There is a need to develop early biomarkers of acute kidney injury following cardiac surgery, where morbidity and mortality are increased by its presence. Plasma cystatin C (CyC) and plasma and urine ...Neutrophil Gelatinase Associated Lipocalin (NGAL) have been shown to detect kidney injury earlier than changes in plasma creatinine in critically ill patients. In order to determine the utility of urinary CyC levels as a measure of kidney injury, we prospectively collected plasma and urine from 72 adults undergoing elective cardiac surgery for analysis. Acute kidney injury was defined as a 25% or greater increase in plasma creatinine or renal replacement therapy within the first 72 hours following surgery. Plasma CyC and NGAL were not useful predictors of acute kidney injury within the first 6 hours following surgery. In contrast, both urinary CyC and NGAL were elevated in the 34 patients who later developed acute kidney injury, compared to those with no injury. The urinary NGAL at the time of ICU arrival and the urinary CyC level 6 hours after ICU admission were most useful for predicting acute kidney injury. A composite time point consisting of the maximum urinary CyC achieved in the first 6 hours following surgery outperformed all individual time points. Our study suggests that urinary CyC and NGAL are superior to conventional and novel plasma markers in the early diagnosis of acute kidney injury following adult cardiac surgery.
Molecular dynamics (MD) simulations are increasingly used to elucidate relationships between protein structure, dynamics, and their biological function. Currently, it is extremely challenging to ...perform MD simulations of large-scale structural rearrangements in proteins that occur on millisecond timescales or beyond, as this requires very significant computational resources, or the use of cumbersome “collective variable” enhanced sampling protocols. Here, we describe a framework that combines ensemble MD simulations and virtual reality visualization (eMD-VR) to enable users to interactively generate realistic descriptions of large amplitude, millisecond timescale protein conformational changes in proteins. Detailed tests demonstrate that eMD-VR substantially decreases the computational cost of folding simulations of a WW domain, without the need to define collective variables a priori. We further show that eMD-VR generated pathways can be combined with Markov state models to describe the thermodynamics and kinetics of large-scale loop motions in the enzyme cyclophilin A. Our results suggest eMD-VR is a powerful tool for exploring protein energy landscapes in bioengineering efforts.
Introduction
Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is ...recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council guidelines.
Material And Methods
The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment, and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches.
Results
This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage, resuscitative endovascular balloon occlusion and resuscitative thoracotomy, pericardiocentesis, needle decompression, and thoracostomy.
Conclusions
Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition, and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well-organised team using crew resource management, but also on an institutional safety culture embedded in everyday practice through continuous education, training, and multidisciplinary co-operation.
Abstract The occurrence of cardiovascular dysfunction in sepsis is associated with a significantly increased mortality rate of 70% to 90% compared with 20% in septic patients without cardiovascular ...impairment. Thus, rectification or blockade of myocardial depressant factors should partly ameliorate sepsis progression. Heat shock protein 20 (Hsp20) has been shown to enhance myocardial contractile function and protect against doxorubicin-induced cardiotoxicity. To investigate the possible role of Hsp20 in sepsis-mediated cardiac injury, we first examined the expression profiles of five major Hsps in response to lipopolysaccharide (LPS) challenge, and observed that only the expression of Hsp20 was downregulated in LPS-treated myocardium, suggesting that this decrease might be one of the mechanisms contributing to LPS-induced cardiovascular defects. Further studies using loss-of-function and gain-of-function approaches in adult rat cardiomyocytes verified that reduced Hsp20 levels were indeed correlated with the impaired contractile function. In fact, overexpression of Hsp20 significantly enhanced cardiomyocyte contractility upon LPS treatment. Moreover, after administration of LPS (25 μg/g) in vivo , Hsp20 transgenic mice (10-fold overexpression) displayed: 1) an improvement in myocardial function; 2) reduced the degree of cardiac apoptosis; and 3) decreased NF-κB activity, accompanied with reduced myocardial cytokines IL-1β and TNF-α production, compared to the LPS-treated non-transgenic littermate controls. Thus, the increases in Hsp20 levels can protect against LPS-induced cardiac apoptosis and dysfunction, associated with inhibition of NF-κB activity, suggesting that Hsp20 may be a new therapeutic agent for the treatment of sepsis.
This is a book about collaboration by education professionals on a global scale by first establishing the need for it then outlining how that collaboration can be created.
To test intravenously injected gold nanoparticles for x-ray imaging and radiotherapy enhancement of large, imminently lethal, intracerebral malignant gliomas.
Gold nanoparticles approximately 11 nm ...in size were injected intravenously and brains imaged using microcomputed tomography. A total of 15 h after an intravenous dose of 4 g Au/kg was administered, brains were irradiated with 30 Gy 100 kVp x-rays.
Gold uptake gave a 19:1 tumor to normal brain ratio with 1.5% w/w gold in tumor, calculated to increase local radiation dose by approximately 300%. Mice receiving gold and radiation (30 Gy) demonstrated 50% long term (>1 year) tumor-free survival, whereas all mice receiving radiation only died.
Intravenously injected gold nanoparticles cross the blood-tumor barrier, but are largely blocked by the normal blood-brain barrier, enabling high-resolution computed tomography tumor imaging. Gold radiation enhancement significantly improved long-term survival compared with radiotherapy alone. This approach holds promise to improve therapy of human brain tumors and other cancers.
Abstract Background/Purpose Aspartate aminotransferase-to-platelet ratio index (APRI) has good correlation with liver fibrosis progression in the infant and toddler short-gut population. This study ...applies laboratory liver function testing, including APRI, to monitor liver dysfunction over time for short-gut infants, with further analysis of at-risk subpopulations. Methods Study inclusion criteria included infants younger than 1 year at initial intestinal resection with subsequent continuous parenteral nutrition dependence of 3 months minimum. Bilirubin, aspartate aminotransferase, alanine aminotransferase, APRI, and biopsies were collected for 26 weeks postresection. Subgroup analysis was stratified by (1) estimated gestational age, (2) age at intestinal resection (AGE), and (3) remaining intestinal length. Results Thirty-one children were included, all with AGE younger than 2 months at initial intestinal resection (mean, 13 days). Aminotransferase-to-platelet ratio index was the only marker associated with fibrosis progression (median, APRI by METAVIR grade: F0/F1/F2, 1.9; F3, 5.7; F4, 14.7 P = .02). At 8 and 18 weeks postresection, there are separations seen within study subgroups, indicating the onset and progression of liver dysfunction. Conclusion Aminotransferase-to-platelet ratio index is associated with liver fibrosis progression in this population. There are marked changes in liver dysfunction at 8 and 18 weeks postresection, with subgroup differences within estimated gestational age, AGE, and remaining intestinal length.
Molecular breast imaging (MBI) is a new nuclear medicine technique that utilizes small semiconductor-based γ-cameras in a mammographic configuration to provide high-resolution functional images of ...the breast. Current studies with MBI have used Tc-99m sestamibi, which is an approved agent for breast imaging. The procedure is relatively simple to perform. Imaging can be performed within 5 min postinjection, with the breast lightly compressed between the two detectors. Images of each breast are acquired in the craniocaudal and mediolateral oblique projections facilitating comparison with mammography. Key studies have confirmed that MBI has a high sensitivity for the detection of small breast lesions. In patients with suspected breast cancer, MBI has an overall sensitivity of 90%, with a sensitivity of 82% for lesions less than 10 mm in size. Sensitivity was lowest for tumors less than 5 mm in size. Tumor detection does not appear to be dependent on tumor type, but rather on tumor size. Studies using MBI and breast-specific γ-imaging have shown that these methods have comparable sensitivity to breast MRI. A large clinical trial compared MBI with screening mammography in over 1000 women with mammographically dense breast tissue and increased risk of breast cancer and showed that MBI detected two-to three-times more cancers than mammography. In addition, MBI appears to have slightly better specificity than mammography in this trial. MBI provides high-resolution functional images of the breast and its potential applications range from evaluation of the extent of disease to a role as an adjunct screening technique in certain high-risk populations. MBI is highly complementary to existing anatomical techniques, such as mammography, tomosynthesis and ultrasound.
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