Purification and partial characterization of draculin, the anticoagulant factor present in the saliva of vampire bats (<i>Desmodus rotundus</i>)

From the saliva of the vampire bat Desmodus rotundus, we isolated an unknown anticoagulant protein which we have named draculin. Its molecular mass as determined by non-reduced SDS-PAGE is about 83 kDa. The reduced polypeptide shows a slower migration. HPLC in a molecular sieve matrix yields a single, symmetrical peak corresponding to 88.5 kDa. Isoelectric focusing shows an acidic protein with pI = 4.1–4.2. Aminoacid analysis is compatible with a single chain polypeptide of about 80 kDa. Cyanogen bromide cleavage yields a single 16-aminoacid peptide, corresponding to the amino-terminus of the native molecule. Draculin inhibits the activated form of coagulation factors IX and X. It does not act on thrombin, trypsin, chymotrypsin and does not express fibrinolytic activity. The inhibition is immediate and not readily reversible, with a stoichiometry of about two molecules of draculin per molecule of factor IXa or Xa. Surprisingly, the inhibitory activity against either factor is not affected by the presence of the other. Draculin binds quantitatively to either immobilised factor Xa or factor IXa. Our preliminary interpretation is that there are two forms of draculin that hardly differ in structure. Both bind to factor Xa and to factor IXa but one form inhibits factor Xa and the other inhibits factor IXa. When added to plasma, draculin increases the lag phase as well as the height of the peak of thrombin generation

Global material flow analysis of glass: From raw materials to end of life

Abstract: Global glass production grew to 150 million tonnes (Mt) in 2014, equating to approximately 21 kg per person. Producing this glass is energy intensive and contributes annual CO2 emissions of some 86Mt. An accurate map of the global glass supply chain is needed to help identify emissions mitigation options from across the supply chain, including process energy efficiency and material efficiency options. This map does not yet exist, so we address this knowledge gap by tracing the production chain from raw materials to end of life and producing a global Sankey diagram of container and flat glass making for 2014. To understand future demand for flat glass we also model the stocks of glass in vehicles and buildings. The analysis shows the relative scale of glass flows and stocks worldwide and provides a baseline for future study of the emission mitigation potential of energy and material efficiency of manufacturing with glass

Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients. METHODS: All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0-2, 3-7, 8-14, 15-21, and 22-28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival. RESULTS: Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0-2 (33 (14-64) vs. 11 (4-26) pmol/L; p < 0.001). Serum copeptin at admission was shown to be a predictor of mortality independently of MELD and CLIF-C OF scores. Moreover, baseline serum copeptin was found to be predictive of ACLF development within 28 days of follow-up. CONCLUSIONS: ACLF is associated with significantly higher serum copeptin concentrations at hospital admission compared with those with traditional AD. Copeptin is independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF

An investigation into the correlation of vitamin D status and management outcomes in patients with severe COVID-19 at a South African tertiary hospital

Background: Severe coronavirus disease 2019 (COVID-19) has a poor prognosis, and biomarkers may predict disease severity. The aim of this study was to assess the effect of baseline vitamin D (VitD) inadequacy on the outcomes of patients with severe COVID-19 admitted to the intensive care unit (ICU) of a tertiary hospital in South Africa. // Methods: Patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were recruited during wave II of the pandemic in Cape Town. Eighty-six patients were included in the study. They were categorized into three groups: VitD deficient, VitD insufficient, and VitD sufficient. The VitD deficient and VitD insufficient groups were combined to form a ‘VitD inadequate’ group. Cox regression analysis was done to assess the association between VitD status and mortality. Factors with P < 0.05 in the adjusted multivariable Cox regression analysis were considered statistically significant. // Results: The proportion of VitD inadequacy was 64% (55/86); this group had a significantly higher proportion with hypertension (66%; P = 0.012). The Kaplan–Meier curve showed no significant difference in the probability of survival among the COVID-19 patients admitted to the ICU with or without VitD inadequacy. However, patients with elevated serum creatinine were significantly more at risk of dying (adjusted hazard ratio 1.008, 95% confidence interval 1.002–1.030; P = 0.017). // Conclusions: This study found a high prevalence of VitD inadequacy (combined deficiency and insufficiency) in COVID-19 patients admitted to the ICU. This may indicate a possible risk of severe disease. Whilst there was no statistically significant relationship between VitD status and mortality in this cohort, baseline VitD may be an important prognostic biomarker in COVID-19 patients admitted to the ICU, particularly in those with comorbidities that predispose to VitD deficiency

European Guideline Robin Sequence An Initiative from the European Reference Network for Rare Craniofacial Anomalies and Ear, Nose and Throat Disorders (ERN-CRANIO)

A European guideline on Robin Sequence was developed within the European Reference Network for rare and/or complex craniofacial anomalies and ear, nose, and throat disorders. The guideline provides an overview of optimal care provisions for patients with Robin Sequence and recommendations for the improvement of care.</p

Primary Posterior Tracheopexy in Esophageal Atresia Decreases Respiratory Tract Infections

Background: Esophageal atresia (EA) is often accompanied by tracheomalacia (TM). TM can lead to severe respiratory complaints requiring invasive treatment. This study aims to evaluate if thoracoscopic primary posterior tracheopexy (PPT) can prevent the potential sequelae of TM in patients with EA. Methods: A cohort study including all consecutive EA patients treated between 2014 and July 2019 at the Wilhelmina Children's Hospital was conducted. Two groups were distinguished: (group 1) all EA patients born between January 2014 and December 2016 and (group 2) all EA patients born between January 2017 and July 2019, after introduction of PPT. In the latter group, PPT was performed in EA patients with moderate (33–66%) or severe (67–100%) tracheomalacia, seen during preoperative bronchoscopy. Group differences were assessed using the Fisher's exact test for bivariate variables and the Mann–Whitney U-test for continuous variables. Results: A total of 64 patients were included in this study (28 patients in group 1; 36 patients in group 2). In group 2, PPT was performed in 14 patients. Respiratory tract infections (RTIs) requiring antibiotics within the first year of life occurred significantly less in group 2 (61 vs. 25%, p = 0.004). Brief resolved unexplained events (BRUEs) seemed to diminish in group 2 compared to group 1 (39 vs. 19%, p = 0.09). Conclusion: Thoracoscopic primary posterior tracheopexy decreases the number of respiratory tract infections in EA patients. The clinical impact of reducing RTIs combined with the minimal additional operating time and safety of PPT outweighs the risk of overtreatment

Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis

BACKGROUND & AIMS: Research on vasopressin (AVP) in cirrhosis and its role in the assessment of prognosis has been hindered by the difficulty of measuring AVP levels accurately. Copeptin, a 39-aminoacid glycopeptide, is released from the neurohypophysis together with AVP. Copeptin could have a role as biomarker of prognosis in cirrhosis as it may reflect circulatory dysfunction. The aim of this study is to investigate the role of copeptin as biomarker of disease progression and prognosis in cirrhosis. METHODS: This prospective study is divided in 2 study protocols including 321 consecutive patients. Plasma copeptin levels were measured in all patients at study inclusion. Protocol 1: to investigate the relationship of copeptin with kidney and circulatory function (56 patients). Protocol 2: to investigate the relationship between copeptin and prognosis, as assessed by the development of complications of cirrhosis or mortality at 3months (265 patients admitted to hospital for complications of cirrhosis). RESULTS: Patients with decompensated cirrhosis showed significantly higher plasma copeptin levels compared to those of patients with compensated cirrhosis. Copeptin levels had a significant positive correlation with model for end-satge liver disease (MELD) score, AVP, endogenous vasoconstrictor systems, and kidney function parameters. Patients developing complications of cirrhosis or mortality had significantly higher plasma copeptin levels compared to those of the remaining patients. Plasma copeptin levels were an independent predictive factor of both the development of complications and mortality at 3months. This was confirmed in a validation series of 120 patients. CONCLUSIONS: Copeptin is a novel biomarker of disease progression and prognosis in cirrhosis. LAY SUMMARY: Copeptin is a fragment of the vasopressin precursor, a hormone that is known to be increased in patients with cirrhosis and that plays a role in the development of complications of the disease. Vasopressin is difficult to measure, but copeptin is a more stable molecule and is easier to measure in blood. Solà and Kerbert and colleagues have shown in a series of 361 patients that copeptin is markedly increased in patients with cirrhosis who develop complications during the following 3months, compared to those patients who do not develop complications. Moreover, copeptin correlates with prognosis

Study Protocol PROMETHEUS:Prospective Multicenter Study to Evaluate the Correlation Between Safety Margin and Local Recurrence After Thermal Ablation Using Image Co-registration in Patients with Hepatocellular Carcinoma

Purpose: The primary objective is to determine the minimal ablation margin required to achieve a local recurrence rate of 18 years with Barcelona Clinic Liver Cancer stage 0/A hepatocellular carcinoma (or B with a maximum of two lesions < 5 cm each) are eligible. Patients will undergo dual-phase contrast-enhanced computed tomography directly before and after ablation. Ablation margins will be quantitatively assessed using co-registration software, blinding assessors (i.e. two experienced radiologists) for outcome. Presence and location of recurrence are evaluated independently on follow-up scans by two other experienced radiologists, blinded for the quantitative margin analysis. A sample size of 189 tumors (~ 145 patients) is required to show with 80% power that the risk of local recurrence is confidently below 10%. A two-sided binomial z-test will be used to test the null hypothesis that the local recurrence rate is ≥ 10% for patients with a minimal ablation margin ≥ 2 mm. Logistic regression will be used to find the relationship between minimal ablation margins and local recurrence. Kaplan–Meier estimates are used to assess local and overall recurrence, disease-free and overall survival. Discussion: It is expected that this study will result in a clear understanding of the correlation between ablation margins and local recurrence. Using co-registration software in future patients undergoing ablation for hepatocellular carcinoma may improve intraprocedural evaluation of technical success. Trial registration The Netherlands Trial Register (NL9713), https://www.trialregister.nl/trial/9713