Dependence of cancer cell adhesion kinetics on integrin ligand surface density measured by a high-throughput label-free resonant waveguide grating biosensor

A novel high-throughput label-free resonant waveguide grating (RWG) imager biosensor, the Epic® BenchTop (BT), was utilized to determine the dependence of cell spreading kinetics on the average surface density (vRGD) of integrin ligand RGD-motifs. vRGD was tuned over four orders of magnitude by co-adsorbing the biologically inactive PLL-g-PEG and the RGD-functionalized PLL-g-PEG-RGD synthetic copolymers from their mixed solutions onto the sensor surface. Using highly adherent human cervical tumor (HeLa) cells as a model system, cell adhesion kinetic data of unprecedented quality were obtained. Spreading kinetics were fitted with the logistic equation to obtain the spreading rate constant (r) and the maximum biosensor response (Δλmax), which is assumed to be directly proportional to the maximum spread contact area (Amax). r was found to be independent of the surface density of integrin ligands. In contrast, Δλmax increased with increasing RGD surface density until saturation at high densities. Interpreting the latter behavior with a simple kinetic mass action model, a 2D dissociation constant of 1753 ± 243 μm−2 (corresponding to a 3D dissociation constant of ~30 μM) was obtained for the binding between RGD-specific integrins embedded in the cell membrane and PLL-g-PEG-RGD. All of these results were obtained completely noninvasively without using any labels

Shifting echo chambers in US climate policy networks

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: Data are available from the Climate Constituencies study at http://drfisher.umd.edu/CCP_REVISED.html.Although substantial attention has focused on efforts by the new Administration to block environmental policies, climate politics have been contentious in the US since well before the election of Donald Trump. In this paper, we extend previous work on empirical examinations of echo chambers in US climate politics using new data collected on the federal climate policy network in summer 2016. We test for the similarity and differences at two points in time in homophily and echo chambers using Exponential Random Graph Models (ERGM) to compare new findings from 2016 to previous work on data from 2010. We show that echo chambers continue to play a significant role in the network of information exchange among policy elites working on the issue of climate change. In contrast to previous findings where echo chambers centered on a binding international commitment to emission reductions, we find that the pre-existing echo chambers have almost completely disappeared and new structures have formed around one of the main components of the Obama Administration’s national climate policy: the Clean Power Plan. These results provide empirical evidence that science communication and policymaking at the elite level shift in relation to the policy instruments under consideration.MacArthur Foundatio

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Current understanding of the human microbiome

Author Posting. © The Author(s), 2018. This is the author's version of the work. It is posted here by permission of Nature Publishing Group for personal use, not for redistribution. The definitive version was published in Nature Medicine 24 (2018): 392–400, doi:10.1038/nm.4517.Our understanding of the link between the human microbiome and disease, including obesity, inflammatory bowel disease, arthritis and autism, is rapidly expanding. Improvements in the throughput and accuracy of DNA sequencing of the genomes of microbial communities associated with human samples, complemented by analysis of transcriptomes, proteomes, metabolomes and immunomes, and mechanistic experiments in model systems, have vastly improved our ability to understand the structure and function of the microbiome in both diseased and healthy states. However, many challenges remain. In this Review, we focus on studies in humans to describe these challenges, and propose strategies that leverage existing knowledge to move rapidly from correlation to causation, and ultimately to translation.Many of the studies described here in our laboratories were supported by the NIH, NSF, DOE, and the Alfred P. Sloan Foundation.2018-10-1

Effective cardiac resynchronization therapy for an adolescent patient with dilated cardiomyopathy seven years after mitral valve replacement and septal anterior ventricular exclusion

Cardiac resynchronization therapy (CRT) is a new treatment for refractory heart failure. However, most heart failure patients treated with CRT are middle-aged or old patients with idiopathic or ischemic dilated cardiomyopathy. We treated a 17 year 11 month old girl with dilated cardiomyopathy after mitral valve replacement (MVR) and septal anterior ventricular exclusion (SAVE). Seven years after the SAVE procedure, she presented complaining of palpitations and general fatigue with normal activity. Her echocardiogram showed reduced left ventricular function. Despite of optimal medical therapy, her left ventricular function continued to decline and she experienced regular arrhythmias such as premature ventricular contractions. We thus elected to perform cardiac resynchronization therapy with defibrillator (CRT-D). After CRT-D, her clinical symptoms improved dramatically and left ventricular ejection fraction (LVEF) improved from 31.2% to 51.3% as assessed by echocardiogram. Serum BNP levels decreased from 448.2 to 213.6 pg/ml. On ECG, arrhythmias were remarkably reduced and QRS duration was shortened from 174 to 152 msec. In conclusion, CRT-D is an effective therapeutic option for adolescent patients with refractory heart failure after left ventricular volume reduction surgery

Estrogen aggravates inflammation in Pseudomonas aeruginosa pneumonia in cystic fibrosis mice

<p>Abstract</p> <p>Background</p> <p>Among patients with cystic fibrosis (CF), females have worse pulmonary function and survival than males, primarily due to chronic lung inflammation and infection with <it>Pseudomonas aeruginosa </it>(<it>P. aeruginosa</it>). A role for gender hormones in the causation of the CF "gender gap" has been proposed. The female gender hormone 17β-estradiol (E2) plays a complex immunomodulatory role in humans and in animal models of disease, suppressing inflammation in some situations while enhancing it in others. Helper T-cells were long thought to belong exclusively to either T helper type 1 (Th1) or type 2 (Th2) lineages. However, a distinct lineage named Th17 is now recognized that is induced by interleukin (IL)-23 to produce IL-17 and other pro-inflammatory Th17 effector molecules. Recent evidence suggests a central role for the IL-23/IL-17 pathway in the pathogenesis of CF lung inflammation. We used a mouse model to test the hypothesis that E2 aggravates the CF lung inflammation that occurs in response to airway infection with <it>P. aeruginosa </it>by a Th17-mediated mechanism.</p> <p>Results</p> <p>Exogenous E2 caused adult male CF mice with pneumonia due to a mucoid CF clinical isolate, the <it>P. aeruginosa </it>strain PA508 (PA508), to develop more severe manifestations of inflammation in both lung tissue and in bronchial alveolar lavage (BAL) fluid, with increased total white blood cell counts and differential and absolute cell counts of polymorphonuclear leukocytes (neutrophils). Inflammatory infiltrates and mucin production were increased on histology. Increased lung tissue mRNA levels for IL-23 and IL-17 were accompanied by elevated protein levels of Th17-associated pro-inflammatory mediators in BAL fluid. The burden of PA508 bacteria was increased in lung tissue homogenate and in BAL fluid, and there was a virtual elimination in lung tissue of mRNA for lactoferrin, an antimicrobial peptide active against <it>P. aeruginosa </it>in vitro.</p> <p>Conclusions</p> <p>Our data show that E2 increases the severity of PA508 pneumonia in adult CF male mice, and suggest two potential mechanisms: enhancement of Th17-regulated inflammation and suppression of innate antibacterial defences. Although this animal model does not recapitulate all aspects of human CF lung disease, our present findings argue for further investigation of the effects of E2 on inflammation and infection with <it>P. aeruginosa </it>in the CF lung.</p

What is new in pediatric cardiac imaging?

Cardiac imaging has had significant influence on the science and practice of pediatric cardiology. Especially the development and improvements made in noninasive imaging techniques, like echocardiography and cardiac magnetic resonance imaging (MRI), have been extremely important. Technical advancements in the field of medical imaging are quickly being made. This review will focus on some of the important evolutions in pediatric cardiac imaging. Techniques such as intracardiac echocardiography, 3D echocardiography, and tissue Doppler imaging are relatively new echocardiographic techniques, which further optimize the anatomical and functional aspects of congenital heart disease. Also, the current standing of cardiac MRI and cardiac computerized tomography will be discussed. Finally, the recent European efforts to organize training and accreditation in pediatric echocardiography are highlighted

Chronic ventricular pacing in children: toward prevention of pacing-induced heart disease

In children with congenital or acquired complete atrioventricular (AV) block, ventricular pacing is indicated to increase heart rate. Ventricular pacing is highly beneficial in these patients, but an important side effect is that it induces abnormal electrical activation patterns. Traditionally, ventricular pacemaker leads are positioned at the right ventricle (RV). The dyssynchronous pattern of ventricular activation due to RV pacing is associated with an acute and chronic impairment of left ventricular (LV) function, structural remodeling of the LV, and increased risk of heart failure. Since the degree of pacing-induced dyssynchrony varies between the different pacing sites, ‘optimal-site pacing’ should aim at the prevention of mechanical dyssynchrony. Especially in children, generally paced from a very early age and having a perspective of life-long pacing, the preservation of cardiac function during chronic ventricular pacing should take high priority. In the perspective of the (patho)physiology of ventricular pacing and the importance of the sequence of activation, this paper provides an overview of the current knowledge regarding possible alternative sites for chronic ventricular pacing. Furthermore, clinical implications and practical concerns of the various pacing sites are discussed. The review concludes with recommendations for optimal-site pacing in children

Psychological Functioning and Disease-Related Quality of Life in Pediatric Patients With an Implantable Cardioverter Defibrillator

The objective of this multicenter study was to evaluate psychological functioning and disease-related quality of life (DRQoL) in pediatric patients with an implantable cardioverter defibrillator (ICD) in The Netherlands. Thirty patients were investigated; the mean age was 16.3 years, and the mean duration of implantation was 3.6 years. To assess psychological problems, three domains of the Symptom Checklist (SCL-90-R) were administered to the 25 patients >13 years old. DRQoL was assessed with a disease-specific pediatric questionnaire, the short-form 11-item Worries About (WA)ICDs Scale. Patients ≥13 years old scored significantly higher than the reference group on the domains of anxiety, depression, and sleeping problems of the SCL-90-R (T = 7.5, p < 0.001; T = 5.4, p < 0.001; and T = 7.8, p < 0.001, respectively). Patients who had received an (in)appropriate shock reported more depressive symptoms (T = 2.1, p < 0.03). Patients with >2 years implant duration (N = 19) or who had received an (in)appropriate shock (N = 13) showed lower DRQoL scores on the modified WAICD (T = 2.1, p < 0.04; T = 2.1, p < 0.5, respectively). Age at implantation or underlying disease did not influence psychological problems or DRQoL. Young ICD patients showed more anxiety, depression, and sleeping disorders. Worries were increased among patients with ICD shocks and in those who had their ICD implanted for >2 years. To determine psychological problems and help children to learn to cope with shocks, proper guidance and monitoring of young ICD patients are recommended