CD39 abrogates platelet-derived factors induced IL-1β expression in the human placenta

Tissue insults in response to inflammation, hypoxia and ischemia are accompanied by the release of ATP into the extracellular space. There, ATP modulates several pathological processes, including chemotaxis, inflammasome induction and platelet activation. ATP hydrolysis is significantly enhanced in human pregnancy, suggesting that increased conversion of extracellular ATP is an important anti-inflammatory process in preventing exaggerated inflammation, platelet activation and hemostasis in gestation. Extracellular ATP is converted into AMP, and subsequently into adenosine by the two major nucleotide-metabolizing enzymes CD39 and CD73. Here, we aimed to elucidate developmental changes of placental CD39 and CD73 over gestation, compared their expression in placental tissue from patients with preeclampsia and healthy controls, and analyzed their regulation in response to platelet-derived factors and different oxygen conditions in placental explants as well as the trophoblast cell line BeWo. Linear regression analysis showed a significant increase in placental CD39 expression, while at the same time CD73 levels declined at term of pregnancy. Neither maternal smoking during first trimester, fetal sex, maternal age, nor maternal BMI revealed any effects on placental CD39 and CD73 expression. Immunohistochemistry detected both, CD39 and CD73, predominantly in the syncytiotrophoblast layer. Placental CD39 and CD73 expression were significantly increased in pregnancies complicated with preeclampsia, when compared to controls. Cultivation of placental explants under different oxygen conditions had no effect on the ectonucleotidases, whereas presence of platelet releasate from pregnant women led to deregulated CD39 expression. Overexpression of recombinant human CD39 in BeWo cells decreased extracellular ATP levels after culture in presence of platelet-derived factors. Moreover, platelet-derived factors-induced upregulation of the pro-inflammatory cytokine, interleukin-1β, was abolished by CD39 overexpression. Our study shows that placental CD39 is upregulated in preeclampsia, suggesting an increasing demand for extracellular ATP hydrolysis at the utero-placental interface. Increased placental CD39 in response to platelet-derived factors may lead to enhanced conversion of extracellular ATP levels, which in turn could represent an important anti-coagulant defense mechanism of the placenta

The sleep architecture of Australian volunteer firefighters during a multi-day simulated wildfire suppression: Impact of sleep restriction and temperature

Ferguson, SA ORCiD: 0000-0002-9682-7971; Jay, SM ORCiD: 0000-0002-1447-7008; Smith, BP ORCiD: 0000-0002-0873-3917; Vincent, GE ORCiD: 0000-0002-7036-7823Wildland firefighting exposes personnel to combinations of occupational and environmental stressors that include physical activity, heat and sleep restriction. However, the effects of these stressors on sleep have rarely been studied in the laboratory, and direct comparisons to field scenarios remain problematic. The aim of this study was to examine firefighters' sleep during a three-day, four-night simulated wildfire suppression that included sleep restriction and physical activity circuits representative of firefighting wildfire suppression tasks in varied temperatures. Sixty-one volunteer firefighters (37.5. ±. 14.5 years of age, mean. ±. SD) were assigned to one of three conditions: control (n=25; 8. h sleep opportunities and 18-20. °C), awake (n=25; 4. h sleep opportunities and 18-20. °C) or awake/hot (n=11; 4. h sleep opportunities and 33-35. °C during the day and 23-25. °C during the night). Results demonstrated that amounts of N1, N2 and R sleep, TST, SOL and WASO declined, whilst sleep efficiency increased significantly in the awake and awake/hot conditions compared to the control condition. Results also demonstrated that SWS sleep remained relatively stable in the awake and awake/hot conditions compared to control values. Most importantly, no significant differences were found for any of the sleep measures between the awake and awake/hot conditions. Thus, working in hot daytime temperatures in combination with sleep restriction during the night did not affect patterns of sleep compared to working in temperate conditions in combination with sleep restriction during the night. However, the effects on sleep of high (>25. °C) night-time temperatures with sleep restriction in addition to physical activity remains to be studied. © 2015 Elsevier Ltd

The sleep architecture of Australian volunteer firefighters during a multi-day simulated wildfire suppression: Impact of sleep restriction and temperature

Wildland firefighting exposes personnel to combinations of occupational and environmental stressors that include physical activity, heat and sleep restriction. However, the effects of these stressors on sleep have rarely been studied in the laboratory, and direct comparisons to field scenarios remain problematic. The aim of this study was to examine firefighters' sleep during a three-day, four-night simulated wildfire suppression that included sleep restriction and physical activity circuits representative of firefighting wildfire suppression tasks in varied temperatures. Sixty-one volunteer firefighters (37.5. ±. 14.5 years of age, mean. ±. SD) were assigned to one of three conditions: control (n=25; 8. h sleep opportunities and 18-20. °C), awake (n=25; 4. h sleep opportunities and 18-20. °C) or awake/hot (n=11; 4. h sleep opportunities and 33-35. °C during the day and 23-25. °C during the night). Results demonstrated that amounts of N1, N2 and R sleep, TST, SOL and WASO declined, whilst sleep efficiency increased significantly in the awake and awake/hot conditions compared to the control condition. Results also demonstrated that SWS sleep remained relatively stable in the awake and awake/hot conditions compared to control values. Most importantly, no significant differences were found for any of the sleep measures between the awake and awake/hot conditions. Thus, working in hot daytime temperatures in combination with sleep restriction during the night did not affect patterns of sleep compared to working in temperate conditions in combination with sleep restriction during the night. However, the effects on sleep of high (>25. °C) night-time temperatures with sleep restriction in addition to physical activity remains to be studied. © 2015 Elsevier Ltd

The effects of hydration on cognitive performance during a simulated wildfire suppression shift in temperate and hot conditions

© 2019 The effects on dehydration and cognitive performance from heat and/or physical activity are well established in the laboratory, although have not yet been studied for personnel working in occupations such as wildland firefighting regularly exposed to these types of conditions. This study aimed to investigate the effects of temperature and dehydration on seventy-three volunteer firefighters (35.7 ± 13.7 years, mean ± standard deviation) during a simulation of wildfire suppression under either control or hot (18–20; or 33–35 °C) temperature conditions. Results showed cognitive performance on the psychomotor vigilance task declined when participants were dehydrated in the heat and Stroop task performance was impaired when dehydrated late in the afternoon. Firefighters may be at risk of deteriorations in simple cognitive functions in the heat whilst dehydrated, although may also experience impairments in complex cognitive functions if dehydrated late in the day, irrespective of the environmental temperature

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination

People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of this study was to investigate the impact of COVID-19 vaccination on the haemostatic system in people with type 1 or type 2 diabetes. We evaluated the effects of COVID-19 vaccination (BioNTech Pfizer, Moderna, AstraZeneca) on standard coagulation parameters, whole blood coagulation (Thrombelastometry), platelet function (impedance aggregation), and thrombin generation (calibrated automated thrombography) in people with type 1 diabetes mellitus (n = 41) and type 2 diabetes mellitus (n = 37). Blood sampling points were prior to vaccination and two weeks after the respective vaccination. Thrombelastometry measurements indicated moderately increased clot formation post-vaccination in people with type 1, as well as with type 2, diabetes: “Clot formation times” were significantly shorter, and both “maximum clot firmness” and “alpha angles” were significantly higher, as compared to the respective pre-vaccination values. Therefore, TEM parameters were not altered after vaccination in patients receiving ASA. Moreover, platelet aggregation was enhanced in people with type 1 diabetes, and plasma levels of D-Dimer were increased in people with type 2 diabetes, following COVID-19 vaccination. All other standard coagulation parameters, as well as thrombin generation, were not affected by the vaccination. The coagulation responses of people with diabetes to COVID-19 vaccination were only subclinical and comparable to those observed in healthy individuals. Our findings suggest that people with diabetes do not face an increased activation of the coagulation post-vaccination