Overexpression of facilitative glucose transporter-3 and membrane procoagulation in maternal platelets of preeclamptic pregnancy.

BACKGROUND: Preeclampsia (PE) is a hypertensive disorder during pregnancy that results in significant adverse maternal and neonatal outcomes. Platelet activation is present in PE and contributes to the thrombo-hemorrhagic states of the disorder. However, the mechanisms that initiate and/or sustain platelet activation in PE are ill-defined. OBJECTIVES: We aimed to characterise this mechanism and the procoagulant potentials of platelets in PE. METHODS: In this quantitative observational study, we analyzed platelet procoagulant membrane dynamics in patients with PE (n = 21) compared with age-matched normotensive pregnancies (n = 20), gestational hypertension (n = 10), and non-pregnant female controls (n = 19). We analyzed fluorescently labeled indicators of platelet activation, bioenergetics, and procoagulation (phosphatidylserine exposure and thrombin generation), coupled with high-resolution imaging and thrombelastography. We then validated our findings using flow cytometry, immunoassays, classical pharmacology, and convolutional neural network analysis. RESULTS: PE platelets showed significant ultra-structural remodeling, are more extensively preactivated than in healthy pregnancies and can circulate as microaggregates. Preactivated platelets of PE externalized phosphatidylserine and thrombin formed on the platelet membranes. Platelets' expression of facilitative glucose transporter-1 increased in all pregnant groups. However, PE platelets additionally overexpress glucose transporter-3 to enhance glucose uptake and sustain activation and secretion events. Although preeclampsia platelets exposed to subendothelial collagen showed incremental activation, the absolute hemostatic response to collagen was diminished, and likely contributed to greater blood loss perioperatively. CONCLUSIONS: We revealed 2 bioenergetic mediators in the mechanism of sustained platelet procoagulation in preeclampsia. Although glucose transporter-1 and glucose transporter-3 remain elusive antiprocoagulant targets, they may be sensitive monitors of PE onset and progression.

Hypercoagulability and Inflammatory Markers in a Case of Congenital Thrombotic Thrombocytopenic Purpura Complicated by Fetal Demise.

BACKGROUND: Congenital thrombotic thrombocytopenic purpura (cTTP) is a rare disorder caused by an inherited genetic deficiency of ADAMTS13 and affects less than one per million individuals. Patients who are diagnosed with TTP during pregnancy are at increased risk of maternal and fetal complications including fetal demise. We present a case of a 32-year-old G3P0 (gravida 3, para 0) who presented at 20 weeks gestation with a new diagnosis of congenital TTP (cTTP) and fetal demise. METHODS: We describe the pathophysiology of pregnancy complications in a patient with cTTP using platelet procoagulant membrane dynamics analysis and quantitative proteomic studies, compared to four pregnant patients with gestational hypertension, four pregnant patients with preeclampsia, and four healthy pregnant controls. RESULTS: The cTTP patient had increased P-selectin, tissue factor expression, annexin-V binding on platelets and neutrophils, and localized thrombin generation, suggestive of hypercoagulability. Among 15 proteins that were upregulated, S100A8 and S100A9 were distinctly overexpressed. CONCLUSIONS: There is platelet-neutrophil activation and interaction, platelet hypercoagulability, and proinflammation in our case of cTTP with fetal demise.

Proteomics and Metabolomics Profiling of Platelets and Plasma Mediators of Thrombo-Inflammation in Gestational Hypertension and Preeclampsia.

Platelets may be pivotal mediators of the thrombotic and coagulopathic complications of preeclampsia (PE), linking inflammation and thrombosis with endothelial and vascular dysfunction. Both PE and gestational hypertension (GH) fall within the spectrum of hypertensive complications of pregnancy, with GH being a risk factor for preeclampsia. However, it is unclear what biomarkers distinguish PE from GH. Using a discovery size cohort, we aimed to characterize specific plasma and platelet thrombo-inflammatory drivers indicative of PE and differentiate PE from GH. We performed multiplex immunoassays, platelet and plasma quantitative proteomics and metabolomics of PE patients, comparing with non-pregnant (NP), healthy pregnant controls (PC) and GH participants. The expression pattern of plasma proteins and metabolites in PE/GH platelets was distinct from that of NP and PC. Whilst procoagulation in PC may be fibrinogen driven, inter-alpha-trypsin inhibitors ITIH2 and ITIH3 are likely mediators of thrombo-inflammation in GH and PE, and fibronectin and S100A8/9 may be major procoagulant agonists in PE only. Also enriched in PE were CCL1 and CCL27 plasma cytokines, and the platelet leucine-rich repeat-containing protein 27 and 42 (LRRC27/42), whose effects on platelets were explored using STRING analysis. Through protein-protein interactions analysis, we generated a new hypothesis for platelets' contribution to the thrombo-inflammatory states of preeclampsia.

Coxiella burnetii in the environment: A systematic review and critical appraisal of sampling methods.

Q fever is a zoonotic disease caused by the intracellular bacterium, Coxiella burnetii. Its primary mode of transmission is by inhalation of aerosols originating from infected animals and contaminated environments. The organism has a very low infective dose, can persist in the environment for long periods of time and large outbreaks fuelled by windborne spread have been previously reported. Detection of C. burnetii in the environment is therefore important during human and animal outbreak investigations and for the control and prevention of Q fever. This study aimed to systematically review and critically appraise the published literature on sampling methods used to detect C. burnetii from different environmental samples. A search of four electronic databases with subsequent hand searching identified 47 eligible articles published since 1935. These articles described sampling of dust, air, soil and liquids in attempts to detect C. burnetii during 19 Q fever outbreaks and in 28 endemic settings. Environmental positivity was most commonly associated with ruminant livestock populations. Evidence describing spatio-temporal characteristics and associated geographical dispersion gradients was limited. The most commonly tested sample type was dust which also yielded the highest bacterial loads of >108 bacteria/cloth. The MD8 (Sartorius) air sampler was used widely for air sampling. Soil was the only sample type for which a validated laboratory protocol was established specifically for C. burnetii. Each environmental sample type has its advantages and limitations which are discussed in detail and a simplified framework to guide decisions around environmental sampling for C. burnetii is provided. In any type of environmental sampling, it is recommended to use standardized and validated methods and to match the most ideal sampling strategy and timing with the research context. These conditions are essential to be considered when designing future Q fever management plans that involve environmental sampling for C. burnetii.

Bioconversion of paper mill sludge to bioethanol in the presence of accelerants or hydrogen peroxide pretreatment.

In this study we investigated the technical feasibility of convert paper mill sludge into fuel ethanol. This involved the removal of mineral fillers by using either chemical pretreatment or mechanical fractionation to determine their effects on cellulose hydrolysis and fermentation to ethanol. In addition, we studied the effect of cationic polyelectrolyte (as accelerant) addition and hydrogen peroxide pretreatment on enzymatic hydrolysis and fermentation. We present results showing that removing the fillers content (ash and calcium carbonate) from the paper mill sludge increases the enzymatic hydrolysis performance dramatically with higher cellulose conversion at faster rates. The addition of accelerant and hydrogen peroxide pretreatment further improved the hydrolysis yields by 16% and 25% (g glucose / g cellulose), respectively with the de-ashed sludge. The fermentation process of produced sugars achieved up to 95% of the maximum theoretical ethanol yield and higher ethanol productivities within 9h of fermentation.

Leisure-Time Physical Activity Does not Attenuate the Association Between Occupational Sedentary Behavior and Obesity: Results From Alberta's Tomorrow Project.

BACKGROUND: Sedentary behavior has been proposed as a risk factor for obesity that is distinct from physical inactivity. This study aimed to examine the association between occupational sedentary behavior and obesity, and to determine if this association is independent of leisure-time physical activity (LTPA). METHODS: Fully employed participants enrolled between 2001 and 2008 to Alberta's Tomorrow Project, a prospective cohort study in Alberta, Canada, were studied (n = 12,409). Associations between occupational sedentary behavior and waist circumference (WC), waist-to-hip ratio (WHR), and body mass index (BMI) were examined using multiple binary and multinomial logistic regressions. RESULTS: In men, a positive association was observed between daily occupational sedentary hours and WC, WHR, BMI, and with high risk profiles that incorporated both BMI and WC (P < .01). Controlling for vigorous-intensity LTPA in all models strengthened associations between sedentary behavior and measures of obesity. In contrast, inverse associations were observed for occupational sedentary hours and WHR for women (P < .05). CONCLUSIONS: In fully employed men, occupational sedentary behavior was positively associated with obesity risk that was not attenuated by physical activity. In women, an increase in obesity risk was not observed with sedentary behavior. Gender differences in the health effects of sedentary behavior require further study.

Development and testing of a past year measure of sedentary behavior: the SIT-Q.

BACKGROUND: Most sedentary behavior measures focus on occupational or leisure-time sitting. Our aim was to develop a comprehensive measure of adult sedentary behavior and establish its measurement properties. METHOD: The SIT-Q was developed through expert review (n = 7), cognitive interviewing (n = 11) and pilot testing (n = 34). A convenience sample of 82 adults from Calgary, Alberta, Canada, participated in the measurement property study. Test-retest reliability was assessed by intraclass correlation coefficients (ICCs) comparing two administrations of the SIT-Q conducted one month apart. Convergent validity was established using Spearman's rho, by comparing the SIT-Q estimates of sedentary behaviour with values derived from a 7-Day Activity Diary. RESULTS: The SIT-Q exhibited good face validity and acceptability during pilot testing. Within the measurement property study, the ICCs for test-retest reliability ranged from 0.31 for leisure-time computer use to 0.86 for occupational sitting. Total daily sitting demonstrated substantial correlation (ICC = 0.65, 95% CI: 0.49, 0.78). In terms of convergent validity, correlations varied from 0.19 for sitting during meals to 0.76 for occupational sitting. For total daily sitting, estimates derived from the SIT-Q and 7 Day Activity Diaries were moderately correlated (ρ = 0.53, p < 0.01). CONCLUSION: The SIT-Q has acceptable measurement properties for use in epidemiologic studies.