Continuous Positive Airway Pressure vs. High Flow Nasal Cannula in children with acute severe or moderate bronchiolitis. A systematic review and Meta-analysis.

OBJECTIVE: To compare the safety and effectiveness of Continuous Positive Airway Pressure (CPAP) vs. High Flow Nasal Cannula (HFNC) to prevent therapeutic failure and the need of invasive ventilation in children with acute moderate-severe bronchiolitis. DESIGN: A systematic review and meta-analysis. SETTING: Medline, Embase, Lilacs, Cochrane and gray literature (May 2020) was performed. PARTICIPANTS: Randomized clinical trials patients with moderate to severe bronchiolitis. MAIN VARIABLES: Therapeutic failure, need for invasive ventilation, adverse events, length of PCCU and of hospital stay. INTERVENTION: The quality of the studies was assessed with the Cochrane risk and bias tool. We conducted meta-analysis using fixed effect model and random effects model. RESULTS: Three RCTs were included. Showed less risk of therapeutic failure with CPAP compared with HFNC (RR=0.7; 95%CI 0.5-0.99) developed hours later in patients with CPAP (MD=3.16; 95%CI 1.55-4.77). We did not find differences in other outcomes, such as need of invasive ventilation (RR=0.60; 95%CI 0.25-1.43), apnea (RR=0.40; 95%CI 0.08-1.99), or number of days in the intensive care unit (MD=0.02; 95%CI -0.38 to 0.42), and length of hospitalization (MD=-1.00; 95%IC -2.66 to 0.66). Adverse events (skin lesions) were more common with CPAP (RR 2.47; 95%CI 1.17-5.22). CONCLUSIONS: In moderate/severe bronchiolitis CPAP demonstrated a lower risk of therapeutic failure and a longer time to failure. But more adverse events like nasal injury. There were no differences in other variables.

Continuous Positive Airway Pressure vs. High Flow Nasal Cannula in children with acute severe or moderate bronchiolitis. A systematic review and Meta-analysis / Presión positiva continua en vía aérea (CPAP) vs. Cánula de alto flujo (CAF) en lactantes con bronquiolitis aguda moderada y grave. Revisión sistemática de la literatura y meta-análisis

Objective: To compare the safety and effectiveness of Continuous Positive Airway Pressure (CPAP) vs. High Flow Nasal Cannula (HFNC) to prevent therapeutic failure and the need of invasive ventilation in children with acute moderate-severe bronchiolitis.Design: A systematic review and meta-analysis.SettingMedline, Embase, Lilacs, Cochrane and gray literature (May 2020) was performed.ParticipantsRandomized clinical trials patients with moderate to severe bronchiolitis.Main variablesTherapeutic failure, need for invasive ventilation, adverse events, length of PCCU and of hospital stay.InterventionThe quality of the studies was assessed with the Cochrane risk and bias tool. We conducted meta-analysis using fixed effect model and random effects model.Results: Three RCTs were included. Showed less risk of therapeutic failure with CPAP compared with HFNC (RR=0.7; 95%CI 0.5–0.99) developed hours later in patients with CPAP (MD=3.16; 95%CI 1.55–4.77). We did not find differences in other outcomes, such as need of invasive ventilation (RR=0.60; 95%CI 0.25–1.43), apnea (RR=0.40; 95%CI 0.08–1.99), or number of days in the intensive care unit (MD=0.02; 95%CI −0.38 to 0.42), and length of hospitalization (MD=−1.00; 95%IC −2.66 to 0.66). Adverse events (skin lesions) were more common with CPAP (RR 2.47; 95%CI 1.17–5.22).Conclusion: sIn moderate/severe bronchiolitis CPAP demonstrated a lower risk of therapeutic failure and a longer time to failure. But more adverse events like nasal injury. There were no differences in other variables (AU)

Objetivo: Comparar la seguridad y la efectividad de la presión positiva continúa en la vía aérea (CPAP) y la cánula nasal de oxígeno de alto flujo (OAF) para prevenir el fracaso terapéutico y la necesidad de ventilación mecánica invasiva en niños con bronquiolitis aguda moderada y grave.Diseño: Revisión sistemática y metaanálisis.ÁmbitoBúsqueda en Medline, Embase, Lilacs, Cochrane y literatura gris (hasta mayo 2020).ParticipantesEnsayos clínicos aleatorizados en pacientes con bronquiolitis aguda moderada-grave.IntervencionesLa calidad de los estudios se evaluó utilizando la escala de riesgo de sesgos de Cochrane y se realizó un metaanálisis usando modelo de efectos fijos y de efectos aleatorios.VariablesFracaso terapéutico, necesidad de ventilación invasiva, eventos adversos, estancia en la UCIP y en hospitalización.Resultados: Tres estudios fueron incluidos. Evidenciamos menor riesgo de fracaso terapéutico en los pacientes con CPAP comparados con CAF (RR: 0,7; IC 95%: 0,5-0,99), y este se desarrolló más tarde en los pacientes con CPAP (MD: 3,16; IC 95%: 1,55-4,77). No hubo diferencias en otras variables, como la necesidad de ventilación invasiva (RR: 0,60; IC 95%: 0,25-1,43), apnea (RR: 0,40; IC 95%: 0,08-1,99), estancia en la UCIP (MD: 0,02; IC 95%: −0,38-0,42) y en hospitalización (MD: −1,00; IC 95%: −2,66-0,66). Los eventos adversos (lesiones en piel) fueron más comunes en CPAP (RR: 2,47; IC 95%: 1,17-5,22).Conclusiones: En bronquiolitis moderada y grave el CPAP demostró menor riesgo de fracaso terapéutico y una aparición más tardía, pero más eventos adversos (lesiones en piel). No encontramos diferencias en otras variables (AU)

Continuous Positive Airway Pressure vs. High Flow Nasal Cannula in children with acute severe or moderate bronchiolitis. A systematic review and Meta-analysis.

OBJECTIVE: To compare the safety and effectiveness of Continuous Positive Airway Pressure (CPAP) vs. High Flow Nasal Cannula (HFNC) to prevent therapeutic failure and the need of invasive ventilation in children with acute moderate-severe bronchiolitis. DESIGN: A systematic review and meta-analysis. SETTING: Medline, Embase, Lilacs, Cochrane and gray literature (May 2020) was performed. PARTICIPANTS: Randomized clinical trials patients with moderate to severe bronchiolitis. MAIN VARIABLES: Therapeutic failure, need for invasive ventilation, adverse events, length of PCCU and of hospital stay. INTERVENTION: The quality of the studies was assessed with the Cochrane risk and bias tool. We conducted meta-analysis using fixed effect model and random effects model. RESULTS: Three RCTs were included. Showed less risk of therapeutic failure with CPAP compared with HFNC (RR=0.7; 95%CI 0.5-0.99) developed hours later in patients with CPAP (MD=3.16; 95%CI 1.55-4.77). We did not find differences in other outcomes, such as need of invasive ventilation (RR=0.60; 95%CI 0.25-1.43), apnea (RR=0.40; 95%CI 0.08-1.99), or number of days in the intensive care unit (MD=0.02; 95%CI -0.38 to 0.42), and length of hospitalization (MD=-1.00; 95%IC -2.66 to 0.66). Adverse events (skin lesions) were more common with CPAP (RR 2.47; 95%CI 1.17-5.22). CONCLUSIONS: In moderate/severe bronchiolitis CPAP demonstrated a lower risk of therapeutic failure and a longer time to failure. But more adverse events like nasal injury. There were no differences in other variables.

Evaluation of reference genes for reverse transcription-quantitative PCR assays in organs of zebrafish exposed to glyphosate-based herbicide, Roundup.

Roundup is a glyphosate-based herbicide (GBH) widely used in agriculture and may cause toxic effects in non-target organisms. Model organisms, as zebrafish, and analysis of gene expression by reverse transcription-quantitative PCR (RT-qPCR) could be used to better understand the Roundup toxicity. A prerequisite for RT-qPCR is the availability of appropriate reference genes; however, they have not been described for Roundup-exposed fish. The aim of this study was to evaluate the expression stability of six reference genes (rpl8, ß-act, gapdh, b2m, ef1α, hprt1) and one expressed repetitive element (hatn10) in organs of males (brain, gill, testis) and females (ovary) of zebrafish exposed to Roundup WG at three concentrations (0.065, 0.65 and 6.5 mg N-(phosphonomethyl) glycine/l) for 7 days. Genes were ranked by geNorm, NormFinder, BestKeeper, Delta C t and RefFinder, and their best combinations were determined by geNorm and NormFinder programs. The two most stable ranked genes were specific to each organ: gill (ß-act; rpl8); brain (rpl8; ß-act); testis (ef1α; gapdh); and ovary (rpl8; hprt1). The cat transcript level was used to evaluate the effect of normalization with these reference genes. These are the first suitable reference genes described for the analysis of gene expression in organs of Roundup-exposed zebrafish, and will allow investigations of the molecular mechanisms of Roundup toxicity.

[Mechanisms of pathogenicity and adhesion in Pasteurella haemolytica]. / Mecanismos de patogenicidad y adherencia de Pasteurella haemolytica.

Pasteurella haemolytica is one of the bacteria most commonly isolated from pneumonic cases in ruminants. Some of the mechanisms and factors involved in the pathogenesis of the disease are partially documented; and the early stages of bacterial colonization have not been totally clarified. Therefore a review is presented in this paper, particularly related with the mechanisms of bacterial pathogenicity responsible of pulmonary damage to ruminants, as well as a detailed analysis of the adherence process.

The murine PKR tumor suppressor gene is rearranged in a lymphocytic leukemia.

The double-stranded RNA-dependent kinase, PKR, is encoded by an interferon inducible gene and is largely responsible for the anti-viral effects of this cytokine. Recent studies have shown that PKR may also play a role in the regulation of normal cellular growth. Although numerous examples of viral strategies for inactivation of PKR exist, there is no evidence of PKR inactivation in tumors. We demonstrate here that the Tik gene, which encodes a dual-specificity kinase, is the murine homolog of PKR, the dsRNA-dependent kinase, and has undergone a rearrangement of one allele in a murine lymphocytic leukemia cell. We have cloned a cDNA that corresponds to a mutated transcript from the rearranged mPKR gene and show that while the mutated polypeptide retains its ability to dimerize and bind dsRNA, it is catalytically inactive. Although this mutated mPKR lacks apparent dominant-negative function, the net effect of reduced PKR activity in these cells may be significant.

SHP-1 associates with both platelet-derived growth factor receptor and the p85 subunit of phosphatidylinositol 3-kinase.

The Src homology 2 (SH2)-containing protein tyrosine phosphatase 1, SHP-1, is highly expressed in all hematopoietic cells as well as in many non-hematopoietic cells, particularly in some malignant epithelial cell lines. In hematopoietic cells, SHP-1 negatively regulates multiple cytokine receptor pathways. The precise function and the targets of SHP-1 in non-hematopoietic cells, however, are largely unknown. Here we demonstrate that SHP-1 associates with both the tyrosine-phosphorylated platelet-derived growth factor (PDGF) receptor and the p85 subunit of phosphatidylinositol 3-kinase in MCF-7 and TRMP cells. Through the use of mutant PDGF receptors and performing peptide competition for immunoprecipitation, it was determined that SHP-1 independently associates with the PDGF receptor and p85 and that its N-terminal SH2 domain is directly responsible for the interactions. Overexpression of SHP-1 in TRMP cells transfected with the PDGF receptor markedly inhibited PDGF-induced c-fos promoter activation, whereas the expression of three catalytically inactive SHP-1 mutants increased the c-fos promoter activation in response to PDGF stimulation. These results indicate that SHP-1 might negatively regulate PDGF receptor-mediated signaling in these cells. Identification of the association of SHP-1 with the PDGF receptor and p85 in MCF-7 and TRMP cells furthers our understanding of the function of SHP-1 in non-hematopoietic cells.

Identification of tyrosine 620 as the major phosphorylation site of myelin-associated glycoprotein and its implication in interacting with signaling molecules.

Myelin-associated glycoprotein (MAG) is a myelin-specific cell adhesion molecule of the immunoglobulin supergene family and is tyrosine-phosphorylated in the developing brain. To define the role of MAG in signal transduction, the tyrosine phosphorylation sites were analyzed. The major tyrosine phosphorylation residue was identified as Tyr-620, which was found to interact specifically with the SH2 domains of phospholipase C (PLC gamma). This domain may represent a novel protein binding motif that can be regulated by tyrosine phosphorylation. MAG also specifically bound the Fyn tyrosine kinase, suggesting that MAG serves as a docking protein that allows the interaction between different signaling molecules.

Ras mediates translation initiation factor 4E-induced malignant transformation.

Translation initiation factor eIF-4E binds to the eukaryotic mRNA 5' cap structure (m7 GpppN, where N is any nucleotide). eIF-4E is a limiting factor in translation and plays a key role in regulation of translation. We have shown previously that overexpression of eIF-4E in rodent fibroblasts results in tumorigenic transformation. eIF-4E also exhibits mitogenic activity when microinjected into serum-starved NIH-3T3 cells. To understand the mechanisms by which eIF-4E exerts its mitogenic property, we examined the involvement of the Ras signaling pathway in this activity. Here, we report that Ras is activated in eIF-4E-overexpressing cells, as the proportion of GTP-bound Ras is increased. Overexpression of the negative effector of cellular Ras, GTPase activating protein, causes reversion of the transformed phenotype. Furthermore, we show that neutralizing antibodies to Ras, or a dominant-negative mutant of Ras, inhibit the mitogenic activity of eIF-4E. We conclude that eIF-4E exerts its mitogenic and oncogenic activities by the activation of Ras.