocytotoxin-producing Escherichia coli-associated hemolytic uremic syndrome.

Verocytotoxin (VT)-producing Escherichia coli (VTEC) infection is associated with a spectrum of clinical manifestations that includes diarrhea, hemorrhagic colitis, and the hemolytic uremic syndrome (HUS). The occurrence of HUS in a minority of individuals in outbreaks of VTEC infection is a function of several pathogen and host factors. Pathogen factors include the inoculum size and serotype of the infecting strain, horizontally acquired genetic elements known as pathogenicity islands, and probably the VT type.