Is paediatric endotracheal suctioning by nurses’ evidence based? An International Survey

Background: Endotracheal suction (ETS) is essential in intubated patients to prevent tube occlusion and is one of the most common nursing interventions performed in intensive care.Aim: To explore how paediatric endotracheal suctioning (ETS) practices reflect Evidence-based Practice (EBP) recommendations in Paediatric intensive care units (PICU) worldwide.Study design and methods: A cross-sectional electronic survey linked to a real patient suction episode. Nurses completed the survey following a recent ETS episode. EBP was defined based on four of the American Association for Respiratory Care (AARC) best evidence recommendations: pre-oxygenation before suction, use of a suction catheter no more than half the diameter of the tracheal tube, shallow depth of suction and the continuous suction applied upon withdrawal of the catheter. Participants included PICU nurses who performed ETS in children (0-17 years) excluding preterm neonates.Results: Four hundred and forty-six complete surveys were received from 20 countries. Most nurses (80%, 367/446) reported that their unit had local guidelines for ETS. The most common reason for suctioning (44%) was audible/visible secretions. Over half of ETS episodes (57%) used closed suction. When exploring the individual components of suction, 63% (282/446) of nurses pre-oxygenated their patient prior to suction, 71% (319/446) suctioned no further than 0.5cm past end of the endotracheal tube, 59% (261/446) used a catheter no more than half the diameter of the endotracheal tube and 78% (348/446) used continuous negative pressure. 24% of nurses gave patients an additional bolus of sedative, analgesic and/or muscle-relaxant medication prior to suction; this decision was not related to the child’s history of instability with suction, as there was no significant difference in those who reported patients had a history of being unstable with suction (p=0.80). 26% (117/446) of nurses complied with all four EBP components in the reported suctioning episode.Conclusions: Considerable variation in paediatric endotracheal suctioning practices exists internationally. While most nurses applied single components of evidence-based recommendations during ETT suctioning, just a quarter applied all four elements. Relevance for clinical practice: Nurses’ need to consider and strive to apply EBP principles to common nursing interventions such as ETS

STAT3 and HIF1 signaling drives oncogenic cellular phenotypes in malignant peripheral nerve sheath tumors

Therapeutic options are limited for neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNST) and clinical trials using drug agents have so far been unsuccessful. This lack of clinical success is likely attributed to high levels of intratumoral molecular heterogeneity and variations in signal transduction within MPNSTs. To better explore the variance of malignant signaling properties within heterogeneous MPNSTs, four MPNST cell lines (ST8814, S462, S1844.1, and S1507.2) were used. The data demonstrate that small-molecule inhibition of the MET proto-oncogene and mTOR had variable outcome when preventing wound healing, cell migration, and invasion, with the S462 cells being highly resistant to both. Of interest, targeted inhibition of the STAT3 transcription factor suppressed wound healing, cell migration, invasion, and tumor formation in all four MPNST lines, which demonstrates that unlike MET and mTOR, STAT3 functions as a common driver of tumorigenesis in NF1-MPNSTs. Of clinical importance, STAT3 knockdown was sufficient to block the expression of hypoxia-inducible factor (HIF)1α, HIF2α, and VEGF-A in all four MPNST lines. Finally, the data demonstrate that wound healing, cell migration, invasion, and tumor formation through STAT3 are highly dependent on HIF signaling, where knockdown of HIF1α ablated these oncogenic facets of STAT3

Exploring the Chemical Space of Macro- and Micro-Algae Using Comparative Metabolomics

With more than 156,000 described species, eukaryotic algae (both macro- and micro-algae) are a rich source of biological diversity, however their chemical diversity remains largely unexplored. Specialised metabolites with promising biological activities have been widely reported for seaweeds, and more recently extracts from microalgae have exhibited activity in anticancer, antimicrobial, and antioxidant screens. However, we are still missing critical information on the distinction of chemical profiles between macro- and microalgae, as well as the chemical space these metabolites cover. This study has used an untargeted comparative metabolomics approach to explore the chemical diversity of seven seaweeds and 36 microalgal strains. A total of 1390 liquid chromatography-mass spectrometry (LC-MS) features were detected, representing small organic algal metabolites, with no overlap between the seaweeds and microalgae. An in-depth analysis of four Dunaliella tertiolecta strains shows that environmental factors may play a larger role than phylogeny when classifying their metabolomic profile

Analysis pipelines for cancer genome sequencing in mice

Mouse models of human cancer have transformed our ability to link genetics, molecular mechanisms and phenotypes. Both reverse and forward genetics in mice are currently gaining momentum through advances in next-generation sequencing (NGS). Methodologies to analyze sequencing data were, however, developed for humans and hence do not account for species-specific differences in genome structures and experimental setups. Here, we describe standardized computational pipelines specifically tailored to the analysis of mouse genomic data. We present novel tools and workflows for the detection of different alteration types, including single-nucleotide variants (SNVs), small insertions and deletions (indels), copy-number variations (CNVs), loss of heterozygosity (LOH) and complex rearrangements, such as in chromothripsis. Workflows have been extensively validated and cross-compared using multiple methodologies. We also give step-by-step guidance on the execution of individual analysis types, provide advice on data interpretation and make the complete code available online. The protocol takes 2?7 d, depending on the desired analyses.D.S. is supported by the European Research Council (Consolidator Grant 648521) and the Deutsche Forschungsgemeinschaft (SA1374/4-2; SFB 1321). I.V. is supported by the European Research Council (Starting Grant INTRAHETEROSEQ) and the Spanish Goverment (SAF2016-76758-R). R.R. is supported by the European Research Council (Consolidator Grants PACA-MET and MSCA-ITN-ETN PRECODE), the Deutsche Forschungsgemeinschaft (DFG RA1629/2-1; SFB1243; SFB1321; SFB1335), the German Cancer Consortium Joint Funding Program, and the Deutsche Krebshilfe (70112480)

A Mechanistic and Pathophysiological Approach for Stroke Associated with Drugs of Abuse

Drugs of abuse are associated with stroke, especially in young individuals. The major classes of drugs linked to stroke are cocaine, amphetamines, heroin, morphine, cannabis, and new synthetic cannabinoids, along with androgenic anabolic steroids (AASs). Both ischemic and hemorrhagic stroke have been reported due to drug abuse. Several common mechanisms have been identified, such as arrhythmias and cardioembolism, hypoxia, vascular toxicity, vascular spasm and effects on the thrombotic mechanism, as causes for ischemic stroke. For hemorrhagic stroke, acute hypertension, aneurysm formation/rupture and angiitis-like changes have been implicated. In AAS abuse, the effect of blood pressure is rather substance specific, whereas increased erythropoiesis usually leads to thromboembolism. Transient vasospasm, caused by synthetic cannabinoids, could lead to ischemic stroke. Opiates often cause infective endocarditis, resulting in ischemic stroke and hypereosinophilia accompanied by pyogenic arthritis, provoking hemorrhagic stroke. Genetic variants are linked to increased risk for stroke in cocaine abuse. The fact that case reports on cannabis-induced stroke usually refer to the young population is very alarming

Lateral flow test performance in children for SARS-CoV-2 using anterior nasal and buccal swabbing: sensitivity, specificity, negative and positive predictive values

ObjectiveTo determine if the sensitivity of the lateral flow test is dependent on the viral load and on the location of swabbing in the respiratory tract in children.DesignPhase 1: Routinely performed reverse transcriptase PCR (RT-PCR) using nose and throat (NT) swabs or endotracheal (ET) aspirates were compared with Innova lateral flow tests (LFTs) using anterior nasal (AN) swabs. Phase 2: RT-PCR-positive children underwent paired AN RT-PCR and LFT and/or paired AN RT-PCR and buccal LFT.SettingTertiary paediatric hospitals.PatientsChildren under the age of 18 years. Phase 1: undergoing routine testing, phase 2: known SARS-CoV-2 positive.ResultsPhase 1: 435 paired swabs taken in 431 asymptomatic patients resulted in 8 positive RT-PCRs, 9 PCR test failures and 418 negative RT-PCRs from NT or ET swabs. The test performance of AN LFT demonstrated sensitivity: 25% (4%-59%), specificity: 100% (99%-100%), positive predictive value (PPV): 100% (18%-100%) and negative predictive value (NPV): 99% (97%-99%).Phase 2: 14 AN RT-PCR-positive results demonstrated a sensitivity of 77% (50%-92%) of LFTs performed on AN swabs. 15/16 paired buccal LFT swabs were negative.ConclusionThe NPV, PPV and specificity of LFTs are excellent. The sensitivity of LFTs compared with RT-PCR is good when the samples are colocated but may be reduced when the LFT swab is taken from the AN. Buccal swabs are not appropriate for LFT testing. Careful consideration of the swabbing reason, the tolerance of the child and the requirements for test processing (eg, rapidity of results) should be undertaken within hospital settings.Trial registration numberNCT04629157

Strontium isotopes in Chilean rivers : the flux of unradiogenic continental Sr to seawater

Author Posting. © The Author(s), 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Chemical Geology 268 (2009): 337-343, doi:10.1016/j.chemgeo.2009.09.013.Analyses of Chilean river waters indicate that the average yield of unradiogenic Sr (~ 517 mol Sr km− 2 yr− 1, 87Sr/86Sr ~ 0.7057) from western South America (1,220,853 km2) into the southeastern Pacific Ocean is ~ 2–4 times higher than that from Iceland (~ 110 mol Sr km − 2 yr− 1, 87Sr/86Sr ~ 0.7025) and the Deccan traps, but lower than fluxes of unradiogenic Sr from ocean islands in the Lesser Antilles and Réunion. The Sr flux from western South America accounts for about 1.8% of the annual dissolved Sr delivered to the ocean via rivers. If Chilean rivers analyzed in this study accurately characterize runoff from western South America, active convergent continental margins release about as much unradiogenic Sr to seawater as a 0–1 Myr old mid-ocean ridge segment of equivalent length. Modulations of the flux of unradiogenic Sr from active margins over geologic time scales have to be considered as an additional driving force of change in the marine Sr isotope record, supplementing temporal variations in the submarine hydrothermal flux as a source of unradiogenic Sr to seawater. Such modulations can be driven by changes in the surface exposure of volcanic arc terrains, changes in climate, ocean currents and geographic latitude due to plate tectonics, as well as topographic changes that can affect local rainfall, runoff and erosion.We acknowledge financial 302 support from NSF grant EAR-0519387, from WHOI’s Mary Sears Visitor Program, and thank the German DAAD for travel support for KF

PiggyBac transposon tools for recessive screening identify B-cell lymphoma drivers in mice.

B-cell lymphoma (BCL) is the most common hematologic malignancy. While sequencing studies gave insights into BCL genetics, identification of non-mutated cancer genes remains challenging. Here, we describe PiggyBac transposon tools and mouse models for recessive screening and show their application to study clonal B-cell lymphomagenesis. In a genome-wide screen, we discover BCL genes related to diverse molecular processes, including signaling, transcriptional regulation, chromatin regulation, or RNA metabolism. Cross-species analyses show the efficiency of the screen to pinpoint human cancer drivers altered by non-genetic mechanisms, including clinically relevant genes dysregulated epigenetically, transcriptionally, or post-transcriptionally in human BCL. We also describe a CRISPR/Cas9-based in vivo platform for BCL functional genomics, and validate discovered genes, such as Rfx7, a transcription factor, and Phip, a chromatin regulator, which suppress lymphomagenesis in mice. Our study gives comprehensive insights into the molecular landscapes of BCL and underlines the power of genome-scale screening to inform biology

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries. Funding: Bill & Melinda Gates Foundation