Coexistence of vitreous and crystalline phases of H2O at ambient temperature

Formation of vitreous ice during rapid compression of water at room temperature is important for biology and the study of biological systems. Here, we show that Raman spectra of rapidly compressed water at greater than 1 GPa at room temperature exhibits the signature of high-density amorphous ice, whereas the X-ray diffraction (XRD) pattern is dominated by crystalline ice VI. To resolve this apparent contradiction, we used molecular dynamics simulations to calculate full vibrational spectra and diffraction patterns of mixtures of vitreous ice and ice VI, including embedded interfaces between the two phases. We show quantitatively that Raman spectra, which probe the local polarizability with respect to atomic displacements, are dominated by the vitreous phase, whereas a small amount of the crystalline component is readily apparent by XRD. The results of our combined experimental and theoretical studies have implications for detecting vitreous phases of water, survival of biological systems under extreme conditions, and biological imaging. The results provide additional insight into the stable and metastable phases of H₂O as a function of pressure and temperature, as well as of other materials undergoing pressure-induced amorphization and other metastable transitions.

Life as we know it on Earth depends on water. However, water also poses a critical challenge to life when it freezes at atmospheric pressure and low temperatures. The crystallization of H₂O to form hexagonal ice (ice Ih) under these conditions is accompanied by its well-known expansion, which has a dramatic impact on the structure and function of living cells. This crystallization of H₂O disrupts biological membranes and intracellular organization in living organisms and also displaces and concentrates salts and nutrients in the space between crystals (1). Like many liquids, however, rapid cooling of H₂O at ambient pressure to below its glass-transition temperature results in the formation of an amorphous phase known as low-density amorphous ice. Amorphous solid H₂O provides a chance for biological functions to survive where life otherwise cannot exist. Low-density amorphous ice is not the only amorphous form of H₂O. Ice I_h transforms to high-density amorphous (HDA) ice by application of ∼1 GPa of pressure at temperatures below 130 K (2, 3). In addition, a distinct, very-high-density amorphous state (vHDA) can form by isobaric heating and cooling of the HDA (4). low-density amorphous, high-density amorphous, and very-high-density amorphous state ice thus represent the three dominant, solid amorphous forms of H₂O at low temperatures.Solid amorphous phases of H₂O are broadly important in biology and biological applications. That amorphous H₂O which can exist over a broad range of temperatures, from cryogenic conditions to room temperature, is particularly interesting in the context of biological systems. Managing ice crystals is vital for extremophiles to survive damaging effects of H₂O crystallization. These organisms inhibit the growth of ice crystals and regulate the size and shape of the crystals using special antifreeze proteins (5, 6). Additionally, amorphous phases of H₂O are important in preserving biological samples in cryotomography applications. In cryotomography, the amorphous H₂O at low temperature is utilized routinely for sample preparation (7, 8), and significant efforts have been devoted to increase information obtained from cryotomography techniques. The low-temperature regime of amorphous H₂O routinely accessed in cryotomography creates challenges for light microscopy due to freezing of index-matching medium and objectives, which result in lowering the resolution of light microscopy in these applications. Room-temperature amorphous phases of H₂O are, therefore, advantageous for light microscopy applications and further development of techniques such as correlative light and electron microscopy (9–11).While formation of amorphous phases of H₂O below 200 K has been reported in many studies (2, 3, 12–16), a particularly interesting result is the observation of the Raman signature of HDA ice during fast compression of water at room temperature and moderate pressures (17). On the other hand, independent X-ray diffraction (XRD) measurements of H₂O on fast compression could not verify the formation of amorphous H₂O above 200 K (18). Here, we report high-resolution micro-Raman and synchrotron XRD measurements conducted in parallel in rapidly compressed samples of water in diamond anvil cells (DACs). Our findings, that are supported by molecular dynamics simulations, shed light on the nature of the HDA ice at room temperature and reconciled conflicting previous reports.     

维A类化合物4-APR抑制肿瘤侵袭、转移的作用

用体内外实验模型,研究了新维A类化合物4-乙酰胺苯基维A酸酯(4-APR)对肿瘤侵袭、转移的抑制作用。4-APR 43.3mg·kg^-1po即能减少小鼠Lewis肺癌的自发性肺转移瘤数。半体内实验证明4-APR10^-5mol·L^-1和10^-6mol·L^-1对B16-F10癌细胞的人工肺转移瘤数分别抑制67.9%和36.6%。体外实验显示,4-APR对B16-F10细胞侵袭重组基底膜的抑制率分别为54.2%和41.9%。     

Handheld Echocardiography: Its Role in Intensive Care Units

Hand-held echocardiography (HHE) is being explored for use in the intensive care arena as an extension of the physical examination for real time and iterative information. HHE can help assess chamber size, ventricular function, and presence of fluid collections, and thus is useful in determining etiology of shock and measuring volume status. With additional outcomes and cost-effectiveness research, development of appropriate indications for HHE, and multisociety guidelines on competence assessment and quality control, HHE is expected to be increasingly integrated into intensive care medicine.     

Proximal External Aortic Compression for Life-Threatening Abdominal-Pelvic and Junctional Hemorrhage: An Ultrasonographic Study in Adult Volunteers

Introduction: Following life-threatening junctional trauma, the goal is to limit blood loss while expediting transfer to operative rescue. Unfortunately, life-threatening abdominal-pelvic or junctional hemorrhage is often not amenable to direct compression and few temporizing strategies are available beyond hemostatic dressings, hypotensive resuscitation, and balanced transfusion. Objectives: In this study, we evaluated proximal external aortic compression to arrest blood flow in healthy adult men. Methods: This was a simulation trial of proximal external aortic compression, for life-threatening abdominal-pelvic and junctional hemorrhage, in a convenience sample of healthy adult male volunteers. The primary end points were cessation of femoral blood flow as assessed by pulse wave Doppler ultrasound at the right femoral artery, caudal to the inguinal ligament. Secondary end points were discomfort and negative sequelae. Results: Aortic blood flow was arrested in 12 volunteers. Median time to blood flow cessation was 12.5?seconds. Median reported discomfort was 5 out of 10. No complications or negative sequelae were reported. Conclusion: This trial suggests that it may be reasonable to attempt temporization of major abdominal-pelvic and junctional hemorrhage using bimanual proximal external aortic compression. In the absence of immediate alternatives for this dangerous and vexing injury pattern, there appear to be few downsides to prehospital proximal external aortic compression while concomitantly expediting definite care.     

Evaluation of an education program of patients undergoing oral anticoagulation treatment

OBJECTIVE: To evaluate the therapeutic impact of an education program on patients undergoing oral anticoagulation treatment, within the hospital of Annecy (France). MATERIAL AND METHODS: Groups of 10 patients were invited to participate to two meetings. The education was carried out by two nurses. Thanks to this prospective study, we compare the population before and after education in terms of treatment knowledge and stability. RESULTS: Within 9 months 88 patients have been included, amongst which 55 have attended the two meetings. The average of correct answers to the knowledge evaluation questionnaire distributed before and after 6 months of education were, respectively, 6.63/12, 10.09/12 (P < 0.0001). Through INR controls within the 6 months preceding (424 controls) and the 6 months following the education (619 controls), we observe: an increase of the total INR average in therapeutic zone, from 45% to 61% (P < 0.0001); a decrease of the difference average per patient between the INR value observed and the one targeted: 0.54 before education, 0.40 after education (P = 0.0016); at last, the average phasing per patient under the therapeutic zone increases after education, from 49% to 65% (P < 0.001). CONCLUSION: The education improves objectively the knowledge of patient undergoing AVK. If the size of patient sample is not large enough to prove any consequence on hemorrhagic or thrombotic complications, the education program still improves significantly the treatment stability.     

Comparison of dobutamine stress echocardiography with and without real-time perfusion imaging for detection of coronary artery disease

In a pilot study of 27 patients, those who presented with chest pain underwent 2 dobutamine stress echocardiographic studies, 1 with high mechanical index harmonic imaging to analyze wall motion without contrast and 1 with real-time low mechanical index perfusion imaging with intravenous Optison to assess myocardial perfusion and wall motion. All patients then underwent quantitative coronary angiography. Two independent reviewers demonstrated an improvement in sensitivity when analyzing myocardial perfusion. In the 21 patients who had significant coronary stenoses, 14 had abnormal myocardial perfusion detected at peak stress and 7 had abnormal wall motion detected by standard dobutamine stress echocardiography. There was decreased specificity with perfusion imaging by 1 reviewer. The addition of real-time perfusion imaging after intravenous contrast during dobutamine stress echocardiography has the potential to improve detection of coronary artery disease.     

POLLAR: Impact of air POLLution on Asthma and Rhinitis; a European Institute of Innovation and Technology Health (EIT Health) project

Allergic rhinitis (AR) is impacted by allergens and air pollution but interactions between air pollution, sleep and allergic diseases are insufficiently understood. POLLAR (Impact of air POLLution on sleep, Asthma and Rhinitis) is a project of the European Institute of Innovation and Technology (EIT Health). It will use a freely-existing application for AR monitoring that has been tested in 23 countries (the Allergy Diary, iOS and Android, 17,000 users, TLR8). The Allergy Diary will be combined with a new tool allowing queries on allergen, pollen (TLR2), sleep quality and disorders (TRL2) as well as existing longitudinal and geolocalized pollution data. Machine learning will be used to assess the relationship between air pollution, sleep and AR comparing polluted and non-polluted areas in 6 EU countries. Data generated in 2018 will be confirmed in 2019 and extended by the individual prospective assessment of pollution (portable sensor, TLR7) in AR. Sleep apnea patients will be used as a demonstrator of sleep disorder that can be modulated in terms of symptoms and severity by air pollution and AR. The geographic information system GIS will map the results. Consequences on quality of life (EQ-5D), asthma, school, work and sleep will be monitored and disseminated towards the population. The impacts of POLLAR will be (1) to propose novel care pathways integrating pollution, sleep and patients’ literacy, (2) to study sleep consequences of pollution and its impact on frequent chronic diseases, (3) to improve work productivity, (4) to propose the basis for a sentinel network at the EU level for pollution and allergy, (5) to assess the societal implications of the interaction. MASK paper N°32.     

Mutations in promoter region of thrombomodulin and venous thromboembolic disease

The present study was designed to analyze the thrombomodulin proximal promoter region spanning nucleotides -293 to -12 to search for polymorphisms that could modify thrombomodulin gene expression in patients with venous thromboembolic disease. The study population comprised 205 patients and 394 healthy subjects of similar age and sex distribution. No polymorphisms and only 1 point mutation (G-33A) were found. The G-33A mutation was present at the heterozygous state in 2 patients and in 1 control. Being more frequent in the patients (0.97%) than in the controls (0.25%), the G-33A mutation might be a risk factor for venous thrombosis. To investigate the effect of this mutation on the thrombomodulin promoter activity, the proximal promoter region of the gene (bearing or not bearing the G-33A mutation) was inserted into a promotorless expression vector, upstream of the firefly luciferase gene, and transiently transfected into EA.hy926 endothelial cells. Under the conditions of the assay, the G-33A mutation mildly decreased the promoter activity. This study confirms that abnormalities of the thrombomodulin proximal promoter are not frequent in patients with venous thromboembolism.     

Molecular bases of antithrombin deficiency in French families: identification of seven novel mutations in the antithrombin gene

We have investigated the molecular bases of familial antithrombin deficiency in eight French families. Eight mutations in the antithrombin coding exons were identified, seven of which were novel mutations. In all cases, individuals were heterozygous for the mutation. We found two small frameshift deletions in exon 3a, leading to type I deficiency. Five missense mutations in exons 3b or 5 also caused type I deficiency and their potential consequences on the antithrombin three-dimensional structure were analysed. The last mutation in exon 4 was associated with a type II 'reactive site' deficiency: a dysfunctional antithrombin that is affected in its interaction with thrombin was present in circulation.