SummaryThe area under the thrombin generation curve (the endogenous thrombin potential; ETP) has been proposed as a parameter for plasma-based hypercoagulability and to monitor anticoagulant treatment. We present an ETP assay for the routine laboratory using a centrifugal analyser. Throughput is 30 samples/h, within and between run imprecision is 4-5.6%. Suitable substrates were developed for the ranges of 10-500% and 2-100% of normal.Independent of tissue factor concentration (if >4 pM), the normal value of the extrinsic ETP is 384.8 ±51.7 nM.min. The intrinsic ETP, triggered by ellagic acid, is 414 ± 41 nM.min.The ETP is decreased to 15 and 35% of normal by oral anticoagulation (INR 2.5-4.0) and by heparin administration (APTT 1.5-2.5 X control).The ETP is increased in untreated subjects with congenital antithrombin deficiency and in women using oral contraceptives. In deep vein thrombosis (phlebographically confirmed), it is increased by 29.4% (extrinsic) and 53% (intrinsic). In (angiographically assessed) coronary artery disease the increase is by 10% and 17% respectively.

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The Bacillus cereus group comprises multiple species capable of causing emetic or diarrheal foodborne illness. Despite being responsible for tens of thousands of illnesses each year in the U.S. alone, whole-genome sequencing (WGS) is not yet routinely employed to characterize B. cereus group isolates from foodborne outbreaks. Here, we describe the first WGS-based characterization of isolates linked to an outbreak caused by members of the B. cereus group. In conjunction with a 2016 outbreak traced to a supplier of refried beans served by a fast food restaurant chain in upstate New York, a total of 33 B. cereus group isolates were obtained from human cases ( n = 7) and food samples ( n = 26). Emetic ( n = 30) and diarrheal ( n = 3) isolates were most closely related to B. paranthracis (group III) and B. cereus sensu stricto (group IV), respectively. WGS indicated that the 30 emetic isolates (24 and 6 from food and humans, respectively) were closely related and formed a well-supported clade distinct from publicly available emetic group III genomes with an identical sequence type (ST 26). The 30 emetic group III isolates from this outbreak differed from each other by a mean of 8.3 to 11.9 core single nucleotide polymorphisms (SNPs), while differing from publicly available emetic group III ST 26 B. cereus group genomes by a mean of 301.7–528.0 core SNPs, depending on the SNP calling methodology used. Using a WST-1 cell proliferation assay, the strains isolated from this outbreak had only mild detrimental effects on HeLa cell metabolic activity compared to reference diarrheal strain B. cereus ATCC 14579. We hypothesize that the outbreak was a single source outbreak caused by emetic group III B. cereus belonging to the B. paranthracis species, although food samples were not tested for presence of the emetic toxin cereulide. In addition to showcasing how WGS can be used to characterize B. cereus group strains linked to a foodborne outbreak, we also discuss potential microbiological and epidemiological challenges presented by B. cereus group outbreaks, and we offer recommendations for analyzing WGS data from the isolates associated with them.

Abstract:The increasing pressure on health resources has led to the emergence of risk assessment as an essential tool in the management of cardiovascular disease (CVD). Concern exists regarding the validity of their generalization to all populations. Existing risk scoring models do not incorporate emerging 'novel' risk factors. In this context, the aim of the study was to examine the relevance of British, European, and Framingham predictive CVD risk scores to the asymptomatic high risk Indian population. Blood samples drawn from the participants were analyzed for various 'traditional' and 'novel' biomarkers, and their CVD risk factor profi ling was also done. The Framingham model defi ned only 5% of the study cohort to be at high risk, which appears to be an underestimation of CVD risk in this genetically predisposed population. These subjects at high risk had signifi cantly elevated levels of lipid, pro-infl ammatory, pro-thrombotic, and serological markers. It is more relevant to develop risk predictive scores for application to the Indian population. This study substantiates the argument that alternative approaches to risk stratifi cation are required in order to make them more adaptable and applicable to different populations with varying risk factor and disease patterns.

The prevalence of the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene in Asian Indians from India was determined and the association of the mutant allele with coronary artery disease (CAD) was evaluated in a case-control study. The case group consisted of 251 patients with CAD; 195 male and 56 female aged from 29 to 82 years (mean age +/- SD, 57.5 +/- 10.6 years). The control group consisted of 216 apparently healthy individuals without evidence of CAD; 161 male and 55 female aged from 30 to 83 years (mean age +/- SD, 54.9 +/- 10.4 years). All the patients were assessed by coronary angiography. While 33 patients had normal coronaries, 23, 25 and 39 patients had single-vessel, two-vessel and triple-vessel disease, respectively. Eighty-three patients (33%) had suffered myocardial infarction less than a year to five years earlier. The C677T polymorphism in the MTHFR gene was assessed. While 31% of the controls and 38% of the patients had the heterozygous genotype, 2% of the control group and none of the patients had the mutant homozygous genotype. The overall 'T' allelic frequencies were comparable in control and patient groups (0.18 and 0.19, respectively), but the association of the sum of heterozygous and homozygous genotypes with CAD (1, 2 or 3-vessel disease) was statistically significant for females only [Odds ratio (95% confidence intervals), 2.8 (1.1-6.9), p = 0.023]. No association was found between genotype distribution and previous myocardial infarction or severity of atherosclerosis.