Protocolized Versus Nonprotocolized Weaning to Reduce the Duration of Invasive Mechanical Weaning in Neonates A Systematic Review of All Types of Studies

Mechanical ventilation is one of the most commonly used treatments in neonatology. Prolonged mechanical ventilation is associated with deleterious outcomes. To reduce the ventilation duration, weaning protocols have been developed to achieve extubation in adult and pediatric care in a safe and uniform manner. We performed a systematic review to obtain all available evidence on the effect of protocolized versus nonprotocolized weaning on the duration of invasive mechanical ventilation in critically ill neonates. The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, Web of Science, and the International Clinical Trial Registry Platform were searched until January 2018. Quantitative and qualitative studies involving neonates that investigated or described protocolized versus nonprotocolized weaning were included. Primary outcome was the difference in weaning duration. A total of 2099 potentially relevant articles were retrieved. Three stud

Priming by Chemokines Restricts Lateral Mobility of the Adhesion Receptor LFA-1 and Restores Adhesion to ICAM-1 Nano-Aggregates on Human Mature Dendritic Cells

LFA-1 is a leukocyte specific β2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process is not yet known, despite that the importance of lateral organization and dynamics for LFA-1-mediated adhesion regulation is broadly recognized. Using single particle tracking approaches we here show that LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Addition of soluble monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further reduced LFA-1 mobility and readily bound to the receptor. Overall, our results emphasize the importance of LFA-1 lateral mobility across the membrane on the regulation of integrin activation and its function as adhesion receptor. Importantly, our data show that chemokines alone are not sufficient to trigger the high affinity state of the integrin based on the strict definition that affinity refers to the adhesion capacity of a single receptor to its ligand in solution. Instead our data indicate that nanoclustering of the receptor, induced by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1 high affinity state is transiently triggered by inside-out signals.Peer ReviewedPostprint (published version

Glass Transition Behavior of Polymer Films of Nanoscopic Dimensions

Glass transition behavior of nanoscopically thin polymer films is investigated by means of molecular dynamics simulations. A thin polymer film that is composed of bead-spring model chains and supported on an idealized, fcc lattice substrate surface is studied in this work.Comment: in review, macromolecule

Prognostication using SpO(2)/FiO(2) in invasively ventilated ICU patients with ARDS due to COVID-19-Insights from the PRoVENT-COVID study

Background: The SpO(2)/FiO(2) is a useful oxygenation parameter with prognostic capacity in patients with ARDS. We investigated the prognostic capacity of SpO(2)/FiO(2) for mortality in patients with ARDS due to COVID-19. Methods: This was a post-hoc analysis of a national multicenter cohort study in invasively ventilated patients with ARDS due to COVID-19. The primary endpoint was 28-day mortality. Results: In 869 invasively ventilated patients, 28-day mortality was 30.1%. The SpO(2)/FiO(2) on day 1 had no prognostic value. The SpO(2)/FiO(2) on day 2 and day 3 had prognostic capacity for death, with the best cut-offs being 179 and 199, respectively. Both SpO(2)/FiO(2) on day 2 (OR, 0.66 [95%-CI 0.46-0.96]) and on day 3 (OR, 0.70 [95%-CI 0.51-0.96]) were associated with 28-day mortality in a model corrected for age, pH, lactate levels and kidney dysfunction (AUROC 0.78 [0.76-0.79]). The measured PaO2/FiO(2) and the PaO2/FiO(2) calculated from SpO(2)/FiO(2) were strongly correlated (Spearman's r = 0.79). Conclusions: In this cohort of patients with ARDS due to COVID-19, the SpO(2)/FiO(2) on day 2 and day 3 are independently associated with and have prognostic capacity for 28-day mortality. The SpO(2)/FiO(2) is a useful metric for risk stratification in invasively ventilated COVID-19 patients. (C) 2021 The Authors. Published by Elsevier Inc

Deregulation, Privatisation and Marketisation of Nordic Comprehensive Education : Social Changes Reflected in Schooling

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Kinome Profiling Reveals an Interaction Between Jasmonate, Salicylate and Light Control of Hyponastic Petiole Growth in Arabidopsis thaliana

Plants defend themselves against infection by biotic attackers by producing distinct phytohormones. Especially jasmonic acid (JA) and salicylic acid (SA) are well known defense-inducing hormones. Here, the effects of MeJA and SA on the Arabidopsis thaliana kinome were monitored using PepChip arrays containing kinase substrate peptides to analyze posttranslational interactions in MeJA and SA signaling pathways and to test if kinome profiling can provide leads to predict posttranslational events in plant signaling. MeJA and SA mediate differential phosphorylation of substrates for many kinase families. Also some plant specific substrates were differentially phosphorylated, including peptides derived from Phytochrome A, and Photosystem II D protein. This indicates that MeJA and SA mediate cross-talk between defense signaling and light responses. We tested the predicted effects of MeJA and SA using light-mediated upward leaf movement (differential petiole growth also called hyponastic growth). We found that MeJA, infestation by the JA-inducing insect herbivore Pieris rapae, and SA suppressed low light-induced hyponastic growth. MeJA and SA acted in a synergistic fashion via two (partially) divergent signaling routes. This work demonstrates that kinome profiling using PepChip arrays can be a valuable complementary ∼omics tool to give directions towards predicting behavior of organisms after a given stimulus and can be used to obtain leads for physiological relevant phenomena in planta

Cytomegalovirus antibodies in dried blood spots: a minimally invasive method for assessing stress, immune function, and aging

<p>Abstract</p> <p>Background</p> <p>Cytomegalovirus (CMV) is a prevalent herpesvirus with links to both stress and aging. This paper describes and validates a minimally invasive method for assessing antibodies against CMV in finger stick whole blood spot samples for use as an indirect marker of an aspect of cell-mediated immunity.</p> <p>Results</p> <p>Analysis of CMV in dried blood spot samples (DBS) was based on modifications of a commercially available protocol for quantifying CMV antibodies in serum or plasma. The method was evaluated through analysis of precision, reliability, linearity, and correlation between matched serum and DBS samples collected from 75 volunteers. Correlation between DBS and plasma values was linear and high (Pearson correlation <it>R </it>= .96), and precision, reliability, and linearity of the DBS assay were within acceptable ranges.</p> <p>Conclusions</p> <p>The validity of a DBS assay for CMV antibodies will enable its inclusion in population-based surveys and other studies collecting DBS samples in non-clinical settings, increasing scientific understanding of the interaction of social and biological stress and immune function.</p

Development of the SIOPE DIPG network, registry and imaging repository : a collaborative effort to optimize research into a rare and lethal disease

Diffuse intrinsic pontine glioma (DIPG) is a rare and deadly childhood malignancy. After 40 years of mostly single-center, often non-randomized trials with variable patient inclusions, there has been no improvement in survival. It is therefore time for international collaboration in DIPG research, to provide new hope for children, parents and medical professionals fighting DIPG. In a first step towards collaboration, in 2011, a network of biologists and clinicians working in the field of DIPG was established within the European Society for Paediatric Oncology (SIOPE) Brain Tumour Group: the SIOPE DIPG Network. By bringing together biomedical professionals and parents as patient representatives, several collaborative DIPG-related projects have been realized. With help from experts in the fields of information technology, and legal advisors, an international, web-based comprehensive database was developed, The SIOPE DIPG Registry and Imaging Repository, to centrally collect data of DIPG patients. As for April 2016, clinical data as well as MR-scans of 694 patients have been entered into the SIOPE DIPG Registry/Imaging Repository. The median progression free survival is 6.0 months (95% Confidence Interval (CI) 5.6-6.4 months) and the median overall survival is 11.0 months (95% CI 10.5-11.5 months). At two and five years post-diagnosis, 10 and 2% of patients are alive, respectively. The establishment of the SIOPE DIPG Network and SIOPE DIPG Registry means a paradigm shift towards collaborative research into DIPG. This is seen as an essential first step towards understanding the disease, improving care and (ultimately) cure for children with DIPG.Peer reviewe