155155 research outputs found
Sort by
Tracheal intubation in critically ill adults with a physiologically difficult airway. An international Delphi study.
No full textPURPOSE
Our study aimed to provide consensus and expert clinical practice statements related to airway management in critically ill adults with a physiologically difficult airway (PDA).
METHODS
An international Steering Committee involving seven intensivists and one Delphi methodology expert was convened by the Society of Critical Care Anaesthesiologists (SOCCA) Physiologically Difficult Airway Task Force. The committee selected an international panel of 35 expert clinician-researchers with expertise in airway management in critically ill adults. A Delphi process based on an iterative approach was used to obtain the final consensus statements.
RESULTS
The Delphi process included seven survey rounds. A stable consensus was achieved for 53 (87%) out of 61 statements. The experts agreed that in addition to pathophysiological conditions, physiological alterations associated with pregnancy and obesity also constitute a physiologically difficult airway. They suggested having an intubation team consisting of at least three healthcare providers including two airway operators, implementing an appropriately designed checklist, and optimizing hemodynamics prior to tracheal intubation. Similarly, the experts agreed on the head elevated laryngoscopic position, routine use of videolaryngoscopy during the first attempt, preoxygenation with non-invasive ventilation, careful mask ventilation during the apneic phase, and attention to cardiorespiratory status for post-intubation care.
CONCLUSION
Using a Delphi method, agreement among a panel of international experts was reached for 53 statements providing guidance to clinicians worldwide on safe tracheal intubation practices in patients with a physiologically difficult airway to help improve patient outcomes. Well-designed studies are needed to assess the effects of these practice statements and address the remaining uncertainties
Phosphate deficiency alters transcript isoforms via alternative transcription start sites.
Get PDFAlternative transcription start sites (TSS) are widespread in eukaryotes and can alter the 5' UTR length and coding potential of transcripts. Here we show that inorganic phosphate (Pi) availability regulates the usage of several alternative TSS in Arabidopsis (Arabidopsis thaliana). In comparison to phytohormone treatment, Pi had a pronounced and specific effect on the usage of many alternative TSS. By combining short-read RNA sequencing with long-read sequencing of full-length mRNAs, we identified a set of 45 genes showing alternative TSS under Pi deficiency. Alternative TSS affected several processes, such as translation via the exclusion of upstream open reading frames present in the 5' UTR of RETICULAN LIKE PROTEIN B1 mRNA, and subcellular localization via removal of the plastid transit peptide coding region from the mRNAs of HEME OXYGENASE 1 and SULFOQUINOVOSYLDIACYLGLYCEROL 2. Several alternative TSS also generated shorter transcripts lacking the coding potential for important domains. For example, the EVOLUTIONARILY CONSERVED C-TERMINAL REGION 4 (ECT4) locus, which encodes an N6-methyladenosine (m6A) reader, strongly expressed under Pi deficiency a short noncoding transcript (named ALTECT4) ~550 nt long with a TSS in the penultimate intron. The specific and robust induction of ALTECT4 production by Pi deficiency led to the identification of a role for m6A readers in primary root growth in response to low phosphate that is dependent on iron and is involved in modulating cell division in the root meristem. Our results identify alternative TSS usage as an important process in the plant response to Pi deficiency
Pigment Epithelium-Derived Factor Binding to VEGFR-1 (Flt-1) Increases the Survival of Retinal Neurons.
Get PDFPURPOSE
The purpose of this study was to examine possible involvement of vascular endothelial growth factor (VEGF) receptor (VEGFR)-1/Flt-1 in pigment epithelium-derived factor (PEDF)-promoted survival of retinal neurons.
METHODS
Survival of growth factor-deprived retinal ganglion cells (RGCs) and R28 cells and activation of ERK-1/-2 MAP kinases were assessed in the presence of PEDF, placental growth factor (PlGF), and VEGF using cell cultures, viability assays and quantitation of ERK-1/-2 phosphorylation. VEGFR-1/Flt-1 expression was determined using quantitative PCR (qPCR) and Western blotting. VEGFR-1/Flt-1 was knocked down in R28 cells by small interfering RNA (siRNA). Binding of a PEDF-IgG Fc fusion protein (PEDF-Fc) to retinal neurons, immobilized VEGFR-1/Flt-1 and VEGFR-1/Flt-1-derived peptides was studied using binding assays and peptide scanning.
RESULTS
PEDF in combination with PlGF stimulated increased cell survival and ERK-1/-2 MAP kinase activation compared to effects of either factor alone. VEGFR-1/Flt-1 expression in RGCs and R28 cells was significantly upregulated by hypoxia, VEGF, and PEDF. VEGFR-1/Flt-1 ligands (VEGF and PlGF) or soluble VEGFR-1 (sflt-1) competed with PEDF-Fc for binding to R28 cells. Depleting R28 cells of VEGFR-1/Flt-1 resulted in reduced PEDF-Fc binding when comparing VEGFR-1/Flt-1 siRNA- and control siRNA-treated cells. PEDF-Fc interacted with immobilized sflt-1, which was specifically blocked by VEGF and PlGF. PEDF-Fc binding sites were mapped to VEGFR-1/Flt-1 extracellular domains D3 and D4. Peptides corresponding to D3 and D4 specifically inhibited PEDF-Fc binding to R28 cells. These peptides and sflt-1 significantly inhibited PEDF-promoted survival of R28 cells.
CONCLUSIONS
These results suggest that PEDF can target VEGFR-1/Flt-1 and this interaction plays a significant role in PEDF-mediated neuroprotection in the retina
Aloperine Suppresses Cancer Progression by Interacting with VPS4A to Inhibit Autophagosome-lysosome Fusion in NSCLC.
Get PDFAloperine (ALO), a quinolizidine-type alkaloid isolated from a natural Chinese herb, has shown promising antitumor effects. Nevertheless, its common mechanism of action and specific target remain elusive. Here, it is demonstrated that ALO inhibits the proliferation and migration of non-small cell lung cancer cell lines in vitro and the tumor development in several mouse tumor models in vivo. Mechanistically, ALO inhibits the fusion of autophagosomes with lysosomes and the autophagic flux, leading to the accumulation of sequestosome-1 (SQSTM1) and production of reactive oxygen species (ROS), thereby inducing tumor cell apoptosis and preventing tumor growth. Knockdown of SQSTM1 in cells inhibits ROS production and reverses ALO-induced cell apoptosis. Furthermore, VPS4A is identified as a direct target of ALO, and the amino acids F153 and D263 of VPS4A are confirmed as the binding sites for ALO. Knockout of VPS4A in H1299 cells demonstrates a similar biological effect as ALO treatment. Additionally, ALO enhances the efficacy of the anti-PD-L1/TGF-β bispecific antibody in inhibiting LLC-derived subcutaneous tumor models. Thus, ALO is first identified as a novel late-stage autophagy inhibitor that triggers tumor cell death by targeting VPS4A
Raw major element oxide data obtained by EPMA for volcanic events analysed from two proximal sites from Iceland between 750 and 940 CE
No full textRaw major element oxide data for volcanic events analysed from two proximal sites from Iceland across the period 750-940 CE. Tephra (ash) samples were taken from soil outcrops in Iceland [Atley, 63.67295°N/18.68231°W; Quarry Hafid, 64.054°N/19.786°W] for candidate events and this material was analysed using electron probe micro-analysis (EPMA) at the University of Bern, Switzerland. The location of the outcrop, sample depth, raw oxide values, and correlating horizon are provided
High-resolution ice-core analyses identify the Eldgjá eruption and a cluster of Icelandic and trans-continental tephras between 936 and 943 CE.
Get PDFThe Eldgjá eruption is the largest basalt lava flood of the Common Era. It has been linked to amajor ice‐core sulfur (S) spike in 939–940 CE and Northern Hemisphere summer cooling in 940 CE. Despite itsmagnitude and potential climate impacts, uncertainties remain concerning the eruption timeline, atmosphericdispersal of emitted volatiles, and coincident volcanism in Iceland and elsewhere. Here, we present acomprehensive analysis of Greenland ice‐cores from 936 to 943 CE, revealing a complex volatile record andcryptotephra with numerous geochemical populations. Transitional alkali basalt tephra matching Eldgjá arefound in 939–940 CE, while tholeiitic basalt shards present in 936/937 CE and 940/941 CE are compatible withcontemporaneous Icelandic eruptions from Grímsvötn and Bárðarbunga‐Veiðivötn systems (including V‐Sv tephra). We also find four silicic tephra populations, one of which we link to the Jala Pumice of Ceboruco(Mexico) at 941 ± 1 CE. Triple S isotopes, Δ33S, spanning 936–940 CE are indicative of upper tropospheric/lower stratospheric transport of aerosol sourced from the Icelandic fissure eruptions
Regionale Sprachgeschichte als regionale Systemgeschichte. Pronominale Partitivität und Vergleichskonstruktionen in den Dialekten des nördlichen Rheinlandes
No full textDieser Beitrag verfolgt den Ansatz der strukturellen Dialektologie, um das Inventar an Varianten und deren Distribution im Kleinraum des (historischen) Westdeutschen zu beschreiben, um so einen Beitrag zur regionalen Sprachgeschichte im Sinne von Eickmans (1998 & 2003) zu geben. Fokussiert werden zwei Phänomenbereiche der dialektalen (Morpho-)Syntax: pronominale Partitivität und Vergleichskonstruktionen. Mit Hilfe des Diasystem-Konzepts wird – über isolierte Formen hinaus – die räumliche Verbreitung von dialektalen Subsystemen herausgearbeitet. Die Befunde werden vor dem Hintergrund der Forschungsliteratur diachron interpretiert
The development of an implicit measure of treatment expectations.
No full textIn three preregistered studies, we investigated whether implicit treatment expectations, using a relational implicit measure (the MT-PEP), vary between participants provided opposing information about novel medical treatments (Studies 1 and 2) or who responded based on normative beliefs toward common over-the-counter drugs (Study 3). The studies revealed large Cohen's d effect sizes of both novel and well-known treatment information within the implicit measure. The studies also provide evidence of convergent validity, with MT-PEP scores associated with explicit beliefs about medicine and over-the-counter drug familiarity. Implicit treatment expectations can be assessed and offer a novel tool for the intersection of social psychology and medicine
Data sources:
BORIS Portal Bern Open Repository and I...BAF-Online: Proceedings of the Berner Al...HASBonline – Hefte zur Archäologie des M...Informationswissenschaft: Theorie, Metho...Jahrbuch Diakonie SchweizJournal of Eye Movement ResearchJournal of Radiation Oncology Informatic...BOP SerialsVersants. Revista suiza de literaturas r...BORIS ThesesAccess Repository Dashboard
Do you manage Bern Open Repository and Information System (BORIS)? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!